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Desmoplastic Melanoma...Histology, Biology, And Current Opinions on Management - Gregory A. Hosler, M.D., PhD.


DESMOPLASTIC MELANOMA…HISTOLOGY, BIOLOGY, AND CURRENT OPINIONS ON MANAGEMENT by Gregory A. Hosler, M.D., Ph.D

Desmoplastic melanoma is a histologic subtype of melanoma with a distinct clinical presentation. Patients are often middle age-to-elderly and present with the tumor most often on the head and neck region (Figure 1). The lesion may resemble a scar as it is often a hard nodule or plaque. Pigmentation is variable but often absent. The tumor has ill-defined margins and is very infiltrative, making local control difficult. Sentinel lymph node excision is routinely performed but rarely positive (see Discussion).

The histology can also masquerade as a scar (Figure 2a and 2b). The epidermis is often atrophic and may or may not have a precursor (in situ) lesion. Characteristically, the tumor is in the dermis as spindled melanocytes resembling fibroblasts. Often, there is an edematous or desmoplastic stroma with scattered lymphoid aggregates. Perineural invasion is common. In about one third of the lesions, there are foci of epithelioid or conventional melanoma (Figure 3a and 3b). S-100 and p75 NGF-R immunohistochemical stains can help differentiate tumor from scar.

Discussion:

Reporting of the histologic subtype of melanoma is common practice, but it is unclear what impact, if any, it has on management decisions. One possible exception is desmoplastic melanoma, a distinct subtype with a unique biologic behavior. It is now recognized that desmoplastic melanomas present with greater tumor thickness (Breslow level) than their conventional counterparts but fail to demonstrate a corresponding higher sentinel lymph node involvement or higher mortality. In a large case-matched control study, Livestro, et al showed that while local control of desmoplastic melanoma was more difficult than conventional melanoma, patients with desmoplastic melanoma have lower rates of stage III and stage IV disease (5% vs. 21%), and lower rates of sentinel lymph node involvement (8% vs. 34%). While the differences in biologic behavior are compelling, one may be hesitant to abandon the sentinel lymph node procedure altogether for this subtype given 8% of cases were positive.

In an attempt to identify a patient subpopulation with very low risk for metastases and possible avoidance of the morbidity and cost of an extra procedure, more recent studies have further subdivided desmoplastic melanomas into "pure" and "mixed" forms. Hawkins, et al examined outcome data of 3976 patients with melanoma, 131 with desmoplastic melanoma. They showed only 1% of pure desmoplastic melanomas metastasized to regional lymph nodes compared to 10% with mixed histology and 6% of conventional
melanomas. Additionally, patients with pure desmoplastic melanoma had a 3-fold improvement in five-year survival over patients with conventional melanoma when matched for tumor depth. Pawlik, et al, in a smaller study, showed similar findings.

This idea that pure desmoplastic melanomas behave biologically different from mixed forms and conventional melanoma is gaining traction. Patients with pure desmoplastic melanoma have a 1-2% positive sentinel lymph node rate, arguing that consideration should be made to avoid sentinel node procedures in this population. Of course, before completely abandoning this procedure, there needs to be communication and understanding between the surgeon and pathologist regarding the pure nature of the histology and its implications. Interestingly, it appears that mixed melanomas behave similar to conventional types if not worse, for reasons unknown, reinforcing the importance of complete evaluation of the tumor for mixed histology.

References:

1. Attis MG, Burchette JL, Selim MA, et al. Differential expression of N-cadherin distinguishes a subset metastasizing desmoplastic melanoma.
2. Davison JM, Rosenbaum E, Barrett TL, et al. Absence of V599E BRAF mutations in desmoplastic melanomas. Cancer. 2005 103:788.
3. Hawkins WG, Busam KJ, Ben-Porat L, et al. Desmoplastic melanoma: a pathologically and clinically distinct form of melanoma. Ann Surg Oncol. 2005 12:207.
4. Livestro DP, Muzikansky A, Kaine EM, et al. Biology of desmoplastic melanoma: a case-control comparison with other melanomas. J Clin Oncol. 2005 23:6739.
5. Pawlik TM, Ross MI, Prieto VG, et al. Assessment of the role of sentinel lymph node biopsy for primary cutaneous desmoplastic melanoma. Cancer. 2006 106:900.
6. Posther KE, Selim MA, Mosca PJ, et al. Histopathologic characteristics, recurrence patterns, and survival of 129 patients with desmoplastic melanoma. Ann Surg Oncol. 2006 13:728.