Primary malignant melanoma of the nipple: a case report

Primary melanoma origi­nating on the female nipple remains an extremely rare variant of malignant melanoma and only a few cases haves been reported in the literature. We describe a case of a patient admitted for a black pigment deposition on the left nipple. Surgical resection of the left nipple and areola with clear margins and an axillary lymph node dissection was performed confirming the diagnosis of non-invasive superficial spreading melanoma.

Protein expression of prognostic genes in primary melanoma and benign nevi

Purpose To evaluate the protein expression characteristics of genes employed in a recently introduced prognostic gene expression assay for patients with cutaneous melanoma (CM). Methods We studied 37 patients with CM and 10 with benign (melanocytic) nevi (BN). Immunohistochemistry of primary tumor tissue was performed for eight proteins: COL6A6, DCD, GBP4, KLHL41, KRT9, PIP, SCGB1D2, SCGB2A2. Results The protein expression of most markers investigated was relatively low (e.g., DCD, KRT9, SCGB1D2) and predominantly cytoplasmatic in melanocytes and keratinocytes. COL6A6, GBP4, and KLHL41 expression was significantly enhanced in CM when compared to BN. DCD protein expression was significantly correlated with COL6A6, GBP4, and KLHL41. GBP4 was positively correlated with KLHL41 and inversely correlated with SCGB2B2. The latter was also inversely correlated with serum S100B levels at time of initial diagnosis. The presence of SCGB1D2 expression was significantly associated with ulceration of the primary tumor. KRT9 protein expression was significantly more likely found in acral lentiginous melanoma. The presence of DCD expression was less likely associated with superficial spreading melanoma subtype but significantly associated with non-progressive disease. The absence of SCGB2A2 expression was significantly more often observed in patients who did not progress to stage III or IV. Conclusions The expression levels observed were relatively low but differed in part with those found in BN. Even though we detected some significant correlations between the protein expression levels and clinical parameters (e.g., CM subtype, course of disease), there was no major concordance with the protective or risk-associated functions of the corresponding genes included in a recently introduced prognostic gene expression assay.

High regional mortality due to malignant melanoma in Eastern Finland may be explained by the increase in aggressive melanoma types

Background A regional skin cancer prevention program in Eastern Finland revealed a relatively high age-standardized mortality due to malignant melanoma during 2013–2017. An explanation for this is needed. Purpose To analyse the 543 melanoma samples in 524 subjects collected during 2000–2013 at Kuopio University Hospital and reposited in the Biobank of Eastern Finland. A focus was directed to factors related to metastasis. Methods The samples were analysed anonymously by examining the histopathological report, referral text and the list of diagnoses. A possible state of immunosuppression was evaluated. Results The mean age at the diagnosis of malignant melanoma (MM), lentigo maligna (LM) and melanoma in situ was relatively high, i.e., 66.2, 72.1 and 63.3, respectively. Especially the MM type increased markedly during 2000–2013. In further analyses of a representative cohort of 337 samples, the proportion of nodular melanoma and LM/LMM melanoma was relatively high, 35.6 and 22.0%, respectively, but that from superficial spreading melanoma relatively low (33.8%). Metastasis correlated with immunosuppression, male gender, Clark level, Breslow thickness, ulceration, mitosis count, invasion into vessels and/or perineural area, microsatellites, melanoma subtype, body site, recidivism, and the absence of dysplastic nevus cells. Conclusion The marked increase in aggressive melanomas with associated metastasis, and the relatively high age at diagnosis, can partially explain the mortality.

BRAFV600E Mutant Allele Frequency (MAF) Influences Melanoma Clinicopathologic Characteristics

Background: Cutaneous melanoma shows high variability regarding clinicopathological presentation, evolution and prognosis. Methods: Next generation sequencing was performed to analyze hotspot mutations in different areas of primary melanomas (MMp) and their paired metastases. Clinicopathological features were evaluated depending on the degree of variation of the BRAFV600E mutant allele frequency (MAF) in MMp. Results: In our cohort of 14 superficial spreading, 10 nodular melanomas and 52 metastases, 17/24 (71%) melanomas had a BRAFV600E mutation and 5/24 (21%) had a NRASQ61 mutation. We observed a high variation of BRAFV600E MAF (H-BRAFV600E) in 7/17 (41%) MMp. The H-BRAFV600E MMp were all located on the trunk, had lower Breslow and mitotic indexes and predominantly, a first nodal metastasis. Regions with spindled tumor cells (Spin) and high lymphocytic infiltrate (HInf) were more frequent in the H-BRAFV600E patients (4/7; 57%), whereas regions with epithelial tumor cells (Epit) and low lymphocytic infiltrate (LInf) were predominant (6/10; 60%) and exclusive in the low BRAFV600E MAF variation tumors (L-BRAFV600E). The H-BRAFV600E/Spin/HInf MMp patients had better prognostic features and nodal first metastasis. Conclusions: The H-BRAFV600E MMp were located on the trunk, had better prognostic characteristics, such as lower Breslow and mitotic indexes as well as high lymphocytic infiltrate.

EP.TU.693A rare case of anal melanoma: An entity to be aware of

Aims Anal melanoma is a rare but aggressive malignancy representing a small percentage anorectal cancers. We report a rare case incidentally detected during bowel screening. Methods A 74-year-old female presented for endoscopy after a positive qFIT. She was asymptomatic. During endoscopy, perianal examination revealed a jet black naevus of approximately 3x3cm from 9 to 12’O clock position, overlying the perianal body, involving anal margin to the posterior vagina. General physical, abdominal and rectal examinations were unremarkable. During colonoscopy, a benign polyp was removed from the sigmoid colon. She underwent examination of rectum and vagina under general anaesthetic, and incisional biopsies were obtained. Histopathology confirmed an invasive, superficial spreading malignant melanoma, with a Breslow thickness of 1.5mm and Clark Level IV invasion. Staging CT scans did not reveal metastasis. Following loco-regional MDT discussion, a combined colorectal and plastic surgery was offered. She underwent wide local excision from the posterior vaginal fourchette to the anal canal, bilateral perforator flap reconstruction, and defunctioning sigmoid loop colostomy. Results There were no intraoperative complications. She recovered well post-operatively. After histopathology, her tumour was staged as pT2b, N0, M0. She did not require further treatment post-operatively as per MDTdiscussion. No disease recurrence has been detected yet with 30 months follow up, and she is awaiting reversal of colostomy. Conclusions Prognosis is generally poor in anal melanoma. This case report adds to the limited literature and emphasizs that despite no consensus on management, early detection and surgical resection offers the best chance for favorable outcomes.

Molecular Markers and Targets in Melanoma

Melanoma develops as a result of several genetic alterations, with UV radiation often acting as a mutagenic risk factor. Deep knowledge of the molecular signaling pathways of different types of melanoma allows better characterization and provides tools for the development of therapies based on the intervention of signals promoted by these cascades. The latest World Health Organization classification acknowledged the specific genetic drivers leading to melanoma and classifies melanocytic lesions into nine distinct categories according to the associate cumulative sun damage (CSD), which correlates with the molecular alterations of tumors. The largest groups are melanomas associated with low-CSD or superficial spreading melanomas, characterized by frequent presentation of the BRAFV600 mutation. High-CSD melanomas include lentigo maligna type and desmoplastic melanomas, which often have a high mutation burden and can harbor NRAS, BRAFnon-V600E, or NF1 mutations. Non-CSD-associated melanomas encompass acral and mucosal melanomas that usually do not show BRAF, NRAS, or NF1 mutations (triple wild-type), but in a subset may have KIT or SF3B1 mutations. To improve survival, these driver alterations can be treated with targeted therapy achieving significant antitumor activity. In recent years, relevant improvement in the prognosis and survival of patients with melanoma has been achieved, since the introduction of BRAF/MEK tyrosine kinase inhibitors and immune checkpoint inhibitors. In this review, we describe the current knowledge of molecular pathways and discuss current and potential therapeutic targets in melanoma, focusing on their clinical relevance of development.

599 Intramammary Melanoma Micrometastasis Within A Silicone Implanted Breast

Case Summary Melanoma of the abdominal wall is not uncommon, and sentinel lymph nodes are usually located in the lymphatic drainage basins of the axilla or inguinal region. Less frequently, interval sentinel lymph nodes can be found along the lymphatic vessels between the primary cancer and nearest basin. We present the case of a 53-year-old female with silicone breast implants who underwent scar excision and sentinel lymph node biopsy for a 1mm Breslow thickness superficial spreading melanoma of the abdomen. Two lymph nodes were excised; both lying in the subcutaneous fat at the lateral aspect of the right breast capsule. Lymph node histology revealed a subcapsular melanoma deposit along with silicone lymphadenopathy in the sentinel node, and silicone lymphadenopathy in the second node. Whole body positron emission tomography (PET/CT) and magnetic resonance imaging (MRI) of the brain showed no evidence of metastases or implant rupture. Subsequent MRI breast revealed likely intracapsular implant rupture. The patient was offered removal of implants and remains under follow-up. The unusual location of the sentinel node in our patient highlights the possibility that previous breast augmentation may have altered the pattern of lymphatic drainage to the axilla. In addition, to our knowledge, this is the first reported case of silicone and melanoma deposits in a single sentinel node.

Dermoscopic Criteria, Histopathological Correlates and Genetic Findings of Thin Melanoma on Non-Volar Skin

Dermoscopy is a non-invasive, in vivo technique that allows the visualization of subsurface skin structures in the epidermis, at the dermoepidermal junction, and in the upper dermis. Dermoscopy brought a new dimension in evaluating melanocytic skin neoplasms (MSN) also representing a link between clinical and pathologic examination of any MSN. However, histopathology remains the gold standard in diagnosing MSN. Dermoscopic–pathologic correlation enhances the level of quality of MSN diagnosis and increases the level of confidence of pathologists. Melanoma is one of the most genetically predisposed among all cancers in humans. The genetic landscape of melanoma has been described in the last years but is still a field in continuous evolution. Melanoma genetic markers play a role not only in melanoma susceptibility, initiation, and progression but also in prognosis and therapeutic decisions. Several studies described the dermoscopic specific criteria and predictors for melanoma and their histopathologic correlates, but only a few studies investigated the correlation among dermoscopy, pathology, and genetic of MSN. The aim of this work is to review the published data about dermoscopic features of melanoma, their histopathological correlates with regards also to genetic alterations. Particularly, this review will focus on low-CSD (cumulative sun damage) melanoma or superficial spreading melanoma, high-CSD melanoma, and nevus-associated melanoma.