Clinicopathologic differences in malignant melanoma arising in oral squamous and sinonasal respiratory mucosa of the upper aerodigestive tract

Archives of Pathology & Laboratory Medicine,  Aug 2003  by Prasad, Manju L,  Busam, Klaus J,  Patel, Snehal G,  Hoshaw-Woodard, Stacy,  Et al

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* Objective.-Primary mucosal melanomas are rare tumors. We compare melanomas arising in 2 histologically different mucosa, the stratified oral squamous mucosa and pseudostratified sinonasal respiratory mucosa, to investigate the clinicopathologic influence of native mucosal histology on the tumor.

Methods.-Clinicopathologic features of 36 melanomas arising in the squamous mucosa of the oral cavity were compared with 59 melanomas arising in the sinonasal respiratory mucosa.

Results.-The median age of patients was 61 and 63 years for oral and sinonasal melanomas, respectively, with the squamous and respiratory mucosa covering the maxilla being most frequently involved (68.7% and 66%, respectively). The former had a remarkable male predilection (28 men, 8 women), while the latter affected both sexes equally (29 men, 30 women). The oral melanomas were more likely to be detected in the early in situ or microinvasive stage (4 cases vs none, P = .008) and were more frequently amelanotic (14 vs 12, P = .049) than sinonasal melanomas. The sinonasal melanomas were frequently thicker (median thickness, 9 vs 2.6 mm), polypoid (29 vs none), ulcerated (57 vs 20), and necrotic (57 vs 14) than oral melanoma (P

Conclusion.-Sinonasal melanomas demonstrated aggressive morphologic features significantly more frequently than oral melanomas; however, prognosis remained similar in both groups.

The vast majority (>90%) of melanomas in the head and neck are cutaneous, followed in decreasing order of frequency by ocular and mucosal melanoma (MM). Head and neck MMs constitute 0.7% of malignant melanomas arising in all sites and involve (in decreasing order of frequency) the sinonasal cavity, oral cavity, pharynx, larynx, and upper esophagus.1,2 Oral MMs constitute 0.5% of all oral malignancies, whereas sinonasal MMs constitute less than 7% of all sinonasal neoplasms.3 Their etiology in UV light-protected sites is not fully understood. The role of inhaled and ingested carcinogens in their pathogenesis has been suggested, similar to squamous cell carcinoma,4 but no precursor lesions (eg, melanocytic dysplasia) have been described for primary MM. The relative inaccessibility of the mucosa to self-examination often delays diagnosis, resulting in late detection and poor survival. At presentation, approximately 13% to 19% of patients have lymph node metastases, and another 16% to 20% are likely to develop metastases subsequently. The 5-year survival rate reportedly varies from 0% to 55%.3,5-9

Although the squamous and ciliated columnar respiratory mucosa of the upper aerodigestive tract are both derived from ectoderm, the former is a stratified epithelium, similar to epidermis, whereas the latter is pseudostratified. To investigate whether histologic and microanatomic characteristics of native integument are associated with site-specific clinicopathologic differences in primary MM, we performed a comparative clinicopathologic analysis of 95 primary head and neck MMs.

MATERIALS AND METHODS

Ninety-five cases of primary MM of head and neck (Figure 1, A and B) for which sufficient pathologic material was available for review were identified from the archives (1956-1999) of the Department of Pathology at Memorial Sloan-Kettering Cancer Center, New York, NY. The diagnosis of melanoma was previously established in 62 patients by immunohistochemistry for melanocytic differentiation markers, S100 protein, HMB-45, melan-A, tyrosinase, and microphthalmia transcription factor and by presence of melanin pigment.10 The primary nature of the melanomas was supported by review of the patients' charts to rule out mucosal metastasis in an advanced-stage disseminated cutaneous melanoma and by the presence of melanoma in situ in the adjacent mucosa seen in 31 melanomas arising in squamous mucosa (SQMM) and 42 melanomas arising in respiratory mucosa (RMM) (Figure 1, C and D). The histologic slides from 89 initial tumors, 4 recurrent mucosal tumors, and 2 metastatic deposits of primary MM to lymph node were reviewed. Tumors localized to the mucosa were considered stage I, whereas tumors with regional lymph node involvement and with distant metastasis were considered stages II and III, respectively.8,9

Tumor size and gross appearance were obtained from the pathology report or from clinical examination, as noted in patients' medical charts. The tumor thickness was measured with an ocular micrometer from the most superficial layer of mucosal epithelium, ulcer base, or granular layer of squamous mucosa, to the deepest invasive tumor cell. Presence of in situ melanoma and depth of invasion were noted. Microinvasion was defined similar to cutaneous melanoma as single or clusters of no more than 10 atypical cells present in the lamina propria within less than 0.3 mm of the basement membrane showing no mitoses.9 The tumor cell morphology, architecture, presence of ulceration, necrosis, melanin pigment, and vascular and perineural invasion were noted. Statistical analysis using 2-sided [chi]^sup 2^ analysis and the Fisher exact test was done to compare SQMM and RMM with [alpha] level set at