Nasal Mucosal Desmoplastic Melanoma: A Case Report with Review of the Literature.

Mucosal melanoma is a rare subtype of melanoma that accounts for 1% of all melanomas. The incidence of nasal mucosal melanomas is 0.3 per million. Desmoplastic melanomas are a subtype of melanoma with a reported incidence of 2.0 per million. Although 50% of desmoplastic melanomas are found in the head and neck region, mucosal desmoplastic melanoma is exceedingly rare. In the present study, we report a case of nasal mucosal desmoplastic melanoma and review the literature. A 79-year-old female presented to an outside otolaryngologist with nasal discomfort accompanied by rhinorrhea and was found to have a nasal vestibule mass. An endonasal incisional biopsy was performed yielding a diagnosis of a SOX-10 positive tumor. The patient was referred to our institution for further management. A blue-tinged lesion was identified at the prior biopsy site, and the mass was resected via an open rhinoplasty approach. Final pathology demonstrated an infiltrative spindle cell neoplasm with immunohistochemical patterns supportive of desmoplastic melanoma arising from the nasal vestibule. Due to positive margins, the patient underwent a re-resection with no tumor identified on the re-resected specimen. To our knowledge, this is the third case of nasal mucosal desmoplastic melanoma. We review the clinicopathologic features and management of this rare entity.

Indicadores morfométricos del melanoma maligno de piel / Morfometric indicators in malignant skin melanoma

RESUMEN Fundamento: el melanoma maligno es un tumor con una gran capacidad de invasión y de difícil tratamiento por su elevada agresividad y mortalidad, en este, los estudios morfométricos se hacen necesarios por el valor que aportan en el diagnóstico histológico para mejorar el pronóstico de la enfermedad. Objetivo: describir el comportamiento de indicadores morfométricos como el área nuclear, volumen nuclear y factor de forma nuclear. Métodos: se realizó un estudio de serie de casos de 12 pacientes con el diagnóstico de melanoma maligno de piel en el período septiembre 2015 a septiembre 2017 en la provincia Holguín. Se emplearon métodos teóricos y empíricos, estos últimos basados en técnicas morfométricas, luego se realizó análisis estadístico de los datos obtenidos y se reflejaron en tablas. Resultados: el área y el volumen nuclear muestran valores pequeños. El factor de forma como indicador de pleomorfismo nuclear presentó valores superiores en los casos del estudio que en los descritos en la literatura. Conclusiones: el volumen nuclear muestra valores pequeños, lo que habla a favor de un comportamiento característico de tejido hiperplásico, al igual que el comportamiento del área nuclear, los valores del factor de forma nuclear indican menor pleomorfismo que el descrito en la literatura.

ABSTRACT Background: malignant melanoma is an invasive tumour and difficult to treat due to its high level of mortality and aggressiveness, a morphometry study was required to provide a proper diagnosis of the disease. Objective: to describe the behavior of morphometric indicators as nuclear area, nuclear volume and nuclear shape factor. Methods: a case series study in 12 patients having malignant skin melanoma was carried out, in the period from September 2015 to September 2017 in Holguin Province. Theoretical and empirical methods were used; these last two methods were based on Morphometric techniques. Then a statistical analysis of the information obtained was performed and they were added on a chart. Results: the area and nuclear volume showed low rate. The shape factor showed less levels of pleomorfism than the ones described in specialized literature. Conclusions: when low values of nuclear volume and nuclear area in malignant melanoma are found we are dealing with hyperplastic tissue. The same happens with the incidence of the nuclear area; the values of the nuclear shape factor evidenced less pleomorfi levels than the ones described in specialized literature.

Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain.

BACKGROUND: CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes. OBJECTIVE: We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1. METHODS: We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and noncarriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family. RESULTS: Histologic slides were evaluated for 290 melanomas (139 from 132 noncarriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, and 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in 10 of 15 invasive melanomas (67%) from POT1 carriers (P < .0001 vs noncarriers). This finding was independently confirmed by 3 expert melanoma dermatopathologists in 9 of 15 invasive melanomas (60%). In situ and invasive melanomas from CDKN2A and CDK4 carriers were histologically similar to melanomas from noncarriers. LIMITATIONS: Limited sample sizes for rare melanoma-susceptibility syndromes (CDK4, POT1). CONCLUSION: Spitzoid morphology was associated with POT1 mutations suggesting that telomere dysfunction (POT1 mutations) may contribute to spitzoid differentiation in melanocytic tumors.

Differential expression profile of microRNAs in different types of uveal melanoma / 中华实验眼科杂志

Background Researches showed that microRNA (miRNA) is involved in the pathogenesis and development of many tumors and plays a cancer-suppressing-gene like role or cancer-gene like action.Uveal melanoma (UM) is a common ocular malignant tumor in aduh,and the mechanism of UM pathogenesis and metastasis is still not elucidated.Understanding the differential expression of miRNAs in UM is expected to provide a basis for targeting treatment of UM.Objective This study was to screen and compare the expression profiles of miRNAs in epithelial type and spindle type of UM.Methods The use of specimens of UM and donor eyes was approved by Ethic Commission of Capital Medical University.The specimens of epithelial type (4 specimens) and spindle type (4 specimens) of UM confirmed by histopathology and immunochemistry were collected in Beijing Tongren Hospital from March 2013 to October 2015.The expression profile of miRNA was assayed by miRNA array.Normal uveal specimens were obtained from 8 donors as controls.The differentially expressing miRNAs were screened by intergroup differential folds of ≥2.The genes targeting differentially expressed miRNAs were predicted using multiples online software and the potential signal pathway was further analyzed by bioinformatics method.The microarray outcomes were validated by real-time quantitative PCR.Results Spindle cell type and epithelial cell type of UMs were verified by hematoxylin and eosin staining.Immunochemistry showed that HMB45,melanin-A and S-100 were positively expressed in the two types of UM.Compared with the normal uveal tissue,109 differentially expressed miRNAs,including 29 up-regulated and 80 down-regulated miRNAs were seen in the spindle cell type of UM,and in the epithelial cell type of UM,50 differentially expressed miRNAs were found,including 23 up-regulated and 27 down-regulated miRNAs.In spindle cell type of UM,the up-regulated miRNAs were miR-146a-5p,miR-25-3p and miR-29b-l-5p,and down-regulated ones were miR-126-5p,miR-183-5p and miR-96-5p.In epithelial cell type of UM,the up-regulated miRNAs were miR-155-5p,miR-210 and miR-378a-5p,and down-regulated ones were miR-199a-5p,miR-143-3p and miR-143-5p.In addition,the mutual up-regulated miRNA in both spindle cell type of UM and epithelial cell type of UM were miR-132-3p,miR-21-5p,miR-34a-5p and miR-34b-5p,and mutual down-regulated ones were miR-125b-2-3p,miR-126-3p,miR-199a-3p and miR-214-3p.Bioinformatics analysis showed that the targeting genes predicted by differentially expressed miRNAs participated in a number of biological pathways,including cancer-related pathway,mitogenactivated protein kinase (MAPK) pathway,Wnt signal pathway and intercellular adhesion,endocytosis,prostatic cancer,colorectal cancer pathways.Conclusions Many differentially expressed miRNAs exist among spindle cell type of UM,epithelial cell type of UM and normal uveal tissue.These miRNAs participate in or regulate the biological behaviour of UM via different signal pathways.

Clinicopathologic features of primary cutaneous melanoma: a single centre analysis of a Swiss regional population.

BACKGROUND: Melanoma is a common type of skin cancer with poor survival in advanced stages. Screening efforts aim to detect and tackle tumors at an early stage. However, regional population-based data at the time of initial diagnosis are sparse. OBJECTIVES: To analyse clinical and pathologic tumor characteristics in a Swiss population. MATERIALS AND METHODS: Melanoma samples diagnosed at a large Swiss academic department were evaluated for demographic, clinical and histopathologic data. RESULTS: We analysed a total of 254 melanoma samples. In situ tumors were more common in females than in males (70.6% vs. 29.4%; p = 0.0032). The acro-lentiginous subtype was more common in in situ compared to invasive tumors (14.7% vs. 5.5%; p = 0.0011). Invasive tumors showed a preference for male gender in patients beyond 60 years of age (p = 0.0080). The most frequent anatomic sites were the trunk in males and the legs in females. Regression was more common in males than in females (35.2% vs. 11.7%; p = 0.0001). Breslow's thickness correlated significantly with age but not with gender. Ulceration was common in tumors thicker than 2.01 mm (48.4%; p = 0.0001). Regression was frequently detected in melanomas thinner than 1.00 mm (29.3%; p = 0.0263). CONCLUSION: Screening efforts should target elderly patients. Skin examinations should include acral localisations and focus on the trunk in males and the lower extremities in females. Population-based analyses can help to fine-tune melanoma screening in defined regional populations.

Amelanotic corneally displaced malignant conjunctival melanoma: a case report evaluated with impression cytology / Melanoma amelanótico conjuntival maligno deslocado sobre a córnea com citologia de impressão: relato de caso

Here we describe the case of a 65-year-old Caucasian female who presented with an amelanotic malignant conjunctival melanoma and highlight the clinical and pathological features of this rare entity that displayed exclusive corneal invasive growth without evidence of conjunctival tumors other than primary acquired melanosis. Impression cytology aided in the initial diagnosis. The patient underwent surgical treatment. Histopathology and immunohistochemistry revealed an invasive amelanotic melanoma limited to the cornea and exhibiting S-100, Melan A, and HMB-45 positivity. The absence of pigmentation delayed early clinical detection and treatment. Awareness of this nonpigmented melanoma is important for early recognition and appropriate management.

Os autores descrevem o caso de uma mulher branca de 65 anos que apresentava um melanoma amelanótico maligno conjuntival e destacam as características clínicas e patológicas desta entidade rara com crescimento invasivo exclusivo na córnea sem evidência de tumores na conjuntiva além de melanose adquirida primária sem pigmento. A citologia de impressão auxiliou no diagnóstico inicial. A paciente foi submetida a tratamento cirúrgico. A histopatologia e a imuno-histoquímica revelaram um melanoma amelanótico invasivo limitado sobre a córnea exibindo positividade para proteína S-100, Melan A e HMB-45. A ausência de pigmentação retardou sua identificação clínica e seu tratamento precoce. O conhecimento deste melanoma não pigmentado é importante para o reconhecimento precoce e a conduta apropriada.

Metastatic melanoma presenting as polymorphic ventricular tachycardia.

A 41-year-old woman with metastatic melanoma was admitted to the hospital because of syncopal episodes, which had developed after the administration of an experimental chemotherapy agent that targeted Notch signaling, as part of a phase I clinical trial. Cardiac monitoring revealed recurrent episodes of polymorphic ventricular tachycardia correlating with the patient's syncope. Investigations into the cause of the arrhythmia led to the discovery of metastatic lesions within the left ventricular myocardium. In presenting this case of polymorphic ventricular tachycardia as the antemortem clinical manifestation of metastatic melanoma involving the heart, we discuss the importance of recognizing that cardiac metastases can manifest themselves as arrhythmias in patients with malignant melanoma who are undergoing active anticancer treatment.

The effect of let-7b on melanoma cell proliferation and aerobic glycolysis / 中国医师杂志

Objective To study the influence of let-7b on cell proliferation and aerobic glycolysis of human melanoma cell A375.Methods Transfect A375 cell line with hsa-let-7b oligonucleotide or antisense.Glucose and lactate in medium were determined by spectrophotometry at 24 h and 48 h time point after transfection.The cell proliferation was determined by methylthiazol tetrazolium (MTT) assay.Results Over expression of let-7b in melanoma cell reduced cell proliferation notably,compared to the other groups by MTT(P ＜0.05).However,the glucose consumption and lactate production differences were not observed during 24 h or 48 h ( P ＞ 0.05 ),the blank control group transformed about 57％ and 43％ glucose to lactate during 24 h and 48 h.Conclusions Melanoma cell line A375 has notably aerobic glycolysis hallmark,let-7b could inhibit proliferation of melanoma cell line A375,but it may has no influence on glucose metabolism.

Histopathological analysis of choroidal melanoma / 中华眼底病杂志

Objective To investigate the histopathological characteristics of choroidal melanoma. Methods The histopathological data from 64 patients with choroidal melanoma were analyzed retrospectively. The tumor size and the cytological types were observed and detected. The locations of the tumor were classified according to the involved part invaded by the anterior margine of the tumor, and the degrees of the development of the tumor were graded according to the extent of the outward infiltration of the tumor cells. Results In 64 patients with choroidal melanoma, There were large, medium, and small tumors in 25(39.1%), 31(48.4%), and 8(12.5%) respectively. The spindle cell type was found in 42 patients (65.6%) including spindle cell A and B type in 15(23.4%) and 27(42.3%) respectively; epithelioid and mixed cell type was found in 7(10.9%) and 10(15.6%) respectively; the other types were found in 5(7.8%). Twenty-five cases(39.1%)had no invasion with sclera, 22(34.4%)had but limited to sclera, 12(18.8%)penetrated through sclera and 5(7.8%)had intra-orbit infiltration. Conclusion The histopathological characteristics of choroidal melanoma are multiple, and spindle cell type is the most common one. The choroidal melanoma can easily invade the sclera.