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Primary malignant melanoma, though rare, is believed to be the most common non-epithelial neoplasm of the oesophagus. Compared to epithelial esophageal malignancies, melanoma is more aggressive and metastatic, resulting in poor therapeutic response and prognosis. Immunohistochemical staining is often diagnostic; conventional staining classically reveals epithelioid cells with pigment deposits. We report a case of primary esophageal melanoma in an elderly male who presented with dysphagia, treated palliatively with esophageal stenting.

Abstract Background Cutaneous melanomas account for more than 95% of all cases of primary melanoma, making non-cutaneous primary melanomas truly rare. Cases of primary mucosal melanomas of the oral cavity have been widely described; however, instances of primary melanomas arising from salivary glands have been rarely described. To date, this is only the second case of primary melanoma of the submandibular gland. Case presentation This is a report of a case of a 36-year-old healthy male patient, who was referred to us with the chief complaint of a growing swelling on the left side of his lower jaw. Evaluations revealed an evident facial asymmetry in the frontal view with a firm, non-tender swelling. Initial orthopantomogram did not reveal any alterations in the trabeculation or morphology of the jaws and the surrounding structures. A soft tissue ultrasonography of the left submandibular gland and anterior region of mandible revealed a hypoechoic cystic mass with numerous micro-echoes. Further para-clinical examinations yielded the definitive diagnosis of primary melanoma of the submandibular gland. Moreover, no evidence of distant osteometastasis was observed in whole-body scans. Subsequent surgical management with the approach of excising the submandibular salivary gland and concurrent selective neck dissection was implemented. Conclusions This report emphasizes the importance of thorough examination and prompt referral to designated specialists in cases with suspicious behaviors which are unresponsive to treatments. It can be further concluded that melanoma can mimic a range of benign pathologies; therefore, putting it in the list differential diagnosis of similar lesions seems plausible.

Xiuyun Xuan,1 Yuqi Wang,2 Yanhong Sun,3 Changzheng Huang1 1Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Radiology, Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, 221002, People’s Republic of China; 3Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Yanhong Sun; Changzheng Huang Tel/Fax +86 0571-87783777; Tel/Fax +86 027-85726359Email sunyh1128@zju.edu.cn; hcz0501@126.comBackground: Melanoma is one of the most malignant and aggressive skin tumors, and its incidence is increasing worldwide. However, few studies have investigated the process of tumorigenesis from normal skin to melanoma.Methods: Several bioinformatics analyses, including GEO databases, Oncomine database, TCGA database, STRING, MCODE and cytoHubba plug-ins, GEPIA, TIMER and TRRUST and DGIdb, were performed to disclose the hub genes and immunology implicated in primary melanoma tumorigenesis. Finally, immunohistochemistry (IHC) and quantitative real-time PCR (qPCR) were used to validate the results of bioinformatics analysis in vitro.Results: A total of 295 overlapping DEGs (ODEGs) (157 upregulated and 138 downregulated) and 9 hub genes were identified between primary melanoma and normal skin tissues. Functional analysis of these 9 hub genes indicated that the genes were primarily enriched in cell chemotaxis, the chemokine-mediated signaling pathway, the extracellular region, the extracellular space, chemokine activity and CXCR3 chemokine receptor binding. KEGG pathway enrichment showed that these genes were primarily involved in the chemokine signaling pathway, cytokine–cytokine receptor interaction, the toll-like receptor signaling pathway, the cytosolic DNA-sensing pathway and the TNF signaling pathway. Upregulated CCL5, CCL4, CXCL9 and CXCL10 demonstrated good overall survival (OS), and most of them have a higher expression in stage 0 and 1 of melanoma. Moreover, immune infiltration analysis showed that the above hub genes showed a strong positive correlation between their expression and infiltration of the six immune cell subsets. Transcription factor regulation network suggested that RELA and NFKB1 are the transcription factors of CCL4, CCL5, CXCL10 and CXCL2, while IRF7, IRF3 and IRF1 are the transcription factors of CCL5 and CXCL10. Drug–gene interaction analysis identified 46 drug–gene interactions. In vitro data demonstrated that the level of CCL4, CCL5, CXCL9 and CXCL10 is higher in melanoma than that in normal skin tissues, either at tissue or cell lines level.Conclusion: In summary, we identified 4 key chemokine members related to tumorigenesis and progression in primary melanoma, and these results may help to elucidate melanoma tumorigenesis and facilitate its treatment.Keywords: bioinformatic analysis, primary melanoma, normal skin, prognosis, tumorigenesis

While the tumor immune microenvironment (TIME) of metastatic melanoma has been well characterized, the primary melanoma TIME is comparatively poorly understood. Additionally, although the association of tumor-infiltrating lymphocytes with primary melanoma patient outcome has been known for decades, it is not considered in the current AJCC melanoma staging system. Detailed immune phenotyping of advanced melanoma has revealed multiple immune biomarkers, including the presence of CD8+ T-cells, for predicting response to immunotherapies. However, in primary melanomas, immune biomarkers are lacking and CD8+ T-cells have yet to be extensively characterized. As recent studies combining immune features and clinicopathologic characteristics have created more accurate predictive models, this study sought to characterize the TIME of primary melanomas and identify predictors of patient outcome. We first phenotyped CD8+ T cells in fresh stage II primary melanomas using flow cytometry (n = 6), identifying a CD39+ tumor-resident CD8+ T-cell subset enriched for PD-1 expression. We then performed Opal multiplex immunohistochemistry and quantitative pathology-based immune profiling of CD8+ T-cell subsets, along with B cells, NK cells, Langerhans cells and Class I MHC expression in stage II primary melanoma specimens from patients with long-term follow-up (n = 66), comparing patients based on their recurrence status at 5 years after primary diagnosis. A CD39+CD103+PD-1- CD8+ T-cell population (P2) comprised a significantly higher proportion of intratumoral and stromal CD8+ T-cells in patients with recurrence-free survival (RFS) ≥5 years vs those with RFS

An improved understanding of the impact of skin cancer on patients’ daily life may optimize disease management. This questionnaire survey of adult patients in real-world settings aimed to assess patient perception of the diagnosis announcement, and the impact of the diagnosis on the patients’ professional and personal life. Data from 355 patients with melanoma and 320 patients with basal cell carcinoma (BCC) were analysed. Melanoma significantly impacted the couple, and sexual relationships, as well as family and social life, and reduced the patient’s libido more significantly than did BCC (all p

Introduction: The characteristics and the prognostic value of regression in primary melanomas are controversial. Objectives: To further characterize “hot” and “cold” tumor’s stromas and to investigate the association between dermoscopy, pathology, and the prognostic implications of regression. Methods: A 14-year-collection-based retrospective analysis was carried out on 40 patients with confirmed regressive melanomas. Results: The extent of regression in dermoscopy was associated with the stage of the regression (P = 0.05) and with the MelanA patterns in histology (P = 0.02). Blue-gray and gray-brown color of the peppering (P = 0.01), and the eccentric, multifocal character of the dermoscopic regression (P = 0.05) were associated with “hot” stromas (CD8+, Granzym B+). Focal histologic regression (regressing melanomas) was associated with a good outcome (P < 0.001), while a complete regression (regressed melanomas) was associated with melanoma-related death (P < 0.001). “Hot” stromas (CD8+ were significantly associated with survival at 10 years (P = 0.044), while “hot” stromas (Granzyme B+) were associated with the locoregional extension (P = 0.016), and the initial distant metastasis (P = 0.016). Conclusions: Dermoscopic features of regression in primary melanomas were associated with the stage of regression, its extent, and the “hot” or “cold” nature of the tumor stroma, with prognostic implications.

MicroRNAs (miRNAs) have been proven to regulate the development and progression of cancer through various mechanisms. The aim of the present study was to compare miRNA expression between primary melanomas from different sites. We analyzed the expression of 84 miRNAs in 27 primary melanoma and 5 nevus formalin-fixed paraffin-embedded (FFPE) samples using the Human Cancer PathwayFinder miScript miRNA PCR Array. The FFPE samples were obtained from the archives of the Municipal Clinical Emergency Hospital of Timisoara and included 10 cutaneous melanomas, 10 uveal melanomas, 7 mucosal melanomas, and 5 cutaneous nevi. Out of 84 miRNAs, 11 miRNAs showed altered expression in all types of melanoma compared with the nevi. Among these, miR-155-5p, miR-9-5p, miR-142-5p, miR-19a-3p, miR-134-5p, and miR-301a-3p were upregulated, while miR-205-5p, miR-203a-3p, miR-27b-3p, miR-218-5p, and miR-23b-3p were downregulated. The highest similarity in miRNA expression pattern was found between uveal and mucosal melanoma groups, i.e., 15 miRNAs had altered expression in both groups. Overall, we identified several miRNAs with significantly altered expression in primary melanomas, including those reported for the first time in this type of cancer. Among them, mir-9-5p, mir-203a-3p, mir-19a-3p, mir-27b-3p, and mir-218-5p showed altered expression in all three melanoma types vs. nevi. Further research should explore the potential of these miRNAs in melanoma.

Melanoma is a highly aggressive cancer, attracting increasing attention worldwide. The 5-year survival rate of patients with metastatic melanoma is low. Therefore, it is critical to identify potential effective biomarkers for diagnosis of melanoma metastasis. In the present study, the melanoma cohort and immune genes were obtained from the Cancer Genome Atlas (TCGA) database and the ImmPort database, respectively. Then, we constructed the immune risk score (IRS) using univariate and multivariate logistic analysis. The area under the curve (AUC) of IRS in sequencing samples and the initial diagnosis patients was 0.90 and 0.80, respectively. Besides, IRS could add benefits for metastasis diagnosis. For sequencing samples, IRS (OR = 16.35, 95% CI = 8.74–30.59) increased the odds for melanoma metastasis. Similar results were obtained in the initial diagnosis patients (OR = 8.93, 95% CI = 3.53–22.61). A composite nomogram was built based on IRS and clinical information with well-fitted calibration curves. We further used other independent melanoma cohorts from Gene Expression Omnibus (GEO) databases to confirm the reliability and validity of the IRS (AUC > 0.75, OR > 1.04, and P value < 0.01 in all cohorts). In conclusion, IRS is significantly associated with melanoma metastasis and can be a novel effective signature for predicting the metastasis risk.

Primary spinal melanoma is too rare to have any systemic statistical data on the epidemiology of this disease. We report a 58-year-old woman presented with spastic gait for 10 days, preceded by chronic pain at her left anterior chest that progressively spread to her neck, left shoulder, and arm in half a year. Cervical magnetic resonance imaging (MRI) displayed a well-enhancing focal intraspinal extramedullary tumor at C6/7 level. After surgical resection of the tumor and thorough studies to exclude extraspinal melanoma, the primary spinal melanoma is diagnosed. Postoperative MRI did not disclose any evidence of recurrence at 4 and 21 months later. We present the clinical, radiological, and pathological features of a patient with a primary cervical extramedullary spinal melanoma.

Melanoma in advanced stages is one of the most aggressive tumors and the deadliest of skin cancers. To date, the histopathological staging focuses on tumor thickness, and clinical staging is a major estimate of the clinical behavior of primary melanoma. Here we report on an observational study with in-depth molecular profiling at the protein level including post-translational modifications (PTMs) on eleven primary tumors from melanoma patients. Global proteomics, phosphoproteomics, and acetylomics were performed on each sample. We observed an up-regulation of key mitochondrial functions, including the mitochondrial translation machinery and the down-regulation of structural proteins involved in cell adhesion, the cytoskeleton organization, and epidermis development, which dictates the progression of the disease. Additionally, the PTM level pathways related to RNA processing and transport, as well as chromatin organization, were dysregulated in relation to the progression of melanoma. Most of the pathways dysregulated in this cohort were enriched in genes differentially expressed at the transcript level when similar groups are compared or metastasis to primary melanomas. At the genome level, we found significant differences in the mutation profiles between metastatic and primary melanomas. Our findings also highlighted sex-related differences in the molecular profiles. Remarkably, primary melanomas in women showed higher levels of antigen processing and presentation, and activation of the immune system response. Our results provide novel insights, relevant for developing personalized precision treatments for melanoma patients.

Intra-cranial melanomas are commonly metastatic, from primary melanoma elsewhere in the body. The primary occurrence of a melanoma in the brain parenchyma is rare. We report a case of 26-year aged woman who presented with headache, hearing loss, mild cerebellar signs. On imaging, a space occupying lesion was found in the right cerebellopontine angle and a preoperative diagnosis of schwannoma/ meningioma was made. She underwent right retro-mastoid sub-occipital craniectomy and excision of a blackish vascular tumour. Histopathological examination revealed a melanocytoma intermediate grade, mib Index 4-5%. Search for dermal, mucous and ocular lesions were negative. She received image guidance adjuvant radiation to the post- operative tumour bed to 50.4 Gy/28 fractions @ 180 cGy tumor. She tolerated the treatment well and is symptom free 12 months after treatment. We report a rare case of primary melanocytic tumour of the cerebellopontine angle.

Introduction: It is unusual to have uveal and cutaneous melanoma in the same patient. It is challenging to differentiate between primary uveal melanoma (UM) and melanoma metastatic to the uvea. Objective: The aim of this study is to evaluate the characteristics of patients who presented with concurrent melanomas (primary or metastatic) of the skin and uveal tract. Materials and Methods: Eleven patients with both uveal and cutaneous melanomas were obtained from the McGill University Ocular Pathology Laboratory database. The characteristics included cell type, number of mitotic figures, presence of necrosis, the time interval between primary and secondary melanoma and the presence of metastasis in other organs. Results: Five patients presented with both primary uveal and primary cutaneous melanoma, three patients with UM metastatic to the skin, and three patients with cutaneous melanoma metastatic to the uvea. In all of our cases, there was a time difference between the appearance of cutaneous and UM in the same patient. Conclusion: Patients with two primary melanomas presented with spindle-cell type (uveal tumor), a Breslow index 7 years between tumors. Systemic disease was negative. Patients with metastasis from cutaneous melanoma to the eye and from ocular to the skin showed epithelioid cell type, a Breslow index >1.5 mm,

Amino acid catabolizing enzymes emerged as a crucial mechanism used by tumors to dampen immune responses. The L-phenylalanine oxidase IL-4 induced gene 1 (IL4I1) is expressed by tumor-associated myeloid cells of most solid tumors, including melanoma. We previously provided the only evidence that IL4I1 accelerates tumor growth by limiting the CD8+ T cell mediated immune response, in a mouse model of melanoma cell transplantation. Here, we explored the role of IL4I1 in Ret mice, a spontaneous model of melanoma. We found that IL4I1 was expressed by CD11b+ myeloid cells and that its activity correlated with disease aggressiveness. IL4I1 did not enhance tumor cell proliferation or angiogenesis, but orchestrated the remodeling of the immune compartment within the primary tumor. Indeed, the inactivation of IL4I1 limited the recruitment of polymorphonuclear myeloid-derived suppressor cells and enhanced the infiltration by Th1 and cytotoxic T cells, thus delaying tumor development and metastatic dissemination. Accordingly, human primary melanomas that were poorly infiltrated by IL4I1+ cells exhibited a higher density of CD8+ T cells. Collectively, our findings strengthen the rationale for therapeutic targeting of IL4I1 as one of the key immune regulators.

Objetivo: revisar el diagnóstico clínico, histológico e inmunohistoquímico; las alternativas terapéuticas y los factores que influyen en el pronóstico del melanoma amelanocítico de vagina. Materiales y métodos: se presenta el caso de una paciente de 49 años que consultó por masa vaginal de 8 cm en pared anterior de vagina, nacarada y con fondo necrótico a la Unidad de Patología Cervical y Colposcopia del Hospital de Engativá, institución de segundo nivel de complejidad que atiende pacientes de nivel socioeconómico bajo afiliados al régimen de seguridad pública. Se realizó resección amplia de la lesión. La patología quirúrgica informó melanoma fusocelular y epiteloide maligno. Se realizó una búsqueda sistemática usando las palabras clave: melanoma primario y vagina en las bases de datos Medline vía PubMed, Cochrane y Ebsco. Resultados: se encontraron 489 artículos de los cuales 31 estaban relacionados directamente con el tema, de estos se seleccionaron diez que correspondieron a nueve reportes de caso y a una revisión del tema. El diagnóstico clínico no es fácil. Las proteínas HMB45 y S100 son de gran utilidad en su identificación. La respuesta al tratamiento quirúrgico, la radioterapia y la quimioterapia es pobre. El pronóstico depende de la ploidía, la amelanosis y el índice mitótico. Conclusiones: el melanoma primario de vagina es una neoplasia rara y de mal pronóstico. Hace parte del grupo de melanomas de mucosa que tienen un origen y comportamiento biológico diferente al cutáneo. Tiene tendencia a la diseminación hematógena rápida y a recaídas locales. El tratamiento se basa en cirugía conservadora, radioterapia, quimioterapia y terapia biológica; sin embargo, su eficacia es limitada.Objective: reviewing clinical, histological and immunohistochemical diagnosis, therapeutic alternatives and factors influencing prognosis for amelanotic melanoma of the vagina. Materials and methods: this article presents the case of a 49yearold patient who consulted the Engativá Hospital’s Cervical Pathology and Colposcopy Unit due to an 8 cm diameter necrotic pearlywhite vaginal mass on the anterior vaginal wall. The hospital is a secondary level complexity institution dealing with low socioeconomic level patients affiliated to the public (subsidized) social security (health) system. A broad resection was made of the lesion. Surgical pathology revealed epithelioid fusocellular malignant melanoma. A systematic literature search was made using the following key words: primary melanoma and vagina in Medline databases via Pub Med, Cochrane and Ebsco. Results: 31 of the 489 articles found were directly related to the topic; 10 new case reports and a review were selected. Clinical diagnosis is not easy; HMB45 and S100 proteins are extremely useful in identifying it.Response to surgical treatment, radiotherapy and chemotherapy is poor. Prognosis depends on ploidy, amelanosis and mitotic index. Conclusions: Primary melanoma of the vagina is a rare neoplasm and has a poor prognosis. It forms part of a group of mucosal melanoma having an origin and biological behavior different to that of cutaneous melanoma. It tends to have rapid hematogenous dissemination and local relapses. Treatment is based on conservative surgery, radiotherapy, chemotherapy and biological therapy; however, its effectiveness is limited.

A 64-year-old Japanese woman had a lightly brown-blackish pigmented macule (1.2 cm in diameter) on the left sole of her foot. She received surgical excision following a diagnosis of acral lentiginous melanoma (ALM), which was confirmed histopathologically. One month after the operation, a second melanoma lesion was noticed adjacent to the grafted site. Histopathologically, the two lesions had no continuity, but HMB-45 and cyclin D1 double-positive cells were detected not only on aggregates of atypical melanocytes but also on single cells near the cutting edge of the first lesion. The unique occurrence of a sequential lesion of a primary melanoma might be caused by stimulated subclinical field cells during the wound healing process following the initial operation. This case warrants further investigation to establish the appropriate surgical margin of ALM lesions.

We present a case of trigeminal neuralgia with cranial normal magnetic resonance image (MRI) and computed tomography. The pain was not relieved by carbamazepine and microvascular decompression surgery was done. After two months the pain was similar to the condition before surgery. At this time, MRI showed an expansive lesion in Meckel's cave that was treated with radical resection by extra-dural approach. The pathologic examination revealed a primary melanoma. The follow-up after six months did not show abnormalities.Apresentamos um caso de neuralgia do trigêmeo com investigação radiológica de ressonância magnética (RM) e tomografia computadorizada apresentando resultado normal. A dor não apresentou alívio com carbamazepina, sendo indicado descompressão microvascular do trigêmio. Passados dois meses, o paciente queixava-se de dor com intensidade similar à do pré-operatório. Nova RM mostrou lesão expansiva no cavo de Meckel, a qual foi tratada cirurgicamente por abordagem extra-dural. O exame anatomopatológico foi compatível com melanoma primário. O seguimento radiológico, após seis meses da cirurgia, não apresentou anormalidades.

Black/bluish discolored skin tumor without cuticular covering de novo from site of origin could be a diagnostic feature of melanomas.