Background: The rare desmoplastic and spindle cell variants of malignant melanoma exhibit histological and biochemical features suggestive of early Schwann cell differentiation. These features include a spindle-shaped morphology, neurotropism, and the expression of the low affinity nerve growth factor receptor (p75NGFR).
Methods: We evaluated by immunohistochemistry (using formalin-fixed, paraffin-embedded tissues) nine desmoplastic and three spindle cell melanomas for the expression of peripherin, p75NGFR, neural cell adhesion molecule (CD56/N-CAM), and growth-associated phosphoprotein-43 (GAP-43). Peripherin is expressed in the neural crest and in neurons, but not in cells committed to the Schwann cell lineage. p75NGFR and CD56/N-CAM also are expressed in early neural crest cells, but persist in unmyelinated and early premyelinating Schwann cells. GAP-43 is expressed in unmyelinated Schwann cells, but is downregulated in the later premyelinating to promyelinating stages of cells committed to the Schwann cell lineage.
Results: Peripherin was expressed in 7/12 (58%), p75NGFR in 4/12 (33%), and CD56/N-CAM in 6/12 (50%) of the desmoplastic and spindle cell melanomas. GAP-43 was not expressed (0%) in any of the 12 melanomas (chi2, p = 0.05).
Conclusions: Desmoplastic and spindle cell melanomas express protein markers common to cells of the neural crest and to neurons similar to the immunophenotype previously reported for epithelioid cell melanomas. The expression of peripherin and the lack of expression of GAP-43 further define that these rare subtypes of melanoma do not recapitulate the later committed stages of Schwann cell differentiation.