Oncopathology

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.

Making Sure Your Lab Reports Are Easy to Understand

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Tue, 15 Sep 2009 16:57:00 +0000

A portion of clinical error results from the misinterpretation of laboratory data. Powsner et al reported that surgeons misunderstood 30% of pathology reports.
Whether one communicates test results electronically, by fax, or on paper, one should periodically review the content and layout of the reports to make sure they are as useful as possible. Are the clinicians and caregivers who receive the reports getting the information they need to treat the patient? Is the information clear, accurate, and laid out in such a way that the readers don’t have to struggle to comprehend the data?

Easy Places to Start
Periodically (at a minimum, annually) review all versions of your reports, with the goal of increasing their quality, accuracy, and interpretability. Also review your reports whenever there has been a readability complaint or after a change in testing methodology.
• Make the font size large enough. The report should be quickly and easily readable, at arm’s length, in imperfect lighting, by someone wearing bifocals. The smaller the font, the greater the likelihood of misreading the value.
• Perform legibility tests:
o Fax a sample of your reports to yourself. Are the numbers and text small and fuzzy or are they clear and legible? To simulate what your customers may see, repeat the test using the fax you just received.
o If your reports are being read via a hospital or practice management computer system, verify that your reports display appropriately and legibly on the systems the physicians are using to read the reports.
• Check for complete patient information, including full name, date of birth, and gender.
• Check for specimen source/type, reference ranges or target ranges, and flags ( if indicated).
• Check that Medical Director, facility name, and contact details are on every page of every report.
• Verify any calculated results.
• Check for coding and billing information and any pay-for-performance indicators—e.g., PQRI codes.
• Review the clarity of the interpretation and any comments—e.g., are interpretations clearly associated with the related result?
• Check for reference to prior results, if any. If the result is a critical value, make sure the report includes documentation of appropriate communication—e.g., who notified whom? When? How?

Digging Deeper
There is a lot at stake in one simple lab report. In one study, surgeons misunderstood pathologists’ reports 30% of the time (Powsner). These additional steps can help improve the usability of your reports:
• Standardize the “look and feel” of your results to make them easier to interpret. Putting the same information in the same place, time after time, trains your readers to locate what they are looking for.
• Don’t crowd the data on the page; use sufficient white space to separate columns and lines of numbers.
• All the text should be a good distance from the margins, so no text gets cut off when printing or faxing.
• Enhance your reports with electronic tools such as embedded links to references or other background information—even photos.
• Implement synoptic reports.
• If you use paper charts, consider how you present summary reports and how frequently they are replaced.
• Ask the report recipients for feedback about the information and its presentation. How could you improve the quality and usability of the reports?

Tell the Story
After you have implemented your reporting changes, toot your horn with the administration. Show them the before and after test result reporting formats. Share the metrics of the improvements, including the number of times the improvements will be encountered by clinicians, and the resulting positive impact on patient care.

Reference : College of Americal Pathologist website.(www.cap.org )

Immunopheotype of Gastrointestinal stromal tumours (GIST)

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Thu, 02 Jul 2009 20:03:00 +0000

Histogenesis:
It has been suggested that GISTs originate from the interstitial cell of Cajal (ICC), or from a primitive stem cell that differentiates towards both the ICC and smooth muscle phenotye.

Sites:
GISTs occur at every level of the GI tract. Most tumours arise in the stomach (60%) and about
20–30% occur in the small intestine. Colorectal and oesophageal GISTs account for less than 10%. A small proportion of GISTs arise in extra-GI tract sites including the omentum, mesentery and retroperitoneum.

Morphologic patterns:
GISTs show a spectrum of histological features.Morphologically, the cells of GISTs are spindle, epithelioid, mixed pattern and occasionally pleomorphic.Spindle cell type is the predominant pattern, seen in 70% of GIST cases.

Immunophenotype
The overwhelming majority of GISTs express KIT protein (detected as CD117).The results of KIT immunostaining depend on several technical factors including fixation, tissue preparation, variations in antibody clones in terms of specificity and sensitivity, antibody dilutions and staining techniques. This may account, in part, for the reported immunophenotypic heterogeneity in GISTs. Recently, it has been emphasized that CD117should be performed without epitope retrieval.

Given the potential clinical importance of CD117 immunostaining, optimization of the staining techniques and reproducibility are critical. The pattern of staining is variable Diffuse strong cytoplasmic staining is the predominant pattern. Membranous staining and dot-like ‘golgi pattern’ staining can be identified. It has been suggested that different staining patterns correlate with different types of c-kit mutations. Stromal mast cells and ICC are useful internal positive controls to supplement the normal positive and negative controls.

Immunohistochemical detection of KIT does not necessarily imply c-kit activation. Indeed, CD117 is expressed by other tumour types such as melanoma and soft tissue sarcomas including dermatofibrosarcoma protuberans, synovial sarcoma and angiosarcomas. Therefore, CD117 immunoreactivity should be interpreted in the context of morphology and clinical setting.However, it is increasingly recognized that a high level of KIT expression is not characteristic for tumours with non-mutant KIT isoforms or tumours harbouring PDGFRA mutations.
CD34 is a transmembrane glycoprotein present on human haematopoietic progenitor cells and vascular endothelium. CD34 is detectable in approximately 70% of GISTs. The oesophageal and rectal GISTs have the highest frequency of CD34 positivity, whereas small intestinal tumours are the lowest percentage of CD34 positivity.

Actin expression is reported in approximately 30% of cases.Smooth muscle actin (SMA)expression is often reciprocal with CD34 expression: the SMA-positive tumours are often CD34 negative and vice versa. Some tumours may show a mosaic pattern with actin-positive and CD34-negative areas and vice versa.
Desmin-positive immunostaining is uncommon and, if present, is often limited to scattered tumour cells. Prominent staining is more common in epithelioid neoplasms. GISTs are generally negative for S100. Focal positive staining for cytokeratin markers can be seen especially in malignant epithelioid GISTs.

Proliferation markers (Ki-67, MIB-1 and proliferating cell nuclear antigen (PCNA)) may aid in tumour evaluation. It has been reported that tumours with more than 10% of nuclei that are positive for the KI-67 analogue are associated with metastases and poor survival rate.

In other studies, the MIB-1 index was not superior to mitotic count as a prognostic factor. Alterations of the tumour suppressor gene p16INK4A have been shown to be an independently poor prognostic factor.It has been previously regative p16 immunostaining is associated with malignant behaviour in GISTs.

GISTs with PDGFRA mutations are usually CD117 negative but may respond to STI-571; therefore, KIT detection may not be required for the treatment eligibility for Imatininb.

References:
1)Rubin BP, Fletcher JA, Fletcher CD. Molecular Insights into the histogenesis and pathogenesis of gastrointestinal stromal tumors. Int J Surg Pathol 2000;8:5–10.
2)Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM.Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the
interstitial cells of Cajal. Am J Pathol 1998;152:1259–69.
3) Miettinen M, Lasota J. Gastrointestinal stromal tumors—definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis.
Virchows Arch 2001;438:1–12.
4)M.Sabah et al.Gastrointestinal stromal tumours: An update.Current Diagnostic Pathology (2005) 11, 400–410

Significance of Atypical Small Acinar Proliferation (ASAP) in Prostate needle biopsy

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Mon, 25 May 2009 18:29:00 +0000

Many time while reporting prostate needle biopsy, we come across features, which are suspicious for malignancy, but hinder a definitive diagnosis of carcinoma, because of concern about over diagnosis. These are the cases, which are labelled as ASAP, -atypical small acinar proliferation.

Diagnostic criteria for ASAP :
For pathologists, 3 questions need to be answered before the diagnosis of cancer in a small lesion:
• Would you be absolutely confident of this biopsy diagnosis if it were followed by a negative radical prostatectomy?
• Would another colleague pathologist agree with the diagnosis of cancer?
• Can you confidently support the diagnosis of adenocarcinoma based solely on this biopsy?

If the answer to any of these questions is “No,” then use of the more conservative diagnosis of ASAP is recommended.

Reasons for the Diagnosis of ASAP are :

Small number of acini in the focus of concern.
Small focus size, average 0.4 mm in diameter.
Loss of focus of concern in deeper levels.
Distortion of acini raising concern for atrophy.
Lack of convincing features of cancer (insufficient nucleomegaly or nucleolomegaly).
Foamy cytoplasm raising concern for foamy gland carcinoma.
Conflicting immunohistochemical findings.

Significance of ASAP. -

Prostate cancer is found in up to 60% of repeat biopsies after the diagnosis of ASAP. Thus
ASAP in a biopsy is a significant predictor for concurrent or subsequent cancer. The high predictive value of atypical small acinar proliferation (ASAP) for subsequent adenocarcinoma indicates a need for repeat biopsy.

References:

1. Borboroglu PG, Sur RL, Roberts JL, et al. Repeat biopsy strategy in patients with atypical small acinar proliferation or high grade prostatic intraepithelial neoplasia on initial prostate needle biopsy. J Urol. 2001;166:866–870.
2. Cheville JC, Reznicek MJ, Bostwick DG. The focus of “atypical glands,suspicious for malignancy” in prostatic needle biopsy specimens: incidence,histologic features, and clinical follow-up of cases diagnosed in a community practice. Am J Clin Pathol. 1997;108:633– 640.
3. Iczkowski KA, Bassler TJ, Schwob VS, et al. Diagnosis of “suspicious for malignancy” in prostate biopsies: predictive value for cancer. Urology.1998;51:749 –757; discussion 757–748.

4. Isabelle Meiers, at el. Atypical Small Acinar Proliferation in the prostate :Pathology Case reviews • Volume 13, Number 4, July/August 2008;13: 129–134

Sentinel Lymph Node Biopsy in Melanoma (SLNB)

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Mon, 18 May 2009 20:08:00 +0000

Clinical Significance of Sentinel Lymph node in melanoma. :

SLNB is very accurate in predicting the status of the remaining regional lymph nodes.
It is currently the most significant independent prognostic indicator for survival when compared with all other factors, including tumour thickness and the presence of ulceration.

According to some studies, the relapse rate for H&E detected SLN positive patients is higher (up to 67%), whereas the relapse rate for SLN negative patients is low (2–6%) during the same period.

Indications for SLNB procedure :

Primary Melanoma with thickness greater than 1.0 mm,
or
Primary Melanoma less than 1mm with Clark's level four or five or presence of ulceration.

Pathology Protocol:

The current standard for the diagnosis of SLN metastasis is based on routine H&E histology and immunohistochemistry (IHC).
I follow the Cochran Method.It is as follows:
1. The lymph node is either bivalved or cut into 3 mm blocks, depending on the size of the node.
2. Sections 1, 3, and 5 are stained with haematoxylin and eosin (H&E),
3. Sections 2 and 4 are immunohistochemically stained for S-100 and HMB-45.

The sensitivity of detection is increased with IHC, multiple sectioning and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. The role of such molecular genetic techniques in identifying melanoma proteins remains undefined, despite greater sensitivity.

Caution.:
‘‘Surgeons should be aware that the subcapsular region is crucial in sentinel lymph node (SLN) evaluation and the architecture of the SLN can be disrupted easily if the procedure is not carried out with care.’’

To reduce the false negative rate, surgeons should avoid crushing and excessive cautery usage to preserve the integrity of the SLN. It is also important not to cut into the SLN and complete excision of the whole SLN is crucial.

False positive results. :
False positives resulting from,

Benign naevic cells raise concern and necessitate further refinement. Naevic cells are usually present within the capsule (intracapsular) or within the trabeculae, and typically stain negatively, or only faintly positively, with HMB-45.

Reactive dendritic cells, nerve fragments, and benign naevic cells may each stain positively for S100. HMB-45 stain allowed us to differentiate benign naevic cells from their malignant counterparts.
Examination at the subcapsular level, combined with the use of S100 staining, is the most practical and sensitive method to ensure the detection of micrometastatic nodal disease.

References:
· Gershenwald JE, Thompson W, Mansfield PF, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel node status in 612 stage I or II melanoma patients. J Clin Oncol 1999;3:976–83.
· Balch CM, Buzaid AC, Atkins MB, et al. Final version of the American joint committee on cancer staging system for cutaneous melanoma. J Clin Oncol2001;19:3635–48.
· White RR, Stanley WE, Johnson JL, et al. Long-term survival in 2,505 patientswith melanoma with regional lymph node metastasis. Ann Surg 2002;235:879–87.
· McCready DR, Ghazarian DM, Hershkop MS, et al. Sentinel lymph-nodebiopsy after previous wide local excision for melanoma. Can J Surg 2001;44:432–4.
· Cochran AJ, Huang RR, Guo J, et al. Current practice and future directions inpathology and laboratory evaluation of the sentinel node. Ann Surg Oncol 2001;8(9S):13–17.
· Jansen L, Nieweg OE, Peterse JL, et al. Reliability of sentinel lymph node biopsy for staging melanoma. Br J Surg 2000;87:484–9.
· C A Murray, W L Leong, D R McCready and D M Ghazarian Histopathological patterns of melanoma metastases in sentinel lymph nodes J. Clin. Pathol. 2004;57;64-67

Work up of Carcinoma of Unknown Primary (CUP)

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Mon, 04 May 2009 14:45:00 +0000

It is often important to determine the site of origin of a metastatic carcinoma of unknown primary site, particularly because this may affect the choice of the treatment. Determination of the primary site may take several steps.
Clinical features, such as age, sex, and site of metastases may give a first indication.
A detailed pathologic examination of the most accessible biopsied tissue specimen is mandatory in CUP cases. Pathologic evaluation typically consists of hematoxylin-and-eosin stains and immunohistochemical tests. Electron microscopy is rarely used currently, although it may beselectively useful when making treatment decisions.
Role of Serum Tumor Markers and Cytogenetics
Most tumor markers, including CEA, CA-125, CA 19-9, and CA 15-3, when elevated, are nonspecific and not helpful in determining the primary tumor site.
Men who present with adenocarcinoma and osteoblastic metastasis should undergo a PSA test. Patients with an elevated PSA should be treated as having prostate cancer.
In patients with undifferentiated or poorly differentiated carcinoma (especially with a midline tumor), elevated Beta-human chorionic gonadotropin (B-hCG) and alpha fetoprotein(AFP) levels suggest the possibility of an extragonadal germ cell (testicular)tumor.
Cytogenetic studies had a larger role in the past, although interpretation of these older studies can be challenging. With the availability of immunohistochemical stains, cytogenetic cytogenetic analyses are indicated only occasionally.

Role of Immunohistochemistry
CK 7 and CK20 are two of the most commonly used CKs in surgical pathology.
A 5% cut-off percentage for positivity may eliminate more “false positive” results.

(1) CK7+/CK20+ in carcinomas of bile duct, lung-mucinous bronchioloalveolar, pancreas; urothelium; also primary mucinous tumors of ovary (74%), upper GI tract (78%), endocervix

(2) CK7+/CK20- in carcinomas of bile duct, breast, endocervical and endometrial adenocarcinoma, esophagus (distal,), lung (not mucinous, bronchioloalveolar), salivary gland, thyroid; also mesothelioma

(3) CK7-/CK20+ in carcinoma of colon (particularly early stage); CK20 is less sensitive for poorly differentiated colonic carcinoma; primary mucinous tumors of lower GI tract (79%,) and primary bladder adenocarcinomas (29%,)

(4) CK7-/CK20- in carcinomas of adrenal cortex and prostate

(5)CK7 and CK20 can be used to distinguish primary lung carcinoma (CK7+/CK20-) from metastatic colonic carcinoma to lung (CK7-/CK20+)

(6)CK7 cab be used to distinguish chromophobe carcinoma (diffuse CK7+ staining) and oncocytoma (usually CK7-)

(7)CK 20 can be used to distinguish Merkel cell carcinoma (CK20+, dot like, TTF1 -) and metastatic small cell carcinoma of lung (CK20-, TTF1+)

Additional immunostains for further work up.
BRST-1,ER,PR,Gross cystic disease fibrous protein-15--> Breast cancer
Thyroid transcription factor 1---> Lung and thyroid cancer
Thyroglobulin ---> Thyroid cancer
Chromogranin, synaptophysin, NSE,CD56---> Neuroendocrine cancer
CDX-2 ---> Gastrointestinal cancer
Calretinin, mesothelin---> Mesothelioma
Leukocyte common antigen---> Lymphoma
S-100, HMB-45---> Melanoma
URO-III, thrombomodulin ---> Bladder cancer
AlphaFetoprotein ---> Hepatocellular cancer, germcell cancer
Beta-Human chronic gonadotropin --->Germ cell cancer
Prostate specific antigen ---> Prostate cancer
Please review following powerpoint presentation for work up of CUP.

Use of algorithm in IHC

Molecular Cancer Pathology Update

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Thu, 23 Apr 2009 12:53:00 +0000

Genetic variant may eventually enable clinicians to differentiate between aggressive, indolent prostate tumors.
Medscape reported, "One of the biggest issues in prostate cancer is differentiating between men who have aggressive tumors that could be fatal and men who have indolent tumors that might never become clinically significant."

But, findings from a University of California-San Francisco study may ease some of that difficulty. The team identified a genetic variant, which "is located on the KIAA1217 gene," saying that "it shows a person's predisposition to aggressive prostate cancer." The hope is that it will, will enable clinicians to identify with more certainty men who are likely to have aggressive disease," which "could result in less overtreatment."

Updates on Molecular Cancer Pathology

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Wed, 22 Apr 2009 14:09:00 +0000

1) Molecular profiling may help determine patient's response to cancer therapies, research suggests.
A pilot study of molecular profiling of tumors, helped to identify therapies that ultimately had an impact on the disease.The University of Texas MD Anderson Cancer Center and the Memorial Sloan-Kettering Cancer Center are "striving to profile individual tumors so that therapy can be personalized, which means that it has a better chance of working because it targets specific mutations found in that tumor. This also prevents patients from being exposed to drugs that have a limited chance of success, eliminating toxicity and improving quality of life.

2 )Scientists developing new techniques for detecting CTCs in cancer patients' blood-Medscape report
Measuring "circulating tumor cells (CTCs) in the blood of cancer patients" gives "an indication of whether or not the patient is responding" to treatment. Presently, "there is only one commercially available product to measure CTCs -- CellSearch (Veridex LLC)." Now, one device in development "promises to be cheaper and faster," say University of California-Los Angeles researchers. The "new technique is based on a microfilter device."

3) Bladder cancer cells may have two distinct genetic patterns, research suggests.
Bladder cancer cells have two distinct genetic patterns, depending on whether they are invasive or not," say University of Southern California-Los Angeles scientists. The "discovery opens the possibility of monitoring the disease by a simple urine test," which would enable clinicians to sidestep "invasive procedures."

4) Immune cells could be reprogrammed to attack prostate cancer, scientists say.
Reprogrammed immune cells could become targeted 'killing machines' against prostate cancer." In fact, "these reprogrammed T cells sharply reduced the levels of prostate specific antigen (PSA) in two patients with metastatic prostate cancer," scientists at the Roger Williams Medical Center said. But first, the team had to "isolate a patient's T cells from a blood sample and use genetic engineering techniques to make them sensitive to a molecule that only occurs in prostate cancer -- prostate specific membrane antigen, or PSMA."

5) Researchers say presence of certain variants in MC1R gene may increase melanoma risk.
Researchers from the University of Pennsylvania "analyzed 779 patients with melanoma and compared them to 325 healthy people." The investigators found that the "presence of certain variants in the MC1R gene was linked with at least a twofold increased risk of melanoma, and was largely confined to those people who would not normally be considered at increased risk."

False positive diagnosis in breast FNAC.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Mon, 20 Apr 2009 21:09:00 +0000

Some common lesion leading to false positive diagnosis in FNA of breast are listed with Keys to differentiate them.
Artifactual Atypia
Most common of these is disruption of cell aggregates by too vigorous smearing, which can mimic the loss of cohesion characteristic of malignant epithelial cells .
Excessive smearing pressure can also cause smudging of nuclei, giving a false impression of nuclear enlargement and pleomorphism.
Dying artifacts in alcohol-fixed Pap smears have a similar effect.

Hormonal Stimulation and Physiologic :Hyperplasia in Pregnancy and Lactation
Physiologic hyperplasia of acinar epithelial cells in late pregnancy and lactation can look worrying in FNA smears.
Key: The recognition of milky secretion is the main clue to a correct diagnosis to be correlated with clinical information.

Reactive Atypia
This is seen in mastitis fat necrosis, postoperative repair, and post radiation.
Key: Correct clinical information is important. A history of previous tissue injury and the presence of acute inflammatory cells (not just lymphocytes) rarely seen in breast cancer call for caution and careful evaluation of the nuclear structure of atypical cells.

Fibroadenoma
Epithelial atypia, most likely hormone related, can be prominent in smears of fibroadenoma. This is the most frequent cause of false positive diagnosis in breast FNA.
Key: In most cases, the atypical cells constitute only a minor part of the cell population. The presence of benign components is a safeguard against an erroneous malignant diagnosis.

Papillary Lesions
The combination of high cellularity, loss of cell cohesion, and variable nuclear atypia sometimes seen in smears from benign papillary lesions may raise a suspicion of malignancy. A false positive diagnosis is possible, particularly if a papillary microarchitecture is notidentified.
Key: In general, the presence of background apocrine cells, foam cells, and single bipolar nuclei suggest a benign papilloma.
REFERENCES
1. Franze´n S, Zajicek J. Aspiration biopsy in diagnosis of palpable lesions of the breast. Acta Radiol. 1968;7:241–262.
2. Zajdela A, Ghossein NA, Pilleron JP, et al. The value of aspiration cytology in the diagnosis of breast cancer: experience at the Foundation Curie. Cancer. 1975;35:499–506.
3. Greenberg M. Diagnostic pitfalls in the cytological interpretation of breast cancer. Pathology. 1996;28:113–121.

Reporting parameters for positive prostate needle biopsy

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Tue, 07 Apr 2009 19:36:00 +0000

According to college of American pathologists (CAP)the mandatory items for reporting positive prostate biopsies are:

Histologic type - typically adenocarcinoma (conventional/acinar, not otherwise specified)
Histologic grade –primary (predominant) Gleason pattern + secondary (worst remaining) Gleason pattern
Total Gleason score
Tumour Quantitation - 3 possible methods for tumor qyuantification;
1) % of prostatic tissue involved by tumour
2 ) total linear mm of carcinoma
3) number of positive cores/total number of cores
Periprostatic fat and seminal vesicle invasion should always be looked for and reported if identified, given their importance in developing an optimal treatment plan.

Optional parameters

Reporting the presence or absence of perineural invasion and lymphatic/small vessel invasion is completely optional.

Perineural invasion is of debatable prognostic significance and we likely continue to reported simply because we have always done so.

Reporting the presence of high grade PIN in biopsies with adenocarcinoma is also completely optional.

Interestingly, inflammation is listed as an optional item. It has been my experience that many clinicians will be interested in knowing about coexisting inflammation in positive biopsies (especially if it is appreciable in amount) as it may be of use in interpreting serum PSA at the time of the positive biopsy.

Importance of Immunohistochemistry in the Evaluation of follicular lymphoid lesion

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Mon, 06 Apr 2009 12:58:00 +0000

Before discussing the utility of particular immunostains, it is important to review and understand some basics about the normal lymphoid follicle, in order to interpret the immunostains appropriately.
The difference between a primary follicle and a secondary follicle:
A primary or "resting" follicle: - a collection of B-cells in the cortex of the lymph node that has not been antigenically stimulated, and because of this, it does not have a germinal center.
A secondary follicle:- Once a primary follicle has been antigenically simulated, it acquires a germinal center, and at this point is referred to as secondary follicle.
Differential diagnosis of lymphoid lesion with follicular structures or nodules, :-
1) Resting (primary) follicles,
2) Secondary follicles (as a reflection of reactive follicular hyperplasia),
3) Follicular lymphoma,
4) Mantle cell lymphoma with a nodular growth pattern.
5) B cell SLL/CLL with prominent pseudofollicular proliferation centers.

Many times the distinction of non-neoplastic lymphoid follicles vs. neoplastic lymphoid follicles can be readily made on standard H&E morphology alone.
As we all know however, we see cases where this distinction is challenging, and in other situations we are faced with minuscule or suboptimal material.By understanding the expected phenotype of the lymphoid cells within each of the various types of lymphoid follicles, one can frequently render a confident diagnosis, even in the face of suboptimal material or a minimal biopsy sample.

The lymphocytes in primary (resting) follicle express B cell markers (such as CD20, CD79a, or Pax-5) and BCL2.CD23 may be positive or negative, but they lack BCL6,CD10, CD5, and cyclin D1, and they have a low Ki-67 proliferative fraction.
In contrast, in the germinal center of a secondary follicle, the lymphoid cells lack BCL2, CD5,CD23, and cyclin D1, express both BCL6 and CD10, and have a very high proliferative fraction, approaching 100%.
In follicular lymphoma, the neoplastic cells express B-cell markers, BCL2 and BCL6, and lack CD5, CD23 and cyclin D1, with a variable Ki-67 proliferative fraction. Most but not all follicular lymphomas express CD10, and some grade 3 follicular lymphoma lack BCL2.
In mantle cell lymphoma, the lymphocytes express B-cell markers, BCL2, CD5, and cyclin D1, typically lack BCL6 and CD23.
And finally, in B-cell small lymphocytic lymphoma/CLL, the neoplastic cells express B-cell markers,CD5, CD23, and BCL2, but lack BCL6, cyclin D1, and CD10.

Caveats for immuno interpretation:
Since some of these follicular or nodular structures to some extent consist of mixed B and T-cell populations, there are often minor populations of cells staining for the markers above that are listed as lacking, and for that reason in some cases it is easiest to interpret the immunostain results on low-power.
For example, in the case of primary (resting) follicles, there are often a small number of background cells that may express BCL6, CD10, and CD5. It is always a good idea to compare the extent of reactivity of the markers discussed with the extent of reactivity of the associated B cell markers. Finally, it must be kept in mind that CD23 stains a subset of the follicular dendritic cells (FDC) that may be present in these conditions, so care must be taken to not misinterpret CD23 reactivity of FDC as reactivity of the lymphocytes. Finally, it is worthwhile to note that some follicular lymphomas contain impressive numbers of non-neoplastic T-cells. Another point that must be made is this: "tumors do not read textbooks". As such, not all lymphoid proliferations will neatly fit into the expected patterns of reactivity discussed
above. For example, we have seen clear-cut cases of both follicular lymphoma and mantle cell lymphoma that have expressed strong CD23, a few mantle cell lymphomas that have expressed BCL6, and we have even seen a rare case of follicular lymphoma that expressed CD5.

Click on the images to enlarge them.

References:
1) CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas.Dogan A, Bagdi E, Munson P. Am J Surg Pathol. 2000 Jun;24(6):846-52.
2) Abnormal expression of bcl-10 protein in extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue lymphoma typeLi BZ, Zhou XY, Ye HT, Yang WT, Fan YZ, Lu HF, Shi DR. Zhonghua Bing Li Xue Za Zhi. 2007 Dec;36(12):819-24. Chinese.
3) Propath focus –Immunohistochemistry in the Evaluation of Follicular or Nodular Lymphoid Lesions, R. T. Miller, M.D

Sentinel Lymph Node Mapping-Pathology Protocol in Breast Cancer.

noreply@blogger.com (Dr.Prashant A.Jani M.D.FRCPC) — Mon, 30 Mar 2009 22:30:00 +0000

Sentinel Lymph Node Mapping-Pathology Protocol.

Sentinel lymph node mapping is now performed on selected patients who opt for conservative surgery to treat their breast cancer.
The procedure involves the surgical identification of those axillary lymph nodes that theoretically would be the first ‘‘sentinel’’ nodes to receive the lymphatic drainage from the breast harboring the invasive cancer. If these nodes are pathologically negative, the patient is spared the morbidity associated with a standard axillary node dissection.

Surgical identification is based on the peritumoral injection of radioactive solutions and/or colored dyes. The surgeon then massages the breast to facilitate permeation of the solution into the lymphatic system. Several hours after the injection, the patient is taken to the operating room, where the surgeon uses a radioactive counter to locate the ‘‘hot’’ lymph node. If a colored dye has been used, visual inspection of the axilla usually identifies the sentinel lymph node. Usually, the pathologist receives 1 to 3 lymph nodes for evaluation.

Some centers use cytologic imprints, either with or without frozen section evaluation,at the time of surgery to determine whether the sentinel node is involved by metastatic tumor. If the imprintsare positive, then the surgeon proceeds to an axillary node dissection. Other hospitals submit their sentinel lymph node biopsies for routine processing without intraoperative consultation.
Once the specimen is received in the pathology laboratory, the pathologist must carefully dissect out all the nodes and record the number and sizes. If it is technically feasible, each node should be serially sectioned at 2- to 3-mm intervals, parallel to the long axis, and entirely submitted for evaluation. One hematoxylineosin–stained section should be cut from each block for light microscopy. Additional unstained levels may also be requested at the time of sectioning, in the event that immunohistochemical analysis of the node will be required to confirm the diagnosis of metastatic disease. Although some studies advocate using immunohistochemistry on all histologically negative lymph nodes, the current College of American Pathologists guidelines state that this procedure is not the standard of care for pathologic evaluation of sentinel lymph nodes in patients with invasive breast cancer.

Metastasis and prognosisMacrometastases (>2 mm) have a clear influence on prognosis
Micrometastases (>0.2 mm, < or =" 2">
References:
Cserni G. Evaluation of sentinel lymph nodes in breast cancer. Histopathology 2005;46:697–702.
Weaver DL. Pathological evaluation of sentinel lymph nodes in breast cancer: a practical academic perspective from America. Histopathology 2005;46:702–6.
Bobrow L, Pinder S. Histopathology and the SLN. In: Sentinel lymph node biopsy handbook—NEW START. London: RoyalCollege of Surgeons of England; 2004. p. 88–94.

Oncopathology

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

Making Sure Your Lab Reports Are Easy to Understand

Immunopheotype of Gastrointestinal stromal tumours (GIST)

Significance of Atypical Small Acinar Proliferation (ASAP) in Prostate needle biopsy

Sentinel Lymph Node Biopsy in Melanoma (SLNB)

Work up of Carcinoma of Unknown Primary (CUP)

Molecular Cancer Pathology Update

Updates on Molecular Cancer Pathology

False positive diagnosis in breast FNAC.

Reporting parameters for positive prostate needle biopsy

Importance of Immunohistochemistry in the Evaluation of follicular lymphoid lesion

Sentinel Lymph Node Mapping-Pathology Protocol in Breast Cancer.