Oncopathology Update

Evaluation of the Surgical Specimen After Neoadjuvant Systemic Therapy

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Tue, 23 Mar 2021 17:30:00 +0000

Clinical information required for pathologic evaluation

It is important that the multidisciplinary team (e.g., surgeons, radiologists, and pathologists) communicate as a team for patient care; this is covered in detail in our companion multi-disciplinary paper.41 At a bare minimum, the request form must clearly indicate neoadjuvant systemic therapy has been given, along with the location and pretreatment size of the tumor(s). A suggested template requisition form that can be sent with the specimen is included below

Specimen handling

Priorities for evaluation of the surgical specimen are different after neoadjuvant systemic therapy, with emphasis on informed and accurate evaluation of tumor response to treatment. In general, one should apply the principles within national and institutional guidelines for standardization of processing and reporting of breast specimens, such as those noted above. Ideally, specimens should be sliced when fresh to identify the markers of the original tumor bed and to ensure formalin penetration.

Residual tumor is usually less well defined and softer than untreated tumor, making it more difficult to detect grossly. Therefore, careful mapping and more extensive sampling is required for histopathologic study. It is strongly recommended that an image of the sliced specimen be recorded (radiograph, photograph, photocopy, or drawing) and then used as a map for the sections taken, so that the histopathologic findings of any residual disease in the breast can be more easily understood. For example, the sections taken can be drawn on a printed image of the sliced specimen and then scanned into the pathology database for viewing at the time of histopathologic study. More precise imaging of the gross specimen and correlation with the histopathologic sections will decrease the number of sections taken from the breast, and increase the efficiency and accuracy of pathologic assessment. This can save time and money while enabling consistent and careful pathologic interpretation. The recommendations below will attempt to supplement existing national guidelines for specific situations encountered in the neoadjuvant setting; however, the pathologist should use sound clinical judgment on a case-by-case basis.

Sampling of small lumpectomy specimens. Many institutional standard operating procedures call for thinly slicing and submitting small specimens in their entirety (e.g., <5 cm in greatest diameter in Yale University’s standard operating procedure, and <30 g in the Dutch national guideline26) in a manner that allows reconstruction of the specimen at the time of microscopic evaluation through accurate description or with the help of a diagram. Unfortunately, this approach does not allow for tissue collection for research. Clinical judgment should be applied in this setting. If there is obvious gross residual tumor, then a research sample can be taken without compromising accurate histological assessment. In cases where the macroscopic findings are nonspecific, or there is clinical doubt about the location of the tumor bed, then consideration should be given to submitting the entire specimen. Research samples may still be taken by thinning the blocks and submitting the trim, or, alternatively, small cylinders of tissue can be taken with a punch biopsy tool. Depending on the type of processing used for the research tissue, histology can still be evaluated if deemed clinically necessary, such as hematoxylin and eosin-stained sections of research blocks. A previous international working group has addressed the collection of research tissue in the neoadjuvant setting in detail.43

It is important to document that these small resections have adequately excised the lesion. The tumor bed/clip must be identified. Tumor bed extending to the margins should be documented.

Sampling of large lumpectomy/mastectomy specimens (partial submission). Targeted representative sections can be taken from larger specimens, but it is essential to carefully and accurately represent the tumor bed in a manner that can be retrospectively mapped to the gross and/or radiologic findings. This enables more accurate estimation of the extent of residual disease. Correlation with clinical and imaging findings is imperative to ensure the correct area is sampled. Sampling should include grossly visible tumor bed and/or the location of any marker clips and immediately adjacent tissue to encompass the area suspected of involvement by carcinoma before treatment (Figure 3). This area to be sampled is referred to as the pretreatment area of involvement in the discussion below. Degree of sampling is then determined by the pretreatment size in addition to any visible tumor bed or grossly visible residual disease.

Problems related to sampling for histologic evaluation. Gross residual tumor may or may not be present after neoadjuvant therapy (top left). Even when the tumor bed is entirely submitted, histologic evaluation has limits (top center). The blue and black slides represent different levels obtained from the same block. The blue slides show a complete response. The black slides show minimal residual microscopic disease. Partial response shows various patterns and the decrease in cellularity is often heterogeneous (right). In these cases, random sampling of tumor can lead to very different estimates of tumor cellularity (bottom center). Random sampling with the blue blocks would conclude a complete response. Random sampling with the black blocks would document residual disease. Often, the microscopic tumor extends beyond a grossly visible tumor bed (bottom left). The largest cross-section of tumor bed is sampled for an estimate of tumor cellularity.

Ideally, the specimen is sliced to reveal the largest cross-section of the pretreatment area of involvement. Block(s) representing the full face of the pretreatment area of involvement should be taken of every 1 cm slice containing pretreatment area of involvement, or, for very large tumors, five representative blocks of a cross-section of pretreatment area of involvement per 1–2 cm of pretreatment size, up to a total maximum of ∼25 blocks. In the absence of trial-based evidence as to the degree of sampling required, the committee felt this to be a pragmatic approach that should be sufficient to determine the presence of pathological complete response. The US Food and Drug Administration, in their guidance, have recommended taking ‘a minimum of one block per cm of pre-treatment tumor size, or at least 10 blocks in total, whichever is greater’.34 The extent of sampling should be guided by good clinical judgment on a case-by-case basis—informed, directed sampling is more important than blindly taking a prescribed number of blocks. For assessment of cellularity of very large tumor beds, five representative blocks are sufficient to represent the largest cross-section of residual tumor bed and calculate the Residual Cancer Burden.45

Precise description must be used to allow reconstruction of the specimen during histologic evaluation for accurate measurements and cellularity estimates. We strongly recommend visual images, such as photographs, specimen radiographs, or sketched diagrams, with annotations to indicate the sites where tissue sections were taken for histopathologic evaluation.

If no residual disease is seen on initial sections, or if the distribution of the disease does not correspond to the initial gross impression, then a second pass may be needed to submit further blocks. Additional blocks, including sections documenting margins, should be obtained as with non-neoadjuvant specimens.

Laboratories with access to large tissue cassettes are encouraged to utilize this technique as a superior method for mapping the residual tumor bed. Large cassettes enable sampling of a bigger area with fewer blocks, with the entire lesion often captured on a single slide. This simplifies reconstruction of the extent of residual disease, measurement of lesion size, and examination of margins.46

In cases where the above cutoffs would not result in submission of the entire tumor bed, remaining tissue can be sampled for research. Areas with grossly visible tumor can easily be sampled. Cases where the above cutoffs result in submission of the entire tumor bed can be sampled for research as described in the section ‘Sampling of small lumpectomy specimens’ under ‘Specimen handling’ above. If only formalin-fixed, paraffin-embedded tissue is needed, additional blocks can be submitted from a second pass for research from areas that had residual tumor on microscopy.

Multiple lesions in lumpectomy or mastectomy. In specimens containing multiple lesions, each lesion should be handled as a single lesion as described under ‘Sampling of large lumpectomy/mastectomy specimens (partial submission)’ above, with the addition of blocks of tissue taken from in between the lesions to ensure that they are truly separate and to evaluate the presence of other intervening disease, such as DCIS.

Microscopic reporting

Prognostic and predictive factors traditionally evaluated in surgical specimens following primary surgery are all relevant in the neoadjuvant systemic therapy setting. Although some familiar prognostic information may be altered by treatment (e.g., tumor grade and histological type) or may be less reliable (lymph node and margin status), much can be gained from the opportunity to evaluate response to treatment.

Histologic tumor type and grade. The method for determination of histologic tumor type and tumor grade is identical to that used for non-neoadjuvant specimens, although it is not clear whether these add prognostic information to the pretreatment results. Tumors with a typical appearance of no special type before treatment may have a lobular growth pattern following neoadjuvant chemotherapy.47 Treatment can cause nuclear hyperchromasia and pleomorphism; however, the findings should be compared with the pretreatment biopsy before assuming they are treatment-related. The mitotic rate may be reduced by treatment; this finding is associated with a better prognosis (disease-free survival and overall survival)48 and lower risk of developing distant metastases.49 Clonal heterogeneity within the tumor may be reflected by variable response to therapy, and by areas with different morphology and grade. A comment regarding the presence of such heterogeneity should be made in the report, and is important when choosing blocks for postneoadjuvant systemic therapy hormone receptor and HER2 assessment.

If multiple, morphologically distinct tumors are present that are clearly separated by adipose tissue, they should be reported as separate lesions. However, it should be noted that the largest residual primary tumor is used for determination of both Residual Cancer Burden and yp stage. Note that ypT stage is defined by the largest contiguous focus of invasive cancer, whereas Residual Cancer Burden uses the two dimensions of the largest residual area of residual invasive cancer (i.e., that does not need to be contiguous) in the tumor bed.

Size and extent. Tumor size/extent is often more difficult to assess after neoadjuvant systemic therapy. There are two main patterns of tumor response following neoadjuvant systemic therapy—concentric shrinking and the scatter pattern (Figure 3). Measurement of lesion size in this latter scenario may be difficult. Our suggested approach is described in Table 1.

Cellularity. In addition to its effect on tumor size, neoadjuvant systemic therapy often has a profound effect on tumor cellularity. Tumor size may not decrease, but overall cellularity may be markedly reduced (Figure 3), making residual tumor cellularity an important factor in assessing response.50 Comparison of pre- and post-treatment cellularity is the key element of several systems for grading response.7, 13, 15, 42 If a formal classification system for grading of response is used, this should be noted in the report. As tumor cellularity is often heterogeneous, the pretreatment core biopsy may not be representative of the entire tumor. Similarly, changes in tumor cellularity induced by neoadjuvant systemic therapy can be heterogeneous and therefore more extensive sampling may be needed to accurately assess cellularity. The descriptions of these scoring systems do not explicitly state how to deal with this heterogeneity, and it can be tempting only to assess the most cellular areas of the tumor.

The Residual Cancer Burden system does not require pretreatment cellularity, but proposes standardized sampling of the specimen with assessment of the average cellularity across the largest two-dimensional area of residual tumor bed. For Residual Cancer Burden, the tumor bed area is defined by the two largest dimensions of gross tumor bed defined by macroscopic examination with or without accompanying specimen radiography, but can be later revised after these corresponding slides have been reviewed under the microscope. Hence, the importance of accurate block description and advisability of an illustrative map to determine how the slides map to the gross tumor bed (described above). The online cellularity standard provided in the Residual Cancer Burden website45 and the images in the publication for the Miller–Payne score are useful aids for pathologists in estimating cellularity.15 The presence or absence of residual DCIS, and the percentage of residual tumor present as in situ disease, should also be documented as per the Residual Cancer Burden.

We advocate submitting the largest cross-section of the residual tumor bed with the relevant sections noted in the pathology report.

Lymphovascular invasion. The presence or absence of lymphovascular invasion should be documented (Figure 4). There are insufficient data on the independent prognostic significance of lymphovascular invasion in neoadjuvant specimens. See Table 1 for suggested approaches to assessing and reporting lymphovascular invasion.

Extensive lymphovascular space invasion after chemotherapy. In this case, an invasive tumor focus was not identified despite extensive sampling. The axillary nodes were positive for residual metastatic carcinoma

Margins. In cases with variable response leading to multiple, small foci of residual disease in a subtle tumor bed, carcinoma may extend beyond an apparently negative margin. Tumor bed extending to the margins, and which margin is involved, should be documented (Figure 5).

Evaluation of the axilla after treatment

Several studies have shown that posttreatment nodal status is an important determinant of disease-free survival and overall survival, regardless of response within the breast.32, 35, 36, 37, 38, 39, 40 Currently, lymph node staging in patients who have received neoadjuvant systemic therapy is usually performed by either sentinel lymph node biopsy or axillary lymph node dissection. The accuracy of sentinel lymph node biopsy for staging postneoadjuvant systemic therapy is still under investigation, especially in patients with clinically positive nodes before treatment.44, 51 The paradigm in surgical management of the axilla is evolving,34 and is the subject of ongoing investigation.44, 51 This is reflected in the use of the phrase ‘sampled regional lymph nodes’ by the US Food and Drug Administration in its proposed definition of pathological complete response.34

The procedure for evaluating sentinel lymph nodes and axillary lymph nodes should be the same as for non-neoadjuvant specimens. All surgically removed lymph nodes should be sectioned at 2 mm intervals and entirely submitted for histologic evaluation. Some special considerations apply, however.

Some studies have indicated a lower number of lymph nodes identified at axillary lymph node dissection after neoadjuvant systemic therapy, whereas others have found no significant difference following careful pathological evaluation.52, 53, 54 Pathologists evaluating axillary lymph node dissection tissue should subject any tissue that may represent lymph node for microscopic evaluation.

The size of the largest metastatic deposit should be measured microscopically and the presence or absence of any extranodal extension documented. Postneoadjuvant systemic therapy tumor cells are often present as scattered single cells within an area of reactive stromal changes or lymphoid tissue. When measuring the size of the metastasis in this context, the size of the area that is even partly involved by metastatic tumor should be measured, and not just the size of the largest tumor cluster. Clearly separate smaller foci in a node are not included in the maximum size measurement. As micrometastases and isolated tumor cells found after neoadjuvant systemic therapy are predictors of worse survival, specimens with nodal micrometastases or isolated tumor cells should not be designated as having pathological complete response.40, 55 Our suggested approach to assessing isolated tumor cells in this context is provided in Table 1.

The presence of treatment effect in the lymph nodes in the form of fibrosis (Figure 6), mucin pools, or large aggregates of foamy histiocytes identifies a subset of patients with an outcome intermediate between that of completely node negative and node positive after neoadjuvant systemic therapy.56 However, small fibrous scars in lymph nodes can also be seen in patients without treatment, and in patients who have had a previous biopsy it can be impossible to reliably distinguish biopsy site changes from regressed metastasis.57 Previously involved nodes may also look completely normal after treatment. The latter scenario can cause concern when there was histologically proven metastasis before treatment, but evidence of a positive node cannot be found in the final surgical specimen. In this setting, the specimen (including axillary tail, if a mastectomy) should be carefully reexamined to ensure all nodes have been retrieved, and the patient reexamined, before assuming there has been complete response. Clipping the involved node before treatment can also be of value in determining nodal response.

Lymph node showing zonal areas of fibrosis after chemotherapy indicative of metastasis with response to therapy (courtesy of Elena Provenzano). (a) Low-power image of lymph node showing zonal fibrosis indicating site of metastasis. (b) On higher magnification of a different node, residual islands of tumor cells are present in a setting of reactive fibrosis with hemosiderin-laden macrophages, consistent with chemotherapy effect.

In some centers, sentinel lymph nodes are assessed by molecular assays (e.g., one-step nucleic acid amplification) without any morphological evaluation. This does not allow assessment of response in the node; moreover, one-step nucleic acid amplification is usually not calibrated to detect isolated tumor cells.58 Therefore, we do not recommend the use of these techniques in the neoadjuvant setting.

Pathological complete response

Our group agrees with the following core principle of the definition of pathological complete response as proposed by the US Food and Drug Administration: ‘Pathological complete response is defined as the absence of residual invasive cancer on…. evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy.’34 However, we advocate that the presence of invasive tumor cells is considered residual disease regardless of the method of detection—that is, hematoxylin and eosin or immunohistochemistry—although the latter is not routinely recommended. The alternative definition, requiring absence of both DCIS and invasive carcinoma in the breast, can also be used. The definition of pathological complete response chosen should be agreed between pathologists and clinicians within individual institutions, and clearly stated in the report. If the patient is enrolled in a clinical trial, the definition of pathological complete response prescribed by the trial standard operating procedure should be included as part of the report with an explanatory note. Regardless of which definition is used, the presence/absence and extent of residual DCIS should be reported as detailed in our recommended template (Table 2).

Microscopically, the tumor bed may be identified as a focal area of loose, edematous reactive stroma with a variable inflammatory cell infiltrate that may include collections of lipid or hemosiderin-laden macrophages, lymphocytes, and plasma cells. Background breast lobules often appear hyalinized and atrophic with a perilobular lymphocytic infiltrate.

We would like to stress the following. Accurate, reproducible documentation of pathological complete response requires adequate sampling of the correct area of the breast. Overly exhaustive sampling and histologic evaluation of the entire tumor bed are generally not required and are far less valuable than intelligent mapping of the correct locations within the specimen. Therefore, correlation of clinical and imaging information and markers of the tumor site with gross pathology of the specimen are indispensible.

Retesting of markers in the postneoadjuvant therapy specimen

Reassessment of hormone receptor and HER2 status in residual cancer after neoadjuvant systemic therapy is variable between individual centers, with no consensus regarding if and when retesting of markers is advisable. The clinical utility of reassessing marker status in the surgical specimen may depend on the results from the core biopsies taken before neoadjuvant systemic therapy. If retesting is performed, it may be done on either the residual primary tumor or residual nodal disease if the latter contains a better representation of residual tumor cells. Our recommendations are provided in Table 3.

Finally, in some centers, assessment of Ki67 labeling index is performed before and after neoadjuvant systemic therapy. Posttreatment Ki67 index has been shown to correlate with long-term outcome after both neoadjuvant endocrine59 and chemotherapy,60, 61 although its routine use in clinical practice has not yet been formally recommended because of lack of standardization in its assessment.62, 63, 64 Proliferation is commonly reduced by neoadjuvant systemic therapy and hence, in addition to Ki67, results of multigene assays that include proliferation genes may also change if assessed before and after treatment.65

Minimum data set to be reported by pathologists

A suggested summary template for reporting neoadjuvant systemic therapy specimens is presented in Table 2, with minimum data set items highlighted. The US National Cancer Institute’s Breast Oncology Local Disease (BOLD) Task Force has also recommended standardized data elements for collection in preoperative breast cancer clinical trials.66

Conclusion

Postneoadjuvant systemic therapy histopathological changes are complex, and careful systematic review of the specimen is required for accurate diagnosis and follow-up treatment. For pathological complete response to be used as an indicator of response to novel therapies, it is essential to have a standardized way in which residual disease is measured and reported. We designed the recommendations specifically for the clinical trial setting; however, they can be optionally incorporated into routine practice because, in our opinion, standardization is most effective when uniformly applied. Hopefully, such standardization will improve our knowledge and ability to compare outcomes, promote the submission of specimens for translational research, and facilitate the more timely introduction of new agents.

The recommendation of this committee is that pathologic reports of residual disease after neoadjuvant chemotherapy and/or targeted therapy in clinical trials should include the following information:

Pathological Complete Response or Residual Disease. This should separately describe whether there was residual invasive cancer in the breast, in situ cancer in the breast, and the pathologic status of the regional lymph nodes.
Residual Cancer Burden as the preferred method for more detailed quantification of residual disease. The report should provide the final residual tumor dimensions, cellularity of cancer in the final tumor bed area and the proportion of in situ component within that cancer, and the number of positive nodes and the size of the largest metastasis, as well as the Residual Cancer Burden score and class.
ypTN Stage. The report should separately report the ypT and ypN stages and the pathologist should use the most current edition of the American Joint Committee on Cancer/Union for International Cancer Control staging definitions when evaluating tumor size after neoadjuvant chemotherapy.

Reference:

Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group

Elena Provenzano,
Veerle Bossuyt,
Giuseppe Viale,
David Cameron,
Sunil Badve,
Carsten Denkert,
Gaëtan MacGrogan,
Frédérique Penault-Llorca,
Judy Boughey,
Giuseppe Curigliano,
J Michael Dixon,
Laura Esserman,
Gerd Fastner,
Thorsten Kuehn,
Florentia Peintinger,
Gunter von Minckwitz,
Julia White,
Wei Yang &
W Fraser Symmans
on behalf of the Residual Disease Characterization Working Group of the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration

Modern Pathology volume 28, pages1185–1201(2015)Cite this article

Neuroendocrine tumors of GI Tract.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Wed, 22 Jan 2020 15:26:00 +0000

The World Health Organization (WHO) classifies neuroendocrine neoplasms as well-differentiated neuroendocrine tumors (either the primary tumor or metastasis) and poorly differentiated neuroendocrine carcinomas.

Historically, well-differentiated neuroendocrine tumors have been referred to as “carcinoid tumors,” a term which may cause confusion because clinically a carcinoid tumor is a serotonin-producing tumor associated with functional manifestations of carcinoid syndrome.

The use of the term “carcinoid” for neuroendocrine tumor reporting is therefore discouraged for these reasons.

Immunohistochemistry and other ancillary techniques are generally not required to diagnose well-differentiated neuroendocrine tumors. Specific markers that may be used to establish neuroendocrine differentiation include chromogranin A, synaptophysin, and CD56.
Because of their relative sensitivity and specificity, chromogranin A and synaptophysin are recommended.

Recommended Grading System for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors

Because of site-specific similarities in histology, immunohistochemistry, and histochemistry, neuroendocrine tumors of the digestive tract have traditionally been subdivided into those of foregut, midgut, and hindgut origin . In general, the distribution pattern along the gastrointestinal (GI) tract parallels that of the progenitor cell type, and the anatomic site of origin of GI neuroendocrine tumors is an important predictor of clinical behavior.

Tumor Size
For neuroendocrine tumors in any part of the gastrointestinal tract, size greater than 2.0 cm is associated with a higher risk of lymph node metastasis. For jejunoileal tumors, nodal metastases occur in about 12% of patients with tumors smaller than 1.0 cm and in most patients with tumors larger than 1.0 cm. Thus, treatment for small intestine neuroendocrine tumor includes complete resection with regional lymphadenectomy.

Immunohistochemistry in the Differential Diagnosis of Cutaneous Basal Cell Carcinoma

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Tue, 20 Nov 2018 16:15:00 +0000

Basal cell carcinoma and squamous cell carcinoma are two of the most common cutaneous tumors seen by pathologists. In the large majority of cases, the distinction between these two tumors is readily made on the basis of standard H&E morphology. However, many of us see cases from time to time that for one reason or another (minuscule biopsy, mishandled specimen, crushed beyond recognition, dryed out, poorly fixed, etc., etc.), it is difficult to know for certain whether one is dealing with a squamous carcinoma or a basal cell carcinoma. This month, we discuss several immunostains that can be of utility in approaching this problem.

It is worth mentioning that both basal cell carcinoma and cutaneous squamous cell carcinoma characteristically express strong and diffuse high molecular weight cytokeratin, cytokeratin 5 (or cytokeratin5/6) and nuclear p63, so the absence of staining with these markers (assuming adequate tissue and technique of course) should lead you to consider another diagnosis.

EMA is a useful antibody for this problem, since basal cell carcinomas are negative for EMA, although occasionally lumina associated with sebaceous differentiation in these tumors may show EMA positivity. In contrast, most squamous cell carcinomas of the skin will have substantial EMA immunoreactivity.

Ber-EP4 is also a useful marker, as basal cell carcinomas are typically positive for this marker, unlike cutaneous squamous carcinoma. Interestingly, non-cutaneous squamous carcinomas (e.g., pulmonary squamous carcinoma) may express Ber-EP4, so conceivably reactivity of Ber-EP4 in a known cutaneous squamous tumor might suggest the possibility of metastatic squamous carcinoma, although I do not know of any published reports that have specifically addressed that question.

Interestingly, smooth muscle actin (SMA) has been found to be expressed in a significant number of basal cell carcinomas of the skin (13 of 17 cases in one study). Indeed, we have observed strong SMA reactivity in a number of basal cell carcinomas that we have stained, although the frequency of reactivity is not as high in our hands as in some published series. Cutaneous squamous carcinomas are negative for SMA.

BCL-2 has been reported by some authors to be useful in this situation, since basal cell carcinomas are typically diffusely positive for this marker. Cutaneous squamous cell carcinomas are generally negative, although some authors describe focal positivity enough to 26% of cutaneous squamous carcinoms.

In summary, when faced with the differential diagnosis of cutaneous basal cell carcinoma versus cutaneous squamous carcinoma, a reasonable first approach would be to employ immunostains for EMA and Ber-EP4. If these results are not diagnostic, immunostains for SMA and BCL-2 would be worth a try. Again, if the tumor in question does not show strong high molecular weight cytokeratin, cytokeratin 5, cytokeratin 5/6, and nuclear p63, consideration of another diagnosis would be prudent. Results of expected staining in these tumors are listed in table below.

REFERENCES:

1. Wick MR: Practical immunohistology of cutaneous neoplasms: an update. Presentation at the American Society of Dermatopathology Companion Meeting, 2004 Annual Meeting of the United States and Canadian Academy of Patholgy, Vancouver, BC, March 7, 2004.

2. Jimenez FJ et al: Ber-EP4 immunoreactivity innormal skin and cutaneous neoplasms. Mod Pathol8(8): 854-858, Oct 1995.

3. Peterdy G et al: Immunohistochemical separationof microcystic adnexal carcinoma from basal cellcarcinoma and squamous cell carcinoma. ModPathol 14(1):72A (abstract # 407), Jan 2001.

4. Varma M et al: Expression of smooth muscle antigensin basal cell carcinomas of skin. Mod Pathol12(1):65A (abstract # 365), Jan 1999.

5. Williams GA et al: Immunoreactivity for alphasmoothmuscle actin aids in the separation of basalcell carcinoma from both squamous cell carcinomaand trichoepithelioma. Lab Investig 78(1):54A(abstract # 303), Jan 1998.

6.Rodney T. Miller, M.D., Director of Immunohistochemistry

Tumor Size (Size of Invasive Carcinoma) in Breast Carcinoma

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Thu, 12 Apr 2018 15:33:00 +0000

Breast Carcinoma reporting;

Tumor Size (Size of Invasive Carcinoma)

The size of an invasive carcinoma is an important prognostic factor.
The single greatest dimension of the largest invasive carcinoma is used to determine T classification
The best size for AJCC T classification should use information from imaging, gross examination, and microscopic evaluation.
Visual determination of size is often unreliable, as carcinomas often blend into adjacent fibrous tissue.
The size by palpation of a hard mass correlates better with invasion of tumor cells into stroma with a desmoplastic response.
Sizes should be measured to the nearest millimeter.
In some cases, the size may be difficult to determine.

How to measure size of breast invasive carcinoma:

A. Invasive carcinoma with surrounding ductal carcinoma in situ (DCIS). The size only includes the area of the invasive carcinoma and does not include the adjacent DCIS. The size should be measured to the closest 1 mm.

Invasive carcinoma and DCIS: The size measurement includes only the largest area of contiguous invasion of stroma. Surrounding DCIS is not included in the size measurement.

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B. Small invasive carcinoma with prior core needle biopsy. The size of the carcinoma in the core needle biopsy should not be added to the size of the carcinoma in the excisional specimen, as this will generally overestimate the true size. The best size for classification must take into consideration the largest dimension of the carcinoma in both specimens as well as the size by imaging before the core needle biopsy.

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C. Small invasive carcinomas with adjacent biopsy site changes. In some excisional specimens, a small carcinoma will be present adjacent to a relatively large area of biopsy site changes. The actual size cannot be determined with certainty. The size in the core needle biopsy, in the excisional specimen, and by imaging should be considered to determine the best size for classification.

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D. Multiple invasive carcinomas. If multiple carcinomas are present, the size of the largest invasive carcinoma is used for T classification. The modifier “m” is used to indicate that multiple invasive carcinomas are present.

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E. Multiple invasive carcinomas in close proximity. It may be difficult to distinguish multiple adjacent carcinomas from one large invasive carcinoma. Careful examination of the specimen with submission of tissue between grossly evident carcinomas is essential. Correlation with imaging findings can be helpful. Generally, microscopic size confirmation of the largest grossly identified invasive carcinoma is used for T classification.

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F. Invasive carcinomas that have been transected. If an invasive carcinoma has been transected and is present in more than 1 tissue fragment, the sizes in each fragment should not be added together, as this may overestimate the true size. In many cases, correlation with the size on breast imaging will be helpful to choose the best size for classification. In other cases, the pathologist will need to use his or her judgment in assigning an AJCC T category.

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DCIS with microinvasion:

Microinvasion is defined by the AJCC as invasion measuring 1 mm or less in size.
If more than 1 focus of microinvasion is present, the number of foci present, an estimate of the number, or a note that the number of foci is too numerous to quantify should be reported.
In some cases, immunoperoxidase studies for myoepithelial cells may be helpful to document areas of invasion and the size of the invasive foci.
Invasive tumors that are larger than 1.0 mm but less than 2.0 mm are rounded up to 2.0 mm.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Tue, 03 Apr 2018 21:06:00 +0000

Grade Group in reporting of prostate acinar adenocarcinoma:

The 9 Gleason scores (2-10) have been variably lumped into different groups for prognosis and patient management purposes. Epstein and associates proposed grouping scores into 5 prognostic categories, grade groups 1-5.
This grade grouping, shown below in the table, strongly correlate with biochemical recurrence and have been incorporated into the new Partin tables.
At the 2014 ISUP Consensus Conference, details of this prognostic system were clarified and it was recommended for usage together with the Gleason system.
This grade grouping has also been subsequently validated by other independent studies in surgical and radiation cohorts show significant correlation with survival.
The new grade grouping has been endorsed in the 2016 WHO classification.
The grade grouping has also been endorsed by ISUP and is referred to as ISUP grade in some publications. Like Gleason scoring in needle biopsies, the grade group can be applied at core, specimen, or case levels.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Wed, 28 Mar 2018 20:10:00 +0000

Methods for estimating the size/extent of DCIS in specimen.

Why to measure size of DCIS in specimen:

Higher rates of invasive cancer detected according to DCIS size.
Progression to invasive cancer occurred in 10% of DCIS patients with a DCIS tumor size between 2.5 to 3.5 cms, 57% for tumor size 3.6 to 4.5 cms and 71% for tumors between 4.5 and 6 cms.
Tumors over 2.5 cms have a higher risk of progressing to invasive cancers.

J Exp Clin Cancer Res. 2006 Jun;25(2):223-7.

There are multiple methods for estimating the extent of DCIS (see Figure):

DCIS in 1 block: The area involved by DCIS can be measured from a single slide, if DCIS is present in only 1 block. If separate foci are present, the largest distance between foci should be reported. This method will underestimate the extent of DCIS when multiple blocks are involved and should not be used in such cases.

Serial sequential sampling: The entire specimen is blocked out in such a way that the location of each block can be determined. The extent of the DCIS can be calculated by using a diagram of the specimen, the thickness of the slices, and the location of the involved blocks.7-9 This method is recommended for all excisions likely to harbor DCIS or with previously diagnosed DCIS (eg, by diagnosis on a prior core needle biopsy).

Nonsequential sampling: The number of blocks involved by DCIS is correlated with the extent of DCIS up to 40 mm.8 Multiplying the number of blocks involved by DCIS by the approximate width of a tissue section gives an estimate of the extent. In 2 studies, multiplying by 3 mm underestimated the extent of DCIS, and multiplying by 5 mm may overestimate the extent.8,9 Therefore, multiplying by 4 mm is recommended unless there is additional information that a different number would yield a more accurate result. This method may underestimate extent if not all areas of DCIS are sampled. Therefore, it is recommended that all tissue likely to be involved by DCIS be sampled (eg, all grossly abnormal tissue and all tissue with radiologically suspicious calcifications). When feasible, the entire specimen should be examined microscopically.

This method may result in a larger estimation of extent than the serial sequential sampling method when DCIS is present in a large volume of tissue in 3 dimensions rather than in a predominantly linear distribution. The best estimate for correlation with outcomes (eg, residual disease or recurrence) will require further studies.

This method can be applied to any specimen and will give a better estimation of extent than measuring extent on a single slide when multiple blocks contain DCIS.

• Margins: If DCIS involves or is close to 2 opposing margins, the distance between the margins can be used as the extent of the DCIS within the specimen.

• Gross lesions: In some cases of high-grade DCIS, there may be a gross lesion that can be measured. Confirmation of the gross size must be confirmed by microscopic evaluation.

The largest estimate obtained using any of these methods should be used to report the estimated size (extent) of the DCIS.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Wed, 27 Jan 2016 17:30:00 +0000

Pathology, classification, and grading of neuroendocrine

tumors arising in the digestive system

The terminology of gastroenteropancreatic (GEP) neuroendocrine neoplasms has evolved over the past two decades to reflect a separation into two major categories:

●Well-differentiated neuroendocrine tumors (NETs) show a solid, trabecular, gyriform, or glandular pattern, with fairly uniform nuclei, salt-and-pepper chromatin, and finely granular cytoplasm. These tumors were traditionally referred to as carcinoid and pancreatic neuroendocrine (islet cell) tumors. Although carcinoid tumors and pancreatic NETs may have similar characteristics on routine histologic evaluation, they have a different pathogenesis and biology.

●Poorly-differentiated neuroendocrine carcinomas, which are high-grade carcinomas that resemble small cell or large cell neuroendocrine carcinoma of the lung . Poorly differentiated neuroendocrine carcinomas are often associated with a rapid clinical course, while well-differentiated NETs generally have a much better prognosis, with an overall five-year survival of approximately 67 percent

Histologic appearance of the spectrum of neuroendocrine tumors arising in the gastrointestinal tract

Well-differentiated NET shows an organoid pattern and difficult-to-find mitotic activity on H&E stain (panel A),

( Panel C) the proliferative rate (as measured by the Ki67 labeling index) is very low (<1 percent="" span="">

poorly-differentiated neuroendocrine carcinoma shows frank features of carcinoma with numerous mitotic figures and tumor necrosis on H&E stain (panel B),the Ki67 labeling index is very high (80% in this case) (panel D).

Scientists Convert Human Skin Cells Directly Into Brain Cells

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Sun, 26 Apr 2015 10:42:00 +0000

Using a finely tuned cocktail of small molecules, researchers from Washington University in St. Louishave successfully converted adult skin cells into the major type of brain cell affected in the fatal neurodegenerative disorder Huntington’s disease. For the first time, this was achieved without the need to go through a stem cell intermediate, avoiding the production of other types of cell. Importantly, when the researchers transplanted these cells into the brains of mice, they survived and showed similar properties to native cells. While it is still in the early days, these preliminary results could suggest that in the future, this technique may be developed further to help patients with Huntington’s. The work has been published in Neuron.

Huntington’s disease is an inherited brain disorder that causes the progressive degeneration of nerve cells, or neurons. This disease predominantly affects a type of cell called medium spiny neurons (MSNs), which are crucial for movement control. As they are gradually lost in the brain, the patient experiences involuntary muscle movements and cognitive decline. While there is currently no cure, a future possible treatment avenue could involve replacing the lost cells in the brain. But first, researchers need to work out a way to not only produce these cells, but also to ensure they are not rejected by the patient, which is what the Washington University scientists are working towards.

Previous work by this team found that it is possible to turn skin cells into different types of brain cell by exposing them to two small molecules of RNA, a similar molecule to DNA. These specific "microRNAs” unravel target stretches of DNA, or genes, which are responsible for the identity of the cell. In doing so, proteins called transcription factors can access the DNA sequences, which result in the expression of genes which govern the development of neurons. Armed with this knowledge, the researchers added to these cells the same transcription factors present in brain regions containing MSNs. This combination of ingredients was found to result in the direct conversion of skin cells into this specific type of neuron.

“We think that the microRNAs are really doing the heavy lifting,” co-first author Matheus Victor said in a news-release. “They are priming the skin cells to become neurons. The transcription factors we add then guide the skin cells to become a specific subtype, in this case medium spiny neurons. We think we could produce different types of neurons by switching out different transcription factors.”

When the researchers analyzed these reprogrammed cells, they were found to show similar gene expression profiles to human MSNs. Furthermore, after they were transplanted into the brains of mice, they survived for over 6 months, exhibited similar properties to the native MSNs and even connected to distant neuronal targets in the brain.

The researchers are now taking this work one step further by using the same technique on skin cells taken from Huntington’s patients. To investigate whether these cells can alleviate some of the symptoms associated with the disease in animals, the researchers plan to transplant these cells into mouse models of Huntington’s.

How Do You Get Pancreatic Cancer?

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Tue, 11 Mar 2014 17:49:00 +0000

)

Invasive Micropapillary Carcinoma of the Breast

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Sat, 01 Mar 2014 22:08:00 +0000

Definition

Breast carcinoma with a prominent (pseudo) micropapillary pattern

Diagnostic Criteria

Numerous small pseudo-papillary clusters of cells
- No fibrovascular cores
- Frequent central lumen formation in clusters
- Peripherally located nuclei frequently bulge out with knobby appearance, "the hedgehog" tumor
Clusters surrounded by clear spaces
- One or only a few clusters per space
- Scant mucin rarely detectable in spaces
Spaces surrounded by loose fibrocollagenous stroma
Frequent high nuclear grade reported in some series
Frequently has abundant eosinophilic cytoplasm
Frequent lymphatic involvement
Occasional psammoma bodies
Associated DCIS may be of various types
- Not related to micropapillary DCIS
Pattern may be predominant or focal
- No clinical difference between predominant and focal cases
- No reported cutoff for minimal significant amount of pattern
- Report such cases as mixed
Frequently mixed with infiltrating ductal carcinoma

Rarely mixed with other type

Clinical

Incidence
- Pure about 1%
- Mixed about 4-7%
Frequent local recurrence (70-90%)
Poor prognosis
- Approximate 40% dead of disease in three years
- Not independent of stage
  - Linked to high incidence of nodal involvement
Rare cases reported in males

Grading / Staging / Report

Grading

Bloom-Scarff-Richardson grading scheme is most widely used
Total score and each of the three components should be reported
Based on invasive area only

Tubule formation	Score
>75% tubules	1
10-75% tubules	2
<10 span="" tubules="">	3

Nuclear pleomorphism (most anaplastic area)	Score
Small, regular, uniform nuclei, uniform chromatin	1
Moderate varibility in size and shape, vesicular, with visible nucleoli	2
Marked variation, vesicular, often with multiple nucleoli	3

Mitotic figure count per 10 40x fields (depends on area of field, see key below)					Score
0.096 mm2	0.12 mm2	0.16 mm2	0.27 mm2	0.31 mm2
0-3	0-4	0-5	0-9	0-11	1
4-7	5-8	6-10	10-19	12-22	2
>7	>8	>10	>19	>22	3

Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece: 0.096 mm2
AO with 10x eyepiece: 0.12 mm2
Nikon or Olympus with 10x eyepiece: 0.16 mm2
Leitz Ortholux: 0.27 mm2
Leitz Diaplan: 0.31 mm2
Mitotic count figures based on original data presented for Leitz Ortholux by Elston and Ellis 1991, with modifications based on pubished and measured areas of view
Evaluate regions of most active growth, usually in cellular areas at periphery
We employ strict criteria for identification of mitotic figures

Sum of above three components	Overall grade
3-5 points	Grade I (well differentiated)
6-7 points	Grade II (moderately differentiated)
8-9 points	Grade III (poorly differentiated)

Staging

Micropapillary carcinoma is associated with frequent lymph node metastases
- Seen even with primary tumors <1 cm="" span="">
- Seen even with mixed tumors with small micropapillary component
- Nodal involvement is frequently by micrometastases

TNM staging is the most widely used scheme for breast carcinomas but is not universally employed
Critical staging criteria for regional lymph nodes
- Isolated tumor cell clusters
  - Usually identified by immunohistochemistry
    - Term also applies if cells identified by close examination of H&E stain
  - No cluster may be greater than 0.2 mm
  - Multiple such clusters may be present in the same or other nodes
- Micrometastasis
  - Greater than 0.2 mm, none greater than 2.0 mm
- Metastasis
  - At least one carcinoma focus over 2.0 mm
    - If one node qualifies as >2.0 mm, count all other nodes even with smaller foci as involved
  - Critical numbers of involved nodes: 1-3, 4-9 and 10 and over
- Note extranodal extension

Report

Excisions: the following are important elements that must be addressed in the report for infiltrative breast carcinomas
- Grade
  - Total score and individual components
- Size of neoplasm
  - Give 3 dimensions or greatest dimension
  - Critical cutoffs occur at 0.5 cm and at 2 cm
- Margins of resection
  - Measure and report the actual distance of both invasive and in situ carcinoma
- Angiolymphatic invasion
  - Indicate if confined to tumor mass, outside tumor mass or in dermis
- (Extensive DCIS is not currently felt to be a significant predictor of behavior)
- Results of special studies performed for diagnosis
- Results of prognostic special studies performed
  - ER, PR, Proliferation marker, Her2neu
  - If studies were performed on a prior specimen, refer to that report and give results
Needle or core biopsies
- Provisional grade may be given but may defer to excision for definitive grade
- Presence of absence of angiolymphatic invasion
- Results of special studies performed for diagnosis
- Results of prognostic special studies if performed
  - ER, PR, Proliferation marker, Her2neu
  - State if studies are deferred for a later excision specimen
Regional lymph nodes

Report findings as described above

Paget's disease if Nipple- Review

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Fri, 28 Jun 2013 15:06:00 +0000

Clinical:

Approximately 1%–3% of women with adenocarcinoma of the breast have Paget disease. Clinically-Paget disease has common dermatitis-like appearance, as originally described in 1874, when Sir James Paget recorded that such lesions may resemble “ordinary chronic eczema” or present as nipple erosion or ulceration. Paget disease often has a deceptively banal clinical morphology but should lead the list of differential diagnoses when evaluating unilateral lesions of the nipple–areola complex in adults.

Paget disease presenting with nipple erosion.

Most women with the histopathologic finding of Paget disease have a clinical abnormality of the nipple. However, in at least 10% of affected patients, Paget disease is found incidentally, during microscopic examination of mastectomy specimens.

Underlying invasive ductal carcinoma or DCIS, detected in more than 90% of patients with Paget disease, is multifocal in about 50% of cases and does not necessarily occur near or contiguous with the nipple–areola complex.

In addition, because of the practice shift from mastectomy to breast-conserving surgery, a patient whose nipple–areola complex was spared during surgery may present with Paget disease or epidermotropic metastatic breast cancer to the nipple after diagnosis and treatment of primary breast cancer.

Histopathology:

Paget disease is characterized by intraepidermal infiltration with large cells that have abundant pale cytoplasm and hyperchromatic nuclei often with prominent nucleoli.

Potential histopathologic pitfalls include pronounced epidermal hyperplasia or denuded epithelium, sometimes mandating additional biopsy. The latter is particularly problematic when Paget cells completely separate from surrounding keratinocytes. Although this phenomenon has been described as acantholysis, Paget disease cells do not have intercellular connections with keratinocytes; they instead are tucked individually or in clusters between normal epithelial cells.

When the appearance of acantholysis is pronounced, pemphigus may be included in the differential diagnosis. Large acantholytic-like Paget disease cells may mimic the cytopathic effect of herpes simplex or varicella-zoster infection, particularly when their nucleoli are inconspicuous.

Large, rounded, “acantholytic” cells in Paget disease of the nipple

Intraepidermal clefting and stromal inflammation in Paget disease of the nipple

Infiltration of epithelium by pale cells and stromal inflammation in Paget disease involving the areola

Immunohistochemical stains often are necessary to confirm the diagnosis of Paget disease because the differential diagnosis may include SCC in situ, malignant melanoma in situ, and rarely other entities such as Langerhans cell histiocytosis.

Pigmented Paget disease and pigmented epidermotropic metastatic breast cancer have been reported. In contrast with melanoma, pigmented Paget disease usually is negative for S100, Melan A, and HMB-45.

In contrast with SCC in situ, Paget disease cells typically express low–molecular-weight keratins 7 and CAM 5.2 but not keratin 20 or high–molecular-weight keratins.

Paget disease tends to be estrogen- and progesterone-receptor negative and androgen-receptor positive, especially in patients with high-grade underlying ductal carcinoma.

HER2 overexpression often is a feature of cases associated with underlying ductal carcinoma.

Immunohistochemical stain for keratin 7 highlights epithelial infiltration with Paget disease cells

Immunohistochemical stain for Cam 5.2 highlights epithelial infiltration with Paget disease cells.

HER2 expression in Paget disease.

The histopathologic differential diagnosis also should include benign conditions characterized by pale-clear intraepidermal cells; these include pagetoid dyskeratosis, thought to be due to chronic irritation of the nipples, and clear-cell papulosis, a rare eruption affecting children that manifests as hypopigmented macules, mainly along milk lines.

These 2 disorders of large pale cells usually are distinguishable from Paget disease morphologically. Both are characterized by pale cells with limited (if any) pleomorphism; these cells tend to be larger than surrounding keratinocytes and are distributed singly or in small clusters set neatly in an otherwise normal-appearing epidermis, without discohesion. The clear cells of pagetoid dyskeratosis are positive for high–molecular-weight keratins, rather than low–molecular-weight keratins. Clear-cell papulosis typically has a profile similar to that of Paget disease, including expression of keratin 7, CAM5.2, and lack of staining for estrogen receptor, but appears to be negative for HER2.

REFERENCES

1. Ackerman AB, Kessler G, Gyorfi T, et al. Contrary view: the breast is not an organ per se, but a distinctive region of skin and subcutaneous tissue. Am J Dermatopathol. 2007; 29: 211–218.

2. Gouon-Evans V, Rothenberg ME, Pollard JW. Postnatal mammary gland development requires macrophages and eosinophils. Development. 2000; 127: 2269–2282.

3. Sternlicht MD. Key stages in mammary gland development: the cues that regulate ductal branching morphogenesis. Breast Cancer Res. 2006; 8: 201.

4. De Giorgi V, Grazzini M, Alfaioli B, et al. Cutaneous manifestations of breast carcinoma. Dermatol Ther. 2010; 23: 581–589.

5. Aftab K, Idrees R. Nipple adenoma of breast: a masquerader of malignancy. J Coll Physicians Surg Pak. 2010; 20: 472–474.

Role of Excisional lymph node biopsy, Core needle biopsy and FNAC in Lymphoma diagnosis

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Tue, 29 Jan 2013 16:52:00 +0000

The newly developed and more sophisticated techniques for analysis of lymphoma cells have provided us with the tools necessary for precise classification of non-Hodgkin’s lymphoma. Nonetheless, routine histologic studies remain the gold standard for diagnosis.

Excisional Biopsy

A well-processed hematoxylin and eosin (H&E) stained section of an excised lymph node is the mainstay of pathologic diagnosis. Most often, the diagnosis of difficult lesions relies heavily on a careful assessment of the underlying architecture. Lymphoma diagnoses are much less about cytologic detail and far more about altered architecture. For example, follicular small-cleaved cell lymphoma (FSC) is characterized by an abundance of neoplastic lymphoid follicles containing monomorphous small-cleaved lymphocytes. The individual cells themselves, however, are otherwise typical small cleaved lymphocytes seen in the benign follicles of reactive lymph nodes.

The loss of normal nodal architecture that accompanies an infiltrate is of paramount importance in making a diagnosis. An incisional lymph node provides only a glimpse of the architecture, making interpretation difficult. Our surgical colleagues must be instructed to biopsy the most clinically significant site, and whenever possible, to remove an intact lymph node for pathological processing. The tissue should be delivered fresh to pathology at an appropriate time of the day in order to maximize the material for lymphoma protocol studies.

Many hematopathologists prefer to triage the material using imprint preparations, whereby a fresh cut surface of the node is touched onto glass slides for Romanowsky staining. Experienced pathologists are able to make a good approximation of the disease process based on the touch prep morphology, thus resulting in the efficient ordering of additional tests.

When the size of the tissue is limiting, the first priority must be to process the material routinely for fixation and H&E sections. Properly fixed specimens can be used for regular histologic examination, paraffin(Drug information on paraffin) section immunoperoxidase staining, and depending on the fixative, for gene rearrangement studies by polymerase chain reaction (PCR). Although B5 is the optimal fixative for routine lymphoid histology and is preferred for immunoperoxidase studies, it precludes PCR studies in most laboratories. Formalin fixation is preferred when the biopsy is small because all of the above studies, including PCR, can be performed.

Diagnosing Disease at Extranodal Sites—Approximately 30% to 35% of cases of non-Hodgkin’s lymphoma in adults present primarily at extranodal sites. Much less is known about the molecular mechanisms involved in these disorders in comparison to node-based disease. Therefore, it is important to remember to process extranodal biopsy material for lymphoma protocol studies whenever there is a suspicion of a hematolymphoid neoplasm.

Molecular genetic and cytogenetic data from gastric and pulmonary resection specimens have enormous potential to provide insights into the pathogenesis of mucosal-associated lymphoid tissue (MALT) lymphomas but, unfortunately, lymphoma protocol is frequently overlooked in this setting. Nonetheless, examination of a well-processed H&E section from an excisional biopsy by an experienced hematopathologist will be sufficient to establish a diagnosis in the majority of cases.

Needle-Core Biopsy & FNAC

Needle-core biopsies have a role in lymphoma pathology, although it remains limited.The use of 14 to 22 gauge needles under ultrasound or radiological guidance to establish a diagnosis of non-Hodgkin’s lymphoma is problematic because of technical difficulties with biopsy crush artifact, inadequate sampling, and the usual vagaries of lymphoma pathology. Although this technique has advantages over fine-needle aspiration (FNA), it should be used judiciously as a diagnostic tool for patients with suspected non-Hodgkin’s lymphoma.

Needle-core biopsies do allow a minimal assessment of architecture in addition to immunostaining procedures, but interpretation can be problematic in cases of T-cell rich B-cell lymphoma, angioimmunoblastic-type peripheral T-cell lymphoma, or MALT lymphoma where much of the lymphoid infiltrate is reactive.

A careful review of most excisional lymph node biopsies demonstrates marked cytologic and architectural variation throughout the section, underscoring the complexity of non-Hodgkin’s lymphoma diagnoses in what would otherwise be considered routine circumstances.

Needle-core biopsies are unable to detect this variability, leading to the possibility of incorrect diagnoses in many cases. Although recent studies have recommended increased use of these techniques, patient selection and failure to provide convincing evidence that the “right treatment” decision was made in the majority of cases hamper their interpretation. Also, many of these studies included patients with an established diagnosis of either non-Hodgkin’s lymphoma or Hodgkin’s disease—an approach that differs significantly from a diagnostic procedure.

In managing ill patients or those with significant comorbid disease who are unable to tolerate an invasive surgical procedure, needle-core biopsies offer a better alternative to FNA for the diagnosis of intra-abdominal or thoracic disease. Ideally, two or three cores should be obtained with one core routinely processed for histology and the remainder used for lineage and clonality studies. In this setting, cautious interpretation of the biopsy by an experienced hematopathologist and integration of the results of the ancillary studies should allow a reasonable treatment decision to be made in most cases.

Micropapillary Carcinoma of the Breast

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Wed, 24 Oct 2012 18:39:00 +0000

-Micropapillary breast carcinoma (or invasive micropapillary carcinoma IMPC) is a type of otherwise 'typical' invasive ductal carcinoma which exhibits a unique and characteristic growth pattern.

-Invasive micropapillary breast carcinoma is a very aggressive form of breast cancer, with a very high rate of lymph node metastasis.(The rate of lymph node involvement is estimated at between 75% and 100%).

-Skin invovlement (skin retraction) is another occassional feature of invasive micropapillary carcinoma of the breast, and is observed in about 20-23% of all cases.

Histological aspects of invasive micropapillary carcinoma of the breast

Histologically, invasive micropapillary breast carcinoma is characterized by:

-Clusters of cohesive tumor cells within quite prominent 'clear spaces', which resemble dilated angiolymphatic vessels.

-The nuclei of tumor cells around the periphery can often bulge with a kind of 'knobby' appearance.

- It is also quite common to see lymphatic involvement with invasive micropapillary breast cancers.

The aggressiveness of invasive micropapillary carcinoma may be related to the inverse polarity of the tumor cell clusters and lymphotropism

-Invasive micropapillary breast carcinoma tumors will often show lymphocytic infiltration.

-They tend to accumlate in the breast stroma, often forming a lymphoid follicle. The presence of lymphocytes within the tumor will tend to suggest a more aggressive cancer; more likely to metastize to the lymph nodes.

-Invasive micropapillary breast cancer is also characterized histologically by an 'inverse polarity' of the tumor cell clusters. To clarify, within the breast the 'functional unit' of the breast duct wall is a 'polar' double-layered tube consisting of luminal epithelial cells surrounded by myoepithelial cells and a basement membrane. In other words, there is an order; an asymmetrical organization from 'outer to inner', and without this polarity, the breast ducts would not able to properly excrete and transport breast milk. But with micropapillary breast carcinoma (and some other breast cancers) this polarity is reversed. The clusters of malignant cells which formed have the myoepithelial cells outside of the epithelial-derived cells, with the basal layer exposed.

Hormone receptor status is high for micropapillary breast cancer, somewhat against the norm

-Breast cancers which have higher positive rates for various hormone receptors are usually considered to have a more positive outlook. For one thing, they tend to be more responsive to chemotherapy.

-With invasive micropapillary breast cancers, about 70% tend to be ER positive and around 60% are positive for progesterone receptors. HER2 overexpression may be anticipated in approximately 40% of cases.

-For most breast cancers this degree of positive hormone receptivity would be a hopeful indicator.

-In invasive micropapillary breast carcinoma,however, hormone receptor status appears to have no particular significance to the outlook.

Factors most likely to affect the prognosis of invasive micropapillary breast cancer

-The mortality rate for micropapillary breast cancer is unfortunately quite high, at over 40%.

-The average interval between full presentation of the disease and death is about 3 years. -The factors which seem most likely to affect a poor prognosis are skin involvement, and nodal status.

-However, once lymph node metastasis is confirmed, the outlook for invasive micropapillary breast cancer does not differ significantly from other breast cancers which have metastized to the lymph nodes.

-Skin invasion is a signficant predictor of a poor prognosis with invasive micropapillary breast cancer, leading to mortality in about 50% of all cases in which it occurs.

-Aspects of the tumor which are most likely to influence the risk of metastasis are the histologic grade (based on the number of atypical cells and the rate of mitosis), lymphocyte infiltration, and lymphatic vessel density.

Treatment for invasive micropapillary carcinoma of the breast

-Invasive micropapillary breast carcinoma is a highly aggressive from of breast cancer which requires the earliest possible diagnosis and aggressive intervention and management.

-The high rate of local recurrence and high probability of lymph node metastasis will usually prompt the surgeon to suggest either a modified or full radical mastectomy, though breast conserving surgery is attempted in a minority of situations.

- Axillary dissection will usually accompany a modified or radical mastectomy.

-Adjuvant treatment with chemotherapy is often utilized as well, but usually only if there is evidence of axillary node metastasis, or when there is not yet lymph node metastasis but the tumor is larger than 1 cm.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Mon, 02 Apr 2012 20:38:00 +0000

Immunohistochemistry

Immunohistochemistry in the differential diagnosis of
clear cell carcinomas from the kidney, liver, and lung

Clear cell carcinoma is a common specimen seen by many surgical pathologists. Given an appropriate clinical context (for example, a patient with a large kidney mass), determining the nature and origin of a clear cell carcinoma can be very easy. However, in other situations this can be a challenging task, primarily because of the tremendous degree of overlap in the morphologic appearance of clear cell carcinomas from different primary sites. This month, we discuss the utility of a number of immunostains in the differential diagnosis of the more common types of clear cell carcinoma. Clear cell carcinoma can arise as a primary site in virtually any organ in the body. It is also well known that there are many other types of clear cell neoplasms, including mesenchymal, melanocytic, neuroendocrine, and even lymphoid clear cell tumors. However, if we limit our discussion to clear cell carcinomas, in our consultation service at ONCOPATH Diagnostics, the most common primary sites that we see are kidney, lung, and liver (clear cell hepatoma).

Low molecular weight cytokeratin should be per-formed in essentially all of these cases, primarily to document the fact that you are indeed dealing with a carcinoma, rather than another type of clear cell neo-plasm. Virtually all clear cell carcinomas of the kidney and clear cell hepatomas express low molecular weight cytokeratin, although on some occasions the expression may be focal or weak. Most clear cell carcinomas of the lung also express low molecular weight cytokeratin,although there is a subpopulation of clear cell squamous carcinomas that may lack staining with this reagent (They stain with high molecular weight cytokeratin).

High molecular weight cytokeratin (clone 34βE12) is a very useful reagent to approach thisdifferential diagnosis. In the vast majority of cases, clear cell carcinoma of the kidney and clear cell hepatoma are completely negative for reactivity with this antibody. As such, if substantial high molecular weight cytokeratin reactivity is observed, you are usually safe crossing kidney and liver off of your list of potential primary sites. Parenthetically, to my knowledge substantial expression of high molecular weight cytokeratin also renders adrenal cortical carcinoma highly unlikely.

Cytokeratin AE1/AE3 is worthwhile to employ inthis situation, primarily because most hepatomas are negative or only focally weakly reactive for this anti-body. We have seen a small number of hepatomas that express strong cytokeratin AE1/AE3, but they represent <5% of the cases of hepatoma that we see on our consultation service. As such, strong reactivity with AE1/AE3 usually allows one to place clear cell hepatoma much lower on the list of potential primary sites. The large majority of lung carcinomas express AE1/AE3, and most clear cell carcinomas of the kidney also express AE1/AE3, although it may be patchy and weak, a point to keep in mind when dealing with a small sample of tumor.

Vimentin is an important antibody for approachingthis differential diagnosis. The vast majority of hepatomas are negative for vimentin, whereas essentially all clear cell carcinomas from the kidney express vimentin. As such, substantial expression of vimentin argues against clear-cell hepatoma. Clear cell lung carcinoma expresses vimentin in a variable fashion, some cases positive, and some cases negative.
Because of its specificity for lung tumors, TTF-1 is worth adding to the antibody panel, since reactivity with TTF-1 argues in favor of pulmonary primary origin (although clear-cell squamous carcinoma of lung is TTF-1 negative). We have never seen TTF-1 reactivity in renal cell carcinoma or in hepatoma.

Monoclonal CEA can alsobe of use in this situation, since clear cell carcinoma of the kidney and clear-cell hepatoma are negative for monoclonal CEA (although we have seen a small number of hepatomas that show a focal canalicular pattern of staining with monoclonal
CEA, similar to but substantially weaker than the canalicular pattern that can be seen with polyclonal CEA). A significant proportion of pulmonary clear cell carcinomasexpress CEA, which if present argues against kidney and liver origin. By employing this relatively small panel of antibodies, one can often determine the most likely possibility for primary origin of a clear cell carcinoma. In some situations, additional immunostains may be required to firm up the diagnosis, but that discussion is beyond the scope of this newsletter.

forward to a friend www.OncoPathDx.com

India's first virtual Cancer Pathology diagnostic centre in Pune

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Thu, 26 Jan 2012 17:51:00 +0000

It is my great pleasure to inform you that Oncopath Diagnostics-India's first virtual Cancer Pathology centre has started at Pune. !!!!

With the help of India's first and Only digital pathology slide scanning system at Oncopath diagnostics, pathologists from USA, UK and Canada will be able to provide expert consultation to patients in India !!!!

This will specially helpful for patients and physicians/pathologists in getting second/expert opinion in difficult cases.

VALUE ADDED SERVICES OF ONCOPATH DIAGNOSTICS

The highly qualified medical staffs includes including well known national and International pathologists specialised in breast pathology, genitourinary pathology, OBGYN Pathology, GI / liver pathology, dermatopathology, hematopathology, surgical pathology, and oncologic surgical pathology.
India’s First and Only Cancer Diagnostic laboratory with Whole slide Digital Imaging and Analysis system.
Multi-tier pathologist review on all cases by well known national and international pathologists.
Reporting will be done as per the standards of college of American Pathologists.
Large in house inventory of histochemical and immunoperoxidase stains.
Thin prep cytology services.
Completely automated tissue processing with automated slide stainers for IHC and special stains.
Web-based Reporting system.
Rapid Turn-Around Time- Report turn-around time of 2-3 days for biopsies and 3-5 days for large cases.
Distribution of Reports-Reports sent back to your office via the Internet and Fax.

Some of the newspaper articles published in local news papers in India ,which highlights Oncopath Diagnostics work in India are mentioned below.

Newspaper articles: click the below links

-Indian express

- sakal

More info. about Oncopath Diagnostics is available at www.OncopathDx.com

The Role of Inflammation in Cancer

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Wed, 28 Sep 2011 16:49:00 +0000

Highlights

Precancerous inflammation can cause increased genetic and epigenetic damage
Aberrant oncogenic signaling can induce inflammation
The inflammatory response in cancer tissues elicits tumor tissue remodeling and metastases

Brief summary:

Cancer related inflammation can fall into one of two categories: 1. precancerous inflammation lesions and 2. Inflammation that is present in almost all cancer tissues including those that have no precancerous inflammation lesions. The connection between inflammation and cancer can be thought of as consisting of two pathways: an extrinsic mechanism, where a constant inflammatory state contributes to increased cancer risk (such as inflammatory bowel disease); and an intrinsic mechanism, where acquired genetic alterations (such as activation of oncogenes) trigger tumor development (Fig. 1).

The former can increase the risk to cancer development, while the latter are necessary to maintain and promote cancer progression. The roles and the relationship between the two pathways in the cancer development process depend on their specific interactions between genetic/epigenetic factors and environmental factors. The accumulated evidence, obtained using in vivo and in vitro genetic disease models and the analysis of clinical patient samples by various methods including PCR analysis, strongly favors the theory that both precancerous inflammation and inflammation stemming from genetic alteration can cause cell transformation and promote tumor progression. There is strong evidence that inflammation contributes to the incidence of and mortality resulting from a number of tumor types. Examining this relationship via real-time PCR analysis of gene expression and epigenetic state in the inflammatory and tumor microenvironment will contribute to our understanding of cancer initiation and progression and will aid in the discovery of biomarkers for clinical use and drug development (1-3).

Fore more ...Please click here

Minimal Reporting Guidelines for the Treatment of Cancer Patients

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Mon, 05 Sep 2011 05:55:00 +0000

Minimal Reporting Guidelines for the Treatment of Cancer Patients

As laboratory physicians, our contribution to patient care is knowledge: this is the starting point from which all informed therapeutic intervention proceeds. How that knowledge is obtained and communicated is the art and science of our profession. These minimal diagnostic guidelines are designed to be used as an aid, not a constraint, in that process. The guidelines are presented in a specific format out of necessity, but any format that effectively communicates the necessary information in a given pathology report is valid. Furthermore, it is accepted that not all of the information specified by these guidelines may be available at the time of diagnosis. Specific examples may include estrogen receptor or C-ERB B2 status of breast tumours or adequate information for meaningful pathologic staging. A lack of this information should not prevent the timely release of a final diagnosis in any case. It is assumed that the pathologist will provide all pertinent information that is available, either at the time of initial diagnosis, or further along in the course of the patient’s care.

Minimal Reporting Guidelines – Breast Carcinoma

Microscopic Diagnosis

(Right/Left) Breast, (core biopsy, wire local. biopsy, lumpectomy, mastectomy specimen)

a) Invasive carcinoma, histologic type

b) Greatest linear tumour dimension (define gross or microscopic measurement) of invasive

carcinoma, specify, if multifocal

c) Extent (% of total tumour volume) type and grade, (low, intermed., high) of intraductal

component (w/wo comedonecrosis)

d) Histologic grade of invasive carcinoma (Nottingham modification, Bloom and Richardson)

Nuclear grade - low = 1

- intermediate = 2

- high = 3

Mitotic rate* - <4/sq mm = 1 (low)

- 4-7/sq mm = 2 (intermediate)

- >7/sq mm = 3 (high)

Tubule formation - >75% = high = 1

- 10-75% = intermediate = 2

- <10% = low = 3

Add points for each feature to obtain total score

3-5 points = well differentiated

6-7 points = moderately differentiated

8-9 points = poorly differentiated

e) Venous or lymphatic space invasion (identified/not identified); specify if multiple vessels

involved; (specify if dermal lymphatics are involved)

f) Surgical Margins (positive/negative, indeterminate; site specific, focal or extensive, closest

approach of invasive/in-situ tumour to margins in mm)

g) Lymph node status (x of y lymph nodes positive for metastatic carcinoma, size of largest

metastasis, with/wo extranodal tumour spread). Note 2002 changes to TNM staging for

microscopic lymph node metastasis.

h) Involvement of skin, nipple, or skeletal muscle by invasive carcinoma (present/absent)

i) Index microcalcifications present (if seen in specimen radiograph)

j) Status of background breast tissue (atypical hyperplasia, benign mass forming lesions)

k) Status of estrogen receptors (all invasive CAs)

Status of progesterone receptors (all ER negative tumours)

Status of Her 2-neu expression (all metastatic positive CAs)

Report should indicate tissue block suitable for immunohistochemical prognostic markers.

Cut off for ER/PR is 5% of tumour cell nuclei staining. Her2-neu expression should be

reported as negative, equivocal (1+ to 2+), or positive (3+). All equivocal Her2-neu

immunostaining should be referred for FISH analysis.

L ) pTNM tumour stage

Minimal Reporting Guidelines – Melanoma

Microscopic Diagnosis

Skin of (site), (biopsy/excision)

a) Positive for invasive malignant melanoma, (histologic type)

b) Clark’s Level

II – papillary dermis invasion

III – fills papillary dermis, abuts retic. dermis

IV – into reticular dermis

V – into subcutis

c) Breslow Depth (mm, from granular layer)

d) Ulceration (present/absent)

e) Dermal Satellitosis (present/absent)

f) Mitotic figures/square mm

g) Vascular space invasion (present/absent)

h) Margins of excision (positive/negative, closest approach in mm)

i) Lymph node status (if applicable)

Minimal Reporting Guidelines – Soft Tissue Sarcoma

Microscopic Diagnosis

Soft tissue of (site), (resection/biopsy)

a) Sarcoma type

b) Tumour size (3 dimensions)

c) Tumour grade (Trojani system)

Differentiation score –

Close resemblance to adult tissue 1

Tumour type clearly recognized 2

Undifferentiated sarcoma 3

Necrosis score –

None 0

<50% 1

>50% 2

Mitotic score –

0-9 per 10 hpf 1

10-19 per 10 hpf 2

20 or more per 10 hpf 3

Total score –

2,3 = Grade 1

4,5 = Grade 2

6,7,8 = Grade 3

* NOTE: Alveolar and embryonal rhabdomyosarcoma, neuroblastoma, Ewing’s sarcoma

and PNET are, by definition, high grade sarcomas.

d) Vascular space invasion (present/absent)

e) Surgical resection margin

i) positive/<2 cm from margin/>2 cm from margin

ii) nearest margin location (sup/inf/med/lat, ant/post)

iii) composition of nearest margin (muscle, vessel, fascia, skin, etc.)

Minimal Reporting Guidelines – Laryngeal Carcinoma

Microscopic Diagnosis

Larynx, radical resection

a) Positive for invasive squamous cell carcinoma (histologic subtype, if applicable)

b) Tumour site

c) Tumour size

d) Tumour grade (well, moderately, poorly differentiated)

e) Direct tumour extension (commissure, ventricle, false cords, subglottis)

f) Depth of invasion

g) Vascular space invasion

h) Perineural invasion

i) In-situ component (present/absent)

j) Surgical margins and distance from margins

k) Lymph node status (Site specific: submandibular; upper jugular; mid jugular; lower jugular;

posterior cervical; juxtathyroid; paratracheal. Size of largest metastasis and extranodal

tumour spread should be mentioned.)

l) pTNM tumour stage

Minimal Reporting Guidelines – Thyroid Carcinoma

Microscopic Diagnosis

Thyroid, (right/left lobe or total) resection

a) Positive for (papillary/follicular/medullary/other) carcinoma

b) Tumour location (or locations if multicentric)

c) Greatest linear tumour dimension

d) Encapsulation (complete/incomplete/absent); w/wo invasion

e) Extrathyroidal extension (present/absent, include measurement)

f) Vascular space invasion

g) Surgical margins (if positive, include measurement)

h) Lymph node status (ipsilateral, midline, bilateral, mediastinal)

i) Status of non-neoplastic thyroid (thyroiditis, nodular hyperplasia)

j) pTNM tumour stage

Minimal Reporting Guidelines – Lung Carcinoma

Microscopic Diagnosis

Lung, (lobectomy, pneumonectomy, side)

a) Histologic tumour type (small cell/non small cell/other)

b) Greatest single tumour dimension

c) Location – <2 cm from bronchial resection margin

>2 cm from bronchial resection margin

d) Bronchial margin pos/neg

e) Pleural involvement (into visceral pleura, through pleura, extension into chest wall)

f) Lymphangitic spread (present/absent)

g) Direct venous invasion

h) Lymph node involvement (Subdivide ipsilateral peribronchial/hilar nodes from

extrapulmonary mediastinal/subcarinal nodes. Direct extension counts as lymph node

involvement.)

i) Lung parenchyma away from tumour

j) pTNM tumour stage

Minimal Reporting Guidelines – Upper Gastrointestinal and Ileocolic

Microscopic Diagnosis

Esophagus/Stomach/Duodenum/Small Bowel/Colon Resection

a) Positive for (well, moderately, poorly) differentiated carcinoma (specify type)

b) Longitudinal tumour dimension; polypoid, semicircumferential, circumferential lesion

c) Depth of invasion (submucosa, muscularis propria, perivisceral adipose tissue, peritonealized

serosa, extension into adjacent organs) measure the depth of extension beyond the muscularis

propria in mm.

d) Surgical margins (proximal, distal, radial; distance to radial margins in mm.) Direct tumour

extension within 1 mm or a positive lymph node at the radial resection margin is considered a

positive margin.

e) Venous space invasion (present/absent)

f) Lymph node status *(x of y lymph nodes positive for metastatic carcinoma). Any mesenteric

tumour deposit with a rounded contour counts as a replaced lymph node. Stellate deposits are

defined as angiolymphatic tumour spread.

g) Perforation (present/absent)

h) Status of non-carcinomatous mucosa (Barrett’s mucosa, gastritis, multifocal dysplasia).

i) pTNM tumour stage.

* A minimum of 12 lymph nodes are required to accurately predict pNO stage.

Minimal Reporting Guidelines – Rectum

Microscopic Diagnosis

Rectum, resection

a) Positive for (well, moderately, poorly) differentiated adenocarcinoma (if specific subtype,

define).

b) Tumour site (anterior, posterior, left, right; above or below peritoneal reflection).

c) Longitudinal tumour dimension and fraction of rectal circumference involved by tumour.

d) Depth of invasion (submucosa, muscularis propria, perirectal adipose tissue, peritonealized

serosa, adjacent structures). Measure distance of tumour extension beyond muscularis

propria in mm.

e) Surgical margins (proximal, distal, radial). Measure closest approach of tumour to radial

margin in mm. (Direct tumour extension within 1 mm or a positive lymph node at the radial

margins are defined as a positive margin).

f) Completeness of mesorectal excision specimen (essentially complete with minimal

defects/incomplete with exposure of rectal muscularis propria).

g) Venous space invasion (present/absent).

h) Lymph node status *(x of y lymph nodes positive for metastatic carcinoma). Any mesenteric

tumour deposit with a rounded contour counts as a replaced lymph node. Stellate deposits are

defined as angiolymphatic tumour spread.

i) Perforation (present/absent).

j) Status of noncarcinomatous mucosa (adenomas, CIBD, multifocal dysplasia).

k) pTNM tumour stage.

* A minimum of 12 lymph nodes are required to accurately predict pNO stage.

Minimal Reporting Guidelines – Pancreatic/Biliary Carcinoma

Microscopic Diagnosis

Pancreas/common bile duct, total/subtotal resection

a) Positive for carcinoma of (tumour site: common bile duct, ampulla, pancreatic head, etc.)

b) Tumour size (significant discrepancies between gross and microscopic estimates are

common. Unless microscopic growth is confluent, the gross estimate is preferred.)

c) Tumour subtype (solid, cystic, papillary, tubular, signet -ring cell, acinic cell, neuroendocrine)

d) Tumour grade (well, moderately, poorly differentiated)

e) In situ component (present/absent)

f) Vascular space invasion (present/absent)

g) Perineural invasion (present/absent)

h) Direct tumour extension (ie., duodenum, bile ducts, peripancreatic tissue, stomach, spleen,

bowel, large vascular channel)

i) Surgical margins: radial, ductal (if subtotal pancreatectomy or CBD resection)

j) Lymph node status: separate regional (peripancreatic, hepatic artery, peripyloric, celiac,

mesenteric, periaortic) lymph nodes from distant metastases

k) Status of non-neoplastic pancreas/bile ducts (pancreatitis, gallstones, sclerosing cholangitis)

l) pTNM tumour stage

Minimal Reporting Guidelines – Cervical Carcinoma

Microscopic Diagnosis

Cervix, cone excision or Uterus, resection

a) Cervical tumour cell type

b) Grade of invasive carcinoma

c) In situ component (present/absent)

d) Depth and breadth of invasive component

e) Vascular space invasion (present/absent)

f) Extension beyond cervix (parametrium, pelvic wall, vagina, bladder)

g) Resection margins (ectocervical, endocervical, deep; with closest approach in mm; define if

mucosal margin is positive for in situ or invasive disease)

h) Lymph node status

i) FIGO tumour stage

Minimal Reporting Guidelines – Vulva (non-melanoma)

Microscopic Diagnosis

Vulva, (simple/radical) resection

a) Vulvar tumour cell type

b) Tumour grade (well, moderately, poorly differentiated)

c) Depth of invasion and overall tumour size

d) Vascular space invasion (present/absent)

e) In-situ component (present/absent)

f) Extension to extra-vulvar sites (mention if present)

g) Surgical margins (peripheral, deep, vaginal; define if positive for in situ or invasive disease).

h) Lymph node status

i) Status of non-neoplastic mucosa (condyloma)

j) FIGO tumour stage

Minimal Reporting Guidelines – Endometrial Carcinoma

Microscopic Diagnosis

Uterus (tubes, ovaries), resection (curettings)

a) Positive for (endometrioid, papillary serous, clear cell, etc.) adenocarcinoma

b) FIGO tumour grade –

1 - 5% or less solid growth

2 - 6-50% solid growth

3 - more than 50% solid growth

(Morular growth excluded. High grade nuclei raises tumour grade by 1. Serous and clear

cell carcinomas are almost always grade 3.)

c) Myometrial invasion (none, inner ½ of myometrium, outer ½ of myometrium). (If possible,

measure maximum depth of invasion and thickness of uninvolved myometrium at this site.)

d) Vascular space invasion

e) Cervical involvement (absent, noninvasive, invasive)

f) Extrauterine spread (bladder, bowel)

g) Status of non-carcinomatous endometrium

h) Lymph node status (if submitted)

i) FIGO tumour stage

Minimal Reporting Guidelines – Ovarian Carcinoma

Microscopic Diagnosis

(Right/left/bilateral/TAHBSO) Ovary, resection

a) Positive for (endometrioid, serous, mucinous) adenocarcinoma.

(Borderline tumours are reported using the same guidelines.)

b) Tumour Grade (Invasive carcinoma only, Silverberg)

Nuclear score - 1, 2, 3

Mitotic score - <10 per 10 hpf = 1

10-24 per 10 hpf = 2

25 or more per 10 hpf = 3

Architecture score - glandular = 1

papillary = 2

solid = 3

Total score: 3-5 = Grade 1

6-7 = Grade 2

8-9 = Grade 3

c) Ovarian surface involvement (present/absent)

d) Tumour capsule intact/ruptured

e) Tumour involvement unilateral/bilateral

f) Extraovarian spread (define sites of implants, invasive or non-invasive; size of implants

g) Status of peritoneal washings (if known)

h) Lymph node status (if submitted)

i) FIGO tumour stage

Minimal Reporting Guidelines – Penis for Squamous Carcinoma

Microscopic Diagnosis

Penis, resection

a) Positive for invasive squamous cell carcinoma

b) Tumour site (urethra, foreskin, glans, shaft)

c) Tumour grade (well, moderately, poorly differentiated, or verrucous)

d) Tumour extension: subepithelial connective tissue, tunica albuginea, corpus spongiosum,

corpus cavernosum, urethra

e) Vascular space invasion (present/absent)

f) In situ component (present/absent/extent, multifocal)

g) Surgical margins: urethra, corpora, skin; define if positive for in situ or invasive disease

h) Lymph node status

i) Status of non-neoplastic epithelium (condyloma, inflammatory process)

j) pTNM tumour stage

Minimal Reporting Guidelines – Testis for Germ Cell Tumour

Microscopic Diagnosis

(Right/Left) Testis, radical orchidectomy

a) Positive for (germ cell tumour type)

b) Tumour size

c) Tumour extension (limited to seminiferous tissues, extension into rete testis/tunica

albuginea/epididymis or spermatic cord)

d) Vascular space invasion (present/absent, non-seminomatous GCT only)

e) Estimated percent of different germ cell components (mixed GCT only)

f) Surgical margins (peritesticular, adnexal structures, spermatic cord)

g) Status of lymph nodes (if submitted)

h) Status of non-neoplastic testis: spermatogenesis, intratubular germ cell neoplasm

i) pTNM tumour stage

Minimal Reporting Guidelines – Radical Prostatectomy for Prostatic Carcinoma

Microscopic Diagnosis

Prostate, radical resection

a) Positive for prostatic adenocarcinoma

b) Gleason primary and secondary grades and total score (omit if treatment effect evident)

c) Sites involved (peripheral/transitional zone; single or both lobes; apex, mid or bladder base)

d) Greatest single tumour dimension

e) Estimated percent of gland involvement

f) Tumour extension: limited to gland, periprostatic fat, seminal vesicles

g) Vascular space invasion

h) Surgical margins: peripheral, apex, bladder neck (define: mm, involvement, type of tissue

involved – capsule/soft tissue)

i) Lymph node status (x of y positive, site specific)

j) Status of non-malignant prostate (PIN)

k) Status of prostatic urothelium (if abnormal)

l) pTNM tumour stage

Minimal Reporting Guidelines – Prostate Needle Biopsies

Microscopic Diagnosis

Prostate, needle biopsy (or biopsies xN)

a) Positive for prostatic adenocarcinoma

b) Gleason primary and secondary grade and score

c) Number of and location of cores involved (if multiple at one site)

d) Greatest single linear tumour dimension (confluent growth)

e) Vascular space invasion (present/not identified)

f) Extraprostatic fat involvement (present/not identified)

g) High Grade PIN (report if present only)

* NOTE: Use these same criteria for reporting TUPR specimens. Substitute number of chips involved

(eg., 4 of 20 chips positive) for linear tumour dimension. Report prostatic urothelium and

seminal vesicle status, if present.

Gleason Grading (omit if treatment effect evident)

1) Single, separate uniform glands closely packed, with definite edge.

2) Single, separate uniform glands loosely packed, with irregular edge.

3) Single, separate, scattered glands (very small or uniform) or smoothly circumscribed

papillary/cribriform masses.

4) Fused glands with ragged infiltration, with or without large pale cells (hypernephroid).

5) Solid masses with any necrosis (comedocarcinoma) or anaplastic raggedly infiltrating.

Gleason Score

Predominant pattern plus the worst of any additional patterns.

If only one pattern is seen, the grade is doubled to arrive at score.

Minimal Reporting Guidelines – Bladder Carcinoma

Microscopic Diagnosis

Urinary Bladder (transurethral resection/radical cystectomy or cystoprostatectomy)

a) Positive for urothelial carcinoma (subtype, invasive/noninvasive)

b) Tumour site(s) (single or multifocal)

c) Tumour size

d) Tumour depth of invasion (lamina propria, submucosa, inner or outer half of muscularis

propria, extravesicle)*

e) Involvement of ureters, urethra, prostate or seminal vesicles

f) Vascular space invasion (present/absent)

g) Histologic grade of invasive component (1,2,3)

h) High grade flat carcinoma in situ (present/absent)

i) Surgical margins

i) ureters

ii) urethra

iii) perivesical

iv) periprostatic

j) Lymph node status (if submitted)

k) Prostate Gland (as per prostatectomy guidelines)

l) pTNM tumour stage

* NOTE: Report should delineate, where possible, invasion into bladder lamina propria versus

submucosa.

Minimal Reporting Guidelines – Renal Carcinoma

Microscopic Diagnosis

(Right/Left) Kidney, (segmental, simple, radical) resection

a) Positive for renal cell carcinoma, histologic subtype

b) Tumour site(s) (pole, mid region, capsule, multiple)

c) Tumour size

d) Nuclear grade (Fuhrman)

Grade 1: round nuclei: nucleoli visible only at x 400 magnification

Grade 2: slightly irregular nuclei; nucleoli visible at x 200 magnification

Grade 3: irregular nuclei; nucleoli visible at x 100 magnification

Grade 4: enlarged pleomorphic nuclei or giant cells

e) Tumour extension (capsular perforation, renal pelvis, adrenal, renal vein, IVC)

f) Surgical margins (perinephric, hilar vascular, ureteric)

g) Lymph node status (if submitted)

h) Status of non-malignant renal tissue

i) pTNM tumour stage

GROSS AND MICROSCOPIC NOTES ON PATHOLOGY REPORTING OF EXCISIONAL BREAST BIOPSIES OR MASTECTOMY SPECIMENS

REPORT

a) Specimen

· 3 dimensional size and nature of specimen perimeter (ie.,specify if fragmented)

b) Invasive carcinoma

i) Size in mm

· re-evaluate maximum exact size of apparent T1 or T2 invasive carcinoma (exclude

size of DCIS if it is major part of tumour nodule) microscopically

· note critical invasive carcinoma size threshold for node negative cases: <20 mm

versus > 21 mm for chemo, Grade III duct < 10 versus > 10 mm for chemo, and

potentially at 5 and 10 mm thresholds for necessity of node dissection

ii) Type

· duct, lobular, mixed, and other variants

iii) Grade

· I-III/III Nottingham modification of Bloom and Richardson scoring system

· architecture – tubule; nuclear grade; mitosis

· record overall average for tubula r differentiation, but highest (even focal) nuclear

grade and mitotic rate; ie., consider grade heterogeneity

iv) Single or multifocal

· specify details for each focus

v) Margin status

· exact distance in mm (eg., touching inked margin, <1 mm, 1 – 2 mm, 2 – 5 mm, >5

mm or indeterminate)

· amount of invasive carcinoma at margin (eg., transected, focal microscopic,

number of mm and sections with close/positive margins)

· exact location of all positive and close (<5 mm) margins composition of margin,

eg., breast parenchyma, fascia, skeletal muscle, skin, etc.

vi) Peritumoral lymphatic and vascular invasion

· record only if definite lymphatic invasion, as may lead to chemotherapy for node

negative T1 carcinoma.

· comment if lymphatic invasion is extensive (multiple vessels involved)

· perineural invasion is of lesser importance unless a large nerve is involved near the

margin

· true peritumoral venous invasion is rare

vii) Skin or skeletal muscle involvement

viii) ER, PR & HER2 (see latter)

c) Ductal Carcinoma In-Situ

· size, grade and distance to closest margins (0 – 10 mm) are important treatment

parameters for cases with DCIS only (re: Van Nuys Prognostic System)

i) Size

· 15, 25, 40 and 50 mm size thresholds for DCIS potentially clinically important.

· often DCIS size can only be evaluated by summing up thickness of sequentially

submitted blocks

ii) Nuclear Grade (I – III) +/- necrosis

iii) Type

· cribriform, solid, micropapillary, other

d) ADH, ALH and LCIS

· Comment about extent

· Relationship to margin generally not pertinent

· Differentiate solid DCIS from LCIS at margins

e) Lymph Nodes

i) Number

· exact number obtained and number positive

ii) Size of positive nodes

· maximal size of largest metastatic carcinoma deposit (not just size of enlarged

node)

iii) Extranodal soft tissue extension (comment if focal or extensive)

iv) Perinodal lymphatic or venous invasion

RECOMMENDATIONS FOR OPTIMAL HANDLING

OF COLORECTAL CARCINOMA SPECIMENS

GROSS SPECIMEN HANDLING

1) For rectal resection specimens, identify the peritoneal reflection for orientation. This well be

located at the anterior superior aspect of the rectum. Ink all nonperitonealized radial rectal margins.

For colonic specimens, locate the mesenteric resection margin, where the surgeon’s knife has cut

through the mesentery to remove it from the abdomen, and ink this nonperitonealized surface.

2) Open and rinse the bowel (starting at the proximal end for rectal specimens, and from both ends for

colonic specimens) but stop when the scissors reach the tumour. Do not longitudinally transect the

tumour. Leave the tumour intact and fix the partially opened specimen for 48 hours.

3) After fixation, slice the bowel through the area of the tumour involvement in radial sections (like a

sausage) at 5 mm intervals.

4) Examination of these slices should allow measurement of the circumference of the bowel involved

by tumour, gross assessment of the radial margin, and identification of the minimum 12 pericolic or

perirectal lymph nodes.

HINT: Reportedly, most of the lymph nodes will be found at the outer edge of the specimen.

5) Lymph nodes should be submitted for histology in their entirety (bisect them if they are big, but try

to be accurate on the count. The radial resection margin of a total mesorectal excision should be

sampled in three tissue blocks (one should suffice for the mesenteric root of a colonic specimen) at

the site of closest approach by tumour. Proximal and distal resection margins only require

sampling if closer than 3 cm to the tumour, in the fixed state.

NOTES ON MICROSCOPIC REPORTING

1) Radial resection margins and depth of invasion are separate criteria with different clinical

implications. Extension of a cecal carcinoma to the mesenteric resection margin without extension

to the peritonealized serosal surface is a T3 lesion with residual disease. Involvement of the serosa

is T4 disease but is considered completely excised.

2) Tumour at the serosal surface with an inflammatory response is the same as tumour on the serosal

surface (identical clinical implications).

3) If we can’t find 12 lymph nodes, we are obliged to go back to the bottle and look for more. This

recommendation is based upon validated studies indicating that a minimum of 12 lymph nodes is

required in order to accurately stage a patient as n0. If less than 12 nodes are examined, and the

pathologist diagnoses the case as negative for node metastasis, there is a significant chance that

the pathologist is wrong. However, if the surgeon has not provided an adequate mesenteric pedicle,

we will not find many nodes. It is advisable to provide a 1 dimension assessment of the width of

the mesentery, along with the length of the specimen, in the gross description. This measuresment

is likely to prevent arguments about who’s dissection (the pathologist’s or the surgeon’s) was

inadequate. Reporting on more than 15 lymph nodes provides no additional information.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Thu, 25 Aug 2011 21:32:00 +0000

Mimics of Prostate Cancer –

Atrophy

looks suspicious for adenocarcinoma at first glance.
the nuclei are small and hyperchromatic.
No prominent nucleoli are seen.
Some glands are lined by obviously benign flattened atrophic epithelium.
The immunostain for high molecular weight cytokeratin can be helpful in distinguishing between atrophy (fragmented basal cell layer) from atrophic variant of prostatic adenocarcinoma (no basal cell layer).

Atypical adenomatous hyperplasia

It may show the infiltrative architecture of cancer,
lacks the cytologic features such as prominent nucleoli.
The immunostain for high mol. wt. Cytokeratin will show fragmented basal cell layer in most cases.

Post-Atrophic Hyperplasia

Post-atrophic hyperplasia architecturally mimics adenocarcinoma
lacks the cytologic features.
In difficult cases, the immunostain for high mol. wt. cytokeratin can be performed which would show at least a few basal cells in post-atrophic hyperplasia.

Sclerosing Adenosis

small glands with infiltrative growth pattern in a cellular spindled stroma.
The plump spindle cells in the stroma are nicely seen here.
The lining acinar epithelial cells lack cytologic atypia – no significant nuclear or nucleolar enlargement is seen
Myoepithelial differentiation in basal cells of the acini of Sclerosing adenosis is illustrated with the immunostain for muscle specific actin.

Cowper's Glands

They have a lobular configuration and are often associated with skeletal muscle fibers
The glands are lined by goblet cells distended with mucin.
The small hyperchromatic nuclei are pushed to the periphery.
Sometimes ducts lined by cuboidal cells are present in the center of the lobules.

Mucinous Metaplasia

Mucinous metaplasia is seen in about 1% of prostates.
It may occasionally resemble prostatic adenocarcinoma. However, it lacks prominent nucleoli and the does not show immunoreactivity for PSA and PAP.
The cells are positive for PAS, mucicarmine and Alcian blue.

Prostatic xanthoma

Prostatic xanthoma is an uncommon benign lesion that may mimic high-grade prostatic adenocarcinoma.
It consists of lipid-laden macrophages that may be arranged in small circumscribed nodules or infiltrating cords extending into the stroma
diffusely positive for CD68 (shown here), and negative for CAM5.2, PSA, and PSAP.

Thanks to Dr.Dharam Ramnani for the images.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Thu, 25 Aug 2011 21:27:00 +0000

Protocol for Synpotic reporting of Breast excision specimen with diagnosis of Ductal Carcinoma In Situ (DCIS) of the Breast

Protocol applies to DCIS without invasive carcinoma or microinvasion.
The complete pathology report should include following parameters.

Specimen type.

___ Partial breast
___ Total breast (including nipple and skin)
___ Other (specify):
___ Not specified

Procedure

___ Excision without wire-guided localization
___ Excision with wire-guided localization
___ Total mastectomy (including nipple and skin)
___ Other (specify): ____________________________
___ Not specified

Lymph Node Sampling (select all that apply)

___ No lymph nodes present
___ Sentinel lymph node(s)
___ Axillary dissection (partial or complete dissection)
___ Lymph nodes present within the breast specimen (ie, intramammary lymph nodes)
___ Other lymph nodes (eg, supraclavicular or location not identified)
Specify location, if provided: _________________________

Specimen Integrity

___ Single intact specimen (margins can be evaluated)
___ Multiple designated specimens (eg, main excisions and identified margins)
___ Fragmented (margins cannot be evaluated with certainty)
___ Other (specify): __________________________________

Specimen Size (for excisions less than total mastectomy)

Greatest dimension: ___ cm

*Additional dimensions: ___ x ___ cm

___ Cannot be determined

Specimen Laterality

___ Right
___ Left
___ Not specified

Size (Extent) of DCIS ( Click here for more info about measuring size of DCIS)

Estimated size (extent) of DCIS (greatest dimension using gross and microscopic evaluation): at least ___ cm
*Additional dimensions ___ x ___ cm
*Number of blocks with DCIS: ___
*Number of blocks examined: ___
Note: The size (extent) of DCIS is an estimation of the volume of breast tissue occupied by DCIS.

Histologic Type

___ Ductal carcinoma in situ. Classified as Tis (DCIS) or Tis (Paget)

*Architectural Patterns (select all that apply)

___ Comedo
___ Paget disease (DCIS involving nipple skin)
___ Cribriform
___ Micropapillary
___ Papillary
___ Solid
___ Other (specify: ___________________)

Nuclear Grade

___ Grade I (low)
___ Grade II (intermediate)
___ Grade III (high)

Necrosis

___ Not identified
___ Present, focal (small foci or single cell necrosis)
___ Present, central (expansive “comedo” necrosis)

Margins (select all that apply)

___ Margins cannot be assessed

___ Margin(s) uninvolved by DCIS

Distance from closest margin: ___ mm

*Specify margins:

*Distance from superior margin: ___ mm

*Distance from inferior margin: ___ mm

*Distance from medial margin: ___ mm

*Distance from lateral margin: ___ mm

*Distance from anterior margin: ___ mm

*Distance from posterior margin: ___ mm

*Distance from other specified margin: ___ mm

*Designation of margin: ______________________

___ Margin(s) positive for DCIS

*Specify which margin(s) and extent of involvement:

*___ Superior margin

*___ Focal

*___ Minimal/moderate

*___ Extensive

*___ Inferior margin

*___ Focal

*___ Minimal/moderate

*___ Extensive

*___ Medial margin

*___ Focal

*___ Minimal/moderate

*___ Extensive

*___ Lateral margin

*___ Focal

*___ Minimal/moderate

*___ Extensive

*___ Anterior margin

*___ Focal

*___ Minimal/moderate

*___ Extensive

*___ Posterior margin

*___ Focal

*___ Minimal/moderate

*___ Extensive

*Treatment Effect: Response to Presurgical (Neoadjuvant) Therapy

*___ No known presurgical therapy
*___ No definite response to presurgical therapy
*___ Probable or definite response to presurgical therapy

Lymph Nodes (required only if lymph nodes are present in the specimen)

Number of sentinel nodes examined: ____
Total number of nodes examined (sentinel and nonsentinel): ____
Number of lymph nodes with macrometastases (>0.2 cm): ____
Number of lymph nodes with micrometastases (>0.2 mm to 0.2 cm and/or >200 cells): ____
Number of lymph nodes with isolated tumor cells (<0.2 mm and ≤200 cells): ____
Size of largest metastatic deposit (if present): ____

Note: The sentinel node is usually the first involved lymph node. In the unusual situation in which a sentinel node is not involved by metastatic carcinoma, but a nonsentinel node is involved, this information should be included in a note.

*Extranodal extension:

*___ Present
*___ Not identified
*___ Indeterminate

*Method of Evaluation of Sentinel Lymph Nodes (select all that apply)

*___ Hematoxylin and eosin (H&E), 1 level
*___ H&E, multiple levels
*___ Immunohistochemistry
* ___ Sentinel lymph node biopsy not performed
*___ Other (specify): _______________________

Pathologic Staging (pTNM)

TNM Descriptors (required only if applicable) (select all that apply)

___ r (recurrent)
___ y (post-treatment)

Primary Tumor (pT)

___ pTis (DCIS): Ductal carcinoma in situ
___ pTis (Paget): Paget disease of the nipple not associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) in the underlying breast parenchyma.

Note: If there has been a prior core needle biopsy, the pathologic findings from the core, if available, should be incorporated in the T classification. If invasive carcinoma or microinvasion were present on the core, the protocol for invasive carcinomas of the breast¹ should be used and should incorporate this information.

Regional Lymph Nodes (pN) (choose a category based on lymph nodes received with the specimen; immunohistochemistry and/or molecular studies are not required)

Note: If internal mammary lymph nodes, infraclavicular nodes, or supraclavicular lymph nodes are included in the specimen, consult the AJCC Staging Manual for additional lymph node categories.

Modifier (required only if applicable)

___ (sn) Only sentinel node(s) evaluated. If 6 or more sentinel nodes and/or nonsentinel nodes are removed, this modifier should not be used.

Category (pN)

___ pNX: Regional lymph nodes cannot be assessed (eg, previously removed, or not removed for pathologic study)

___ pN0: No regional lymph node metastasis identified histologically

Note: Isolated tumor cell clusters (ITC) are defined as small clusters of cells not greater than 0.2 mm or single tumor cells, or a cluster of fewer than 200 cells in a single histologic cross-section.^# ITCs may be detected by routine histology or by immunohistochemical (IHC) methods. Nodes containing only ITCs are excluded from the total positive node count for purposes of N classification but should be included in the total number of nodes evaluated.

___ pN0 (i-): No regional lymph node metastases histologically, negative IHC

___ pN0 (i+): Malignant cells in regional lymph node(s) no greater than 0.2 mm and no more than 200 cells (detected by H&E or IHC including ITC)

___ pN0 (mol-): No regional lymph node metastases histologically, negative molecular findings (reverse transcriptase polymerase chain reaction [RT-PCR])

___ pN0 (mol+): Positive molecular findings (RT-PCR), but no regional lymph node metastases detected by histology or IHC

___ pN1mi: Micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm).

___ pN1a: Metastases in 1 to 3 axillary lymph nodes, at least 1 metastasis greater than 2.0 mm

___ pN2a: Metastases in 4 to 9 axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm)

___ pN3a: Metastases in 10 or more axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm)

^# Approximately 1000 tumor cells are contained in a 3-dimensional 0.2-mm cluster. Thus, if more than 200 individual tumor cells are identified as single dispersed tumor cells or as a nearly confluent elliptical or spherical focus in a single histologic section of a lymph node, there is a high probability that more than 1000 cells are present in the lymph node. In these situations, the node should be classified as containing a micrometastasis (pN1mi). Cells in different lymph node cross-sections or longitudinal sections or levels of the block are not added together; the 200 cells must be in a single node profile even if the node has been thinly sectioned into multiple slices. It is recognized that there is substantial overlap between the upper limit of the ITC and the lower limit of the micrometastasis categories due to inherent limitations in pathologic nodal evaluation and detection of minimal tumor burden in lymph nodes. Thus, the threshold of 200 cells in a single cross-section is a guideline to help pathologists distinguish between these 2 categories. The pathologist should use judgment regarding whether it is likely that the cluster of cells represents a true micrometastasis or is simply a small group of isolated tumor cells.

Distant Metastasis (M)

___ Not applicable

___ cM0(i+): No clinical or radiographic evidence of distant metastasis, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastasis

___ pM1: Distant detectable metastasis as determined by classic clinical and radiographic means and/or histologically proven larger than 0.2 mm

Note: The presence of distant metastases in a case of DCIS would be very unusual. Additional sampling to identify invasive carcinoma in the breast or additional history to document a prior or synchronous invasive carcinoma is advised in the evaluation of such cases.

*Additional Pathologic Findings

*Specify: ____________________________

*Ancillary Studies

*Estrogen Receptor (results of special studies performed on this specimen or a prior core needle biopsy)

*___ Immunoreactive tumor cells present

*___ No immunoreactive tumor cells present

*___ Pending

*___ Not performed

*___ Other (specify): _____________________

*Name of antibody: ___________________

*Name of vendor: ___________________

*Type of fixative: ________________

*Progesterone Receptor (results of special studies performed on this specimen or a prior core needle biopsy)

*___ Immunoreactive tumor cells present

*___ No immunoreactive tumor cells present

*___ Pending

*___ Not performed

*___ Other (specify): _____________________

*Name of antibody: ___________________

*Name of vendor: ___________________

*Type of fixative: ________________

*Microcalcifications (select all that apply)

___ Not identified
___ Present in DCIS
___ Present in non-neoplastic tissue
___ Present in both DCIS and non-neoplastic tissue

*Clinical History (select all that apply)

The current clinical/radiologic breast findings for which this surgery is performed include:

*___ Palpable mass

*___ Radiologic finding

*___ Mass or architectural distortion

*___ Calcifications

*___ Other (specify): _________________________

*___ Nipple discharge

*___ Other (specify): ____________________

*___ Prior history of breast cancer

*Specify site, diagnosis, and prior treatment: ______________________

*___ Prior neoadjuvant treatment for this diagnosis of DCIS

*Specify type: ______________________

*Comment(s)

For specimens with a known diagnosis of DCIS (eg, by prior core needle biopsy) it is highly recommended that the entire specimen is examined using serial sequential sampling to exclude the possibility of invasion, to completely evaluate the margins, and to aid in determining extent. If an entire excisional specimen or grossly evident lesion is not examined microscopically, it is helpful to note the approximate percentage of the specimen or lesion that has been examined.

Ref. College of American pathologist.

Breast Carcinoma vs. Pulmonary Adenocarcinoma

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Thu, 30 Dec 2010 03:51:00 +0000

Some authors have estimated that 4-9% of patients with breast carcinoma will eventually develop second pulmonary carcinomas. As a result, many pathologists have been faced with the problem of trying to determine whether a particular lung carcinoma represents metastatic breast carcinoma or a new primary pulmonary adenocarcinoma. This month, we will briefly review antibodies that may be useful in addressing this differential diagnostic problem.

GCDFP-15 (gross cystic disease fluid protein-15): This marker has good specificity for breast carcinoma, although its sensitivity is not high, as only about 50% of breast carcinomas express this marker. Another potential problem with this marker (particularly when dealing with small biopsy specimens) is that it is often expressed in a focal fashion, occasionally in only a very small percentage of tumor cells. Therefore, the possibility of sampling error must always be kept in mind when dealing with small biopsy specimens stained for this marker. Although I have seen it very rarely expressed in lung carcinoma (<1% of cases), reactivity with this marker supports breast origin over lung origin.

TTF-1 (thyroid transcription factor-1) and PE-10 (surfactant protein A): These two antibodies are wellknown for their ability to serve as markers of pulmonary origin. Only nuclear reactivity with TTF-1 should be assessed, and TTF-1 stains roughly 75% of pulmonary adenocarcinomas. The sensitivity of PE-10 (a cytoplasmic antigen) is substantially less, and from my experience I would estimate that about 30-40% of pulmonary adenocarcinomas express PE-10. It is also important to keep in mind that thyroid carcinoma may express both of these markers (particularly TTF-1), so metastatic thyroid carcinoma to the lung is a potential diagnostic trap. In this situation, identification of reactivity with monoclonal CEA can provide additional support for a primary pulmonary origin, since substantial CEA reactivity is very uncommon in papillary and follicular carcinomas of the thyroid. (Parenthetically, medullary carcinoma of the thyroid characteristically expresses strong and diffuse CEA). I have never personally observed expression of TTF-1 in a breast carcinoma.

Villin: Villin is a marker that is expressed in a very high percentage of GI and related (pancreatic, bile duct, etc.) adenocarcinomas, but it is also expressed in a subpopulation of pulmonary adenocarcinomas. Since it is extremely uncommon for breast carcinoma to show substantial villin immunoreactivity, identification of this marker in a tumor provides evidence against a breast primary origin.

H&E sections (top left and top right) of a lung tumor biopsy from a 65
year-old female with a prior history of ER negative, PR negative invasive
ductal breast carcinoma. Original slides on the breast tumor
were not available for comparison. The villin immunostain (bottom
left) was strongly positive, rendering breast origin highly unlikely.
Pulmonary origin was confirmed by positivity for TTF-1 (bottom middle)
and PE-10 (bottom right).

Estrogen and Progesterone Receptors: It is wellknown that estrogen and progesterone receptors are expressed in the majority of breast carcinomas. Although past conventional wisdom dictated that lung adenocarcinoma was always negative for ER, it is important to realize that a small but significant percentage (probably THE FOCUS Immunohistochemistry H&E sections (top left and top right) of a lung tumor biopsy from a 65 year-old female with a prior history of ER negative, PR negative invasive ductal breast carcinoma. Original slides on the breast tumor were not available for comparison. The villin immunostain (bottom left) was strongly positive, rendering breast origin highly unlikely. Pulmonary origin was confirmed by positivity for TTF-1 (bottom middle) and PE-10 (bottom right). GCDFP-15 about 5-10%) of lung adenocarcinomas do indeed express estrogen receptors (at least when using the 1D5
antibody), and I have seen expression of ER in unequivocal lung adenocarcinomas on multiple occasions. In most instances it is expressed in a "low-level" fashion in lung adenocarcinoma, with a subpopulation of tumor cells showing weak to moderate reactivity. However, on a few occasions I have observed strong reactivity in lung tumors, including several from male patients. When employing the 6F11 clone, Dabbs et al have reported ER positivity in 67% of lung adenocarcinomas! I have not personally observed significant expression of progesterone receptors in lung adenocarcinoma. Obviously, it is always helpful if one is aware of the ER and PR status of the original breast tumor when dealing with potential second primary carcinomas in patients with a prior history of breast carcinoma.

Immunostains on lung FNA cell block from a female smoker with
prior breast carcinoma. The ER immunostain (left) showed moderate
positivity, but the TTF-1 immunostain (right) was strongly positive.
Further history indicated that this patient had a small tubular
carcinoma with no regional node metastases, that was morphologically
different from the lung tumor. This case represented a primary
pulmonary adenocarcinoma that expressed ER. Obviously,
relying on a single ER immunostain to work up this case may have
led to an erroneous diagnosis, underscoring the importance of appropriate
panels of immunostains in working up such cases.

BCL-2: Alsabeh et al published a paper in 1996 calling attention to the potential application of BCL-2 immunostaining to this differential diagnostic problem. In a series of 208 breast carcinomas, 79.3% of the breast tumors expressed BCL-2, in contrast to only 5.6% of 54 lung adenocarcinomas. As such, immunoreactivity with BCL-2 supports breast over lung primary origin.

HBME-1: Miettinen and Kovatich found that HBME- 1 showed significant expression in only 9% (3 of 34 cases) of invasive ductal carcinomas examined, whereas this marker showed significant expression in 45% (23 of 51 cases) of lung adenocarcinomas. As such, expression of HBME-1 favors lung primary over breast primary.

S100 Protein and CEA: Some authors report S100 reactivity in 15-30% of breast carcinomas, but only rarely in lung adenocarcinoma. In addition, others report that CEA may also be useful in this situation, in that strong diffuse expression of CEA is more common in lung carcinoma than breast carcinoma. However, in my practice I have not been impressed with utility of CEA for distinguishing lung from breast carcinoma.

SUMMARY: In summary, I think the combination of TTF-1, GCDFP-15, villin, ER, and PR represents a useful initial panel to attempt to distinguish breast carcinoma from pulmonary carcinoma (keeping in mind that some lung carcinomas may show expression of ER). If the initial battery of immunostains is not diagnostic, other markers such as PE-10, BCL-2, HBME-1, and S100 protein would be reasonable markers to consider.

REFERENCES:
1. Miettinen M, Kovatich AJ: HBME-1. A Monoclonal Antibody Useful in the Differential Diagnosis of Mesothelioma, Adenocarcinoma, and Bone Tumors. Applied Immunohistochemistry 3(2): 115-122, 1995.
2. Alsabeh R, Wilson CS, Ahn CW, et al: Expression of BCL-2 by Breast Cancer: A Possible Diagnostic Application. Modern Pathology 9(4):439-444, 1996.
3. Raab SS, Berg LC, Swanson PE, Wick MR: Adenocarcinoma in the Lung in Patients with Breast Cancer. A Prospective Analysis of the Discriminatory Value of Immunostains. American Journal of Clinical Pathology 100:27-35, 1993.
4. Wick MR, Lillemoe TJ, Copland GT et al: Gross Cystic Disease Fluid Protein-15 as a Marker for Breast Cancer: Immunohistochemical Analysis of 690 Human Neoplasms and Comparison with Alpha-Lactalbumin. Human Pathology 20 (3):281-287, 1989.
5. Kaufman O, Dietel M: Thyroid Transcription Factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B. Histopathology 36:8-16, 2000.
6. Dabbs DJ, Liu Y, Raab SS et al: Immunohistochemical Detection of Estrogen Receptor in Pulmonary Adenocarcinomas is Dependent Upon the Antibody Used. Modern Pathology 13 (3):208A, abstract #1227, 2000.
7. Bejarano PA, Baugman RP, Biddinger PW et al: Surfactant Proteins and Thyroid Transcription Factor-1 in Pulmonary and Breast Carcinomas. Modern Pathology 9(4):445-452, 1996.
8. Nicholson AG. McCormick CJ, Shimasato Y et al: The Value of PE-10 (SP-A, Lung), a Monoclonal Antibody against Pulmonary Surfactant, in Distinguishing Primary and Metastatic Lung Tumours. Histopathology 27(1):57-60, 1995.

Breast Core needle biopsy procedure

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Wed, 29 Sep 2010 16:28:00 +0000

Patients undergo breast core biopsy generally due to one of the 3 main reasons:

1) Presence of a mass or mass-like lesion either clinically palpable or diagnosed on imaging.
2) Presence of suspicious calcifications on screening mammography.
3) Nipple discharge or skin/nipple changes.

Advantages of breast core needle biospy over Fine needle aspiration cytology (FNAC) are as follows:

•Most cases can be definitely categorised
•Provides architectural information
•Microcalcifications can be directly visualised

The biopsy techniques and imaging modalities used by radiologists vary and is generally dependent on the type of lesion, most suitable method for visualization, and patient related factors.
• Calcifications are most obvious on screening mammograms and are amenable to stereotactic core biopsy.
• A mass lesion is generally best seen under ultrasound (US) guidance

Imaging modality used for biopsy are :-
• Stereotactic
• Ultrasound (US)
• Magnetic Resonance Imaging (MRI)

Stereotactic breast core needle biopsy :
–Uses X-ray imaging for localizing and targeting a lesion
– Calcifications and masses visualized on a mammogram can be biopsied
– Patient is placed in prone or upright position
– Generally performed using a Vaccume Assited Device (VAD)
– Needle gauges range from 7-14 depending on the lesion biopsied

Not all mammographically detected lesions/changes are biopsied. Radiologists use a method of scoring called Breast Imaging and Radiologists Scoring (BI-RADS) system to assess if the lesion identified on imaging requires a biopsy. Any lesion with a score of 4 is biopsied.

Ultrasound (US) guided core biopsy offers several advantages over stereotactic biopsy.
1. US is a real time procedure, i.e. it is possible to follow the motion of the biopsy needle as it moves through the breast tissue.
2. Since it does not require breast compression, US guided core biopsy procedure may be more comfortable to the patient.
3. US guided biopsy is faster, cheaper, avoids ionizing radiation and allows biopsy of areas hard to reach (under the arm or close to the chest wall) via stereotactic biopsy.

Ultrasound guded biopsy

Some difficult to see lesions are generally more obvious under magnetic resonance imaging (MRI). MRI is also used in some high risk patients to detect early lesions. Some breast centers have also started using bilateral breast MRI after the diagnosis of invasive cancer to exclude the possibility of multifocal disease, although the significance of this practice is currently debated. MRI guided core biopsies are more cumbersome than other methods and requires administration of gadolinium and therefore cannot be performed in pregnant patients.

Type of biopsy devices used for biopsy-

– Automated large core (ALC)

– Vacuum assisted device (VAD)

– Total removal device (TRD)

The type of biopsy devices used may also vary by the type of imaging technique employed to perform the procedure. The vacuum assisted devices (VAD) have largely replaced automated large core (ALC) devices for stereotactic and MRI guided biopsies, but ALC devices are still used for US guided core biopsies. ALC with 14-gauge needle or a VAD with 7-14 gauge needle can be used in an US guided core biopsy A VAD offer several advantages over ALC devices. VAD allows single insertion of the needle to obtain large amount of tissue which results in more accurate diagnosis and less false negatives. To further reduce the underestimation of disease, total removal devices (TRD) have recently been introduced that can be used under stereotactic or US guidance. This biopsy system requires an 8 mm skin incision and removes an intact portion of breast tissue preserving the architecture of the lesion. More experience is required for its diagnostic and therapeutic use.

Breast Biopsy -video

Microcystic adenocarcinoma of the prostate-pseudobenign carcinoma

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Tue, 13 Apr 2010 20:43:00 +0000

Reference :

Microcystic Adenocarcinoma of the Prostate: A Variant of Pseudohyperplastic and Atrophic Patterns : Yaskiv, Oksana et al.
The American Journal of Surgical Pathology: April 2010 - Volume 34 - Issue 4 - pp 556-561

Do you see anything in this prostate that's worrisome for malignancy?

dilated glands admixed with small acini in a nodule

I don't, at least not at this power, and yet this is an example of "microcystic" adenocarcinoma of the prostate. Higher power will show clear-cut cytologic features of malignancy.
If this doesn't concern you about the risk of scanning prostate slides at 4x, it should!

Microcystic adenocarcinoma with dilated and crowded glands displaying a predominantly flat lining layer

Microcystic adenocarcinoma with jumbled arrangement of dilated malignant glands.

Microcystic adenocarcinoma with atrophic features.

Dilated malignant glands with adjacent usual small acinar adenocarcinoma glands for size reference

Numerous crystalloids in dilated glands of microcystic adenocarcinoma.

Nuclear atypia with prominent nucleoli in the lining layer of 2 microcystic adenocarcinoma glands.

Microcystic adenocarcinoma extending into periprostatic adipose tissue, along with several small acinar adenocarcinoma glands.

Overerexpression of α-methylacyl CoA racemase in microcystic adenocarcinoma, with luminal accentuation. No basal cells are detected with this p63/AMACR cocktail immunohistochemical stain.

Overexpression of AMACR with granular cytoplasmic signal in microcystic adenocarcinoma gland with basal cell absence (right). Internal control benign atrophic glands on left show basal cell presence, with p63 marker, and lack of AMACR staining.

Basal cell absence in microcystic adenocarcinoma (left) compared with benign atrophic glands with basal cells (right), as assessed with 34βE12 immunostain.

Microcystic adenocarcinoma in needle biopsy tissue

Reference :

Microcystic Adenocarcinoma of the Prostate: A Variant of Pseudohyperplastic and Atrophic Patterns : Yaskiv, Oksana et al.The American Journal of Surgical Pathology: April 2010 - Volume 34 - Issue 4 - pp 556-561

Cystic glandular dilatation is a common finding in benign prostatic tissues, being identified in benign prostatic hyperplasia (BPH) in the transition zone and as cystic atrophy in the peripheral zone. Diagnostic awareness that acinar prostatic adenocarcinoma may exhibit cystic dilatation is important to avoid underdiagnosis of prostatic adenocarcinoma.

Cystic change in adenocarcinoma of the prostate is unusual and may be confused with benign cystic atrophy.Microcystic adenocarcinoma of the prostate is a distinctive histomorphologic presentation of prostatic adenocarcinoma that is deceptively benign-looking at low magnifications.

Detection of intraluminal crystalloids or wispy blue mucin at low magnification, immunostains for α-methylacyl CoA racemase, and basal cells, and a search for adjacent usual small acinar adenocarcinoma are helpful diagnostic aids. Diagnostic awareness of this growth pattern of prostatic carcinoma is important to avoid underdiagnosis of adenocarcinoma of the prostate.

High Grade Prostatic Intraepithelial Neoplasia (HGPIN)

noreply@blogger.com (Dr.Prashant Jani) — Tue, 02 Mar 2010 21:39:00 +0000

High Grade Prostatic Intraepithelial Neoplasia (HGPIN):
Common questions asked about HGPIN are :
-How do we as pathologists make these diagnoses?
-What do they mean for the patient in terms of cancer risk?
-What is/are the optimal strategies for follow-up so that if cancer does eventually develop it is caught at an early, curable stage?

Pathology criteria for diagnosis of HGPIN:

-Architecturally benign acini/ducts lined by atypical cells.
-These cells show large nuclei and prominent nucleoli (cytologic features of carcinoma).
-Generally at least 10% of the luminal cells should show these features to make the diagnosis.

Diagnosis of HGPIN has been shown to be reproducible. Low grade prostatic intraepithelial neoplasia has poor reproducibility (even among experts), ill defined diagnostic criteria, and no true clinical relevance. It is for these reasons that I do not personally diagnose LGPIN.

Risk of subsequent cancer:

-In previous studies the risk of carcinoma on follow-up biopsy for a HGPIN diagnosis has been reported to be as high as 50%, however, when the data is based on series with increased case numbers, this decrease to around 25%.

-Number of cores with high grade PIN predicts risk of subsequent cancer (1 core-30%, 3 cores-40%, 4+ cores-75%).In addition, morphologic patterns of HGPIN (i.e. flat, tufted, micropapillary, cribriform) have not been shown to be predictive of subsequent carcinoma.

Follow up strategy for patients with HGPIN:

Although there have been several follow-up strategies for patients with a diagnosis of HGPIN, many recommend re-biopsy within 3-6 months. One protocol includes biopsies at 3-6 months for 2 years, followed by yearly biopsies for life.
In a recent study, recommendation was made that in the absence of other clinical indicators worrisome for cancer, men do not need a routine repeat biopsy within a year following a HGPIN diagnosis. As the natural history of HGPIN in any given patient is not known, the decision to take additional biopsies past 1 year is best made on a patient by patient basis with a frank discussion between the physician and patient.

Various studies have shown that in patients with prior diagnosis of HGPIN, cancer is often diagnosed in adjacent sites and even within the contralateral lobe. It is for this reason that when re-biopsy is performed for HGPIN sampling should be concentrated in the region of the previous HGPIN with the rest of the gland sampled so as not to miss small foci of cancer. Specimens should be meticulously labeled as to site (in addition to patient identification) and optimally no more than 2 cores should be submitted per container.

Summary:

1. HGPIN is characterized by architecturally benign glands lined by cells which are morphologically similar to prostate cancer, and is the putative precursor of prostate cancer.

2. Unlike HGPIN the diagnosis of LGPIN is not reproducible and carries no clinical significance.

3. While earlier reports described the risk of cancer following a diagnosis of HGPIN as high as 50%, more current reviews suggest that the risk may be much lower.

4. Men with a diagnosis of HGPIN (especially those with HGPIN focally) may not need re-biopsy for up to one year after initial diagnosis. Repeat biopsies should concentrate on the area of previous HGPIN, but also include sampling of the entire gland.
(Thanks to Dr.Dharam Ramnani for allowing to use the above images for this site.)
References:
1. Epstein JI, Herawi M. Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care. The Journal of Urology 2006; 175: 820-834.
2. Bishara T, Ramnani DM, Epstein JI. High grade prostatic intraepithelial neoplasia on needle biopsy risk of cancer on repeat biopsy related to number of involved cores and morphologic pattern. The American Journal of Surgical Pathology 2004; 28: 629-633.
3. Bostwick DG, Qian J. High-grade prostatic intraepithelial neoplasia. Modern Pathology 2004; 17: 360-379.

Desmoplastic melanoma, a common missed diagnosis.

noreply@blogger.com (Dr.Prashant Jani) — Sat, 07 Nov 2009 01:21:00 +0000

Introduction:

Although desmoplastic melanoma represents less than 2 percent of all melanomas, it's frequently misdiagnosed, due to a lack of distinctive clinical presentation features. Histologic diagnosis is rarely straightforward either.

Patients are often middle age-to-elderly and present with the tumor most often on the head and neck region. The lesion may resemble a scar as it is often a hard nodule or plaque.
Pigmentation is variable but often absent. The tumor has ill-defined margins and is very infiltrative, making local control difficult. Sentinel lymph node excision is routinely performed but rarely positive.

Histology :
The histology can also masquerade as a scar . The epidermis is often atrophic and may or may not have a precursor (in situ) lesion. Characteristically, the tumor is in the dermis as spindled melanocytes resembling fibroblasts.Often, there is an edematous or desmoplastic stroma with
scattered lymphoid aggregates. Perineural invasion is common.In about one third of the lesions, there are foci of epithelioid or conventional melanoma.

S-100 and HMB45 immunohistochemical stains can help differentiate tumor from scar.
At low power, there is a fibrotic lesion in the dermis with scattered lymphoid aggregates.

The lesion is paucicellular, but there is cellular atypia .

Reporting of the histologic subtype of melanoma is common practice, but it is unclear what impact, if any, it has on management decisions. One possible exception is desmoplastic melanoma, a distinct subtype with a unique biologic behavior. It is now recognized that desmoplastic melanomas present with greater tumor thickness (Breslow level) than their conventional counterparts but fail to demonstrate a corresponding higher sentinel lymph node involvement or higher mortality.

Some authors have further subdivided desmoplastic melanomas into "pure" and "mixed" forms. Pure (primarily fibrotic) and mixed varieties, which include features common to conventional melanoma and desmoplastic areas. As per these recent studies only 1% of pure desmoplastic melanomas metastasized to regional lymph nodes compared to 10% with mixed histology.

References:
1. Attis MG, Burchette JL, Selim MA, et al. Differential expression of N-cadherin distinguishes a subset metastasizing desmoplastic melanoma.
2. Davison JM, Rosenbaum E, Barrett TL, et al. Absence of V599E BRAF mutations in desmoplastic melanomas. Cancer. 2005 103:788.
3. Hawkins WG, Busam KJ, Ben-Porat L, et al. Desmoplastic melanoma:a pathologically and clinically distinct form of melanoma. Ann Surg Oncol. 2005 12:207.

Dysplasia in Inflammatory Bowel Disease

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Thu, 24 Sep 2009 14:39:00 +0000

As we all know, chronic inflammatory bowel disease (IBD) presents a risk for dysplasia and subsequent malignancy in patients with long standing disease.

The risk for adenocarcinoma increases with a number of factors including

the linear extent of disease within the bowel,
early age at onset of disease,
severity of disease and duration of disease.

The pathologic reporting of endoscopic biopsy specimens with inflammatory bowel disease must convey the information the clinician needs in a clear and consistent manner in order to properly manage the patient's disease.

Every biopsy report should, of course, give an assessment of the disease activity and distribution. In addition, the pathologist must render an opinion on the presence or absence of dysplasia. The "second line" diagnosis must reflect one of three choices regarding dysplasia in the biopsy:

1. Negative for dysplasia

2. Indefinite for dysplasia

3. Positive for dysplasia

Low grade
High grade

Agreeing on the terminology is relatively easy. Agreeing on the morphologic presence or absence of dysplasia is another issue.

Studies have shown poor interobserver reproducibility with regard to recognizing and diagnosing dysplasia. Low grade dysplasia (LGD), as one might guess, suffers from the worst interobserver variability.

The more marked the cytologic changes (high grade dysplasia) the easier it is to recognize and agree upon amongst pathologists.

This variability is one reason that many suggest surveillance for LGD. The histologic parameters which define dysplasia in the colon are consistent regardless of the subtype of IBD - Crohn's colitis or ulcerative colitis.

Negative for dysplasia

The lack of dysplasia in a chronic IBD biopsy is stated as "negative for dysplasia". That phrase should be included in biopsies that are completely normal or indistinguishable from non-IBD biopsies. This could be found in biopsies obtained from an area of the colon that is not affected by the disease or in an area that is completely quiescent perhaps from treatment.

Reactive changes that can and areseen in colitis biopsies are also included in the "negative for dysplasia" category. Some refer to such changes as "baseline atypia"; regardless, that limited spectrum is devoid of dysplasia and falls under the heading of "negative".

Indefinite for dysplasia

This category sometimes suffers from a lack of respect or credibility; however, it is a defined, accepted and even required category in properlyinterpreting dysplasia in IBD.

It is not a crutch upon which uncertain and weak willed pathologists lean. The changes that are included in the indefinite category must be recognized as such lest one either overcalls or undercalls dysplasia when it cannot be unequivocally determined whether it is present or absent. One such example is when dysplasia shows partial surface maturation. That is, the involvement of the surface epithelium by dysplastic change and not just the basal, proliferating portions of crypts is required to make a diagnosis of dysplasia. If the surface is partially involved or shows incomplete maturation then indefinite is the proper designation.

A biopsy that shows marked acute inflammation, erosion or ulceration that has cytologic changes that absent the inflammation would be called dysplastic must be designated as indefinite. This use is intended to recognize that the presence of inflammation makes diagnosing dysplasia with certainty nearly impossible.

Positive for dysplasia- low and high grade .

If there is flat dysplasia present in a biopsy, then one of the above choices (low grade or high grade) ought to appear in the report.

Criterias:

Low grade dysplasia: basally oriented nuclei; mild nuclear enlargement, nuclear crowding and hyperchromasia; decreased intracellular mucin High grade dysplasia: prominent nuclear stratification (compared to low grade) with many nuclei in luminal half of cell; more significant hyperchromasia and pleomorphism; may have marked architectural distortion with a villous or nodular growth pattern resembling adenoma or with cribriforming
The best tool that a pathologist has in effectively interpreting IBD biopsies for dysplasia is the most basic one - the simple hematoxylin and eosin stained tissue section. Ancillary tests such as immunohistochemistry have not proven as effective as the simple histologic evaluation of the H&E stain.

Experience of the pathologist in seeing and appropriately interpreting dysplasia in IBD biopsies is of critical importance.

Proper written and verbal communication between the gastrointestinal pathologist and the endoscopist is essential in going from the correct interpretation to the proper clinical course.

This is of paramount importance in interpreting polypoid dysplasia and distinguishing between a sporadic adenoma and a dysplasia associated lesion or mass (DALM).

SELECTED REFERENCES

Riddell RH, Goldman H, Ransohoff DF, et al: Dysplasia in inflammatory bowel disease: Standardized classification with provisional applications. Hum Pathol 14:931-968, 1983.
Bernstein CN, Blanchard JF, Kliewer E, et al: Cancer risk in patients with inflammatory bowel disease: A population-based study. Cancer 91: 854-862, 2001.
Odze RD, Goldblum JR, Noffsinger A: Interobserver variability in the diagnosis of ulcerative colitis-associated dysplasia by telepathology. ModPathol 15:379-386, 2000.

Oncopathology Update

Evaluation of the Surgical Specimen After Neoadjuvant Systemic Therapy

Clinical information required for pathologic evaluation

Specimen handling

Microscopic reporting

Evaluation of the axilla after treatment

Pathological complete response

Retesting of markers in the postneoadjuvant therapy specimen

Minimum data set to be reported by pathologists

Conclusion

Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group

Neuroendocrine tumors of GI Tract.

Immunohistochemistry in the Differential Diagnosis of Cutaneous Basal Cell Carcinoma

Tumor Size (Size of Invasive Carcinoma) in Breast Carcinoma

Scientists Convert Human Skin Cells Directly Into Brain Cells

How Do You Get Pancreatic Cancer?

Invasive Micropapillary Carcinoma of the Breast

Definition

Diagnostic Criteria

Clinical

Grading / Staging / Report

Paget's disease if Nipple- Review

Role of Excisional lymph node biopsy, Core needle biopsy and FNAC in Lymphoma diagnosis

Micropapillary Carcinoma of the Breast

India's first virtual Cancer Pathology diagnostic centre in Pune

VALUE ADDED SERVICES OF ONCOPATH DIAGNOSTICS

The Role of Inflammation in Cancer

Minimal Reporting Guidelines for the Treatment of Cancer Patients

Protocol for Synpotic reporting of Breast excision specimen with diagnosis of Ductal Carcinoma In Situ (DCIS) of the Breast

Procedure

Lymph Node Sampling (select all that apply)

Specimen Size (for excisions less than total mastectomy)

Specimen Laterality

*Tumor Site (select all that apply)

Histologic Type

*Architectural Patterns (select all that apply)

Margins (select all that apply)

Lymph Nodes (required only if lymph nodes are present in the specimen)

Pathologic Staging (pTNM)

Primary Tumor (pT)

Regional Lymph Nodes (pN) (choose a category based on lymph nodes received with the specimen; immunohistochemistry and/or molecular studies are not required)

Modifier (required only if applicable)

Distant Metastasis (M)

*Additional Pathologic Findings

*Estrogen Receptor (results of special studies performed on this specimen or a prior core needle biopsy)

*Progesterone Receptor (results of special studies performed on this specimen or a prior core needle biopsy)

*Microcalcifications (select all that apply)

*Clinical History (select all that apply)

*Comment(s)

Breast Carcinoma vs. Pulmonary Adenocarcinoma

Breast Core needle biopsy procedure

Microcystic adenocarcinoma of the prostate-pseudobenign carcinoma

High Grade Prostatic Intraepithelial Neoplasia (HGPIN)

Desmoplastic melanoma, a common missed diagnosis.

Dysplasia in Inflammatory Bowel Disease