Micropapillary Carcinoma of the Breast

-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.

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.

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India's first virtual Cancer Pathology diagnostic centre in Pune

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

1. 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.
2. India’s First and Only Cancer Diagnostic laboratory with Whole slide Digital Imaging and Analysis system.
3. Multi-tier pathologist review on all cases by well known national and international pathologists.
4. Reporting will be done as per the standards of college of American Pathologists.
5. Large in house inventory of histochemical and immunoperoxidase stains.
6. Thin prep cytology services.
7. Completely automated tissue processing with automated slide stainers for IHC and special stains.
8. Web-based Reporting system.
9. Rapid Turn-Around Time- Report turn-around time of 2-3 days for biopsies and 3-5 days for large cases.
10. 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