Pathology of the Head and Neck

Nasal Cavity and Paranasal Sinuses Chapter 2 55Table 2.2. Sinonasal undifferentiated tumors. Immunohistochemistry and genetics.CK NSE S-100 CG SYN NF EBV L MIC-2 t11;22AmplN-mycSNUC + ± – – – – – – – – –SCC + + – ± + – – – – – –PSNPC + – – – – – + – – – –SNML – – – – – – + + – – –PNET – + + ± + – – – + + –ONB – + (+) + + + – – – – –MNB – + – + + + – – – – +SNUC sinonasal undifferentiated carcinoma, SCC small cell (neuroendocrine) carcinoma, PSNPC primary sinonasal nasopharyngealtypecarcinoma, SNML sinonasal malignant lymphoma, PNET primitive neuroectodermal tumour, ONB olfactory neuroblastoma,MNB metastatic neuroblastoma, CK cytokeratin, NSE neuronal specific enolase, S-100 Protein S-100, CG chromogranin, SYN synaptophysin,NF neurofilaments, EBV Epstein-Barr virus, L lymphoma markers, MIC-2 CD99, t(11;22) EWS-FLI1, Ampl amplification, (+)positive only in sustentacular cellssitu hybridisation are of great help in difficult cases.All three, NPC, PSNPC, and SNUC, react positively forlow molecular weight cytokeratins and EMA. In contrast,NPC and PSNPC are positive for EBV, whereasSNUC is negative. Until very recently, confusion ofNPC and PSNPC with SNUC has led to the belief thatsome SNUC were related to EBV. The sharp distinctionof these entities is crucial because NPC and PSNPChave a better prognosis and are more responsive to radiationtherapy than SNUC.2.11.6 Malignant MelanomaICD-O:8720/3Sinonasal melanomas represent between 0.5 and 1.5% ofall melanomas [25, 82, 157] and between 3 and 20% ofsinonasal malignant neoplasms [25, 74]. They most frequentlydevelop after the fifth decade of life [25, 42, 250]and seem to originate from melanocytes present in themucosa of the respiratory tract [25, 58, 275]. In our experience,it is not uncommon to see melanomas arising in anarea of squamous metaplasia . In contrast to Caucasians,black Africans often show visible pigmentation at sitescorresponding with the common locations of intranasalmelanomas, of which they have a higher incidence [148].Although there is not a significant sex predilection, menseem to be affected more than women [25, 29, 42]. Thesigns and symptoms of presentation of sinonasal melanomasare not specific. Epistaxis and nasal obstruction arefrequent when located in the nasal cavity.Grossly sinonasal malignant melanomas are eitherpigmented (black-brown) or non-pigmented (pink-tan)lesions. In the nasal cavity, they commonly arise in theanterior portion (Fig. 2.11a) of the septum and presentas tan-brown polypoid formations, with occasional ulceratedand hemorrhagic areas. When arising withinsinuses, they present as extensive and widely infiltrativetumours. The development of an intranasal malignantmelanoma in an inverted papilloma has been reported[99].The histological features of sinonasal melanomasmay be as polymorphic as in their cutaneous counterpart.Metastatic disease needs to be ruled out, beforethey are labelled as primary tumours. Primary melanomasmay be recognised by the presence of junctionalactivity (Fig. 2.11c) or by the finding of an intraepithelialcomponent in the adjacent mucosa; nevertheless,these features are usually lost in advanced stages of thedisease. Histologically, melanomas are composed of mediumto large cells that may be polyhedral, round, fusiform(Fig. 2.11b), pleomorphic, microcytic, or a mixtureof them. Usually, they have finely granular cytoplasmand nuclei with one or more eosinophilic nucleoli. Mitoticactivity is prominent. A rare balloon cell variantwith clear cytoplasm may mimic various types of clearcell tumours (see Chap. 5). Osteocartilaginous differentiationhas also been observed [244]. The cells of sinonasalmelanoma grow in solid, loosely cohesive, storiform,pseudo-alveolar or organoid patterns [25]. Two-thirdsof sinonasal melanomas contain some intracytoplasmicbrown pigment (Fig. 2.11d) [25], which has to be confirmedas melanin by Masson-Fontana or Grimelius silverstains. However, in the sinonasal tract non-pigmentedmelanomas are not uncommon; in our Barcelona seriesup to 40% of the sinonasal melanomas are amelanotic.When melanin is scarce or is not found, diagnosismay be difficult, and special techniques are mandatory.Immunohistochemically, the cells of amelanotic melanomasare negative for cytokeratin and positive for vimentin,S-100 protein and HMB-45 [65, 82, 209], as well asanti-tyrosinase and other newly reported markers [207].Electron microscopy reveals the presence of pre-melanosomesand/or melanosomes.