Case Of Metastatic Melanoma Research Articles

S1911 A Rare Presentation of Metastatic Melanoma With Obstructive Jaundice and Pancreatitis Due to Pancreatic Metastasis With Invasion into the Common Bile Duct

Introduction: Malignant melanoma is a highly aggressive cancer with high rates of metastasis. Here we present a case of metastatic melanoma of the pancreas which invaded into the common bile duct leading to a unique presentation of obstructive jaundice and pancreatitis. Case Description/Methods: An 84-year-old male presented with epigastric abdominal pain. 3-years prior he had wide local excision for cutaneous malignant melanoma of the upper back (R0 resection). His abdominal pain had worsened over the last 4-weeks and was preceded by jaundice and unintentional weight loss. Initial studies were significant for elevated alkaline phosphatase (1295), AST (270) ALT (212), total bilirubin (10.1) and lipase (12085). Computed tomography (CT) showed a 2.4 cm lesion in the pancreatic head along with dilated pancreatic duct and biliary dilation. Carbohydrate antigen 19-9 (CA19-9) was elevated (628). Cholangiogram showed a 15 mm distal biliary stricture with upstream dilation. Brushings of the biliary stricture were unsatisfactory due to insufficient cells. Subsequent endoscopic ultrasound (EUS) demonstrated a 25mm by 25mm mass in the pancreatic head invading the distal CBD. Fine-needle aspiration (FNA) showed a poorly differentiated malignancy with epithelioid and focal spindle cell features with positive S100 and SOX-10 immunophenotype. Findings consistent with melanoma. Additional imaging did not reveal other potential sites of metastasis. The patient has since been discharged and is undergoing further evaluation. Discussion: Approximately one-third of patients with malignant melanoma develop metastases. However, metastatic melanoma of the gastrointestinal system is only seen in 2-4% of patients affected by cutaneous melanoma. This patient had a unique presentation with invasion of his pancreatic lesion into the distal common bile duct which lead to obstructive jaundice and pancreatitis. Pancreatitis as a result of metastatic melanoma is a rare presentation only described in a few case reports. Based on imaging it appears the patient initially had isolated metastatic disease of the pancreas which then invaded into the common bile duct. Isolated pancreatic metastasis represents less than 1% of all metastatic melanomas. It is difficult to differentiate a primary cancer from metastatic disease of the pancreas based on imaging alone. The use of EUS-FNA is essential for diagnosis. Though the exact prognosis of metastatic melanoma of the pancreas is unclear, generally metastatic melanoma carries a poor prognosis.

An Unusual Case of Malignant Melanoma with Metastasis to the Placenta During Pregnancy.

IntroductionWe describe an unusual case of metastatic melanoma of the brain with an unknown primary site during pregnancy.Case DescriptionA 35-year-old woman in the third trimester of pregnancy presented with ataxia, nausea, vomiting, headaches and diplopia. CT of the brain revealed a hyper-attenuating 2.1 cm mass in the fourth ventricle with mild obstructive hydrocephalus. A healthy newborn was delivered by urgent caesarean section. Craniotomy and resection of the brain lesion confirmed melanoma. Pathology of the placenta reported a ‘focal nest of melanocytes identified in intervillous space’.DiscussionBrain and maternal placenta pathology findings were consistent with melanoma, making this case relevant because of the possibility of metastatic melanoma in a fetus.ConclusionEpidemiological data on congenital and infantile melanoma are scarce. Also, there is no database for long-term follow-up of children born to pregnant mothers with metastatic melanoma. Delayed presentation of melanoma in the child cannot be ruled out.LEARNING POINTSMelanoma brain metastasis is an uncommon initial presentation during pregnancy.During pregnancy, vague symptoms such as headaches and nausea can easily be attributed to the pregnancy itself rather than more serious conditions like cancer.Metastatic melanoma diagnosed during pregnancy with disease in the placenta is a rare occurrence and should trigger close follow-up of the neonate secondary to concerns of transplacental metastasis.

Application of immunohistochemical staining of PRAME in differential diagnosis between melanoma and melanocytic nevus

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) in differential diagnosis of benign and malignant cutaneous melanocytic lesions. Methods: Fifty-nine cases of melanoma (50 cases of skin primary melanoma, and 9 cases of metastatic melanoma) and 48 cases of melanocytic nevus (40 cases of common nevus and 8 cases of dysplastic nevus) were subject to PRAME immunohistochemistry staining.The difference of PRAME expression between melanoma and melanocytic nevus was analyzed. Results: Among the 50 patients with primary cutaneous melanoma, there were 23 males and 27 females ranging in age from 33 to 87 years (average age 62.4 years, median age 64.5 years). Among the 9 metastatic melanoma there were 7 males and 2 females ranging in age from 40 to 82 years (average age 64 years, median age 65 years). Twenty-six cases (26/50, 52.0%) of cutaneous primary melanoma and 4 cases (4/9) of metastatic melanoma showed diffuse positive PRAME staining. 40 cases (40/40, 100%) of common nevus and 8 (8/8) cases of dysplastic nevus were PRAME negative. Compared with melanocytic nevus group, the melanoma group included more cases with diffuse positive PRAME staining (P<0.05). The sensitivity and specificity of using PRAME to differentiate primary cutaneous melanoma from melanocytic nevus in the cohort is 52.0% and 100%. Conclusions: There is a significant difference in the expression of PRAME between melanoma and melanocytic nevus.Thus, PRAME can be used as an auxiliary diagnostic tool for differentiating benign from malignant cutaneous lesions.

Metastatic malignant melanoma of the breast: report of a case and review of the literature

Melanoma is the most rapidly increasing cancer in the world. Associated morbidity and mortality are mainly related to metastatic potential. Metastases to the breast from malignant melanoma are rare and represent only 1.3%-2.7% of reported cases. The aim of this study was to present a rare case of metastatic malignant melanoma to the breast. A 51-year-old woman was admitted for management of a palpable mass of the left breast. The past medical history referred to a sizable nodular melanoma that was removed from her back. Classification of the breast lesion was BI-RADS 5. Core needle biopsy was compatible with the diagnosis of malignant melanoma. Immunohistochemical evaluation was positive for Mart1 and Ki67. Subsequent staging was indicative of multiple secondary foci in the liver and bones. The patient was administered a combination of PD L1 inhibitor nivolumab with the anti-CTLA4 inhibitor ipilimumab followed by additional targeted therapy with the BRAF inhibitor vemurafenib. Metastasis to the breast from malignant melanoma is extremely rare. Nevertheless, breast metastases must be suspected in patients with a history of malignant melanoma. Moreover, recent breakthroughs in the Braf and MEK inhibitors and immune checkpoint inhibition therapies have impressively improved prognosis in patients affected by melanoma.

Novel chloroquine derivative suppresses melanoma cell growth by DNA damage through increasing ROS levels.

Melanoma is a fatal cancer with a significant feature of resistance to traditional chemotherapeutic drugs and radiotherapy. A mutation in the kinase BRAF is observed in more than 66% of metastatic melanoma cases. Therefore, there is an urgent need to develop new BRAF‐mutant melanoma inhibitors. High‐dose chloroquine has been reported to have antitumour effects, but it often induces dose‐limiting toxicity. In this study, a series of chloroquine derivatives were synthesized, and lj‐2‐66 had the best activity and was selected for further investigation. Furthermore, the anti‐BRAF‐mutant melanoma effect and mechanism of this compound were explored. CCK‐8 and colony formation assays indicated that lj‐2‐66 significantly inhibited the proliferation of BRAF‐mutant melanoma cells. Flow cytometry revealed that lj‐2‐66 induced G2/M arrest in melanoma cells and promoted apoptosis. Furthermore, lj‐2‐66 increased the level of ROS in melanoma cells and induced DNA damage. Interestingly, lj‐2‐66 also played a similar role in BRAF inhibitor‐resistant melanoma cells. In summary, we found a novel chloroquine derivative, lj‐2‐66, that increased the level of ROS in melanoma cells and induced DNA damage, thus leading to G2/M arrest and apoptosis. These findings indicated that lj‐2‐66 may become a potential therapeutic drug for melanoma harbouring BRAF mutations.

Screening of Autophagy-Related Prognostic Genes in Metastatic Skin Melanoma.

Cutaneous melanoma refers to a common skin tumor that is dangerous to health with a great risk of metastasis. Previous researches reported that autophagy is associated with the progression of cutaneous melanoma. Nevertheless, the role played by genes with a relation to autophagy (ARG) in the prediction of the course of metastatic cutaneous melanoma is still largely unknown. We observed that thirteen ARGs showed relations to overall survival (OS) in the Cox regression investigation based on a single variate. We developed 2-gene signature, which stratified metastatic cutaneous melanoma cases to groups at great and small risks. Cases suffering from metastatic cutaneous melanoma in the group at great risks had power OS compared with cases at small risks. The risk score, T phase, N phase, and age were proved to be individual factors in terms of the prediction of OS. Besides, the risk scores identified by the two ARGs were significantly correlated with metastatic cutaneous melanoma. Receiver operating characteristic (ROC) curve analysis demonstrated accurate predicting performance exhibited by the 2-gene signature. We also found that the immunization and stromal scores achieved by the group based on large risks were higher compared with those achieved by the group based on small risks. The metastatic cutaneous melanoma cases achieving the score based on small risks acquired greater expression of immune checkpoint molecules as compared with the high-risk group. In conclusion, the 2-ARG gene signature indicated a novel prognostic indicator for prognosis prediction of metastatic cutaneous melanoma, which served as an important tool for guiding the clinical treatment of cutaneous melanoma.

Fine-needle aspiration cytological findings in three cases of metastatic amelanotic melanoma to the parotid gland with divergent differentiation.

This report presents the clinical and pathologic findings of three cases of metastatic amelanotic melanoma to the parotid gland. Two of the patients had a primary cutaneous tumor. Fine-needle aspiration of the parotid showed clusters of epithelioid cells and/or spindle-shaped cells with vesicular nuclei, macronucleoli, and abundant eosinophilic cytoplasm. In addition, one had striking balloon-cell features. In the immunohistochemical study, the tumors expressed S-100, HMB-45 antigen, Melan-A, and SOX10, and focally smooth-muscle actin, cytokeratin, CD56, p63, and synaptophysin. The diagnosis was challenging because the tumors were clinically thought to be primary parotid lesion and showed unusual immunohistochemical labeling for SMA, cytokeratins, p63, and neuroendocrine markers. Furthermore, the long clinical history in two of the cases made the diagnosis of a metastatic lesion less likely. Diagnostic errors can be reduced by integrating cytomorphologic, histologic, immunohistochemical, and clinical findings.

전신전이를 동반한 비부비동 점막 흑색종의 면역치료 1예

Sinonasal mucosal melanoma (SMM) is rare form of melanoma and accounts for 4%-13% of all sinonasal malignant tumor. SMM is characterized by aggressive growth with high locoregional recurrence and distant metastasis. Immunotherapy has been known as effective therapeutic strategies in metastatic melanoma. Immune checkpoint inhibitors; anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and antigrogrammed cell death 1 (PD-1), demonstrated the improved prognosis in advanced malignant melanoma. Recently, authors experienced a case of SMM patient with locoregional and distance metastasis, who was successfully treated with anti-PD-1 monoclonal antibody. We report a case of metastatic malignant melanoma with literature review. (J Clinical Otolaryngol 2021;32:265-269)

Sinusoidal Growth Pattern of Hepatic Melanoma Metastasis: Implications for Histopathologic Diagnosis.

Metastatic tumors interface with liver in multiple patterns, of which, the rare "sinusoidal" growth pattern can be subtle and easily overlooked on biopsy. We sought to characterize the metastasis-to-liver interface patterns of melanoma compared with other tumor types and assess the incidence of metastatic melanoma in histologically normal-appearing targeted liver lesion biopsies. Liver lesion samples from 54 melanoma patients were assessed. Nearly normal-appearing cases, defined as no obvious malignancy on routine hematoxylin and eosin stain (n=24), were stained with SOX10 and confirmed with MelanA. Tumor-to-liver interface patterns were determined in biopsies overtly positive for metastatic melanoma (n=30) versus other hepatic metastases as controls (colon, n=28; breast, n=20; pancreaticobiliary, n=20; and neuroendocrine, n=28). Of the 24 nearly normal-appearing liver biopsies from melanoma patients, 3 had subtle melanoma cells detected in sinusoids, confirmed with immunohistochemistry. Of 30 livers overtly positive for melanoma, 8 showed the sinusoidal pattern, compared with none in other metastases. In total, 11/33 (33%) cases of metastatic melanoma liver biopsies demonstrated the sinusoidal pattern. We describe 11 metastatic melanoma cases in liver with the rare sinusoidal pattern, 3 of which were subtle and easy to miss on routine hematoxylin and eosin stain. Given that sinusoidal metastasis does not elicit a tissue reaction, it is prudent for the pathologists to be aware of this pattern of metastases and have a low threshold to order immunostains for accurate diagnosis and optimal patient care.

Arginine deprivation therapy induces apoptotic cell death in melanoma brain metastasis

Abstract Aims The development of melanoma brain metastasis (MBM) occurs in ~50% of metastatic melanoma cases, and significantly worsens prognosis to a median survival of 12.8 months. Melanoma is often reported as an arginine auxotroph due to transcriptional silencing of argininosuccinate synthase 1 (ASS1). Arginine deiminase (ADI) is a non-mammalian enzyme which depletes blood arginine by converting it to citrulline and ammonia, and in its pegylated form ADI shows clinical efficacy in the treatment of a number of cancers via exploiting tumour arginine auxotrophy, resulting in targeted arginine deprivation of tumour cells. While cutaneous melanoma is the prototype cancer for this therapy, studies to date have excluded central nervous system metastasis. We have demonstrated that patient derived primary MBM models are sensitive to arginine deprivation in vitro, confirmed suitable clinical biomarkers of sensitivity, and established the mechanism of tumour cell specific cytotoxicity. Method Patient derived primary cultures of MBM were established and subject to treatment with arginine deprivation. Gene expression and methylation analysis was examined by RT-qPCR, western blot, Illumina mRNA sequencing and Illumina methylated DNA immunoprecipitation-sequencing (MeDIP-seq) on ADI treated and untreated samples. Cell death, cytotoxicity induction and caspase-3 and-7 recruitment was analysed using an Incucyte S3 live-cell imager, by fluorescently labelling cells with Incucyte Cytolight Red Rapid dye, Cytotox Green dye and Caspase-3/7 Green dye, and imaging cells every 2 hours over the course of 2 weeks. 3D spheroid growth and invasion was measured by culturing cells as tumour spheroids before treating with ADI, and imaging spheroids every 2 hours for 2 weeks using an Incucyte S3 live-cell imager. Nuclear leakage and mitochondrial morphology was observed by fluorescently staining treated and untreated cells with DAPI and MitoTracker Red, and imaging on a Leica DMi8 confocal microscope. Results Primary MBMs differentially express ASS1 at substantially lower levels than non-cancerous melanocytes, however some models are capable of upregulating ASS1 following confrontation with arginine deprivation. Despite this, long-term sensitivity of primary MBMs to arginine deprivation was observed in both 2D and 3D models. In addition, arginine deprivation was seen to inhibit MBM invasion in a 3D model – an important feature in MBM pathogenesis. Initially, autophagy was induced in arginine deprived MBM, however in all models the induction of cytotoxicity correlated with recruitment of caspase-3 and -7, and intrinsic apoptotic cell death confirmed. Nuclear leakage, and eventually complete nuclear destruction was observed, in addition to mitochondrial fragmentation. Conclusion Arginine deprivation is highly effective in reducing 2D and 3D MBM growth, as well as limiting invasion. While apoptotic cell death was observed in all models, the initial induction of autophagy could pose threat of resistance development in a clinical setting, and so combinational therapies with autophagic inhibitors and/or additional apoptotic inducers should be investigated. It is unclear whether nuclear leakage and mitochondrial degradation are the cause or product of apoptosis. Considering the strong clinical evidence for the use of arginine deprivation in non-CNS metastatic melanoma and the results of this study, arginine deprivation is a highly suitable treatment for pre-surgical MBM to limit invasion and increase resection, and for post-surgical continuation.

Who's Driving? Switch of Drivers in Immunotherapy-Treated Progressing Sinonasal Melanoma.

Simple SummaryHere, we monitored the course of the disease and treatment of sinonasal melanoma patients. Since treatment options are rare, immunotherapy is often the treatment of choice. However, intrinsic or acquired resistance to treatment may occur. We assessed the mutational status of the tumors and metastases during the course of therapy and recognized a switch of the oncogenic drivers to mutant NRAS in progressing disease. As a switch of drivers (other than the addition of a second driver) has not been reported yet, longitudinal molecular testing and the awareness of molecular heterogeneity of sinonasal melanoma is crucial.Mucosal melanoma can be driven by various driver mutations in genes such as NRAS, KIT, or KRAS. However, some cases present with only weak drivers, or lacking known oncogenic drivers, suggesting immunotherapy over targeted therapy. While resistance mechanisms to immunotherapy in cutaneous melanoma have been uncovered, including alterations in JAK1/2, B2M, or STK11, a switch of oncogenic drivers under immunotherapy has not yet been observed. We report three cases of metastatic sinonasal melanoma that switched oncogenic drivers from KRAS, KIT, or no driver to NRAS during or after immunotherapy, thereby showing progressive disease. One of the cases presented with three spatially separate driver mutations in the primary tumor, whereas the NRAS clone persisted under immunotherapy. In comparison, three different control cases receiving radiotherapy only did not show a change of the detectable molecular drivers in their respective recurrences or metastases. In summary, these data provide an important rationale for longitudinal molecular testing, based on evidence for an unforeseen recurrent event of molecular driver switch to NRAS in progressing sinonasal melanoma. These findings provide the basis for further studies on a potential causal relation of emerging NRAS mutant clones and immunotherapy.

Metastatic melanoma as femoral vein deposits: A case report

Malignant melanoma is most dangerous of all skin cancers. It is strongly linked to mutations caused by UV radiation in sunlight. Melanoma most commonly arises from the skin, other sites are oral, anogenital mucosal surface, oesophagus, meninges and uvea of the eye. We present a case of metastatic melanoma in right inguinal lymph nodes along with femoral vein deposits whose primary lesion was in skin over right foot. Single distant metastasis had a longer survival than patients with two metastatic sites or a combination of three or more. Due to patient’s negligence and limited knowledge, malignant melanoma becomes a dangerous skin cancer. It start with a painless induration (very small size) and gradually growing in thickness. On further disease progression, regional lymph node involment is seen and later metastasize to other sites. This make the disease with very less survival outcome. Keywords: Malignant melanoma, Femoral vein, Metastatic melanoma.

Predictors of the response to nivolumab immunotherapy in the second or subsequent lines for metastatic non-small cell lung cancers.

Checkpoint inhibitors represent the first therapeutic class to replace chemotherapy lines for the treatment of metastatic non-small cell lung cancer (NSCLC), due to improved overall survival and tolerability. Nivolumab, a fully human anti-programmed cell death-1 immunoglobulin G4 monoclonal antibody, is the first immune checkpoint inhibitor approved by the US Food and Drug Administration in 2014 for cases of metastatic melanoma and in 2015 for cases of squamous cell lung cancer and kidney cell cancer. The present study aimed to identify predictive markers (favorable or unfavorable) for time to treatment discontinuation using nivolumab in the second or subsequent line of therapy of metastatic NSCLC cases. Analysis of a group of 78 NSCLC patients treated with nivolumab allowed the identification of negative predictive markers, related to the presence of metastases (adrenal in men under 65 years, liver, brain and the number of metastatic sites) and the hematological profile (neutrophilia at the initiation of treatment and lymphocyte variation at 6 weeks of treatment).

Ultrastructural and clinical features of central nervous system melanoma:Analysis of nine cases

ABSTRACT To investigate the ultrastructural and clinical characteristics of melanoma of the central nervous system (CNS). The clinical and electron microscopy pathology data of nine patients with melanoma surveyed from 1993 to 2017 were analyzed. All the CNS melanomas were confirmed by transmission electron microscopy (TEM), including eight cases of primary melanomas and one case of metastatic melanoma. In this study, four stage II melanosomes were intracranial space-occupying, three of which were malignant melanoma, the other one was melanoma. Among the five stage IV melanosomes, four cases were intraspinal space-occupying, the other one was intracranial space-occupying, and the pathological diagnoses were all melanoma. At present, TEM is an important tool for the diagnosis of CNS melanomas. Malignant melanoma has high malignancy and recurrence rate and poor prognosis, while benign melanoma with relatively low recurrence rate, so we speculate that patients with mainly immature melanosomes are more likely to exhibit recurrence.

Prognostic Significance of Epidermal Growth Factor Receptor Expression in Distant Metastatic Melanoma from Primary Cutaneous Melanoma.

BackgroundEpidermal growth factor receptor (EGFR) is overexpressed in many cancers. However, EGFR expression in melanoma and its role are conflicting.ObjectiveThis study aimed to evaluate EGFR expression in distant metastatic melanoma and analyze its relationship with histologic and clinical characteristics and survival.MethodsDiagnostic tissues from 55 cases of distant metastatic melanoma was evaluated by immunohistochemistry for EGFR expression. Clinicopathologic features and survival outcomes were analyzed according to EGFR expression.ResultsThe positive EGFR expression in distant metastatic melanoma was significantly correlated with the absence of ulceration. The EGFR expression in distant metastatic melanoma was significantly associated with poor survival, under the conditions of male sex and primary cutaneous melanoma without ulceration or Breslow thickness ≤4.0 mm. This study bears limitations of a retrospective study in a single institution.ConclusionEGFR immunostaining had predictive values for survival outcome. The EGFR expression in distant metastatic melanoma in male, no ulcer, or Breslow thickness ≤4.0 mm appeared to be involved in disease progression.

A rare cause of hemobilia: Metastatic melanoma of the gallbladder

Introduction: Gallbladder melanoma is an extremely rare entity, even more so in living patients, as many remain asymptomatic. Patients usually present with symptoms resembling acute cholecystitis, however here we present a case of metastatic melanoma of the gallbladder presenting with hemobilia. Case Report: An 82-year-old lady with a history of skin cancer excisions, including melanoma, many years ago, presented with anemia of unknown origin. A computed tomography (CT) scan was performed, demonstrating a gallbladder mass and hemobilia. She successfully underwent open cholecystectomy, partial liver resection, and lymph node dissection, which on histopathology, demonstrated metastatic melanoma. She remains disease free eight months later. Conclusion: Although melanoma of the gallbladder is rare, in patients with a past history of melanoma, a high index of suspicion should be maintained if there are concerning signs, such as anemia, without a clear cause. With early identification and surgical intervention, a patient’s survival rate can be optimized.

Primary and Metastatic Malignant Melanomas of the Digestive System

Purpose: Primary and metastatic digestive system malignant melanomas are extremely rare. In our study, we aimed to compare lymph node metastasis with clinical and pathological parameters in gallbladder, stomach, small intestine and anorectal region malignant melanomas. Materials and methods: This retrospective study included 20 cases diagnosed with malignant melanoma in the gastrointestinal tract organs between January 2010 and January 2020 at XXXXXXXXXXXX. In our study, we wanted to evaluate the relationship between regional lymph node metastasis and age, gender, tumor localization, tumor size, extraintestinal melanoma history, melanin pigment, neutrophil-lymphocyte ratio and post-diagnosis life span in primary and metastatic malignant melanoma cases. We also reviewed the origin and literature of the cells from which melanoma originates in the digestive system. Results: There was a statistical relationship between tumor diameter and regional lymph node metastasis (p =0.000). As the tumor diameter increased, the lymph node metastasis rate increased. There was a relationship between survival and gender, tumor localization, distant metastasis, primary and metastatic digestive system melanoma (all p <0.05). Most of the men and those who did not metastasize away from the digestive system were alive. All patients with melanoma metastases to the digestive system and all patients with gallbladder and small intestine localization were alive. Our 70 year old patient with gallbladder primary malignant melanoma was the oldest patient we could identify in the literature. Conclusions: Regardless of cutaneous or origin, all melanomas originate from melanocytes, cells derived from embryological nerve crest. Malignant melanoma can be primary in every region, more frequently in the anorectal region in the gastrointestinal tract. The most common metastasis is to the small intestine. Accurate diagnosis is vital in places where it is rarely seen, such as the digestive system. Recently, in metastatic melanoma, immuno-oncological agents are used in adjuvant therapy to help prevent metastatic spread of the disease. Thanks to these treatments, it is reported that more than half of patients with melanoma who have the risk of metastasis after surgical resection provide recurrence-free survival. Although it is very rare, it should be kept in mind that there may be primary or metastatic malignant melanoma in the evaluation of digestive system biopsies.

Uncommon case of the acral melanoma with chondro-osseous metaplasia

Aim. This study aimed to improve the diagnostics of acral melanoma and investigate tumor morphological features of the chondroid and osseous matrix.&#x0D; Materials and methods. The article presents a clinical case of metastatic acral melanoma with chondroid and osseous metaplasia in a 60-year-old patient. Cytological, histologic, immunohistochemical, and molecular genetic studies were performed.&#x0D; Results. A conglomerate of lymph nodes was noted in the inguinal region of the patient. Oxyphilic chondroid masses and tumor cells with morphological features of sarcoma were revealed using thin-needle aspiration biopsy. On physical examination, pink-colored subcutaneous neoplasm was discovered in the skin of the heel. Histological examination of the primary neoplasm and inguinal lymph node was performed. Melanoma with chondro-osseous metaplasia was diagnosed. Immunohistochemical examination of the tumor revealed some pronounced diffuse expressions of S-100 protein, HMB-45, and focal expression of Melan A in tumor cells. The sample was tested to detect BRAF mutation, and no mutations were found.&#x0D; Conclusion. Morphological diagnostics of acral melanoma with chondro-osseous metaplasia is characterized by a high risk of diagnostic error. Therefore, additional immunohistological, molecular, and genetic studies should be used in the diagnostics of acral melanoma with chondro-osseous metaplasia.

PRAME expression in 155 cases of metastatic melanoma.

PRAME (preferentially expressed antigen in melanoma) is a promising immunohistochemical marker in distinguishing benign from malignant primary cutaneous melanocytic lesions and lymph node deposits. We hypothesize that PRAME may also reliably identify melanoma metastases that are clinically detected in skin, lymph nodes, or small intestine. A total of 155 cases of metastatic melanoma to lymph node (N = 54) and non-lymph node (N = 101) sites were stained with an antibody against PRAME. Nuclear expression was scored in tumor cells as negative, 1% to 25% (1+), 26% to 50% (2+), 51% to 75% (3+), or 76% to 100% (4+). PRAME expression was seen in 151/155 (97.4%) cases, with 4+ expression in 64 cases (41.3%), 3+ expression in 46 cases (29.7%), 2+ expression in 18 cases (11.6%), and 1+ expression in 23 cases (14.8%). Lymph node metastases were more likely to show lower expression as compared to metastases to other anatomic sites (P = 0.003). A high level of PRAME immunoreactivity was identified in this cohort of metastatic melanoma. Lymph node metastases showed more focal or absent PRAME expression as compared to metastases to other sites. Overall, PRAME is a useful tool for confirming the diagnosis of melanoma in a metastatic setting, in both nodal and visceral deposits.

S2862 Bowel Within the Bowel; A Case of Metastatic Melanoma Presenting as Small Bowel Intussusception

INTRODUCTION: Melanoma is notorious for metastasizing to almost any part of the body. Metastasis to the gastrointestinal tract is most commonly diagnosed on autopsy. A clinical diagnosis is rare and occurs in approximately 2% of cases. We present a rare case of metastatic melanoma to the small bowel that presented as melena and ultimately caused small bowel intussusception. CASE DESCRIPTION/METHODS: 84-year-old male was admitted to the hospital with one-week history of melena and worsening abdominal pain. Past medical history was significant for stage IIB metastatic melanoma. Melanoma was first diagnosed on bottom of right foot 10 years prior to admission and was treated with surgical excision and adjuvant pegylated interferon. Patient had recurrence of melanoma on his back 1 year prior to presentation and underwent surgical excision and was treated with nivolumab. Physical examination revealed two new dermal nodules on the left chest. Laboratory investigations showed a decrease in hemoglobin from 11.5 g/dl three months prior to 9.5 g/dl. Esophagogastroduodenoscopy (EGD) was remarkable for a large, purplish, smooth mass in the third portion of the duodenum which was biopsied. Colonoscopy was unremarkable. Histologic examination revealed neoplastic cells positive for MART-1 and negative for CD3 and CD20. Immunohistochemical staining demonstrated that the malignant cells were positive for S100 which confirmed the diagnosis of metastatic melanoma. The patient was discharged however again presented to the Emergency Department with severe abdominal pain. Computed tomography with contrast showed small bowel intussusception within the left mid abdomen with dilated loops of small bowel proximally and collapsed loops of small bowel distally. Patient was taken for an emergent laparoscopic small bowel resection due to concern of ischemia. He was found to have multiple intra-abdominal lesions studding the small bowel and mesentery. Further metastatic workup revealed lesions in the lungs and the brain suggestive of advanced disease. Decision was made to proceed with palliative ipilimumab chemotherapy and radiation. DISCUSSION: Small bowel tumors are rare, accounting for only 3–6% of all GI tumors. Small bowel melanomas can be primary or metastatic lesions. Clinical presentation of GI metastases includes abdominal pain, overt bleeding, anemia, intestinal obstruction or rarely intussusception. Surgery may not be curative, however is the treatment of choice as it is effective in palliating symptoms and may prolong survival.Figure 1Figure 2