Melanoma primario maligno variedad rabdoide. A Propósitode un caso / Malignant primary melanoma rhabdoid variety. about a case

Resumen El melanoma primariovariedad rabdoide es unapresentación pocofrecuente.Reconocido como un subtipo histopatológico distinto de melanoma maligno generalmente observado en tumores metastásicos o recurrentes.El diagnóstico definitivo requiere el estudio de inmunomarcación y la identificación de células neoplásicas con marcadores melanocíticos. Clínicamente se han reportado mayormente de tipo nodular y amelanótico.

Summary Rhabdoid melanoma has been recognized as a histopathological subtype of malignant melanoma. It generally presents as a recurrent tumor, so its presentation as a primary lesion is infrecuent.Definitive diagnosis requires the study of immunostaining and the identification of neoplastic cells with melanocytic markers. Clinically, mostly nodular and amelanotic types have been reported.

Responses of melanoma cells to photobiomodulation depend on cell pigmentation and light parameters.

Melanoma is a highly aggressive skin cancer that requires new approaches for its management. Low-level laser therapy, currently named photobiomodulation therapy (PBM), has been used to improve different conditions but its effects and safe use on melanoma remain unexplored. Herein, we investigated the PBM impact on melanoma cells differing by pigmentation using near-infrared (NIR) and red lasers in vitro. In vivo, we evaluated the effects of the red laser on melanoma-bearing mice. Amelanotic (SK-MEL-37) and melanotic (B16F10) cells were exposed in vitro to a NIR (780 nm, 40 mW) or a red laser (660 nm, 40 mW) in 3 different light doses: 30, 90, and 150 J/cm2 and responses were assessed regarding mitochondrial activity, invasiveness, migration, and VEGF production. In vivo, melanoma-bearing mice received the red laser delivering 150 J/cm2 directly to the tumor on 3 consecutive days. Mice were monitored for 15 days regarding tumor progression and mouse survival. We noticed that amelanotic cells were unresponsive to NIR light. In contrast, NIR irradiation at 30 J/cm2 promoted an increase in the invasiveness of pigmented cells, even though all light doses have inhibited cell migration. Regarding the red laser on pigmented cells, the highest light dose (150 J/cm2) decreased the VEGF production and migration. In vivo, melanoma-bearing mice treated with red laser showed smaller tumor volume and longer survival than controls. We conclude that PBM appears to be safe for amelanotic non-pigmented melanoma but triggers different responses in melanotic pigmented cells depending on light parameters. Additionally, a high dose of red laser impairs the invasive behavior of melanoma cells, probably due to the decrease in VEGF synthesis, which may have contributed to tumor arrest and increased mouse survival. These findings suggest that red laser therapy could be a new ally in the supportive care of melanoma patients.

Melanoma del cuerpo ciliar en un adulto joven: reporte de caso / Ciliary body melanoma in a young adult: a case report

Resumen Reporte de un caso: Femenino de 29 años de edad sin comorbilidades, con baja visual progresiva en ojo derecho de 1 mes de evolución. A la exploración oftalmológica agudeza visual de ese ojo en 20/80, conjuntiva bulbar superior con vaso centinela, masa retroiridiana color naranja vascularizada que subluxa el cristalino hacia inferior. Por ultrabiomicroscopía se evidencia una masa en domo dependiente del cuerpo ciliar de 4.87x5.74mm con reflectividad interna media y regular. Se realiza primeramente BAAF reportando melanoma, después se hace enucleación con resultado histopatológico de melanoma amelanótico. Posterior, se realiza implante de prótesis cosmética y se encuentra en seguimiento por oncología sin presentar datos de actividad tumoral después de 4 años. Discusión: Los melanomas uveales son la causa más común de tumores malignos intraoculares primarios en adultos, localizados principalmente en coroides (90%), siendo extremadamente rara su aparición en el cuerpo ciliar (6%) e iris (4%). El abordaje de un tumor del cuerpo ciliar debe incluir una anamnesis y exploración física completa con estudios paraclínicos adecuados para poder discernir entre los diagnósticos diferenciales. El ultrasonido ocular es el estudio auxiliar más importante ya que brinda características típicas propias del tumor. El tratamiento continúa basado en el COMS con un pronóstico sombrío. Los factores de mal pronóstico son presencia de metástasis, tamaño del tumor, extensión extraocular y estirpe epitelioide. Limitaciones: No se contaban con todas las alternativas de tratamiento. Originalidad: Caso inusual en pacientes jóvenes y por su sitio.

Abstract: Case report: 29-year-old female with no comorbidities, with progressive vision loss in the right eye of 1 month's evolution. On ophthalmological examination, visual acuity was 20/80, superior bulbar conjunctiva with sentinel vessel, vascularised orange retroiridian mass generating a lens subluxation inferiorly. Ultrabiomicroscopy revealed a dome-shaped mass dependent on the ciliary body measuring 4.87x5.74mm with medium and regular internal reflectivity. A FNA was done and melanoma was reported, then enucleation was performed with histopathological findings of amelanotic melanoma. Subsequently, a cosmetic prosthesis was implanted and the patient has been followed up by oncology with no evidence of tumour activity after 4 years. Discussion: Uveal melanomas are the most common cause of primary intraocular malignant tumours in adults, mainly located in the choroid (90%), being extremely rare in the ciliary body (6%) and iris (4%). The approach to a ciliary body tumour should include a complete anamnesis and physical examination with appropriate paraclinical studies to be able to discern between differential diagnoses. Ocular ultrasound is the most important ancillary study as it provides typical features of the tumour. Treatment is still based on COMS and the prognosis remains poor. Poor prognostic factors are the presence of metastases, tumour size, extraocular extension and epithelioid lineage. Limitations: Not all treatment alternatives were available. Originality: Unusual case in young patients and because of its site.

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.

Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives.

Malignant melanoma represents the most aggressive type of skin cancer. Modern therapies, including targeted agents and immune checkpoint inhibitors, have changed the dismal prognosis that characterized this disease. However, most evidence was obtained by studying patients with frequent subtypes of cutaneous melanoma (CM). Consequently, there is an emerging need to understand the molecular basis and treatment approaches for unusual melanoma subtypes. Even a standardized definition of infrequent or rare melanoma is not clearly established. For that reason, we reviewed this challenging topic considering clinical and molecular perspectives, including uncommon CMs-not associated with classical V600E/K BRAF mutations-malignant mucosal and uveal melanomas, and some unusual independent entities, such as amelanotic, desmoplastic, or spitzoid melanomas. Finally, we collected information regarding melanomas from non-traditional primary sites, which emerge from locations as unique as meninges, dermis, lymph nodes, the esophagus, and breasts. The aim of this review is to summarize and highlight the main scientific evidence regarding rare melanomas, with a particular focus on treatment perspectives.

Melanoma desmoplásico mixto / Mixed desmoplastic melanoma

El melanoma desmoplásico es una variedad infrecuente de melanoma que se distingue por su presentación clínico-patológica y su comportamiento biológico. El diagnóstico temprano es un desafío por su presentación clínica variable, con predominio del componente dérmico y la frecuente ausencia de pigmento. En la histología se lo divide en puro y mixto y esta clasificación tiene importantes implicancias pronósticas. El espesor de Breslow promedio al momento del diagnóstico es mayor que en otras variantes de melanoma, sin embargo, la tendencia a generar metástasis ganglionares es menor.

Desmoplastic melanoma is a rare presentation of melanoma with a different clinical behavior compared to other histological variants. Its diagnosis in early stages is a challenge due to its variable clinical presentation, with a predominant dermal component and the frequent absence of pigment. Its histology is divided into pure and mixed type, and this classification has important prognostic implications. The average Breslow thickness at diagnosis is higher than in other melanoma variants. However, the tendency to lymph node metastasis is low.

[Mixed desmoplastic melanoma]. / Melanoma desmoplásico mixto.

Desmoplastic melanoma is a rare presentation of melanoma with a different clinical behavior compared to other histological variants. Its diagnosis in early stages is a challenge due to its variable clinical presentation, with a predominant dermal component and the frequent absence of pigment. Its histology is divided into pure and mixed type, and this classification has important prognostic implications. The average Breslow thickness at diagnosis is higher than in other melanoma variants. However, the tendency to lymph node metastasis is low.

El melanoma desmoplásico es una variedad infrecuente de melanoma que se distingue por su presentación clínico-patológica y su comportamiento biológico. El diagnóstico temprano es un desafío por su presentación clínica variable, con predominio del componente dérmico y la frecuente ausencia de pigmento. En la histología se lo divide en puro y mixto y esta clasificación tiene importantes implicancias pronósticas. El espesor de Breslow promedio al momento del diagnóstico es mayor que en otras variantes de melanoma, sin embargo, la tendencia a generar metástasis ganglionares es menor.

Melanoma lentigo maligno amelanótico / Amelanotic lentigo maligna melanoma

RESUMEN El melanoma lentigo maligno es un subtipo de melanoma invasor, que se localiza en áreas fotodañadas de cara y cuello, manifestándose como una mácula no muy definida, de varios colores de la gama del marrón y negro. La variante amelanótica es infrecuente en cualquiera de los subtipos cutáneos de melanoma. Presentamos el caso de una mujer de 63 años, que presentó un melanoma lentigo maligno de subtipo amelanótico y de localización infrecuente, en miembro inferior.

SUMMARY Lentigomalignamelanoma is a subtype of invasive melanoma, located in photodamaged skin, particularly of the face and neck. It appears as an ill- defined macula, of heterogeneous color, ranging from brown to black. The amelanotic variant is infrequent in any of the cutaneous melanoma subtypes. We report the case of a 63-year-old woman with amelanoticlentigomaligna melanoma, located in her lower right limb.

c-Kit immunoexpression patterns differ in melanotic and amelanotic canine oral melanomas / Análise qualitativa quanto à diferença da imunoexpressão do gene c-Kit em melanomas melânicos e amelânicos da cavidade oral em cães

Melanomas are the most common oral malignancy in dogs. Cell proliferation and connexin expression has been shown to differ in canine melanotic and amelanotic oral melanomas. This study aimed to analyze the c-Kit protein expression in melanotic and amelanotic melanomas from canine buccal cavity. A total of 34 canine buccal melanomas (19 melanotic and 15 amelanotic).were collected. The amelanotic melanomas presented faster evolution and higher incidence of metastasis than melanotic tumors. A significantly higher number of c-Kit positive cells were observed in amelanotic neoplasms. In addition, the intensity of c-Kit immunolabeling was predominantly stronger in amelanotic melanomas. These results confirm a potential role for c-Kit in canine oral melanomas with clear differences in expression patterns between the two histological types of tumor, melanotic and amelanotic. This study highlights the importance of a detailed study of c-Kit mutations in canine oral melanomas to better understand the molecular mechanisms implicated in the development of this disease...

Melanomas são as mais frequentes neoplasias malignas da cavidade bucal de cães. Sabe-se que a proliferação de células e expressão de conexina diferem em melanomas melanóticos e amelanóticos da cavidade bucal de cães. Este estudo analisou a expressão da proteína c-Kit em melanomas melanóticos e amelanóticos da cavidade bucal canina. Um total de 34 melanomas bucais caninos (19 melanóticos e 15 amelanóticos) foram coletados. Os melanomas amelanóticos apresentaram evolução mais rápida e maior incidência de metástase. Foi constatado um número significativamente maior de células positivas para c-Kit em neoplasias amelanóticas. Além disso, a intensidade de imunomarcação de c-Kit foi predominantemente mais forte em melanomas amelanóticos. Estes resultados confirmam um papel potencial para c-Kit em melanomas orais caninos, com diferenças claras em padrões de expressão entre os dois tipos histológicos de tumor, melanóticos e amelanóticos. Este trabalho destaca a importância de um estudo detalhado das mutações c-Kit em melanomas orais caninos para ser possível a melhor compreensão dos mecanismos moleculares envolvidos no desenvolvimento da doença...

c-Kit immunoexpression patterns differ in melanotic and amelanotic canine oral melanomas / Análise qualitativa quanto à diferença da imunoexpressão do gene c-Kit em melanomas melânicos e amelânicos da cavidade oral em cães

Melanomas are the most common oral malignancy in dogs. Cell proliferation and connexin expression has been shown to differ in canine melanotic and amelanotic oral melanomas. This study aimed to analyze the c-Kit protein expression in melanotic and amelanotic melanomas from canine buccal cavity. A total of 34 canine buccal melanomas (19 melanotic and 15 amelanotic).were collected. The amelanotic melanomas presented faster evolution and higher incidence of metastasis than melanotic tumors. A significantly higher number of c-Kit positive cells were observed in amelanotic neoplasms. In addition, the intensity of c-Kit immunolabeling was predominantly stronger in amelanotic melanomas. These results confirm a potential role for c-Kit in canine oral melanomas with clear differences in expression patterns between the two histological types of tumor, melanotic and amelanotic. This study highlights the importance of a detailed study of c-Kit mutations in canine oral melanomas to better understand the molecular mechanisms implicated in the development of this disease(AU)

Melanomas são as mais frequentes neoplasias malignas da cavidade bucal de cães. Sabe-se que a proliferação de células e expressão de conexina diferem em melanomas melanóticos e amelanóticos da cavidade bucal de cães. Este estudo analisou a expressão da proteína c-Kit em melanomas melanóticos e amelanóticos da cavidade bucal canina. Um total de 34 melanomas bucais caninos (19 melanóticos e 15 amelanóticos) foram coletados. Os melanomas amelanóticos apresentaram evolução mais rápida e maior incidência de metástase. Foi constatado um número significativamente maior de células positivas para c-Kit em neoplasias amelanóticas. Além disso, a intensidade de imunomarcação de c-Kit foi predominantemente mais forte em melanomas amelanóticos. Estes resultados confirmam um papel potencial para c-Kit em melanomas orais caninos, com diferenças claras em padrões de expressão entre os dois tipos histológicos de tumor, melanóticos e amelanóticos. Este trabalho destaca a importância de um estudo detalhado das mutações c-Kit em melanomas orais caninos para ser possível a melhor compreensão dos mecanismos moleculares envolvidos no desenvolvimento da doença(AU)

Melanoma amelanótico em cães: estudo retrospectivo de 35 casos (2004-2010) e caracterização imuno-histoquímica / Amelanotic melanoma in dogs: a retrospective study of 35 cases (2004-2010) and immunohistochemical characterization

Melanomas são tumores agressivos de melanócitos que ocorrem principalmente na cavidade oral, nas junções mucocutâneas e na pele de cães. Este tipo de neoplasma pode apresentar diversos graus de pigmentação melânica, incluindo total ausência (melanomas amelanóticos [MA]). Os arquivos de biópsia do SPV-UFRGS, que compreendem o período de 2004 a 2010, foram revisados e levantados os casos de neoplasias melanocíticas em cães. Realizou-se estudo retrospectivo de 35 casos de MA e caracterização pela imuno-histoquímica (IHQ). As principais raças acometidas foram o Poodle, Dachshund e Cocker Spaniel, mas o maior número de casos foi observado em cães sem raça definida (SRD). A idade média desses cães foi de 10,7 anos (variação de 5 a 18 anos) e não houve predileção por sexo. As principais localizações incluíram cavidade oral (57,1%) e dígitos (17,1%). Histologicamente, 40% dos MA foram classificados como epitelioides, 34,3% como mistos e 25,7% como fusiformes. Na avaliação IHQ, 86,6% dos casos foram positivos para a vimentina, 70% para a proteína S-100 e 56,6% para o melan-A. Os resultados obtidos neste trabalho possibilitam concluir que os cães com MA caracterizavam-se por serem velhos. A forma celular mais observada foi a epitelioide. Devido a pouca diferenciação desses tumores, ressalta-se a importância da realização do painel imuno-histoquímico, sobretudo da proteína S-100, que apresentou melhor marcação que o melan-A.(AU)

Melanomas are aggressive tumors of melanocytes. They are common in dogs and involve mainly the oral cavity, mucocutaneous junction, and skin. Furthermore, these tumors could be highly pigmented or lack pigment. The biopsies archives from SPV-UFRGS, 2004 to 2010, were retrieved and melanocytic neoplasms in dogs were revised. A retrospective study of 35 cases of amelanotic melanomas (AM) was performed, also immunohistochemistry (IHC) characterization was evaluated. The dogs more affected were mixed breed followed by Poodle, Dachshund and Cocker Spaniel. The average age of the dogs was 10.7 years (5-18 years in age) and there was no sex predilection. The locations of the neoplasms were the oral cavity (57.1%) and digits (17.1%). Histologically, 40% were classified as epithelioid, 34.3% mixed and 25.7% spindle. The positive immunostaining for vimentin, S-100 protein and melan-A were 86.6%, 70%, and 56.6% respectively. These results indicated the most affected dogs with AM were elderly. Epiteliod classification was the most observed histologically. It is important to perform IHC, due to lacking of differentiation of AM, mainly, anti S-100 protein that showed to be the best option of positive marker, even better to Melan-A.(AU)

Melanoma amelanótico em cães: estudo retrospectivo de 35 casos (2004-2010) e caracterização imuno-histoquímica / Amelanotic melanoma in dogs: a retrospective study of 35 cases (2004-2010) and immunohistochemical characterization

Melanomas são tumores agressivos de melanócitos que ocorrem principalmente na cavidade oral, nas junções mucocutâneas e na pele de cães. Este tipo de neoplasma pode apresentar diversos graus de pigmentação melânica, incluindo total ausência (melanomas amelanóticos [MA]). Os arquivos de biópsia do SPV-UFRGS, que compreendem o período de 2004 a 2010, foram revisados e levantados os casos de neoplasias melanocíticas em cães. Realizou-se estudo retrospectivo de 35 casos de MA e caracterização pela imuno-histoquímica (IHQ). As principais raças acometidas foram o Poodle, Dachshund e Cocker Spaniel, mas o maior número de casos foi observado em cães sem raça definida (SRD). A idade média desses cães foi de 10,7 anos (variação de 5 a 18 anos) e não houve predileção por sexo. As principais localizações incluíram cavidade oral (57,1%) e dígitos (17,1%). Histologicamente, 40% dos MA foram classificados como epitelioides, 34,3% como mistos e 25,7% como fusiformes. Na avaliação IHQ, 86,6% dos casos foram positivos para a vimentina, 70% para a proteína S-100 e 56,6% para o melan-A. Os resultados obtidos neste trabalho possibilitam concluir que os cães com MA caracterizavam-se por serem velhos. A forma celular mais observada foi a epitelioide. Devido a pouca diferenciação desses tumores, ressalta-se a importância da realização do painel imuno-histoquímico, sobretudo da proteína S-100, que apresentou melhor marcação que o melan-A.

Melanomas are aggressive tumors of melanocytes. They are common in dogs and involve mainly the oral cavity, mucocutaneous junction, and skin. Furthermore, these tumors could be highly pigmented or lack pigment. The biopsies archives from SPV-UFRGS, 2004 to 2010, were retrieved and melanocytic neoplasms in dogs were revised. A retrospective study of 35 cases of amelanotic melanomas (AM) was performed, also immunohistochemistry (IHC) characterization was evaluated. The dogs more affected were mixed breed followed by Poodle, Dachshund and Cocker Spaniel. The average age of the dogs was 10.7 years (5-18 years in age) and there was no sex predilection. The locations of the neoplasms were the oral cavity (57.1%) and digits (17.1%). Histologically, 40% were classified as epithelioid, 34.3% mixed and 25.7% spindle. The positive immunostaining for vimentin, S-100 protein and melan-A were 86.6%, 70%, and 56.6% respectively. These results indicated the most affected dogs with AM were elderly. Epiteliod classification was the most observed histologically. It is important to perform IHC, due to lacking of differentiation of AM, mainly, anti S-100 protein that showed to be the best option of positive marker, even better to Melan-A.

Melanoma amelanótico en ciego / Cecal amelanotic melanoma

Paciente varón de 73 años que acude a emergencia con anemia severa (Hb 4.9 g/dL), refiriendo un mes con deposiciones oscuras, astenia y pérdida significativa de peso. La evaluación endoscópica alta no encontró lesiones potencialmente sangrantes. Posteriormente se constató la presencia de heces sanguinolentas rojizas tipo enterorragia y se realizó una colonoscopía, en la cual se encontraron dos lesiones elevadas en el ciego: una pedunculada (con sangrado activo rezumante) y otra sésil, ambas fueron extirpadas; el estudio de anatomía patológica demostró que correspondían a melanoma amelanótico de ciego. El examen físico no reveló lesiones neoplásicas dérmicas. El sangrado digestivo recurrente obligó a realizar una nueva colonoscopia que demostró una nueva lesión sangrante de ciego. Fue intervenido quirúrgicamente con una cecostomía y extirpación de la lesión cecal. La tomografía demostró metástasis en mediastino y en la cirugía se encontraron implantes metastásicos en hígado e intestino delgado. El paciente continuó tratamiento en oncología médica. Nosotros reportamos el presente caso, por ser la hemorragia digestiva una forma inusual de presentación clínica del melanoma maligno metastásico.

A 73 year old male patient who presented to emergency with severe anemia (Hb 4.9 g / dL), referring to a month with dark stools, fatigue and significant weight loss. The high endoscopic evaluation found no potentially bleeding lesions. Subsequently, we confirmed the presence of red blood in stools, like enterorrhagia and underwent a colonoscopy, in which two elevated lesions were found in the cecum: a pedunculated (with active bleeding, oozing) and other sessile; both were removed. the pathology showed that corresponded to amelanotic melanoma in cecal region. Physical examination revealed no malignant skin lesions. Recurrent gastrointestinal bleeding forced to make another colonoscopy that showed new bleeding lesion of the cecum. He was operated with a cecostomy and cecal excision of the lesion.. The tomography scan showed metastases in mediastinum and surgical implants were found in liver metastases and small intestine. The patient continued treatment in medical oncology. We report this case, because gastrointestinal bleeding is an unusual clinical presentation of malignant melanoma.