Malignant Melanoma Presenting as a Parotid Mass in a Middle-aged Woman with Metastasis to the Breast

Introduction: Malignant melanomas of the parotid gland are relatively uncommon and usually seen as metastases from cutaneous or mucous sites of the head and neck region. Some malignant melanomas may metastasize before they regress. Therefore, identifying the primary origin of metastatic melanoma is sometimes difficult. Furthermore, metastasis to the breast from an extramammary site is uncommon and challenging. It may present as a well-defined rounded mass that histopathologically mimics the various architecture and cellular phenotypes. In addition, the immunohistochemical stains of some metastatic melanomas are equivocal and challenging. Case Presentation: We presented a case of parotid gland malignant melanoma in a 42-year-old woman with metastasis to the breast in a short interval. Biopsy of parotid and breast lesions showed loss of immune-reactivity for several melanoma markers and was initially considered as malignant peripheral nerve sheath tumor and primary breast tumor, respectively. Conclusions: This case highlights the importance of obtaining past clinical history in surgical pathology cases to make a correct diagnosis. It also enhances our understanding regarding malignant melanoma as a mysterious tumor with various morphology and immunophenotype.

Clinicopathological Demographics of Malignant Melanoma of the Vulva and Vagina in Japan

Objective: Malignant melanomas of the vulva (VuM) and vagina (VaM) represent a unique subgroup of rare malignant melanomas with critical biological properties and treatment differing from that of other cancers. In Japan, adequate surveys on these have not been performed. The objective of this study was to elucidate the clinicopathological demographics and the outcomes of VuM and VaM in Japan.Methods: This retrospective observational study included women with invasive VuM or VaM, identified from older medical records in Japan. Clinical data were collected and the Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Univariate and multivariate regression models were used to identify factors significantly related to survival.Results: A total of 217 patients were identified: 109 (50.2%) with VuM and 108 (49.8%) with VaM. The median PFS was 16.8 months in patients with VuM (95% confidence interval [CI] 23.1-87.7) and 15.6 months in patients with VaM (95% CI 8.4-12.6). The median OS was 43.9 months (95% CI 60-138) and 31.1 months (95% CI 24.8-45.3) in patients with VuM and VaM, respectively. Multivariate analysis showed that a >III American Joint Committee on Cancer (AJCC) disease stage (hazard ratio [HR] = 2.063; 95% CI = 0.995-4.278) was associated with poorer PFS, and unknown surgical margin was the only independent factor influencing OS (HR = 2.188; 95% CI = 1.203-3.977).Conclusions: The overall outcomes of VuM and VaM remain poor in Japan. The AJCC stage and the surgical margin are significant predictors of survival.

Quantitative Expression of TYR, CD34, and CALD1 Discriminates Between Canine Oral Malignant Melanomas and Soft Tissue Sarcomas

Canine oral malignant melanomas (OMMs) exhibit a variety of morphologic phenotypes, including a spindloid variant. The microscopic diagnosis of spindloid OMMs is based on junctional activity and/or the presence of melanin pigment. In the absence of these features, spindloid OMMs are difficult to differentiate from soft tissue sarcomas (STS). An antibody cocktail (MDX) that includes Melan-A, PNL2, and tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2) is the current gold standard for identifying amelanotic OMMs by immunohistochemistry (IHC). However, MDX is less sensitive for diagnosing spindloid amelanotic OMMs. This raises concern for biopsy specimens that lack overlying epithelium, making it potentially difficult to differentiate OMM from STS by IHC. The goal of this study was to identify additional markers to help differentiate between STS and OMMs that lack pigment and junctional activity. SOX-10 has recently been proposed as a sensitive marker for melanocytes in humans but has not been validated in dogs. Similarly, RNA expression for various genes has been analyzed in humans, but not in the context of diagnosing canine melanocytic neoplasms. For this retrospective study, formalin-fixed, paraffin-embedded tissues from 20 OMMs, 20 STS, and 20 oral spindle cell tumors (OSCTs) that lacked junctional activity and pigmentation were selected. IHC for MDX, SOX-10, and laminin, in parallel with RT-qPCR of TYR, SOX10, CALD1, CD34, DES, and LAMA1, was performed in all cases. TYR, CD34, and CALD1 were the most discriminatory genes in differentiating between OMM and STS, all having 100% specificity and 65, 95, and 60% sensitivity, respectively. While all 20 OMMs were immunohistochemically labeled for SOX-10, two STS were also labeled (100% sensitivity and 90% specificity). MDX IHC labeled all 20 OMMs and no STS. Surprisingly, none of the 20 OSCTs expressed TYR RNA above the cutoff, and 14/20 OSCTs expressed CALD1 or CD34 RNA above the cutoff, thereby confirming them as STS. Four OSCT were suspect STS, and no OSCTs were confirmed as OMMs based on IHC and RNA expression patterns. In conclusion, the RNA levels of TYR, CD34, and CALD1 should be evaluated in suspected amelanotic OMMs that are negative for MDX to accurately differentiate between OMM and STS.

Expression of S100, HMB45 and Melan A in Oral Mucosal Melanoma

Background: Malignant melanomas of the oral cavity are rare tumours. The diagnosis of mucosal melanoma can be difficult especially when it presents itself in its amelanotic form. Methodology: An electronic search was carried out on Pubmed and Medline database to find studies addressing this question published between Jan 2001 and April 2020. Multiple studies are done to determine the staining and positivity of the above mentioned three markers were found. A total of 4 studies were finally selected for this review which tried to determine the efficiency of these three markers in the diagnosis of oral mucosal melanomas. Results: The patient’s data that stained positive S100, HMB45 and Melan A from 4 studies were selected. Conclusion: S100 continues to remain the most sensitive marker for melanoma with its promising ability in diagnosing the desmoplastic variant. The lack of specificity is still a drawback of S100.

Correlation Between KIT Expression and c-Kit Mutations in 2 Subtypes of Canine Oral Melanocytic Neoplasms

c-Kit mutations have been reported in 15% to 40% of certain human melanoma subtypes, including those histologically similar to canine oral malignant melanomas. Therapeutic response to tyrosine kinase inhibitors has been demonstrated in those human patients. As canine oral malignant melanomas tend to have a poor prognosis despite aggressive surgical removal, evaluation of KIT expression and identification of c-Kit mutations in canine oral melanocytic neoplasms was performed to determine if there is any indication that tyrosine kinase inhibitor drugs might effectively treat any of these cases. This study evaluated 27 canine oral malignant melanomas and 12 canine histologically well-differentiated oral melanocytic neoplasms for activating c-Kit mutations, determined differences in immunohistochemical expression of KIT and c-Kit mutation status, and determined if KIT expression could predict c-Kit mutation status. Among samples that contained intraepithelial nests of neoplastic melanocytes in the KIT-labeled sections, KIT was expressed within cells in these nests in 22/23 (96%) malignant melanomas and 5/7 histologically well-differentiated neoplasms. KIT was expressed in 10% to 30% of neoplastic melanocytes in the lamina propria in 3/24 (13%) malignant melanomas, but 0/9 (0%) histologically well-differentiated neoplasms. Next-generation sequencing identified 85 variants in c-Kit, including 9 nonsynonymous mutations that resulted in amino acid changes predicted to affect protein function. c-Kit mutations with predicted deleterious protein effects were more common in malignant melanomas (8/27 [30%] vs 1/12 [8%]). There was no apparent relationship between detected c-Kit mutations and KIT expression. These results do not support the use of therapies that target c-Kit.

Duodenal Metastasis From a Rectal Malignant Melanoma Primary: A Case Report

Duodenal melanoma constitutes a very small number of gastrointestinal malignant melanomas. The small intestine is a common site for the metastatic spread of cutaneous melanomas; however, its metastatic involvement from a primary rectal melanoma origin has seldom been reported. We present the histopathologic features of an unusual case of primary rectal melanoma metastasizing to the duodenum.