Pathology of the Head and Neck

88 J.W. Eveson3long-standing areas of oral hyperpigmentation, but theyrarely arise from pre-existing benign melanocytic naevi.The majority of cases are painless in the early stages andform irregular, black or brownish flat, raised or nodularareas that are frequently multicentric. Rarely, they areamelanotic and may be reddish in colour. Nodular areasare usually a feature of more advanced tumours andmay be ulcerated and associated with pain and bleeding.Invasion of the underlying bone is common and teethinvolved may loosen or exfoliate. In most cases there isinvolvement of the cervical lymph nodes at presentationand half of patients have distant metastases.Purely nodular melanomas are relatively rare andmost tumours have a radial growth element similar tothat seen in cutaneous acral lentiginous melanoma togetherwith evidence of upward migration. Oral melanomashave been divided into:1. In situ oral mucosal melanomas;2. Invasive oral mucosa melanomas;3. Mixed in situ and invasive oral mucosal melanomas.Fig. 3.14. In situ melanoma showing atypical melanocytes widelydispersed throughout the epitheliumAbout 15% of oral mucosal melanomas are in situ and30% are invasive [9]. Fifty-five percent of melanomashave a combined pattern. Borderline lesions have beentermed atypical melanocytic proliferations [75].Microscopically, in situ melanomas show an increasein atypical melanocytes. Although these atypical melanocyteshave angular and hyperchromatic nuclei, mitosestend to be sparse. The melanocytes may form aggregatesor be irregularly distributed in a junctional location.The characteristic nested or thequal pattern commonlyseen in cutaneous melanomas is less frequentlyobserved in mucosal lesions. Sometimes the melanocytesare dispersed throughout the epithelium and thismay be combined with a junctional pattern (Fig. 3.14).Sequential biopsies have shown increases in the densityof the junctional atypical melanocytes over time. Atypicalmelanocytes can extend down the excretory ducts ofthe underlying minor salivary glands. However, there isusually no inflammatory response to in situ lesions.The melanocytes present in invasive melanomasshow a variety of cell types including epithelioid, spindleand plasmacytoid. They typically have large, vesicularnuclei with prominent nucleoli. Mitoses may be present,but usually not in large numbers. They are usuallyaggregated into sheets or alveolar groups and less commonlyneurotropic or desmoplastic configurations areseen. About 10% of cases are amelanotic. Over 95% of lesionsare anti S-100 antigen-positive [10] and more specificmarkers include HMB45, Melan-A and antityrosinase[144].Atypical melanocytic proliferation or hyperplasia isthe term used for lesions with equivocal histopathologicalfeatures, but the criteria for inclusion in this categoryare rather ill-defined [176]. These include oral mucosallesions with melanocytes containing angular or hyperchromaticnuclei with very infrequent mitoses. Melanocyticatypia can vary from mild to severe [75].Oral melanomas are much more aggressive than theircutaneous counterparts. The prognosis of oral melanomasis poor with a 5-year survival rate of less than 20%[9], and even Stage I tumours have a 5-year survival rateof less than 50%. The conventional depth of invasionindicators such as Breslow thickness and Clark’s levelstend to be of little value in mucosal melanomas, as manypresent at an advanced stage and most are deeper than4 mm [145]. Histological features associated with a poorprognosis include evidence of vascular invasion, cellularpleomorphism, necrosis and amelanotic tumours [14,75, 123, 145].3.5.4 Addison DiseaseAddison disease is rare with an estimated annual incidenceof 0.8 cases per 100,000 of the population inWestern societies. It is due to bilateral destruction of theadrenal cortex. Formerly, the most common cause wastuberculosis. Most cases now are due to organ-specificauto-immune destruction and opportunistic infectionssuch as histoplasmosis in patients with AIDS. Due tothis, it is likely that the number of patients with Addisondisease will increase significantly. Addison diseasemay be associated with autoimmune polyglandular deficiencytype I (Addison disease, chronic mucocutaneouscandidosis, hypoparathyroidism) and autoimmunepolyglandular deficiency type II (Addison disease, primaryhypothyroidism, primary hypogonadism, insulindependentdiabetes, pernicious anaemia, vitiligo) [130].Clinically, there is usually slowly progressive weakness,lassitude and weight loss. Gastro-intestinal symptomscan include diarrhoea or constipation and anorexia,nausea and vomiting. Postural hypotension is a commonsymptom. An early sign is pigmentation of the skinand oral mucosa secondary to increased adrenocortico-