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%). Altogether 9/73 cases (12%) showed expression of >1 intermediate filament. All S100-protein-negative
melanomas showed anomalous intermediate filament expression (
keratin--one case,
desmin--three cases,
neurofilament protein--one case). Anomalous intermediate filament or
synaptophysin expression was more common in epithelioid (intermediate filament, 27/48, 56%;
synaptophysin, 7/22, 32%) as compared with spindle cell/desmoplastic (intermediate filament, 8/25, 32%;
synaptophysin, 3/12, 25%)
melanomas. Overall, 48% (35/73) of cases showed anomalous expression of at least one intermediate filament. Anomalous expression of all intermediate filaments and
synaptophysin was found in significant subsets of
malignant melanoma, representing potentially serious diagnostic pitfalls. While the inclusion of consultation cases may inflate the frequency of these findings in this series, similar findings were also seen in institutional cases.
Malignant melanoma showing anomalous intermediate filament and
synaptophysin expression may easily be mistaken for
carcinomas,
rhabdomyosarcomas, and
neuroendocrine tumors. Awareness of this phenomenon, careful histopathological evaluation, and an appropriate melanocytic immunohistochemical panel should facilitate the diagnosis of
malignant melanoma with unusual immunophenotypes.