Amelanotic melanoma of the head and neck: analysis of tumor characteristics from the National Cancer Database.

BACKGROUND: Amelanotic melanoma is an extremely rare subtype of cutaneous melanoma. The tumor characteristics are still not well understood, especially for those located in the head and neck. METHODS: Tumor characteristics of patients diagnosed with amelanotic melanoma of the head and neck (AMHN) from January 1, 2004, to December 31, 2015, were analyzed by querying the National Cancer Database. Characteristics of AMHN were subsequently compared with common malignant melanoma of the head and neck (CMMHN). RESULTS: Three hundred and sixty-eight patients were diagnosed with AMHN, and 69,267 were diagnosed with CMMHN. Of those with AMHN, 128 (34.8%) had melanoma located on the scalp and neck, and 172 (46.7%) were diagnosed with an early disease stage (i.e., 0, I, or II). When compared with CMMHN, patients with AMHN were more likely to be diagnosed after 80 years of age (25.3% vs. 18.2%; odds ratio [OR], 3.28; 95% CI, 1.09-9.84; P = 0.03), when Breslow depth was between 2.01 and 4.00 mm (28.5% vs. 6.5%; OR, 1.92; 95% CI, 1.15-3.19; P = 0.01), when ulceration was present (36.7% vs. 9.0%; OR, 1.99; 95% CI, 1.34-2.97; P = 0.001), and when mitotic count was 1 or more/mm2 (40.5% vs. 12.8%; OR; 2.53; 95% CI, 1.09-5.89; P = 0.03). No statistical difference was found for sex, specific location, stage, or lymph node involvement. CONCLUSION: Our study determined that AMHN is associated with older age, increased Breslow depth, presence of ulceration, and greater mitotic count when compared with CMMHN.

Amelanotic melanoma.

Cutaneous amelanotic melanoma (AM) is a rare amelanotic or a hypomelanotic subtype of melanoma, comprising only 0.4-27.5% of all melanoma cases. The mean age of the patients is over 50 years, and the male/female ratio varies from 0.5 to 4. Patients with red hair, type I skin, freckles, lack of nevi on the back, a sun-sensitive phenotype, or previous AM history are more likely to develop AMs. As AMs lack pigmentation, their appearances vary and can mimic many benign and malignant conditions, thus presenting a diagnostic challenge. AMs are composed of greater proportions of nodular melanoma, acral lentiginous melanoma, and desmoplastic melanoma than pigmented melanomas. They also present with thicker Breslow thickness, higher mitotic rate, more frequent ulceration, higher tumor stage, and lower survival than pigmented melanomas.

Characteristics and associations of high-mitotic-rate melanoma.

IMPORTANCE: Mitotic rate is now recognized as having independent prognostic significance in melanoma survival. However, its clinicopathologic associations have not been the focus of any previous study. OBJECTIVE: To identify a set of patient and tumor characteristics associated with high-mitotic-rate melanoma with the aim of facilitating the earlier detection of aggressive primary invasive melanoma. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of patients from a multidisciplinary melanoma clinic based in a public hospital. A total of 2397 cases from January 2006 to December 2011 were reviewed by the Victorian Melanoma Service, and 1441 patients with 1500 primary invasive melanomas were included in the study. MAIN OUTCOMES AND MEASURES: Mitotic rate was measured as number of mitoses per mm2 and analyzed as ordered categories (0, <1, 1 and <2, 2, 3-4, 5-9, and ≥10) according to patient demographics, phenotypic markers, historical data, tumor presentation, and histopathologic features. RESULTS: Melanomas with higher mitotic rates were more likely to occur in men (odds ratio [OR], 1.5; 95% CI, 1.3-1.8), patients 70 years or older (OR, 2.1; 95% CI, 1.7-2.8), and those with a history of solar keratosis (OR, 1.3; 95% CI, 1.1-1.6). These melanomas occurred more frequently on the head and neck (OR, 1.4; 95% CI, 1.0-1.9) and presented more often as amelanotic (OR, 1.9; 95% CI, 1.4-2.5) and rapidly growing (≥2 mm/mo) lesions (OR, 12.5; 95% CI, 8.4-18.5). An association was seen with the nodular melanoma subtype (vs superficial spreading [reference]) (OR, 2.5; 95% CI, 1.8-3.4), greater tumor thickness (vs ≤1 mm [reference]) (>1-4 mm: OR, 4.5; 95% CI, 3.2-6.1; >4 mm: OR, 12.6; 95% CI, 7.5-21.1), and ulceration (OR, 2.0; 95% CI, 1.5-2.7). These histopathologic features, along with amelanosis and rate of growth, remained as significant associations with high mitotic rate in the overall multivariate analysis. CONCLUSIONS AND RELEVANCE: High-mitotic-rate primary cutaneous melanoma is associated with aggressive histologic features and atypical clinical presentation. It has a predilection for the head and neck region and is more likely to be seen in elderly men with a history of cumulative solar damage who present clinically with rapidly developing disease.

CDKN2A and MC1R analysis in amelanotic and pigmented melanoma.

Amelanotic melanoma (AM) is a rare subtype of melanoma with little or no clinically visible pigment; it is more difficult to diagnose than pigmented melanoma (PM), and has a worse prognosis. In the attempt to find a genetic explanation for the distinction between AM and PM, we conducted a case-case study, matching AM and PM patients, and testing them for germline mutations in high- (p16INK4A, p14ARF, CDK4) and low-penetrance (MC1R) melanoma susceptibility genes. Similar CDKN2A mutations were found in both sets of melanomas. A p14ARF splice germline mutation was detected for the first time in an Italian family with AM. This rare mutation, which has been described only once previously, may be involved in predisposition to the amelanotic phenotype in combination with germline MC1R variants and coordinate somatic expression of pigmentation genes and their regulators.

Melanoma amelanótico: a propósito de un caso / Amelanotic melanoma: a purpose of a case

Melanoma es un cáncer de piel originado por los melanocitos, altamente agresivo y letal, con características macroscópica característica; se presenta caso de paciente masculino de 65 años que acude a consulta presentando masa inguinal izquierda de 3 meses de evolución, de crecimietno rápido, 10cm de diámetro, discretamente dolorosa al tacto, con antecedente de amputación supracondilia del miembro inferior ipsilateral hace 6 meses por ulcera varicosa e insuficiencia venosa crónica. Se practica biopsia incisional que reporta melanoma amelanótico una variante atípica de dificil diagnóstico. Actualmente recibiendo quimio y radioterapia.

Digital imaging in differential diagnosis of small choroidal melanoma.

BACKGROUND: To assess the role of digital imaging and a new subtraction method for differential diagnosis of choroidal nevus and small choroidal melanoma. METHODS: Of 241 consecutive patients referred to a tertiary referral center for suspected choroidal melanoma, 110 who underwent digital imaging of the ocular fundus were eligible for this study. Digital color, red-free and red light retinal images were evaluated in a randomized and masked manner and by the subtraction method for diagnosis of the fundus lesion. The reference standard was based on the combined results of ophthalmological examination, including mydriatic ophthalmoscopy, B scan ultrasonography, digital imaging and fluorescein angiography of the ocular fundus. RESULTS: Comparative use of digital color, red-free and red light imaging had 85.7% (95%CI 42.1-99.6) sensitivity, 99.0% (95%CI 94.7-99.9) specificity and 98.2% (95%CI 93.6-99.8) exact agreement versus reference standard in differentiation of small choroidal melanoma from pseudomelanoma. Direct comparison between use of digital images and the reference standard showed excellent agreement in detecting small choroidal melanoma from suspected choroidal lesions (K 0.847; 95%CI 0.639-1.0). The subtraction method was useful to show growth in four of 94 melanocytic choroidal tumors. The mean annual incidence of choroidal melanoma in Southwest Finland was 0.80 per 100.000 population. The most frequent choroidal pseudomelanomas were choroidal melanotic and amelanotic nevi, disciform lesions, congenital hypertrophy of the retinal pigment epithelium, and circumscribed choroidal hemangioma. CONCLUSIONS: Combined use of digital color, red-free and red light imaging was a suitable adjunct in differentiation of small choroidal melanoma from different pseudomelanomas. The subtraction method may reveal early growth of the melanotic choroidal tumors.

Clinical and histologic trends of melanoma.

BACKGROUND: Several changing clinical and histopathologic melanoma trends occurred from the 1950s to the 1980s. OBJECTIVE: The purpose of this study was to evaluate melanoma trends during the past decade and to compare present trends to those documented during the past four decades. METHODS: Sex, age at diagnosis, location, tumor thickness, stage, and histologic subtypes were evaluated from 1984 to 1995 and compared with trends during the past four decades. RESULTS: Most changing trends from the past four decades have slowed or stabilized during the past decade. CONCLUSION: Complete reporting of all melanomas to central tumor registries is necessary to accurately analyze present and future melanoma trends. Ongoing and new prevention and control strategies beginning at birth may be necessary to continue the positive efforts to curtail the melanoma epidemic.

Mucosal melanoma of the head and neck.

Two hundred and fifty-nine patients with mucosal melanoma of the head and neck were reviewed. The data of these patients were obtained from the records of the Department of Head and Neck Oncology at the University of Liverpool and from the Merseyside and Cheshire Cancer Registry. Survival curves were constructed using the life table method and differences were investigated by the Log Rank Test. Prognostic factors were further analysed by Cox's proportional hazards model. Melanomas of the nasal cavities and sinuses accounted for 69%; 22% occurred in the oral cavity and 9% in the pharynx, larynx and upper oesophagus. In 49% treatment was by wide local resection and in 8% by irradiation. Thirty-six per cent had combined modalities of treatment. Primary site recurrence occurred in 52% and 36% developed nodal recurrence. The tumour specific survival at 5 years was 45% at 10 years 28%, at 20 years 17% and closely resembled the observed survival. Young male patients tended to have a favourable prognosis as did those treated surgically. Radiotherapy on its own was ineffective. Amelanotic melanoma had a particularly poor survival. Whereas site had no effect on survival. The study confirms the poor prognosis of mucosal melanoma of the head and neck. Young patients should be offered radical surgical treatment combined with radical radiotherapy if feasible as this offers the best chance of cure.

Pathology and incidence of amelanotic melanomas of the skin in F-344/N rats.

A total of 121 spontaneous amelanotic melanomas of the skin were identified in 70 of 11,171 male and 51 of 10,927 female Fischer-344/N rats in 63 2-yr carcinogenicity studies conducted by the National Cancer Institute's Carcinogenicity Testing Program/National Toxicology Program. Amelanotic melanomas had characteristic anatomical locations and histologic features distinguishable from Schwann cell tumors. Of the 121 tumors, 84, 19, 10, and 8 cases occurred in the pinna, eyelid, scrotum, and perianal region (anus and tail), respectively. Amelanotic melanomas originated from the dermis and consisted of spindle cells arranged in an interlacing fascicular pattern often with a perivascular orientation; epithelioid cells were rarely seen. Only the tumors arising in the pinna metastasized to the lung and/or mandibular lymph nodes. The metastatic rate was 19% (16/84) of the tumors and was clearly increased with an increase in tumor size. Most metastasizing tumors had focal areas consisting of anaplastic spindle cells with an increased number of mitosis. The tumor cells stained positive for S-100 protein but negative for melanin. Ultrastructurally, the tumors were diagnosed as amelanotic melanomas based on the identification of numerous, intracytoplasmic premelanosomes without melanin formation in the tumor cells which were not enveloped by pericytoplasmic basal laminae. One localized amelanotic melanoma of the pinna was successfully transplanted to the subcutaneous tissue in the flank of 3 Fischer-344/N rats.