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

Abstract

Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%).

Composite hemangioendothelioma with neuroendocrine marker expression: an aggressive variant

“…We have specifically used the term 'neuroendocrine marker expression,' rather than 'neuroendocrine differentiation' to describe our cases, because they typically express only synaptophysin and to a lesser extent CD56, in the absence of chromogranin A. Synaptophysin is a transmembrane glycoprotein expressed by neural, endocrine, and neuroendocrine cells that participates in the storage and release of neurotransmitters and acts as a membrane channel protein. 36 Expression of synaptophysin is not, however, limited to neural, neuroendocrine or endocrine tumors, and is well documented in alveolar rhabdomyosarcoma, 37 melanoma, 38 and extraskeletal myxoid chondrosarcoma, 39 among others. Similarly, expression of CD56, a membraneassociated adhesion molecule expressed by a wide variety of cell types, is not at all specific for neural or neuroendocrine tumors.…”

Malignant Melanoma With Rhabdomyosarcomatous Differentiation

“…2,5 A recent large case series that examined aberrant expression of intermediate filaments in malignant melanoma reported 1 case of melanoma with rhabdomyoblastic differentiation based on immunohistochemical staining, highlighting the rarity of this phenomenon. 6 Importantly, rhabdomyoblastic differentiation in malignant melanoma is distinct from rhabdoid melanoma. In this morphological variant, neoplastic cells seem similar to rhabdomyoblasts because of the cytoplasmic accumulation of intermediate filaments and peripherally placed nuclei.…”

Primary corneal malignant melanoma in a horse

“…Additionally, anomalous expression of keratins and other intermediate filaments is a well‐reported phenomenon in some human melanocytic neoplasms (Romano et al . ), which may also explain the cytokeratin expression. Based on the neoplastic cell distribution and other IHC markers in this case, melanocytic neoplasia was considered the most appropriate diagnosis.…”