Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Mucosal Melanomas

Abstract

The updated edition of The World Health Organization Classification of Tumours of the Head and Neck includes discussions on mucosal melanoma of both the sinonasal and oral cavity. Since the prior edition, sinonasal origin is now recognized as the most common site of occurrence of mucosal melanoma in the head and neck (66%) with oral cavity representing 25% of cases. Histologic features of mucosal melanomas vary widely from spindled, epithelioid, and pleomorphic to rhabdoid, plasmacytoid and undifferentiated. Additionally, mucosal melanomas are commonly amelanotic (or minimal pigmentation) (~50%) leading to overlapping features and diagnostic challenges in differentiating mucosal melanomas from other small cell/undifferentiated sinonasal tumors. Since the last edition, formal staging of head and neck mucosal melanomas was added to the American Joint Committee on Cancer entities, though the traditional histologic features that have prognostic significance in cutaneous melanomas fail to stratify mucosal melanomas (i.e. tumor thickness, ulceration). Interestingly, while melanomas of all sites are a malignancy derived from melanocytes, mucosal melanomas are now recognized to have distinct molecular alterations compared to cutaneous or uveal melanomas. BRAF V600E mutations are rare (<6%) in mucosally derived melanomas compared to a rate of 50% in cutaneous melanomas. CD117 (C-Kit) mutations are the most common alteration encountered (~25%) in mucosal sites with potential therapeutic targetability. The recognition of the distinct genetic changes in this subgroup of melanomas means that therapy advances in cutaneous melanomas may not translate to head and neck mucosal melanomas and clinical trials specific to this subgroup of patients are needed.

Keywords: CD117 mutations; Mucosal melanoma; Oral melanoma; Sinonasal melanoma.

Fig. 1

Gross features in mucosal melanoma. a Grossly a darkly pigmented lesion is seen on the mucosa of the turbinate (lateral nasal wall). The presence of pigmentation makes mucosal melanoma the suspected diagnosis clinically. (The scale bar is marking millimeter increments). b This hematoxylin and eosin photomicrograph of a polypoid septal mass shows overlying surface ulceration and marked pigmentation aiding in tumor recognition as a mucosal melanoma

Fig. 2

Morphologic features in mucosal melanoma. Note that pigmentation is not observed in these examples. a The perivascular/peritheliomatous pattern shows tumor cells loosely clinging around a blood vessel. b Spindled cells create a fasciculated pattern of growth of mimicking other neuronal and soft tissue tumors. c A solid sheet of predominantly clear tumor cells show occasional scattered rhabdoid forms. d Epithelioid cells show characteristic prominent nucleoli and mitoses (arrows)

Fig. 3

Intraepithelial involvement in mucosal melanoma and immunohistochemical confirmation of lineage. a Atypical cells are mixed with acute inflammation in this oral biopsy. b An S100 protein immunohistochemical stain on part A highlights the in situ component and invasive tumor nests. c Pagetoid spread may be identified when the surface mucosa is intact. Large atypical melanocytes (arrows) percolate into the overlying respiratory epithelium. Notice that the underlying tumor is without pigmentation or prominent nucleoli. d An immunohistochemical cocktail of melanoma markers (tyrosinase and HMB45) in case C, strongly highlight the tumor cells confirming tumor lineage