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 

The Role of Inflammation in Cancer

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).

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