Case Of Primary Melanoma Research Articles

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.

Epidemiology and Molecular Profile of Mucosal Melanoma: A Population-Based Study in Southern Europe.

Simple SummaryThere are few population-based studies focused on the epidemiology of mucosal melanoma, a rare neoplasm. Its poor prognosis, the different etiology from cutaneous melanoma and the lack of effective treatment beyond corrective surgery, make the knowledge of the mutational profile of this type of cancer a useful tool in understanding its natural history and also for the investigation of new target therapies. The aim of our population-based study is to analyze the incidence and survival of mucosal melanoma, which mainly arises from the head and neck sphere, genitourinary tract and rectal area, and to carry out the mutational analysis of selected cases. We used the Girona Cancer Registry database, which registered all cancer cases in Girona, a province of Spain in southern Europe, during the period of 1994–2018.Background: Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but the prognosis is worse than that of skin melanoma. The analysis of mucosal melanoma’s mutational profile can help to develop target therapies in advanced disease or adjuvant settings. Methods: We analyzed the database of the Cancer Registry of Girona, a region located in the north-east of Spain, in the period of 1994–2018. We selected cases of primary invasive melanoma, excluding those located in the skin, eye, central nervous system and an unknown primary site. Epidemiological analysis included incidence and survival. Mutational profile analysis was performed with a custom gene panel. Results: Forty-two patients were identified: 14 (33%) had vulvar-vaginal melanoma, 15 (35.7%) had rectal melanoma, 12 (28.6%) had melanoma located in the head and neck sphere and 1 male patient had a urethral melanoma. European age-standardized incidence rates for vulvar-vaginal, rectal and head and neck melanoma were 0.09, 0.1 and 0.09 cases/100,000 inhabitant-years, respectively. Five-year observed survival rates were 37.5%, 20% and 25% for these types of cancers. NRAS Q61 was the most frequent mutation found. Conclusion: Our study confirms the steady incidence and low survival of mucosal melanomas in a region of southern Europe. NRAS and NF1 play a role in the molecular landscape of mucosal melanoma. MEK and PI3K/mTOR inhibitors could be reasonable treatment options and are being studied in clinical trials.

Melanocytic lesions of the central nervous system: a case series.

Melanocytic lesions of the central nervous system (CNS) are an infrequent, broad and diverse group of entities, both benign and malignant, found in all age groups, with imaging findings ranging from well-circumscribed focal lesions to diffuse leptomeningeal involvement. On MRI, they are usually distinguished by a high signal on T1WI sequences, given the paramagnetic effect of melanin, thus making it difficult to differentiate among them. To describe the imaging and epidemiological characteristics of a retrospective series of CNS melanocytic lesions. MR images of 23 patients with CNS melanocytic lesions diagnosed between January 2012 and June 2018 were analyzed. Most patients were female (14/23; 61%), with a median age of 47 years (range: 3 weeks to 72 years). The primary melanocytic lesions accounted for 8/19 cases (42.1%), which included neurocutaneous melanosis, meningeal melanocytomas and primary malignant melanomas. Secondary melanocytic lesions (metastatic) accounted for 10/19 cases (52.6%). There was one case of a tumor with secondary melanization, from a melanocytic neuroectodermal tumor of infancy. There were also four cases of primary ocular melanomas. The most frequent findings were the cerebral location, high T1WI signal and marked contrast-enhancement. The present review describes the wide variety of melanocytic lesions that could affect the CNS, emphasizing the MRI characteristics. Knowledge of the imaging, clinical and epidemiological characteristics of CNS melanocytic lesions is essential for their correct interpretation, given the significant overlap between lesion features and the variable prognosis.

A Case of Primary Malignant Melanoma of the Esophagus with Essential Thrombocythemia

症例は74歳の男性で，食事のつかえ感と体重減少を主訴に近医を受診．上部消化管内視鏡にて食道胸部中部から胸部下部の腫瘤を指摘，精査加療目的で当院へ紹介．術前の画像では，不整潰瘍を有する9cmの腫瘍性病変の診断であったが，生検では悪性所見は認めなかった．また，以前より血小板増多を指摘されており，当院初診時の血小板が高値であった．骨髄生検の所見，血液遺伝子検査の結果，骨髄増殖性腫瘍の一病型である本態性血小板血症の診断となった．食道の腫瘍性病変の術前診断でcytoreductive therapyを開始し，血小板数をコントロールの上，安全に胸腔鏡下食道亜全摘術が可能であった．血栓症や出血などの合併症なく，経過は順調で退院となった．

Primary gastric mucosal melanoma: A rare histopathological diagnosis

Primary mucosal melanoma in the gastrointestinal (GI) tract is very rare, as most of the melanomas diagnosed in the GI tract are metastases, secondary to cutaneous melanomas. We report a rare case of primary gastric mucosal melanoma in a 58-year-old male patient who presented with a short history of upper abdominal tightness and pain for 15 days. Upper GI endoscopy revealed a polypoid mucosal mass with ulceration at the gastric antrum of 2 cm × 2 cm dimension, which was diagnosed histopathologically as malignant melanoma. A detailed clinical and laboratory workup did not reveal any other primary site elsewhere and there was no relevant history suggesting a cutaneous melanocytic lesion. Upper GI endoscopy and microscopic tissue examination with immunohistochemistry formed the mainstay of diagnosis of this exceedingly rare neoplasm.

Changing epidemiology and age-specific incidence of cutaneous malignant melanoma in Lithuania: an analysis of national cancer registration data by gender and anatomical site, 1991–2015

The purpose of this study was to investigate the gender-specific and anatomical site-specific incidence of cutaneous melanoma. All cases of primary skin melanoma reported to the Lithuanian Cancer Registry during the period 1991-2015 were included. For the analyses, patients were categorized by sex and melanoma site. Overall age-standardized rate (ASR) of melanoma in the trunk increased 0.8-3.3, while in limbs the ASR increased 1.0-3.4. The highest increase in new cases per 100,000 population (in both sexes) was detected in limbs and it increased over time (from 2.01 per 100,000 in 1991 to 3.65 per 100,000 in 2015). The highest increase in the number of new cases was in limbs with ASR, with a more than 3-fold increase from 1991-2015 (1.4-4.6). A statistically significant increase was observed in mortality of skin melanoma between 1991 and 2015, with the highest annual percentage change (APC) of 5.5 in the trunks of men (95% CI: 5.2-5.9; p < 0.05) and women with APC 3.9 (95% CI: 3.5-4.4, p < 0.05). In our study, we found higher incidence rates of skin melanoma in females. Melanoma was more commonly diagnosed in the trunk of males and limbs of females, with the highest mortality increase in trunk melanoma in both genders.

Primary Small Bowel Melanoma or Small Bowel Metastasis with Vanishing Primary Cutaneous Lesion

The small bowel represents one of the main sites for cutaneous melanoma metastasis; however, numerous cases of primary intestinal melanoma have recently been described. In view of this, we present the case of a 39-year-old woman admitted for nausea, heartburn, abdominal pain, change in bowel habits and weight loss. Contrast-enhanced CT revealed a small bowel mass. Surgical resection of a 6 cm ileal tumour with regional mesenteric lymphadenectomy and end-to-end anastomosis was performed. Histopathological findings indicated the presence of an ileal melanoma metastasis. Subsequent dermatological examination identified a cutaneous lesion on the right forearm, however no malignant cells were found at the histopathological exam. Whole body PET CT with FDG identified multiple frontal and parietal lesions. Genetic testing was positive for BRAF gene V600 E mutation. The patient underwent multiple neurosurgical procedures for the resection of cerebral metastases. Palliative external radiation and chemotherapy was also attempted. After approximately 2 years after the diagnosis, the patient died following multiple episodes of intracranial hypertension.

Magnetic Resonance Imaging findings in Primary Extracutaneous Melanoma from a Tertiary Cancer Care Centre: A Retrospective Cohort Study

Introduction: Extracutaneous melanomas are rare, aggressive type of tumour, clinically and biologically distinct from their cutaneous counterpart. The two large broad categories of the extracutaneous melanomas are ocular and mucosal subtypes. Melanomas are classically hyperintense on T1 weighted images and hypointense on T2 weighted images due to the paramagnetic effects of melanin and presence of paramagnetic elements. Aim: To describe the Magnetic Resonance Imaging (MRI) findings in primary extracutaneous melanomas at various anatomic sites. Materials and Methods: This was a retrospective study in which 13 cases of primary extracutaneous melanomas were identified from Picture Archiving and Communication System (PACS) archive over a period of eight years (January 2013 - December 2020). Location and morphology of the tumour, signal intensity characteristics in T1 weighted, T2 weighted (hyperintense/ isointense/hypointense to adjacent muscle) and Diffusion Weighted Imaging (DWI) (presence or absence of diffusion restriction) were analysed. Results: The ocular melanomas (n=2) were seen as well-defined small intraocular mass attached to the choroid. The mucosal melanomas of the nasal cavity (n=2), rectum (n=4), vagina (n=3) and cervix (n=2) presented as large intraluminal polypoidal masses. Three categories of MRI appearances emerged in this study. Majority of the cases (n=8) showed hyperintense signals in T1- weighted images and hypointense signals in T2 weighted images (category 1). Diffusion restriction was seen in all cases (n=13) with low Apparent Diffusion Coefficient (ADC) values which ranged from 439-966 mm/sec with an average value of 755 mm/ sec. Conclusion: T1 and T2 shortening are typical of melanoma, the absence of these does not exclude the diagnosis. Although diffusion restriction and low ADC values help in the diagnosis of these tumours, they do not tend to play a specific role in the diagnosis.

English

Malignant melanomas mostly begin as an oculocutaneous lesion and then metastasise to other sites over time. Gastrointestinal melanomas are rare but primary intestinal melanomas are extremely rare. They account for 1 - 3 % of malignant tumours of GI tract.1,2 Although few cases have been reported, the existence of primary intestinal melanoma is still doubtful. It is difficult to differentiate between primary and secondary intestinal melanomas based on their clinical picture alone. Some authors believe that the metastatic melanoma into the intestine manifest symptoms in the patient after complete regression of some old cutaneous lesion.3,4 But some believe that primary melanoma of small intestine originates from Schwannian neuroblast cells, neural crest melanoblasts, or amine-precursor uptake and decarboxylation (APUD) cells through neoplastic changes.5,6 They are unrecognized until late due to absence of symptoms, but if symptoms occur, they include abdominal pain, gastrointestinal bleeding and sometimes with intestinal obstruction and few present acutely with perforation. By any origin, malignant melanoma is an aggressive tumour with very poor prognosis and low survival rates, even after surgery. Here we report a case of primary intestinal melanoma in a young patient who presented as intussusception of small intestine.

A case of primary malignant melanoma of the esophagogastric junction with abscopal effect after nivolumab administration

BackgroundThe abscopal effect is a rare phenomenon in which local irradiation causes tumor regression outside the irradiated area. There have been no reports of abscopal effect in patients with gastrointestinal melanoma with metastasis. Here, we report a case of primary malignant melanoma of the esophagogastric junction with abscopal effect after long-term treatment with nivolumab.Case presentationA 75-year-old woman was referred to our hospital with a gastroesophageal lesion. Upper gastrointestinal endoscopy revealed a raised lesion on the posterior wall of the greater curvature of the cardia and tenderness in the lower esophagus. Immunostaining of the tumor biopsy showed positive staining for Melan-A, human melanoma black-45 (HMB45), and S-100, indicating malignant melanoma of the esophagogastric junction. Contrast-enhanced computed tomography (CT) of the abdomen showed a mildly stained lesion protruding into the cardiac part of stomach and enlarged surrounding lymph nodes. The patient was diagnosed with malignant melanoma of the esophagogastric junction and proximal gastrectomy with lower esophagus resection was performed. Histological examination showed large, round tumor cells with nuclear atypia. Immunostaining was positive for Melan A, HMB45, S-100 protein, and SRY-box transcription factor 10, and the final diagnosis was malignant melanoma of the esophagogastric junction, with regional lymph node metastases. Three months after surgery, follow-up CT indicated left pleural metastasis; therefore, the patient was administered nivolumab, an immune checkpoint inhibitor (ICI). Following three courses of nivolumab, the patient exhibited grade 3 renal dysfunction (Common Terminology Criteria for Adverse Events version 5.0). After that, we have not administered nivolumab treatment. Five months after the development of renal dysfunction, a CT scan demonstrated an unstained nodule within the pancreatic, and the patient was diagnosed with pancreatic metastasis; intensity-modulated radiotherapy was performed. Six months later, CT revealed pancreatic nodule and pleural metastasis was shrunk; after an additional 2 months, pleural metastasis and effusion had disappeared. The patient is alive with no additional lesions.ConclusionsWe report a case of primary malignant melanoma of the esophagogastric junction with an abscopal effect following nivolumab treatment. The findings of this case report suggest that ICIs in combination with radiotherapy may be effective for treating metastatic or recurrent malignant melanoma of the gastrointestinal tract.

Primary orbital melanoma arising in an atypical diffuse (plaque-like) blue naevus/melanocytosis: a case report and review of literature

BackgroundPrimary orbital melanoma is a rare disease and can occasionally develop from a pre-existing neoplasm of the blue naevus family of melanocytic lesions.Case presentationHerein we report a rare case of primary orbital melanoma arising from an unusual atypical diffuse (plaque-like) blue naevus/melanocytosis. A 27 year old man presented with mild pain and swelling of the left eye. Magnetic Resonance Imaging revealed a left lateral episcleral orbital mass and an incisional biopsy confirmed the diagnosis of malignant melanoma. Skin-sparing total left orbital exenteration was performed. Histopathological examination of the exenteration specimen revealed a primary orbital melanoma arising in a pre-existing blue naevus like melanocytosis.We demonstrate the evidence for histological progression, characterise the molecular profile of this tumour and discuss the related literature.ConclusionsThis case emphasises the importance of a meticulous clinicopathological correlation in recognising such a tumour as a primary orbital melanoma rather than a metastasis, which is managed differently.

Melanomas malignos do rebordo alveolar na maxila: apresentação de um caso

A case of primary malignant melanoma on the upper alveolar ridge is reported in a thirsty six year old white woman. A partiar prohthetic denture acted probably as an irritative agent producing prechange of color of alveolor mucosa. Radiumtherapy was done as a palliative treatment. The death due to general metastasis occurred in les e than one yeer. The surgical treatment should be done preferently.

A rare case of primary mucosal melanoma involving the oropharynx

A rare case of primary mucosal melanoma involving the oropharynx

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia

PurposeAtaxia–Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. MethodsFrom 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. ResultsLOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56–4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6–5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case–control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). ConclusionThis study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.

A case of primary malignant melanoma of the red border of the lower lip

According to the literature, the localization of primary melanoma on the lips is rare. Here is our observation.

Uveal melanoma diagnosis and current treatment options (Review).

Uveal melanoma is a rare condition accounting for only 5% of all primary melanoma cases. Still, it is the most frequently diagnosed primary intraocular malignant tumor in adults. Almost 90% of the tumors involve the choroid and only a small percentage affects the ciliary body or the iris. There is a consistent difference in incidence between different regions with individuals of northern European descent having a significantly higher risk as compared to Hispanics, Asians, and Blacks. Among the many risk factors, mutations in the G protein subunit alpha Q (GNAQ) or G protein subunit alpha 11 (GNA11) genes and different receptors are highly suggestive. While iris melanoma can easily be noticed by the patient itself or diagnosed at a routine slit-lamp evaluation, a consistent percentage of posterior uveal tumors are incidentally diagnosed at funduscopic evaluation as they can evolve silently for years, especially if located in the periphery. Uveal melanoma classifications rely on the tumor size (thickness and basal diameter) and also on intraocular and extraocular extension. The differential diagnosis with pseudomelanomas is carried out according to the tumor aspect and position. Iris melanoma has a better prognosis and a lower mortality rate as compared to choroidal melanoma that has a much higher rate of metastasis (50% of the patients) and a subsequent limited life expectancy from 6 to 12 months. While conservative therapeutic options for the primary tumor, relying on different surgical excision techniques and/or irradiation therapies, offer good local tumor control, the treatment options for metastatic disease, although numerous, are still inadequate in preventing a fatal outcome.

Urological Melanoma: A Comprehensive Review of a Rare Subclass of Mucosal Melanoma with Emphasis on Differential Diagnosis and Therapeutic Approaches.

Simple SummaryMucosal melanoma accounts for only about 1% of all melanoma cases worldwide, but achieving the correct recognition, diagnosis and prognosis is of extreme importance for the patient. Moreover, primary melanoma of the urinary tract is a rarity among rarities, accounting for less than 4% of all the mucosal melanomas. The urethra is the most common location for this type of melanoma, followed by the bladder and ureter with decreasing incidences. Patients with this form of melanoma are usually elderly (over 60 years) and asymptomatic or have hematuria symptoms. Compared to other mucosal melanomas, there is not much knowledge of the risk factors, etiology, and molecular characteristics of urological melanoma. In addition, there are no uniform staging systems or treatment protocols available for this disease. A thorough knowledge of the existence and management of this disease entity is essential to allow research advances in this area and, in particular, to devise innovative therapies. In this paper, we focus in detail on melanoma originating from the uropoietic apparatus, discuss the cases reported in literature of this very rare and still partially enigmatic melanoma subclass, and consider the scenario leading to metastasization to neighboring organs.Melanoma is reported as the 19th most common cancer worldwide, with estimated age-standardized incidence rates of 2.8–3.1 per 100,000. Although the origin is most frequently cutaneous, mucosal melanoma has been described several times in literature, and despite its rarity (only 1% of all melanomas), increasing attention is being paid to this disease form. Within this subgroup, melanomas of the uropoetic apparatus are a rarity among rarities. Indeed, less than 50 cases of primary melanoma originating from the urinary bladder have been described, and even less originating from the kidney, renal pelvis and urethra. In this work, we present a detailed review of the literature related to this subclass of mucosal melanoma, delve into the biological landscape of this neoplasm and discuss current approaches, future perspectives and potential therapeutic approaches.

A rare case of polypoid primary anorectal melanoma with subsequent giant stomach metastasis: A gastrointestinal involvement of both primary and metastatic mucosal melanoma.

Melanoma can involve the gastrointestinal apparatus as both primary and metastatic lesions. Primary anorectal mucosal melanoma (ARMM) and metastatic gastric melanoma are rare entities and usually resulted in a poor prognosis. We presented a case of a 61-year-old man who after the complete excision of an ARMM developed a gastric metastasis after almost three years form the complete tumour excision. Upon esophagogastroduodenoscopy, a giant ulcered mass resulted in melanoma metastasis. The patient underwent a near-total gastrectomy. After five months of follow-up, the patient is disease-free. The incidence of ARMMs is increasing, highlighting the necessity of new prevention and treatment strategies in order to achieve a better prognosis for these patients. There are no known risk factor for ARMMs but surgery, together with the combination of anti-CTLA-4 and anti-PD-1 antibodies, are promising therapeutic options. Early and aggressive treatments are required, together with a strict multidisciplinary approach.

Primary Malignant Melanoma of the Small Bowel with Hepatic Metastasis: A Case Report

Primary intestinal melanoma is extremely rare, whereas metastatic melanoma of the small bowel is common. In this report, we present a rare case of primary small bowel melanoma with hepatic metastasis. A 51-yearold man presented with constipation and CT identified an ileal mass without bowel obstruction. CT and MRI revealed hepatic metastasis. Ileal mass was confirmed on laparotomy and histologically diagnosed as melanoma.

Correlation analysis of gene and immune microenvironment for 87 melanoma cases.

e21555 Background: To map the genome of Chinese melanoma patients and explore its correlation with the expression of tumor immune microenvironmental indicators. Methods: Next generation sequencing was performed on 87 cases of primary melanoma that had been surgically removed from Nanjing Drum Tower Hospital from July 2010 to May 2017. Immunohistochemistry was carried out to detect the expressions of PD1, PDL1, CD3+TIL, MSH2, MSH6, PMS2 and MLH1. Results: BRAF mutations were the most common (26.4%), followed by KIT mutations (12.6%) in melanoma patients. RB1 gene copy number deletion (55%) and CDK4 (25%)/CCND1 (22.5%) gene copy number amplification were also common. The prognosis of patients could be distinguished by grouping the expression of PDL1 and TIL, and the difference may be related to the expression of PD1. There were more copy number amplication of genes with poor prognosis in PDL1-TIL- patients. Conclusions: The classification of tumors into four microenvironmental subtypes based on PDL1 and TIL expression is an appropriate method to stratify patients with different clinical outcomes. At the genetic level, there are more copy number amplification of the genes with poor prognosis in patients with TIL-PDL1- type, so the prognosis is always worse than that of patients with TIL+PDL1+ type. Gene may affect the prognosis of patients by affecting the tumor immune microenvironment.