Rare Variant Of Melanoma Research Articles

Pure and Mixed Variants of Desmoplastic Melanoma: A Single-Center, Retrospective, Clinicopathologic Review.

Desmoplastic melanoma (DM) is a rare melanoma variant. Prognostic indicators and survival vary widely and are further confounded by the histopathologic distinction between pure DM (pDM) and mixed DM (mDM) subtypes. The utility of current treatment guidelines is limited by the lack of evidence-based recommendations. To compare the clinicopathologic characteristics of pure and mixed subtypes of DMs. All cases of DM were identified from the Washington University in St Louis institutional pathology database between January 2000 and September 2022. Fifty-two cases were identified and subsequently categorized as pure ( n = 26) or mixed ( n = 26). Clinical and histopathologic data were collected and compared. There were no differences in demographics or tumor location between pure and mixed subtypes. Patients with mDM were more likely to have mitoses present ( p = .03). There were no differences in Breslow depth, tumor diameter, level of invasion, ulceration, and lymphovascular or perineural invasion. The utilization of sentinel lymph node biopsy ( p = .17) and sentinel lymph node positivity ( p = .67) were also similar. Despite histopathologic distinction between pDM and mDM, these subtypes were found to have similar clinicopathologic characteristics, including similar rates of sentinel lymph node metastasis.

A Subungual Nevoid Melanoma of the Right Hallux from a 65-Year-Old Man: A Case Report.

Nevoid melanoma (NeM) is a rare variant of malignant melanoma characterized by slight cellular atypia, polymorphism, and incomplete maturation. It most frequently occurs on the trunk and arms but rarely on the foot. Here, we report a subungual NeM of the right hallux. A 65-year-old man presented with severe pain of 6 months' duration to his right great toe following self-treatment for an ingrown nail. He was evaluated and treated with debridement of the toenail at an urgent medical center 3 months prior. However, this had not relieved his pain. The patient also noticed discoloration of his distal great toe over the past 3 months. Removal of part of the ingrown nail revealed a pigmented mass extending distally from the matrix. Surgical excision of the mass was performed because of the concern for malignancy. The diagnosis of NeM was based on histologic analysis along with enhanced diagnostic modalities. The patient was further treated with surgical amputation of the great toe and anti-programmed cell death-1 therapy. The patient had no relapse at 1-year follow-up. Nevoid melanoma is a rare variant of malignant melanoma on the toes, which needs to be differentiated from a nevus with atypia, with a variety of modalities including cellular and molecular profiling. The optimal treatment is amputation.

Dedifferentiated primary melanoma with rhabdoid features: a case report and literature review

Rhabdoid melanoma is an aggressive, rare variant of melanoma. Herein, we describe a case of rhabdoid melanoma and review the clinicopathological features of this neoplasm. A 59-year-old Caucasian female presented with a large cavitary wound located on her right posteromedial upper torso. Light microscopy of the lesion revealed patternless sheeting of neoplastic cells with cytoplasm containing eosinophilic inclusions and peripherally located large round-to-oval nuclei. Tumor cells stained positive for S100, Sox10, myoD1, desmin, and vimentin. CT imaging of the abdomen, chest, and pelvis demonstrated bilateral cannonball lung tumors, bilateral axillary and mediastinal lymphadenopathy, and a soft tissue mass involving the left upper back. These findings were consistent with a diagnosis of metastatic rhabdoid melanoma, which ultimately resulted in the patient’s demise. Increased awareness of this rare entity is crucial to the practicing physician in order to enhance recognition and provide the best possible healthcare to affected individuals.

PRAME Expression as Helpful Immunohistochemical Marker in Rhabdoid Melanoma.

Background: Rhabdoid melanoma is a rare variant of malignant melanoma with characteristic cytomorphologic features. Due to the potential loss of conventional melanocytic markers, histopathologic diagnosis is often challenging. We hypothesize that immunostaining for PReferentially expressed Antigen in MElanoma (PRAME) might have the potential to uncover the melanocytic origin of these dedifferentiated tumors. Methods: Four cases of rhabdoid primary melanomas were assessed by immunohistochemistry for expression of PRAME and conventional melanocytic markers. Immunohistochemical expression patterns were analyzed in the rhabdoid primaries and, if available, associated metastases. Results: All four cases of rhabdoid primary melanomas showed a strong nuclear positivity for PRAME, while the expression of conventional melanocytic markers S100, MART-1, SOX-10 and HMB-45 was variable between the analyzed cases. Conclusions: In summary, we report four cases of rhabdoid primary melanoma with high to intermediate expression of PRAME despite the partial and variable loss of other melanocytic markers. Hence, PRAME might facilitate the recognition of this highly aggressive entity to avoid misdiagnosis due to histopathologic pitfalls.

Dermoscopic features of nevoid melanoma: a retrospective study.

Nevoid melanoma (NeM) is a rare variant of melanoma resembling melanocytic nevus. The aim of the study was to systematically review the dermoscopic features of NeM. A hospital-based retrospective study was conducted. Dermoscopic features of NeMs diagnosed through excisional biopsy between January 2015 1, and March 1, 2021, were compared to superficial spreading melanomas (SSMs) matched by Breslow's thickness. Then, a literature search was performed. Electronic searches on PubMed database via Medline were conducted to retrieve any manuscript reporting detailed dermoscopic features of histopathologically confirmed NeM. A total of 60 malignant melanomas (MM) comprising 20 NeM and 40 SSM were collected. Twelve out of 20 (60%) NeM showed a nevus-like appearance, including reticular and globular patterns, and in 35% of these cases it was detected because of dermoscopic changes. Then, a total of seven original manuscripts were retrieved from the literature review, comprising 56 cases overall. NeM showed nevus-like pattern in 53% of the cases, multicomponent pattern in 21% and amelanotic in 9%. Enlargement, irregularly distributed dots/globules, irregular pigmentation, and atypical vascular pattern were found in NeM with nevus-like appearance. NeM with multicomponent pattern were characterized by irregular pigmentation, blue-white veil, irregular dots and atypical vascular pattern. Amelanotic NeM is rare and show atypical vascular pattern and milia-like cysts. Dermoscopy of NeM is challenging as it frequently shows a nevus-like pattern, but clues and detection of dermoscopic changes may help to identify it.

Syringotropic Melanoma: A Diagnostic Challenge With Prognostic Implications.

The presence of neoplastic melanocytes within the eccrine apparatus into the reticular dermis and/or subcutaneous tissue is extremely rare. The staging of syringotropic melanomas and their biological behavior are still controversial. We present 6 new cases of syringotropic melanoma and their main histopathologic features; review the previous literature; and discuss about the origin, staging, and prognosis of this rare variant of melanoma.

NCOG-57. NEUROPSYCHOLOGICAL FUNCTION IN MENINGEAL MELANOCYTOMA: A CASE REPORT

Abstract Meningeal melanocytomas are rare tumors derived from leptomeningeal melanocytes. The aggressive subtype is considered a rare variant of malignant melanoma, carrying a poor prognosis. To date, the extant literature is void of any studies that have systematically assessed cognition or neuropsychological function in these patients. We present a case report of a 61-year-old male, right-hand dominant, Caucasian male with 16 years of formal education. He has an unremarkable medical history, and his presenting symptom were syncopal episodes. An extensive work-up revealed a complex pineal region mass. Serum markers (CEA, AFP, and beta HcG) were negative. The patient continued to deteriorate neurologically and underwent a gross total resection of the mass. At the time of resection, there was evidence of definitive leptomeningeal dissemination. Because of the leptomeningeal spread, he underwent whole brain radiation therapy with a boost to the cerebellum and surgical site. He subsequently required implantation of a ventriculoperitoneal shunt for treatment of communicating hydrocephalus. Prior to WBRT, the patient underwent comprehensive neuropsychological testing. According to the patient and his spouse, they estimated functioning at approximately 50% of normal cognition, with precipitous decline noted prior to resection of the lesion. At the time of the exam, he was dependent in essentially all instrumental activities of daily living. The examination identified a pattern consistent with diffuse subcortical involvement, characterized by impairments in cognitive processing speed, attention, working memory and executive function. Conversely, the patient demonstrated no amnesia or higher cortical dysfunction. Moreover, mood, anxiety, or other psychopathology failed to account for his cognitive impairment. In our review, this is the first case in the literature of a patient with meningeal melanocytoma (with leptomeningeal spread) who has been comprehensively assessed neuropsychologically. Conceptualizations, treatment, and prognosis will be discussed.

Lack of distinct molecular profile of Primary Dermal Melanoma

Primary dermal melanoma (PDM) is a rare variant of melanoma which simulates metastatic melanoma to the skin. Diagnosis of PDM cannot be established on histologic grounds alonebut requires absence of evidence of melanoma elsewhere by clinical history and/or imaging studies. Despite this entity being clinically well documented, limited data on molecular characterization are available. We performed comprehensive mutation and copy number variation analysis in a series of PDMs in search for distinctive molecular features.Studies were approved by respective institutional review boards. Six cases fulfilling strict histologic criteria of PDM were identified in patients with absent history of melanoma elsewhere, negative sentinel lymph node biopsies and imaging studies. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue, and five cases passed quality control measures and were subjected to targeted exon sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets 410 panel. Two of five PDM carried NRAS hotspot mutations characteristic of cutaneous melanoma (CM) genomic subtypes. One case showed a probable low-activating NRAS mutation in combination with additional aberrations in other mitogen-activated protein kinase (MAPK) pathway effectors. Hotspot mutations were also identified in the TERT promoter region, and one tumor showed a mutation in the SWI/SNF remodeling complex. No oncogenic mutations were identified in one case. Furthermore, none of the tumors analyzed showed activating mutations in Gα subunits, including GNAQ and GNA11. Copy number alterations included deletions of Chr 9p, characteristic of CM.Despite PDM showing mutational heterogeneity, our findings suggest predominance of MAPK pathway aberrations in agreement with the mutational profile of CMs in general. Given the absence of genetic overlap with other distinct primary dermal melanocytic proliferations, mutational profiling will unlikely aid in the difficult differential diagnosis of PDM versus melanoma metastasis. Thorough metastatic workup remains crucial in establishing this rare diagnosis.

Primary Malignant Melanoma of the Breast: Mankweng Breast Oncology Experience

Malignant melanoma is predominantly a cutaneous and mucous membrane disease. In this case report, we seek to explore and share our local experience of primary malignant melanoma of the breast and give a literature review on the standard of care as well as to stimulate physician awareness. Our interest is on the appreciation of the current lack of set guidelines on how to work-up patients that present with this rare variant of malignant melanoma and to highlight its management.We present here a rare case of a 62 years old female with the primary malignant melanoma of the breast (PMMB).

Analysis of the Correlation Between Metastasis-Related Genes and Immune Infiltration of Uveal Melanoma Using the Weighted Gene Co-Expression Network Analysis and Single Sample GSEA Algorithms

Uveal melanoma is a rare variant of melanoma that primarily occurs in the uvea (including choroid, ciliary body and iris) of the eye. It readily metastasizes to distant organs, especially the liver. Currently, there is no effective treatment for metastatic UVM. Recent studies have revealed that there is an immunoinflammatory phenotype in the UVM microenvironment. Understanding the inflammatory process related to the growth of uveal melanoma and its metastasis may lead to new therapies. During the development of most solid tumors, immune cells and fibroblasts infiltrate into the tumor tissue, promote a tumor microenvironment, activate an immunosuppressive system that includes Treg cells by secreting cytokines, promote tumor angiogenesis, and provide convenient conditions for tumor development and metastasis. In this study, WGCNA analysis was used to identify the types of infiltrating cells in the UVM microenvironment. These included T cells, B cells, tumor-related fibroblasts, HSC, and macrophages. Of these, HSC are important infiltrating cells in UVM. They may be regulated by the cycle genes ANLN and FOXM1 and participate in the development and metastasis.

An interesting case of melanoma with divergent differentiation aberrantly expressing calretinin stain

Metaplastic melanoma or melanoma with divergent differentiation is a rare variant of melanoma with a wide spectrum of mesodermal and ectodermal differentiation. This is a case of metaplastic melanoma with aberrant expression for calretinin stain in the chondroid component and malignant cells adjacent to it. The finding of calretinin positivity in melanoma could be useful in diagnosing metastatic metaplastic melanoma. The awareness of the possibility of aberrant calretinin positivity in metaplastic melanoma with chondroid differentiation is critical to avoid a potential pitfall in misdiagnosing metaplastic melanoma as sarcoma or mesothelioma.

Desmoplastic melanoma

Desmoplastic melanoma is a rare variant of malignant melanoma that accounts for 1-5% of all forms of this neoplasm. It usually affects patients in the 6th and 7th decades of life. A 42-year-old female patient with progressive scalp lesion and diagnosis of desmoplastic melanoma is described, presenting good evolution with immunotherapy using Pembrolizumab, avoiding surgical treatment.

Pathologic Characteristics of Spitz Melanoma With MAP3K8 Fusion or Truncation in a Pediatric Cohort.

Spitz melanoma is a rare variant of melanoma defined by distinct clinical, histologic, and genetic features and affecting patients of all ages. Half of these tumors are driven by fusion of kinase genes including ALK, NTRK1/3, ROS1, RET, MET, or BRAF. We recently reported recurrent fusion or truncation of the potentially targetable serine-threonine kinase gene MAP3K8 in 33% of Spitz melanomas. Here we describe the histologic features of these MAP3K8-rearranged tumors (16 pediatric Spitz melanomas; 1 atypical Spitz tumor), using hematoxylin-eosin slides, p16 immunohistochemistry, and CDKN2A fluorescence in situ hybridization. The lesions consisted of a compound melanocytic proliferation, ranging in thickness from 1.5 to 13.4 mm (median, 3.1 mm), with 8 having a predominant dermal and 3 having a predominant junctional component. The predominant cell type was epithelioid (94%). The epithelioid melanocytes were generally monomorphic and amelanotic, arranged in expansile epithelial aggregates, confluent hypercellular nests, or enlarged syncytial nodules in the dermis. Ulceration was present in 9 of 17 tumors (53%) and deep mitotic figures were seen in 15 of 17 tumors (88%). Complete loss of p16 expression and homozygous CDKN2A deletion were observed in 82% and 70% of tumors, respectively. Recognition of MAP3K8-altered Spitz melanoma may thus be facilitated by these morphologic features, most notably presence of cohesive cellular nodules in the dermis and an epithelioid-cell phenotype.

Desmoplastic melanoma.

Desmoplastic melanoma (DM) is a rare melanoma variant that has unique biology and pathology compared with conventional melanoma (non-DM). Importantly, DM is classified into pure and mixed histologic subtypes, which have been correlated with outcomes. Management of DM broadly mirrors that of non-DM; however, there are unique considerations for DM that influence treatment approaches. This paper will provide a contemporary overview of this disease and will review the literature regarding the management of DM.

In situ nail unit melanoma: epidemiological and clinic-pathologic features with conservative treatment and long-term follow-up.

Nail unit melanoma (NUM) is a rare melanoma variant, usually associated with a poor prognosis because of a delayed diagnosis. Few data are available concerning the management and long-term outcome of in situ NUM. To use a large cohort to provide comprehensive patient data and long-term follow-up information. This will serve to investigate distinctive epidemiological, clinical and histological features of in situ NUM. To report treatment modalities, assess conservative surgery and evaluate its long-term safety. Patients with confirmed diagnosis of in situ NUM were retrospectively reviewed. Demographics, clinical presentation, therapeutic data and follow-up were analysed. Sixty-three cases of in situ NUM were identified as follows: 44 were women (70%), with a mean age of 51 years. The mean duration of symptoms prior to consultation was 4.3 years [range 3 months-28 years]. Clinically, with 58 cases, i.e. (92%) longitudinal melanonychia was the most common clinical presentation. The thumb was the most affected digit, being afflicted in 28 cases: 44%. Medical history found a widening and/or recent darkening of the melanonychia in 46 cases (82%). The treatment consisted of, respectively, 56 En bloc excisions of the nail apparatus 89% of the patients we studied, and seven amputations of the distal phalanx. During the follow-up period (mean: 10 years), two patients presented in situ recurrences. The recognition of a NUM at an in situ stage allows early treatment and curing of this tumour. At this early stage, a 'functional surgery' is a rational approach with an excellent oncologic safety.

Primary myxoid melanoma with dermoscopic findings.

Myxoid melanoma is a rare variant of melanoma, which is characterized by atypical spindle cells and dense mucin deposition in dermis. This tumor is usually seen in elderly people with a similar progress in other variants of melanoma.A 28-year-old male presented to our outpatient clinic with a 6-month history of a slowly growing asymptomatic pink lesion on his arm. Dermoscopic examination revealed pink-white cristalline structures and blue-grayish ovoid globules. The lesion was totally excised with initial diagnosis of basosquamous carcinoma, amelanotic melanoma and basal cell carcinoma. Histopathological examination was consistent with myxoid melanoma.We present this case due to the rarity of myxoid melanoma and occurrence at such a young age.

Histopathological diagnosis of acral lentiginous melanoma in early stages.

Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma.

Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma. We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing. Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL. The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. ©2015 AACR.

NF1 Mutations Are Common in Desmoplastic Melanoma.

Desmoplastic melanoma (DM) is a rare variant of melanoma with distinct clinical, histopathologic, and immunohistochemical features. Clinically, DM differs from conventional melanoma by a higher propensity for local recurrence and less frequent metastatic spread to regional lymph nodes. In its pure form, DM has a distinct appearance displaying a low density of fusiform melanocytes in a collagen-rich matrix. Whereas a number of mutations have been identified in primary melanoma, including BRAF, NRAS, GNAQ, GNA11, and KIT, and the occurrence of these mutations has been found to correlate to some extent with the histopathologic features, anatomic site, and/or mode of sun exposure, no distinct set of mutations has so far been reported for DM. To study the potential association of neurofibromin (NF1) mutations with DM, we examined 15 desmoplastic and 20 non-DMs by next-generation sequencing. Mutations of the NF1 gene were found in 14 of 15 (93%) DMs and 4 of 20 (20%) non-DMs. The high frequency of NF1 mutations in DMs suggests an important role for NF1 in the biology of this type of melanoma.

Primary Malignant Melanoma of Vagina Treated by Total Pelvic Exenteration.

Primary malignant melanoma of vagina is a rare variant of melanoma and usually associated with a grave prognosis. Radical surgery is the only treatment option with reasonable loco regional control. A case of primary malignant melanoma involving whole of vagina infiltrating urethra and reaching up to vulva was treated by surgery and postoperative radiotherapy. The tumor was infiltrating bladder and rectum reaching the anal sphincter. Total pelvic exenteration was done to achieve tumor-free surgical margins. One year after treatment, patient is disease free.