Immunophenotypic Heterogeneity of Primary Sinonasal Melanoma With Aberrant Expression of Neuroendocrine Markers and Calponin

Abstract

Primary sinonasal melanoma is an aggressive tumor that often presents a diagnostic challenge owing to its rarity and variable morphology. Unusual immunophenotypic expression of sinonasal melanoma compounds the problem particularly in a limited tissue sample. We studied immunohistochemical patterns of 5 primary sinonasal melanoma using antibodies against pan-cytokeratin, S-100, HMB-45, Melan-A, chromogranin, synaptophysin, neurofilament protein, and calponin and correlated these patterns with histologic appearance. Sinus/nasal mucosa from non-neoplastic cases were stained for Melan-A to evaluate prevalence of melanocytes in the benign mucosa in comparison to the staining pattern of the mucosa adjacent to the tumor. Similar to previous report, small cell pattern appeared to be over represented in the sinonasal melanoma. Small cell population in 4 cases was almost devoid of pigment, and also was either completely negative or only focally positive for S-100. Three cases stained positive for neuroendocrine markers and neurofilament protein bringing olfactory neuroblastoma and small cell neuroendocrine carcinoma in as differential diagnosis. Three cases were focally positive for calponin without spindle cell morphology or desmoplastic reaction. Immunophenotypic heterogeneity along with the unconventional histomorphology of sinonasal melanoma compounds diagnostic problem and warrants a precautionary approach to avoid misinterpretation. It is necessary to apply a broad panel of immunohistochemistry for the purpose of screening when sinonasal melanoma is considered as a differential diagnosis.

Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases

“…Similarly, Shah et al 33 found only a single neurofilamentpositive melanoma out of 64 examined melanomas. Neurofilament expression has, however, been reported in a higher percentage of melanomas in some small series, including those of Eyden et al, 11 Lee et al, 9 and the previously mentioned abstract published by Azam et al 23 Neurofilament expression has also been reported in very rare melanomas showing overt ganglioneuromatous differentiation. 34 With the exception of the abstract published by Azam et al, 23 we are aware of only a single study that has systematically evaluated glial fibrillary acidic protein expression in melanoma, by Iwamoto et al, 35 showing expression in 9/17 (53%) spindled and 2/10 (20%) melanomas.…”

“…49 On the other hand, round cell melanomas, particularly in the sinonasal region, often show patchy or no S100 protein expression, showing instead uniform expression of more specific melanocytic markers. 9,50 In summary, we have identified aberrant expression of various intermediate filaments, including keratins, desmin, neurofilament protein and glial fibrillary acidic protein, and of the neuroendocrine marker synaptophysin in significant subsets of both epithelioid and spindle melanomas. These findings have obvious implications with regard to the use of ancillary immunohistochemical studies in the diagnosis of melanoma, and emphasize the need to employ a broad panel of markers in the differential diagnosis of poorly differentiated cutaneous tumors and in the setting of metastasis.…”

“…5 It is less widely appreciated that melanomas too may show aberrant expression of various immunohistochemical markers, with a relatively small number of reports, of melanomas showing expression of intermediate filaments other than vimentin (e.g., keratins, desmin, neurofilament protein, and glial fibrillary acidic protein) [6][7][8] and/or neuroendocrine markers. [9][10][11] Over the past several years, we have seen in consultation a significant number of melanomas in which aberrant expression of intermediate filaments and/or neuroendocrine markers obscured the correct diagnosis, and prompted consideration of various non-melanocytic neoplasms, including carcinoma, rhabdomyosarcoma, neural neoplasms, and various neuroendocrine tumors. As no study to date appears to have comprehensively examined this issue, we evaluated a large number of well-characterized melanomas, using contemporary immunohistochemical techniques, to better determine the actual frequency of aberrant expression of these markers.…”

Small round blue cell tumors of the sinonasal tract: a differential diagnosis approach

“…When pigmentation is absent, immunohistochemistry becomes helpful, with S100 protein and SOX10 usually strongly and diffusely reactive, whereas other melanocytic markers (HMB45, tyrosinase, melan A, MITF) are expressed to a variable degree, often based on tumor morphology; 6,7,11,12 in undifferentiated tumors, scant cytoplasm may result in focal or negative reactions, requiring careful high-power examination. Crossreactivity with neuroendocrine markers is rare.…”

“…Crossreactivity with neuroendocrine markers is rare. 12 In general, RAS and then KIT mutations (mutually exclusive) are detected at a distinctly higher rate than cutaneous melanomas, with BRAF mutations rarely detected. [13][14][15] Outcome and management.…”