Desmoplastic Malignant Melanoma: A Study of Ten Cases and Status of BRAF Mutation

Abstract

Background: Desmoplastic malignant melanoma (DM) is a rare variant of melanoma. BRAF gene mutations have been poorly explored in this entity. Objective: To detect BRAF gene mutation in a series of DM. Methods: This is a single-center retrospective study of ten patients with DM, with a biomolecular analysis of BRAF mutation. Results: The male:female ratio was 2.3:1, with a mean patient age of 66.5 years. Melanoma arose in the head and neck region in 3 cases. The mean tumor thickness was 7.97 mm, Clark level was IV or V in all cases. Six melanomas were of the pure DM variant. Three patients had at least one local recurrence, two had regional node metastases, and two experienced systemic metastases which they died of (average follow-up 34.1 months). A V600E BRAF mutation was detected in only one patient. Conclusion: BRAF mutation seems to be a rare event in DM contrary to other melanoma variants.

A nuclear circularity-based classifier for diagnostic distinction of desmoplastic from spindle cell melanoma in digitized histological images

“…Pertinent features of the study cohort are summarized in Table 1. Briefly, these features are in accord with prior publications[32333435] and we consider our study set representative. Classic examples of the histological appearance are shown in Figure 1a and b.…”

“…The applied morphological criteria followed prior publications. [2832333435] Briefly, SM and DM are composed of an invasive proliferation of spindled/fusiform melanocytes that are separated by desmoplasia composed of dense collagen fibers or fibrous stroma. Based on the degree of desmoplasia the following subtypes can be assigned: DM (≥90%), mixed (≥10-90% desmoplasia) or SM (<10%).…”

A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma

“…3,10,[15][16][17][18] Formally, the diagnostic categories in these overtly spindled melanomas are: spindle cell melanoma when the collagen content is o10%, mixed spindle/desmoplastic melanoma when collagen content is 10-90%, and desmoplastic melanoma when the collagen content is 490%. 1,16,19,20 From a practical perspective these formal definitions are problematic. First, superficial or partial biopsies may preclude assessment of the entire lesion.…”

Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis

“…Analysis for mutations currently amenable to therapy (ie, BRAF, NRAS, and KIT) have revealed mutational patterns segregating with the traditional subgroups. Regarding desmoplastic malignant melanoma a complete absence of BRAF mutations 21 as well as a reduced mutation rate 22 has been reported. Recently, Miller et al 23 have observed a lack of BRAF mutations in pure desmoplastic malignant melanoma compared to a low frequency in the mixed subtype and a trend toward an increased RETp frequency in pure desmoplastic malignant melanoma.…”

“…20 Regarding desmoplastic malignant melanoma a complete lack of BRAF mutations was reported in one publication 21 and a markedly decreased frequency of BRAF mutations in another. 22 Subclassification of desmoplastic malignant melanoma into pure and mixed type is not only clinically relevant, but also apparently reflects different mutation patterns as well. Miller et al 23 have recently shown that pure desmoplastic malignant melanoma is devoid of BRAF mutations as opposed to mixed desmoplastic malignant melanoma, which did exhibit BRAF mutations albeit at a low level (6% of cases).…”