Histological, immunological and molecular features of a nasal mucosa primary melanoma associated with nasal melanosis

Abstract

Nasal mucosa melanoma is a rare entity that may occur together with nasal melanosis. The histological and immunological features and loss of heterozygosity analysis of such lesions have not been reported to date. In the study presented here short-term cell cultures were established from the patient's melanoma and subsequent relapses. Histology, immunohistochemistry, reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, human leukocyte antigen analysis, microdissection with subsequent polymerase chain reaction for analysis of loss of heterozygosity were used to characterize the tumour and other cells. Melanoma of the nasal cavity was found, with a surrounding proliferation of atypical melanocytes corresponding to nasal melanosis. Immunoreactivity was found for S-100, gp100, tyrosinase and MelanA protein. Loss of heterozygosity for a p16-flanking marker was found in the tumour and the melanotic cells. Short-term cell cultures expressed tyrosinase and MUC18 at the mRNA level and intercellular adhesion molecule-1 (ICAM-1) and interleukin-12 receptor at the protein level. This is the first time short-term cell cultures have been established and analysed from such a tumour. Melanoma-associated antigens were identified within the tumour. The melanoma and the melanotic cells showed loss of heterozygosity for the p16 gene, which is implicated in melanoma development. This points to a common origin in tumorigenesis. Pathways of tumour escape, such as expression of CD54 and interleukin-10, were observed. The clinical, immunological and molecular features suggest that nasal melanosis should be followed closely.

Expression of p16 in sinonasal malignant melanoma

“…Previous immunohistochemical studies of p16 expression in sinonasal melanoma resulted in similar rate of protein loss [12]. In addition, loss of heterozygosity (LOH) analysis conducted in a case of nasal melanoma and in the adjacent nasal melanosis using a flanking marker for the p16 gene showed LOH in the area of melanosis and complete loss of both alleles within the tumour [8]. Thus, loss of p16 for deletion of the CDNK2A locus may play a major role in the deregulation of cell-cycle control pathways occurring in sinonasal melanoma, and it is likely to be an early event in the development of this tumour.…”

Malignant mucosal melanoma of the nasal cavity: A case report

“…They are positive for S-100 protein and specific melanocytic markers such as melan A and HMB-45 antigens [8]. The diagnosis is further complicated by the absence or presence of scanty melanin pigment as seen in our case.…”

Skin layer-specific Melan-A expression during progression of human cutaneous melanoma: implications for diagnostic applications of the marker

“…Melan-A, a melanocyte differentiation antigen, is one of the most widely used immunohistochemical markers in the identification of metastatic melanoma [8,17,22,27,41,42], detection of melanoma cells [6,43] and diagnosis of several types of primary melanomas [20,23,24,29,[44][45][46][47]. Moreover, Melan-A is known to induce immune T-cell responses and, as such, it is considered as one of the potential targets for the immunotherapy of melanoma [12,[48][49][50][51][52].…”