Melanoma amelanótico diseminado / Disseminated amelanotic melanoma

El melanoma amelanótico es una de las neoplasias con mayor índice de mortalidad por su alta agresividad y baja probabilidad diagnóstica. Afecta a la población de todo el orbe, más frecuente en caucásicos, con predisposición genética y factores de riesgo como la exposición al sol. Presenta tasas de supervivencia menor a 10 por ciento a 5 años y de recurrencia elevadas; con evidencia de procesos metastásicos a distancia en órganos como cerebro, tejido celular subcutáneo, pulmón, peritoneo, hueso, lo que ensombrece el pronóstico. Se presenta el caso de una paciente de 21 años de edad que acude al hospital por presentar lesiones equimóticas, nódulos subcutáneos y cefalea hemicránea izquierda de dos meses de evolución. Se le realizó tomografías de tórax abdomen y resonancia magnética de cráneo y evidenciaron diseminación metastásica. Se realizó estudio histopatológico con inmunohistoquímica que informó melanoma amelanótico(AU)

Amelanotic melanoma is one of the neoplasms with the highest mortality rate because it is highly aggressive and the diagnostic probability is low. It affects the population of the entire globe, more frequent in Caucasians, with genetic predisposition and risk factors such as sun exposure. It presents survival rates of less than 10 percent at 5 years and high recurrence rates; with evidence of distant metastatic processes in organs such as brain, subcutaneous cellular tissue, lung, peritoneum, bone, which casts a shadow on the prognosis. We report the case of a 21-year-old patient who came to the hospital due to ecchymotic lesions, subcutaneous nodules and a two-month evolution of left hemicrania headache. She underwent chest and abdomen tomography and MRI of the skull. They showed metastatic spread. Histopathological study was performed with immunohistochemistry that reported amelanotic melanoma(AU)

Oral Amelanotic Melanomas: Clinicopathologic Features of 8 Cases and Review of the Literature.

Mucosal melanomas are aggressive tumors, rarely observed in the oral cavity. The diagnosis is based on the clinical and microscopical features. Often these tumors had variable amounts of melanin pigmentation. However, when melanin is absent, the tumors are denominated amelanotic, presenting a tendency to misdiagnosis and delayed treatment. The aim of this study was to describe the clinicopathologic features of a series of oral amelanotic melanomas (OAM). Records of all cases of OAM were retrospectively retrieved from oral pathology services from January 2002 to January 2019. Data regarding the clinical features, morphological aspects, immunohistochemical reactions, treatment, and follow-up status were collected. Eight cases of OAM were included, 6 in men and 2 in women (ratio of 3:1) ranging in age from 33 to 77 years (mean 53.6 years). Clinically, the tumors presented as masses or ulcerated swellings. The most common intraoral locations of the tumors were gingiva and palate. Cervical lymph node metastasis was detected in 3 patients at the first examination. All but one patient died from complications of the tumors after a mean follow-up period of 8.5 months. In conclusion, OAM is a very aggressive malignant tumor, and when melanin is absent, an immunohistochemical panel comprising S100, melan A, HMB45, and SOX10 should be performed.

Clinicopathological characteristics and prognosis of amelanotic acral melanoma: A comparative study with pigmented acral melanoma.

We compared the clinicopathological features and prognosis between 16 amelanotic acral melanomas versus 56 pigmented acral melanomas. Amelanotic acral melanomas showed a thicker Breslow thickness (all had a Breslow thickness > 1 mm), more frequent ulceration (15/16, 93.7%) and lower HMB-45 positive rate than pigmented acral melanomas. However, a significant difference in survival was not observed.

Matched analysis of the prognosis of amelanotic and pigmented melanoma in head and neck.

Background: The prognosis of mucosal melanoma is poor, and the difference in clinical prognosis between patients with and without pigment needs further study.Aim: To analyze data with head and neck mucosal melanoma, and compare the prognosis of patients with and without pigment.Material and methods: The patients of amelanotic melanoma were matched with pigmented type according to age, sex, stage, location of disease, treatment history, tobacco and alcohol history. The Kaplan-Meier and Cox proportional risk regression model was used for analyzation.Results: 46 patients of amelanotic melanoma and 46 of pigmented type were included in this study. The overall survival rate and progression-free survival rate of patients with pigmented melanoma were higher than in patients with amelanotic melanoma (HR = 0.533, p = .035, 95% CI = 0.296-0.957; HR = 0.530, p = .034, 95% CI = 0.294-0.953, respectively), and the risk of distant metastases in patients with amelanotic melanoma was significantly higher than that in patients with pigmented melanoma (HR = 0.474, p = .046, 95% CI = 0.228-0.987).Conclusions and significance: The prognosis and disease-free survival of amelanotic melanoma is worse than for the pigmented type group. More identifying the differences in clinical characteristics will help to further individualized treatment decisions.

Clinically amelanotic or hypomelanotic melanoma: Anatomic distribution, risk factors, and survival.

BACKGROUND: The recognition and diagnosis of clinically amelanotic or hypomelanotic melanoma is a challenge. OBJECTIVE: This study aimed to examine the anatomic distribution and risk factors associated with clinically amelanotic or hypomelanotic melanoma and compare the survival of patients with clinically amelanotic or hypomelanotic melanoma with that of patients with pigmented melanoma. METHODS: A prospective cohort study of all cases of primary invasive melanoma managed at a tertiary referral center was performed. RESULTS: There were a total of 3913 invasive melanomas, and 384 (9.8%) were clinically amelanotic or hypomelanotic. Skin phototype I; red as well as blonde hair color; actinic keratoses; nodular, desmoplastic, and lentigo maligna subtype; increased Breslow thickness; and mitoses were independently associated with amelanotic or hypomelanotic melanoma (P < .05). After adjustment for subtype and thickness, the face, ears, lateral aspect of the neck, upper portion of the arm, posterior aspect of the forearm, dorsal aspect of the hand, and anterior aspect of the lower portion of the leg were associated with increased odds of amelanotic or hypomelanotic melanoma when compared with the upper portion of the back (P < .05). Mortality risk from melanoma appeared greater for amelanotic or hypomelanotic melanoma than for pigmented melanoma (hazard ratio, 1.5; 95% confidence interval, 1.1-2.1) but was similar once Breslow thickness was taken into account. LIMITATIONS: Single tertiary referral center. CONCLUSION: Although clinically amelanotic or hypomelanotic melanoma can occur on all body sites, it is more common on chronically sun-exposed areas. Clinicians should have an increased index of suspicion in patients with a sun-sensitive skin phenotype, red hair, and associated actinic keratoses.

Comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study.

IMPORTANCE Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathologic review, or no adjustment for stage limit the interpretation or generalization of results from prior studies.OBJECTIVE To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study.DESIGN, SETTING, AND PARTICIPANTS Survival analysis with a median follow-up of 7.6 years.The study population comprised 2995 patients with 3486 invasive primary melanomas centrally scored for histologic pigmentation from the Genes, Environment, and Melanoma(GEM) Study, which enrolled incident cases of melanoma diagnosed in 1998 through 2003 from international population-based cancer registries.MAIN OUTCOMES AND MEASURES Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively.RESULTS Of 3467 melanomas, 275 (8%) were histopathologically amelanotic. Female sex,nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a coexisting nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally ofa higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (odds ratios[ORs] [95%CIs] between 2.9 [1.8-4.6] and 11.1 [5.8-21.2] for tumor stages between T1b and T3b and ORs [95%CIs] of 24.6 [13.6-44.4] for T4a and 29.1 [15.5-54.9] for T4b relative to T1a;P value for trend, <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than for pigmented melanoma (hazard ratio [HR], 2.0; 95%CI, 1.4-3.0)(P < .001), adjusted for age, sex, anatomic site, and study design variables, but survival did not differ once AJCC tumor stage was also taken into account (HR, 0.8; 95%CI, 0.5-1.2)(P = .36).CONCLUSIONS AND RELEVANCE At the population level, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biological properties of amelanotic melanoma are warranted.

Cell proliferation and expression of connexins differ in melanotic and amelanotic canine oral melanomas.

Melanoma is a malignant neoplasm occurring in several animal species, and is the most frequently found tumor in the oral cavity in dogs. Melanomas are classified into two types: melanotic and amelanotic. Prior research suggests that human amelanotic melanomas are more aggressive than their melanotic counterparts. This study evaluates the behavior of canine melanotic and amelanotic oral cavity melanomas and quantifies cell proliferation and the expression of connexins. Twenty-five melanomas (16 melanotic and 9 amelanotic) were collected from dogs during clinical procedures at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil. After diagnosis, dogs were followed until death or euthanasia. Histopathology confirmed the gross melanotic or amelanotic characteristics and tumors were classified according to the WHO. HMB45 or Melan A immunostainings were performed to confirm the diagnosis of amelanotic melanomas. Cell proliferation was quantified both by counting mitotic figures and PCNA positive nuclei. Expressions of connexins 26 and 43 were evaluated by immunohistochemistry, qRT-PCR and Western blot. Dogs bearing amelanotic melanomas presented a shorter lifespan in comparison to those with melanotic melanomas. Cell proliferation was significantly higher in amelanotic melanomas. Expressions of Connexins 26 and 43 were significantly reduced in amelanotic melanomas. The results presented here suggest that oral cavity melanotic and amelanotic melanomas differ regarding their behavior, cell proliferation and connexin expression in dogs, indicating a higher aggressiveness of amelanotic variants.

Characteristics and survival of patients with invasive amelanotic melanoma in the USA.

Amelanotic melanoma (AM) has not been well characterized on a population-based level. Using cross-sectional, prospective data from 18 Surveillance, Epidemiology, and End Results registries, we carried out χ(2)-tests to compare characteristics of patients with AM with characteristics of patients with melanotic melanoma (MM), the Kaplan-Meier method to calculate 5-year survival among patients with AM and MM by stage, and competing risks regression to generate subdistribution hazard ratios for patients with AM using age, sex, and stage as predictors. We identified 628 cases of AM and 157,524 cases of MM. Patients with AM were more often male and older than patients with MM (P = 0.011 and P < 0.001, respectively). AM was more common on the face/ears compared with MM and less common on the trunk (P = 0.004 and P < 0.001, respectively). Ulceration was over three times more common among patients with AM than among patients with MM (38.0 vs. 12.5%, P < 0.001), and it remained more common among patients with AM even when stratified by Breslow depths of up to 2 mm (P < 0.001). Patients with AM were over three times more likely than patients with MM to have distant disease at diagnosis (10.0 vs. 2.9%, P < 0.001). Five-year melanoma-specific survival was significantly lower in patients with AM than in patients with MM (72.3 vs. 91.1%, P < 0.001). In competing risks regression, only stage was a significant predictor of melanoma-specific death. Our results demonstrate that the demographics of patients with AM and MM differ. AM is more advanced at diagnosis and is often more lethal than MM. Understanding the epidemiology of AM may help identify patients at highest risk and improve strategies for early detection.

Amelanotic melanoma: a detailed morphologic analysis with clinicopathologic correlation of 75 cases.

Amelanotic melanoma can have a varied appearance both clinically and microscopically. Here, we present our experiences with 75 cases of amelanotic melanoma defined clinically as a non-pigmented lesion and histopathologically as a tumor lacking significant melanization. We evaluated microscopic features such as morphology, mitotic count, nuclear atypia and presence of solar elastosis. Our amelanotic melanomas exhibited the following morphology: epitheloid (72%), spindled (18.7%) or desmoplastic (5.3%). In addition, we obtained patient information and clinical presentations on most of the cases (74/75; 98.7%) and follow-up data on 40% (30/75) of the cases. The majority of amelanotic melanomas in men were found on the trunk (13/45; 29%), head and neck (12/45; 26.7%), and lower limb (13/45; 29%) and in women were found on the lower limb (12/30; 40%), upper limb (10/30; 33.3%) and head and neck (6/30; 20%). In addition, we found that an increase in mitotic index correlated with worse survival (p < 0.026), whereas there were no differences in survival for other pathological features, such as nuclear atypia or solar elastosis. Furthermore, in cases with available tissue, all amelanotic melanoma expressed microphthalmia-associated transcription factor and tyrosinase, suggesting that the tumor cells retained melanocytic lineage and an enzyme in melanin formation, respectively. As the occurrence of amelanotic melanoma and the expression melanoma markers were similar to pigmented melanoma, we favor that amelanotic melanoma represents a subtype of melanoma rather than poorly differentiated or de-differentiated melanoma.

Metastatic amelanotic nodular melanoma during pregnancy.

This case report presents a very aggressive course of amelanotic nodular melanoma during pregnancy resulting in death five months after delivery. A 34 year-old Caucasian woman at 19th week of the second pregnancy was diagnosed having amelanotic nodular melanoma (tumor thickness - 2.5 mm) with metastases to the regional right inguinal lymph node. Amelanotic nodular melanoma represents malignant melanocytic tumor of the skin, which clinically mimics a variety of benign and malignant skin conditions and therefore commonly leads to delayed diagnosis. Though primary tumor was excised immediately, other treatment procedures as radical lymphadenectomy and chemotherapy were delayed, and immunotherapy was not given totally. At the 29th week of pregnancy, the woman via naturalem delivered a healthy female child, and the chemotherapy was started. Since pregnancy limits the prescription of immunotherapy and chemotherapy, the prognosis for melanoma during pregnancy detected later than in the second stage is poor and can be illustrated by our reported case. Such patients seems to be at higher risk to develop metastasis of melanoma in the internal organs and occasionally even in the fetus; therefore, they should be timely informed about that.

Anorectal amelanotic melanoma.

OBJECTIVE: Anorectal melanoma is a rare, highly malignant tumour with a poor 5 year survival of 10%. Most anorectal melanomas have gross and/or histologic pigmentation, however about 30% of anorectal melanomas are amelanotic. METHOD: We report three cases of amelanotic anorectal melanomas and integrate our data with six case reports of amelanotic malignant melanoma from the literature. Further we compare clinicopathological data and clinical outcome with large series of anorectal melanomas (both, amelanotic and pigmentated). RESULTS: There were seven females and two males, of median age 62 years (range: 45-75 years). Rectal bleeding was the leading symptom in all cases with a mean duration of 4 months before diagnosis. Eight of nine patients developed distant metastases. Median survival was 14 months (range: 3-60 months). A tumour thickness of < 4 mm was correlated with long-term disease-free survival, whereas tumour thickness of 4 mm or more was correlated with systemic recurrence. CONCLUSION: Early diagnosis is key for efficient treatment and improved survival rate for patients with this unusual variant of melanoma. There is no difference in terms of age, time of diagnosis, stage and survival between pigmented and amelanotic anorectal melanoma.

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.

Oral malignant melanoma in Japan.

Clinical examination was performed on 20 cases of malignant melanoma in the oral region encountered at the First Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University, during the 22-year period from 1970 to 1991. In addition, we reviewed 140 cases reported in the Japanese literature since the last major review in 1974. The results of our study revealed that the clinical course of malignant melanoma in the oral region is worse than oral squamous cell carcinoma and that treatment by radiotherapy is effective in prolonging the life of these patients. Clinically, the tumors were classified into five types: (1) pigmented nodular type; (2) nonpigmented nodular type; (3) pigmented macular type; (4) pigmented mixed type; and (5) nonpigmented mixed type. We suggest that oral malignant melanoma might be different from cutaneous malignant melanoma and that new criteria for diagnosis and therapy for oral disease should be considered.