Recurrent intussusception as initial manifestation of primary intestinal melanoma:Case report and literature review

Enteric intussusception caused by primary intestinalmalignant melanoma is a very rare cause of intestinalobstruction.We herein present a case of a 42-yearold female patient with no prior medical history ofmalignant melanoma,who was admitted with persistentabdominal pain,nausea,and vomiting.A computedtomography scan revealed an intestinal obstruction dueto ileocolic intussusception.An emergency laparoscopy and subsequent laparotomy revealed multiple small solid tumors across the whole small bowel.An oncologic resection was not feasible due to the insufficient length of the remaining small bowel.Only a small segment of ileum,which included the largest tumors causing the intussusception,was resected.The pathologic examination revealed two intestinal malignant melanoma lesions.A systematic clinical examination,endoscopic procedures,and fluorodeoxyglucose positron emission tomography-computed tomography scan all failed to reveal any indication of cutaneous,anal,or retinal melanoma.Hence,the tumor was classified as a primary intestinal malignant melanoma with multiple intestinal metastases.Since a complete oncologic resection of tumors was not possible,in order to prevent future intestinal obstruction,a surgical resection of the largest lesions was performed with palliative intention.The epidemiology,clinical m a n i fe s t a t i o n s,d i a g n o s i s a n d m a n a g e m e n t o f primary intestinal malignant melanoma,and intestinal intussusception in adults are discussed along with a review of the current literature.     

Cardiac metastasis of malignant melanoma: a rare cause of complete atrioventricular block.

Malignant melanoma has an aggressive biological behaviour and a high rate of cardiac involvement. As shown from post-mortem studies, metastases of melanoma can involve any organ and cardiac metastases are frequent. This report describes a case of widespread malignant melanoma in a patient with clinical presentation of complete atrioventricular (AV) block. Thorax CT and transthoracic echocardiography revealed a mass involving the conduction system. By VDD permanent pacing (atrial synchronous ventricular pacing), haemodynamic stability was maintained and the patient remains under follow-up receiving chemo-immunotherapy. In the retrospective analysis of the patient's records, we realized that the AV conduction delay had been progressing for at least 7 months. Cardiac metastasis of malignant melanoma is a common finding and can proceed in the absence of overt clinical manifestations. Therefore, the clinician should be alert to the development of cardiac signs and symptoms in a metastatic melanoma patient and should perform a detailed cardiac examination to exclude cardiac metastasis of the tumour.     

Combination of serum 5-S-cysteinyldopa,melanoma inhibitory activity and IL-8 improves the diagnostic accuracy of malignant melanoma compared with individual markers

Early diagnosis of malignant melanoma is critical for effective treatment and reduced patient mortality. However, current clinical and histological variables show limited accuracy in diagnosis. Serum or urine level of 5-S-cysteinyldopa (5-S-CD) is a commonly used melanoma biomarker in Japan owing to its increased sensitivity compared with other melanoma markers. However, its use as a diagnostic marker has shown some limitations. Therefore, here we examined the combination of 5-S-CD with melanoma inhibitory activity, which showed sensitivity in detecting melanoma comparable with that of 5-S-CD, and interleukin-8, a cytokine linked with melanoma progression, in a cohort of Japanese patients with melanoma. Our results revealed that the triple combination of 5-S-CD, melanoma inhibitory activity, and interleukin-8 showed high diagnostic accuracy in detecting melanoma compared with each of the individual factors. Importantly, the triple marker showed specificity and utility in detecting early-stage melanoma. Our results suggest the utility of the triple marker as a diagnostic biomarker for melanoma patients.     

Malignant melanoma metastatic to the common bile duct

Metastatic melanoma is renowned for its propensity to spread to almost every organ of the body; however, symptomatic metastases within the biliary tree are very rare. We report two cases of bile duct obstruction from metastatic melanoma. The first case was caused by an intraluminal metastatic melanoma to the common bile duct, while the second case was caused by extraluminal involvement. The unique aspects of these cases include clinical presentations masquerading as biliary colic, cholangitis and obstructive jaundice. Management and follow up for 3 years is presented. Aspects of medical and surgical management, as well as a review of the world's literature are discussed.     

BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level

BACKGROUND & AIMS: Anorectal melanoma (AM) is a rare but highly malignant tumor, displaying histologic and immunohistochemical features very similar to cutaneous melanoma (CM). Because BRAF mutations were recently identified in the majority of CM and nevi, we investigated AM for BRAF mutations and mutations of NRAS , an additional component of the MAPK-signalling pathway. METHODS: DNA from formalin-fixed and paraffin-embedded AM was PCR amplified and sequenced. RESULTS: We detected BRAF mutations in 2 of 19 cases and NRAS mutations in none of the cases. Mutations in exon 15 of BRAF were present in only 1 tumor (1 of 19 cases). The A1800T base exchange represented a novel mutation and resulted in a K600N transition in an AM from a 96-year-old white man who presented with rectal bleeding and painful sitting of a few weeks' duration. The second positive AM case, a 69-year-old white man who presented with painless rectal bleeding and clinical symptoms of an intestinal constipation showed a novel missense mutation (C1327T leading to R443W conversion) in BRAF exon 11. None of the AM cases displayed the oncogenic V599E mutation preponderating in CM. CONCLUSIONS: With regard to the frequency of V599E BRAF mutations, AM significantly differs from CM (P < or = .0001), which suggests that BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level.     

Anorectal malignant melanoma: preoperative usefulness of magnetic resonance imaging

Magnetic resonance imaging (MRI) findings in three patients with primary anorectal malignant melanoma are described. Two patients had melanotic and one had amelanotic anorectal melanoma. The findings of MRI with a pelvic coil and an endorectal coil were consistent with pathologic findings. MRI with a pelvic coil demonstrated the melanotic component as high signal intensity on T1-weighted imaging. MRI with a pelvic coil and an endorectal coil was useful for staging anorectal melanoma. This article describes the initial report of the use of an endorectal coil for malignant melanoma of the anorectum.     

The value of melanoma inhibitory activity and LDH with melanoma patients in a Chinese population

Malignant melanoma is a highly malignant tumor originating from the melanocytes of the neural crest, which is prone to metastasis and has a poor prognosis. Previous research demonstrated that melanoma inhibitory activity (MIA) and lactate dehydrogenase (LDH) could serve as serum markers in malignant melanoma and indicate prognosis in the Caucasian race. Researchers suspected that both MIA and LDH could prompt the prognosis of malignant melanoma in the Chinese population. This study aimed to investigate the value of MIA and LDH in the prognosis of acral malignant melanoma.From January 1, 2014, to December 31, 2017, in Jiangsu Province, 44 acral malignant melanoma patients with complete data were chosen from the clinic. The LDH levels were extracted from their clinical data, and MIA levels were measured by enzyme-linked immunosorbent assay method. 8 paired advancing samples before and after metastasis were examined. 22 health donors were matched to the patient group. Receiver operating characteristic (ROC) curves of MIA and LDH were drawn to determine acral malignant melanoma tumorigenesis and metastasis and finally got the cut-off value. Cumulative survival was illustrated with the Kaplan-Meier plot, and factors were compared using the Log-rank test.Compared with age-matched healthy donors, MIA was significantly high in patients (P < .001). Moreover, serum MIA was significantly higher in III-IV stage patients than I-II stage patients (P < .001). However, there was no such association between LDH and melanoma stage and risk. Further study indicated that the MIA cut-off > 914.7pg/mL predicted disease progression with 86.4% specificity and 95.5% sensitivity. In the Kaplan-Meier analysis, MIA levels were independent risk factors for long-term mortality of acral malignant melanoma patients.It concluded that the quantification of MIA in the serum should be performed as a general standard of care in patients at risk of developing metastatic melanoma.     

上消化道恶性黑色素瘤1例报道

原发性食管合外十二指肠球邸恶性黑色素瘤临床较为罕见,为探讨其病理特征、临床诊断及治疗而避免误诊误治,报道1例上消化道恶性黑色素瘤。上消化道黑色素瘤恶性程度高,预后不良,治疗以根治手术切除为主,辅以放疗。     

Combined liver and pancreas resection with biochemotherapy for metastatic ocular melanoma

Systemic therapy alone for metastatic melanoma is relatively ineffective, and surgical resection of metastases to a solitary site remains the best single treatment to improve survival. While cytoreductive surgery plus chemotherapy play a significant role in the management of advanced ovarian cancer, the precise role of surgery as an adjunct to systemic therapy for melanoma metastatic to multiple sites is not well defined. We report a patient with ocular melanoma metastatic to liver and pancreas treated by cytoreductive surgery consisting of mesohepatic resection, distal pancreatectomy, and portal node dissection, followed by biochemotherapy with dacarbazine and interferon alpha. The concept of cytoreductive surgery is reviewed, with particular attention to its use in the management of metastatic melanoma. The patient's postoperative course was unremarkable and she remains alive and asymptomatic with no detectable disease at 20 months' follow‐up. Cytoreductive surgery as a part of an aggressive multidisciplinary approach may play a role in the treatment of cutaneous and ocular melanoma metastatic to multiple visceral sites. Data from well‐designed, innovative clinical trials of cytoreductive surgery and biochemotherapy are required to determine the effectiveness of this multidisciplinary approach.     

Colonic malignant melanoma mimicking colon carcinoma

Primary melanoma originating in the gastrointestinal tract is rare and is usually in the anorectum. We describe a solitary left colonic melanoma in a 59‐year‐old man and review the pertinent literature. Isolated colonic melanoma is a rare diagnosis, and the published literature seems to suggest better outcomes in this group of patients with surgical excision, unlike metastasis elsewhere in the gastrointestinal tract. It is unclear how melanomas arise in tissues with no pigmented cells, as in the colon. It is possible that regressed primaries elsewhere could have been the underlying primary lesion in such patients.     

Metastatic melanoma of the gallbladder： An unusual clinical presentation of acute cholecystitis

Metastatic disease from cutaneous melanoma can affect all organs of the body, and varies in its biological behavior and clinical presentation. We present the case of a 58-year-old man who arrived at our clinic with acute abdominal pain, which, after investigation, was diagnosed as acute cholecystitis. The patient underwent laparotomy and cholecystectomy. Two years ago, he underwent surgical removal of a primary cutaneous melanoma on his right upper back. Pathological examination revealed the presence of malignant melanoma with a metastatic lesion of the gallbladder.     

Primary gastric melanoma： A case report

Melanoma accounts for 1-3 per cent of all malignant tumors. Except cutaneous, other less common melanomas include, among others, those in the GI tract. However, their primary or secondary nature is often difficult to establish. Referring to the stomach, scattered cases of primary melanomas have been reported in the literature. We report a case of a man with an ulcerated sub-mucosal mass at the antrum of the stomach, manifested with dull upper abdominal pain, nausea, vomiting, fatigue and anemia. This lesion was histologically proved to be melanoma. A detailed clinical and laboratory investigation revealed no primary site elsewhere. To our knowledge, very few cases of primary gastric melanoma have been reported. Our case is the fourth ever published and the first located at the antrum of the stomach. The debate upon the primitive nature of such lesions still persists. Thus, specific diagnostic criteria have been proposed.     

Primary melanoma of the oesophagus treated endoscopically. A case report

Primary melanoma is a rare neoplasm of the oesophagus, with dismal outcome in most cases. We report a case of primary melanoma of the oesophagus treated endoscopically, as coexisting illness prohibited surgical resection of the tumour. A review of the literature is made.     

原发性肺恶性黑色素瘤的外科诊治

目的探讨原发性肺恶性黑色素瘤的临床病理特征、诊断和鉴别诊断以及外科治疗。方法分析我院1980至2008年间5例原发性肺恶性黑色素瘤患者的相关临床治疗,并结合文献复习。结果5例患者中男2例,女3例;年龄41-72岁,平均51.6岁;左上叶2例,右上、中和下叶各1例;症状包括咳嗽、咳痰、胸痛和胸闷不适。术后病理诊断为原发性肺恶性黑色素瘤。无手术和术后住院期死亡。结论原发性肺恶性黑色素瘤临床罕见,诊断主要依据影像学检查和病理检查,治疗首选外科手术完整切除。     

Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma

Abstract: Several experimental studies have shown that melatonin has an oncostatic action, either by stimulating host antitumor immune defenses or by directly inhibiting the growth of some cancer histotypes, including melanoma. Our previous clinical studies demonstrated that melatonin may induce stabilization of the disease in untreatable metastatic solid tumor patients, and these results have been confirmed by others, at least in patients with metastatic melanoma. On the contrary, at present there are no data related to the possible efficacy of melatonin as an adjuvant endocrine therapy. This study was performed to investigate the impact of melatonin therapy on the disease-free survival (DFS) in melanoma patients surgically treated for regional node recurrence. The study included 30 node-relapsed melanoma patients, who were randomized to receive no treatment or adjuvant therapy of melatonin (20 mg/day orally in the evening) every day until disease progression. After a median follow-up of 31 months, the percent of DFS was significantly higher in melatonin-treated individuals than in controls. The DFS curve was also significantly longer in melatonin group than in controls. No melatonin-related toxicity was observed. This preliminary study suggests that an adjuvant endocrine therapy with melatonin may be effective in preventing disease progression in node-relapsed melanoma patients.     

原发性食管恶性黑色素瘤的外科诊治

目的探讨原发性食管恶性黑色素瘤的临床病理特征、诊断、鉴别诊断和外科治疗。方法回顾我院6例外科手术切除和病理学确诊原发性食管恶性黑色素瘤的相关临床资料,并分析相关文献。结果6例患者中男5例,女1例,年龄48～66岁,平均55.8岁,临床症状主要为吞咽困难和胸骨后疼痛,均经钡餐检查提示食管肿瘤性病变,食管中段4例,下段2例,术前2例误诊为食管癌,4例胃镜刷咬切片检查提示食管恶性黑色素瘤,均行食管切除和胃代食管吻合术。术后病理诊断为原发性食管恶性黑色素瘤,组织学特征与其他部位恶性黑色素瘤相似,免疫组化表达HMB45、S-100、Vimentin,不表达CgA。结论原发性食管恶性黑色素瘤临床罕见,易误诊,诊断依据临床病理特征、影像学检查,内镜刷片检查有利术前诊断,治疗原则为以外科手术切除为主的综合治疗。     

Primary malignant melanoma of the esophagus successfully treated by an esophagectomy followed by systemic chemotherapy

Primary malignant melanoma of the esophagus is a rare disease that tends to demonstrate an extremely poor prognosis. We herein describe a case of primary malignant melanoma of the esophagus that was successfully treated. The tumor was incidentally detected by a barium swallow examination performed during a routine medical checkup. The tumor was resected by a transhiatal radical esophagectomy. Histologically, the tumor metastasized to one of the perigastric lymph nodes, although tumor invasion was confined to the submucosa at the primary site. Immunohistochemically, the tumor cells were strongly positive for S100 protein and HMB-45. Postoperatively, systemic chemotherapy consisting of DTIC, ACNU, and VCR was administered. The patient has survived without recurrence for 12 months after these treatments. A transhiatal esophagectomy followed by systemic chemotherapy may therefore be an effective treatment for potentially curable primary melanoma of the esophagus.     

MEK1 mutations confer resistance to MEK and B-RAF inhibition

Genetic alterations that activate the mitogen-activated protein kinase (MAP kinase) pathway occur commonly in cancer. For example, the majority of melanomas harbor mutations in the BRAF oncogene, which are predicted to confer enhanced sensitivity to pharmacologic MAP kinase inhibition (e.g., RAF or MEK inhibitors). We investigated the clinical relevance of MEK dependency in melanoma by massively parallel sequencing of resistant clones generated from a MEK1 random mutagenesis screen in vitro, as well as tumors obtained from relapsed patients following treatment with AZD6244, an allosteric MEK inhibitor. Most mutations conferring resistance to MEK inhibition in vitro populated the allosteric drug binding pocket or α-helix C and showed robust (≈100-fold) resistance to allosteric MEK inhibition. Other mutations affected MEK1 codons located within or abutting the N-terminal negative regulatory helix (helix A), which also undergo gain-of-function germline mutations in cardio-facio-cutaneous (CFC) syndrome. One such mutation, MEK1(P124L), was identified in a resistant metastatic focus that emerged in a melanoma patient treated with AZD6244. Both MEK1(P124L) and MEK1(Q56P), which disrupts helix A, conferred cross-resistance to PLX4720, a selective B-RAF inhibitor. However, exposing BRAF-mutant melanoma cells to AZD6244 and PLX4720 in combination prevented emergence of resistant clones. These results affirm the importance of MEK dependency in BRAF-mutant melanoma and suggest novel mechanisms of resistance to MEK and B-RAF inhibitors that may have important clinical implications.     

Successful treatment of primary pulmonary melanoma

Presented is a rare case of a primary melanoma of the lung in an 89 year old male patient. Primary melanoma of the lung has been previously reported in the English literature in about 30 patients. Surgical resection either with lobectomy of pneumonectomy and a lymph node dissection has been shown to be the best chance of long term survival. This is the oldest patient on record where surgical resection was successful.     

Primary advanced esophago-gastric melanoma: A rare case

Primary esophageal or gastric melanoma is a very rare disease with early metastasis. Due to its atypical symptom and less efficiency of chemotherapy and radiotherapy, the prognosis of esophageal or gastric melanoma is still very poor. Surgical resection remains the preferential treatment for esophageal or gastric melanoma. Here we present an extremely rare case of primary advanced esophago-gastric melanoma. Debulking surgery was performed without chemotherapy or radiotherapy. However, abdominal recurrence and hepatic metastases were found within one month by a postoperative follow-up computed tomography. Three and a half months after surgical resection, the patient died of extensive abdominal metastasis.