Pathologic Description Below posted 6-08-2011 (hh)

Swick B, Liu V and Stone M (Dermatopathology UIHC)

Desmoplastic and spindle cell variants of malignant melanoma are characterized by tumor cells with a spindle-shaped morphology within the dermis and/or subcutis.¹ Desmoplastic malignant melanoma is a histologic variant of spindle cell melanoma demonstrating fibrogenic properties in which the atypical invasive malignant spindle-shaped cells are dispersed in a prominent collagenous stroma.^2-5 This spindle-shaped phenotype may also demonstrate neurosustentacular properties manifesting as perineural invasion and/or Schwann cell differentiation.² Spindled malignant melanocytic lesions are often described according to their predominant histologic features as spindle cell malignant melanoma, desmoplastic malignant melanoma, neurotropic/neural differentiated malignant melanoma, or any combination of these features.⁴

Clinically, desmoplastic malignant melanoma usually develops in the elderly on sun exposed skin and commonly presents as a slow growing infiltrated non-specific plaque or nodule that may be amelanotic in up to 50% of lesions.³ In the absence of clinical pigmentation, the lesion is unfortunately often mistaken for a scar or cyst.

Histopathologically, desmoplastic malignant melanoma demonstrates a variably cellular spindle cell proliferation, usually non-pigmented, within a dense fibrous stroma  imparting a low-power “scar-like” appearance to the lesion.⁴ The distribution of spindle cells is usually haphazard within the fibrous stroma.⁶ However, the cells may also form parallel fascicles or demonstrate a storiform pattern with associated collagen trapping mimicking a benign fibrous histiocytoma.⁶ In most cases, the proliferation is asymmetric and associated with patchy mononuclear cell inflammatory infiltrates throughout the tumor.⁴ The cytologic atypia of the individual melanocytes varies from slight to marked and may be associated with only scant mitotic activity.^4,6 Fortunately, even in cases demonstrating subtle cytologic atypia, large hyperchromatic nuclei with peripheral margination of chromatin and a prominent central magenta colored nucleolus (typical of malignant melanoma), can often be found. In some cases, nests or fascicles of epithelioid appearing malignant melanocytes may be present and are often associated with a higher mitotic index.^2,5 An overlying atypical lentiginous junctional melanocytic proliferation, representing lentigo maligna, is present in only 30% of cases.⁶ In the absence of an atypical intraepidermal component, distinguishing desmoplastic malignant melanoma with a subtle pauci-cellular proliferation of melanocytes from a scar is difficult. At the time of diagnosis, desmoplastic melanomas are often deeply invasive with a Clark level of IV or V and an average Breslow thickness of 2.5 mm to 3.6 mm.^5,7 Additional poor prognostic features include neurotropism in approximately 30% of cases.⁸

Spindle cell malignant melanomas are S100 positive in 94% or greater of cases.³ Other than in the associated epidermal component or within a second population of epithelioid appearing melanocytes, spindle cell melanoma is usually negative for Melan-A/Mart-1, HMB-45, tyrosinase, and microphthalmia transcription factor.⁶ In addition to S100, KBA.62 may prove to be another sensitive immunohistochemical marker for spindle cell melanoma. One recent study has demonstrated KBA.62 expression in 75% of desmoplastic malignant melanoma.⁹

Spindle cell melanoma differs from conventional non spindle cell melanomas by a higher propensity for local recurrence and less frequent metastasis to regional lymph nodes at the time of presentation.⁵ In one study of 29 patients with spindle cell melanoma (Breslow thickness 1.6 mm to 8 mm), 28 had negative sentinel lymph node biopsies.¹⁰ In contrast to conventional malignant melanoma, spindle cell malignant melanomas demonstrate behavior similar to soft tissue sarcoma with preferential metastasis to the lungs over regional lymph nodes.^5,11 An exception to this is the presence of an epithelioid cell component within a spindle cell melanoma. These lesions, in addition to mimicking the behavior a typical spindle cell melanoma, may demonstrate a higher rate of local regional lymph node metastasis and a worse overall prognosis compared to a malignant melanoma with a spindle-cell morphology alone.^2,5

 References

1. Huttenbach Y, Prieto VG, Reed JA. Desmoplastic and spindle cell melanomas express protein markers of the neural crest but not of later committed stages of Schwann cell differentiation. J Cutan Pathol 2002;29:562.
2. Skelton HG, Smith KJ, Laskin WB, McCarthy WF, Gagnier JM, Graham JH, Lupton GP. Desmoplastic malignant melanoma. J Am Acad Dermatol 1995;32:717.
3. Longacre T, Egbert B, Rouse R. Desmoplastic and spindle-cell malignant melanoma: an immunohistochemical study. Am J Surg Pathol 1996;20:1489.
4. Tsao H, Sober AJ, Barnhill RL. Desmoplastic neurotropic melanoma. Semin Cutan Med Surg 1997;16:131.
5. Busam KJ, Mujumdar U, Hummer AJ, Nobrega J, Hawkins WG, Coit DG, Brady MS. Cutaneous desmoplastic melanoma reappraisal of morphologic heterogeneity and prognostic factors. Am J Surg Pathol 2004;28:1518.
6. McCarthy SW, Scoyler RA, Palmer AA. Desmoplastic melanoma: a diagnostic trap for the unwary. Pathology 2004;36:445.
7. Quinn MJ, Crotty KA, Thompson JF, Coates AS, O’Brien CJ, McCarthy WH. Desmoplastic and desmoplastic neurotropic melanoma: experience with 280 patients. Cancer 1998;83:1128.
8. Anstey A, McKee P, Jones EW. Desmoplastic malignant melanoma: a clinicopathological study of 25 cases. Br J Dermatol 1993;129:359.
9. Bernaba BN, Vogiatzis PI, Binder SW, Cassarino DS. Potentially useful markers for desmoplastic melanoma: an analysis of KBA.62, p-AKT, and Ezrin. Am J Dermatopathol 2011;33:333.
10. Thelmo MC, Sagebiel RW, Treseler PA, Morita ET, Nguyen LH, Kashani-Sabet M, Leong SP. Evaluation of sentinel lymph node status in spindle cell melanomas. J Am Acad Dermatol 2001;44:451.

11. Jaroszewski DE, Pockaj BA, DiCaudo DJ, Bite U. The clinical behavior of desmoplastic melanoma. Am J Surg 2001;182:590.

    
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