Fluorescence in situ hybridization (FISH). There are a cur-rent set of 4 probes that are used to detect subtle chromosomal aberrations and can be performed on formalin fixed tissues. There are reports that there are sufficient chromosomal alterations present in melanoma that this limited panel of FISH probes can distinguish most melanomas from nevi.

Comparative genomic hybridization (CGH). This is an expensive and labor intensive technique that labels tumor and normal (control) DNA and hybridizes them with normal metaphase chromosomes spreads. This can also be performed on formalin fixed tissues. This technique detects chromosomal number changes/aberrations, and even subtle changes that may not be identified on FISH. In the clinical setting, a second method (FISH) will be needed to confirm the findings.

Polymerase chain reaction (PCR). A somewhat rapid technique that is used for amplifying target DNA material that can be used on formalin fixed tissue.

Laser capture/Cutting Microdissection. This technique is used isolate specific groups of cells without disrupting their molecular state (ie. isolating the melanoma cells from a nevus) for performing molecular studies.

Molecular studies are also being used for predicting the biologic behavior of a melanoma. There have been reports of specific markers, such as melastatin and regulator G protein signaling 1k which correlates with adverse prognosis.

Recent studies also show that specific genetic aberrations of a melanoma can correlate with specific phenotypes. Melanomas with the BRAF mutations are reported to be associated with a younger age and improved survival. Melanomas with the c-kit mutations are associated with acral, mucosal or chronic sun damaged skin.

Molecular studies alone wilI not suffice for making a diagnosis but rather, could possibly be a valuable tool for challenging melanocytic neoplasms in consultation. Molecular technologies could also advance the future classification and management of melanomas.

References

Dadzie O, Neat M, Emley A, Bhawan J, Mahlingam M. Mo-lecular Diagnostics – An Emerg-ing Frontier in Dermatopathol-ogy. Am J Dermatopathol 2011: 33;1:1-13.

It has the capability to:

• Error proof the workflow for the best in positive patient identification
• Move cases through the lab faster, decreasing turn around time
• Provide real-time visibility into lab performance
• Integrate instrumentation into the workflow
• Standardize work at grossing, embedding and microtomy
• Refocus the staff’s time to critical histology tasks

Once the specimen is in the laboratory, VANTAGE©  gives us complete chain of custody and improved quality. Studies have shown that slide labeling alone accounts for 67% of specimen misidentification.

Since implementing VANTAGE©, Clin-Path Diagnostics has reduced slide labeling errors by 99% and eliminated numerous manual steps, saving up to 3 hours/day.

Clin-Path Diagnostics uses VANTAGE© to:

• Print bar coded slide labels, eliminating errors from handwriting
• Eliminate relabeling, as one label works on all Ventana instruments
• Ensure that two patient identifiers are on every slide
• Record and analyze quality issues, making compliance and correction easier

In summary, the VANTAGE© patient focused solution has helped Clin-Path achieve our primary goal of improved patient safety while also enhancing overall laboratory operations.

Dr. Xiang received her Ph.D. in Molecular Genetics and Microbiology at the University of Florida in Gainesville Florida.  She received her Medical Degree from Medical Center of Fudan University, Shanghai, China.  Please join us in welcoming Dr. Xiang to the Phoenix area.

In the August 2011 edition of The American Journal of Dermatopathology, Jag Bhawan and colleagues discuss the various cutaneous neoplasms that may present with Verocay body-like structures (1). A number of heterogeneous tumors have been known to demonstrate this feature, and include epithelial, adnexal, fibrohistiocytic, mesenchymal and melanocytic lesions.

The peculiar arrangement of nuclei in transverse rows in a nerve sheath tumor was first described by Verocay in 1910 (2). This later came to be known eponymously as the Verocay body, referring to the stacked arrangement of elon-gated, palisading nuclei alternating with anuclear zones composed of cytoplasmic processes (Refer to Case 14, page 4). This observation has stood the test of time as a valuable clue for the diagnosis of nerve sheath tumors.

An unusual skin appendageal tumor with similar alternating areas of epithelial cords and stroma,coined a “rippled pattern”, was described by Hashimoto, et al. Since then, a variety of histogenetically diverse neoplasms have been described to contain this “Verocay body-like” pattern. Non-neural tumors that most frequently exhibit this pattern include trichoblastoma, sebaceoma, basal cell carcinoma, dermatofi-broma, leimyoma and very rarely, melanocytic nevi.

The rippled Verocay body-like pattern is often seen in cases of sebaceoma. These tumors show a male predominance and an affinity to arise on the scalp (as opposed to the face), when compared with sebaceomas that lacked this pattern. Within the spectrum of adnexal tumors with a rippled pattern, it is important to make the distinction between sebaceoma and trichoblastoma in view of the association of the former with Muir-Torre syndrome.

Considering the close relationship between melanocytes and Schwann cells, it is surprising that only very rarely do nevi (less than 1 of many thousands encountered in dermatopathology services) show the distinctive Verocay body-like structures that are described herein (Refer to Case 9, page 3). This finding may also be seen rarely in cases of malignant mela-noma, where the schwannian pattern reflects the protean na-ture of these lesions.

References

(1) A Biswas, M.D, N Setia, M.D., J Bhawan, M.D. Cutaneous neoplasms with prominent Verocay body-like structures: the so-called “rippled pattern”. Am J Dermatopath; Vol 33:6, 2011; pp 539-48.

(2) Verocay J. Zur Kenntnis der “neurofibrome” [in German]. Beitr Pathol Anat.1910; 48:1-69.

MTS is inherited in an autosomal dominant manner with high penetrance and predisposes to a variety of malignancies, most commonly colorectal, but also endometrial, ovarian, genitourinary, and others. Importantly many of these malignancies tend to occur at an earlier age in MTS patients.

Diagnosis of MTS can be established based on skin findings alone. Detection of sebaceous neoplasms, including sebaceous adenoma (most common), sebaceous epithelium (sebaceoma) and sebaceous carcinoma, below the neck in a patient under 50 years of age, or in association with keratoacanthomas should raise suspicion for MTS. In addition, specific histologic features of sebaceous tumors, including keratoacanthoma-like or cystic changes, appear to be more commonly associated with MTS.

When MTS is suspected, immunohistochemical analysis of the skin neoplasm can be performed. Immunohistochemical stains are available for the proteins most commonly lost in MTS (MSH2, MLH1, PMS2 and MSH6) and a loss of two or more proteins has a high positive predictive value for the presence of MTS (up 100%).

Once the presence of MTS is confirmed, additional genetic testing is available. When the diagnosis has been established, preventive cancer screening programs of the patient and family members will facilitate early detection and treatment of other malignancies associated with MTS.

Further Reading

1. O. Abbas, M. Mahaling-ham: Cutanneous sebaceous neoplasmas as markers of Muir-Torre syndrome: a diagnostic algorithm. Journal of Cutaneous Pathology 2009; 36:613-619.

2. S. Shalin, S. Lyle, E. Calonje, A. Lazar: Sebaceous neoplasia and the Muri-Torre syndrome: important connections with clinical implications. Histopathology. 2010 Jan; 56(1): 133-47, Review.