Letter to the Editor
To the Editor:
A wide range of histologic patterns mimicking non-melanocytic neoplasms including sarcomas,1 carcinomas, rhabdoid and neuroendocrine tumors,2 lymphomas,3 plasmacytomas, germinal tumors4 have been reported with melanomas. We report a case of primary cutaneous melanoma with areas of pseudorosettes. A 75-year-old woman presented with a single pigmented and ulcerated nodule on the left upper arm growing for several months. Complete surgical excision was performed. The histopathological findings identified a nodular melanoma with Breslow depth of 2.4 mm and Clark level IV with ulceration. After the diagnosis, the patient had a complete wide excision and sentinel node biopsy, which was negative for metastatic disease to the lymph node. Microscopically, the tumor was composed of sheets of atypical and mostly epithelioid-shaped melanocytes with focal areas characterized by cell processes surrounding a central vessel (Fig. 1). Immunohistochemical examination showed that the tumor cells were strongly positive for neuron specific enolase (NSE) (Fig. 2), MART1 (Melan A), and S-100 protein (Fig. 3) and negative for high-molecular weight cytokeratin. The tumor cells showed focal weak positivity with glial fibrillary acidic protein (GFAP), chromogranin, and synaptophysin. Rosettes are a characteristic feature for a variety of tumors. Three primary patterns are identified. They include Flexner-Wintersteiner rosettes, defined by cell processes surrounding a membrane-bound lumen as seen in ependymoma, neuroepithelioma, and retinoblastoma.5 A second type includes perivascular rosettes (also called pseudorosettes) characterized by cell processes surrounding a central vessel present in astrocytoma, ependymoma, oligodendroglioma, meningiomas,6 and occasionally in sarcomas, carcinomas, and melanomas.4,7,8 Thirdly is the Homer-Wright rosettes defined by a central tangle of fibrillary processes seen in ganglioneuroblastoma, medulloblastoma, and retinoblastoma, occasionally in small cell carcinoma, lymphomas,5 and melanomas.9,10 Rare cases of melanomas with neuroendocrine differentiation supported by both immunohistochemistry and by presence of pseudorosettes on light microscopy have been reported in the literature.7-10 Two of these 4 case reports represent non-cutaneous melanomas from uvea7 and cerebellopontine angle,8 respectively. The remaining cases represent metastatic cutaneous melanomas to the lymph nodes. Interestingly, the pseudorosette features were only present within the lymph nodes. These 4 tumors were stained with common neuroendocrine markers. Two of these cases reported negative staining pattern with some of these markers (GFAP in one case and GFAP, synaptophysin, chromogranin, and neurofillament protein (NFP) in the second case).8,9 A third case showed positive staining with NSE only,7 whereas the fourth case showed a strong positive staining with all common neuroendocrine markers such as NFP, synaptophysin, chromogranin, and GFAP. Finally, we found a series of 3 case reports of, respectively, 2 primary cutaneous melanomas with metastasis and 1 case of primary nasal melanoma with metastasis and proven neuroendocrine differentiation based on both immunohistochemistry and electron microscopy findings, yet with no pseudorosette-like features on regular histology in both the primary tumor and the metastasis.11 All these reported cases stained with common melanocytic markers highlighting the melanocytic nature of the tumor beyond any doubts. This is to our knowledge the first case of primary cutaneous melanocytic melanoma with pseudorosette-like features. Malignant melanoma with neuroendocrine differentiation is a rare variant, which needs to be considered as a subclassification of malignant melanomas. Its accurate diagnosis depends on traditional light microscopy findings and immunostaining for both melanocytic and neuroendocrine markers. Additional cases need to be studied before drawing any conclusion in regard to the clinical significance of neuroendocrine differentiation in malignant melanoma.
Marjan Mirzabeigi MD
Joan Guitart MD
Pedram Gerami MD
Northwestern University, Chicago, IL
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