Primary Malignant Melanoma Of Esophagus Research Articles

Clinical characteristics and treatment outcomes of primary malignant melanoma of esophagus: a single center experience

BackgroundPrimary malignant melanoma of esophagus (PMME) is an extremely rare disease with poor prognosis. We aimed to determine the clinical characteristics and treatment outcomes of patients with PMME.MethodsWe retrospectively reviewed 17 patients diagnosed with PMME in Samsung Medical Center between 2000 and 2020 with median 34 months of follow-up. Survival outcomes were analyzed with Kaplan–Meier method.Results15 patients (88.2%) were male and the most common presenting symptom was dysphagia (9/17, 52.9%). On endoscopy, tumors were mass-forming in 15 patients (88.2%) and diffusely infiltrative in two patients (11.8%). Lesions were melanotic in 13 patients (76.5%) and amelanotic in four patients (23.5%). The most common tumor location was lower esophagus (11/17, 64.7%). The disease was metastatic at the time of diagnosis in four patients (23.5%). As for treatment, 10 patients (58.8%) underwent surgery. In all 17 patients, the median overall survival was 10 months. In surgically treated patients, all patients experienced recurrence and the median disease-free survival was 4 months. There was no statistical difference in overall survival between patients with or without surgery. Patients with diffusely infiltrative tumor morphology had better overall survival compared to those with mass-forming tumor morphology (P = 0.048). Two patients who received immunotherapy as the first-line treatment without surgery showed overall survival of 34 and 18 months, respectively.ConclusionsAs radical resection for patients with PMME does not guarantee favorable treatment outcomes, novel treatment strategy is required. Further large-scale studies are warranted to determine the efficacy of immunotherapy for patients with PMME.

Characteristics and prognosis of primary malignant melanoma of the esophagus.

Primary malignant melanoma of esophagus (PMME) is a rare malignant tumor of esophagus. This study aimed to investigate the clinic pathologic characteristics and analyze the factors that might affect the prognosis of PMME patients.A total of 20 PMME patients who underwent surgical treatment in our hospital from 1975 to 2017 were analyzed. The clinical data, surgical and pathologic features of all patients were collected.For 20 PMME patients, the average age was 57.3 ± 10.7 years, and the male patients account for 75%. Most of the tumors (95%) were located in the middle and lower of the esophagus. There were 7 patients with primary tumor invasion beyond the muscular layer (T3 + T4) and 10 patients with lymph node metastasis (LNM). The median survival time of 20 patients was 12 months, and the 1-year and 5-year survival rates were 50% and 16.9%, respectively. The probability of LNM in tumors confined to submucosa (T1) and myometrium (T2) was lower than that in tumors with deeper invasion (T3, T4) (P = .035). Multivariate analysis showed that tumor node metastasis (TNM) staging was the independent prognostic factor for survival of PMME patients (hazard ratio [95% confidence interval], 4.15 [1.36–12.67]; P = .012).For PMME patients, tumors with deeper invasion were more likely to have LNM, and TNM staging was an independent predictor of prognosis for survival. Early detection of the disease and radical resection of the tumor are critical for better survival of the PMME patients.

1371P - Genomic landscape of primary malignant melanoma of esophagus

BackgroundAnti-PD-1 monoclonal antibody monotherapy achieves poor outcomes in mucosal melanoma, but our previous study has demonstrated that primary malignant melanoma of esophagus (PMME) has a dramatically high response rate (ORR 75%). The genomic landscape of PMME and reasons for this finding have not been extensively investigated. MethodsWhole exome sequencing were performed in seven treatment-naive PMME tumor samples and matched normal tissues, and genomic data of eight mucosal melanomas was obtained from the International Cancer Genome Consortium. Comprehensive profiling was performed to analyze the of genetic differences of PMME with mucosal melanoma. ResultsThe mean depth of coverage was 268X (ranged from 100X to 400X), 1203 SNV/InDels were detected in seven PMME samples, with a mean value of 172 mutations. The median tumor mutation burden (TMB) was 3.58 mutations/Mb (range 0.19-9.58 mutations/Mb), which was significantly than mucosal melanoma (P=0.021). The mutation spectrum of SNVs displayed more frequency of T>A transition while less frequency of C>T transversion compared to mucosal melanoma. There were 36 genes found to be mutated in more than two PMME tumor samples, and the most significantly mutated genes were CFH (42.9%, 3/7) and MUC16 (42.9%, 3/7). Both BRAF and NRAS were only found in one sample, and no NF1, KIT and SF3B1 mutation were detected. In total, 671 CNVs were detected, and the most frequently amplification chromosomal regions were 10q and 1p, while most frequently deletion in 1q and 8q. Genetic aberrations were mainly enriched in RTK/RAS and WNT pathways. ConclusionsThe TMB is higher in PMME compared to mucosal melanoma, with the highest mutation frequency in CFH and MUC16. CFH has a critical role in the regulation of complement activation, and MUC16 has been reported to be associated with higher tumor mutation load and outcomes in gastric cancer. In summary, our study reveals that the genomic landscape of PMME is different from mucosal melanoma originates from other mucosal membrane sites, and indicates that CFH and MUC16 mutation might be associated with better response to anti-PD-1 monoclonal antibody in PMME patients. Legal entity responsible for the studyPeking University Cancer Hospital-Beijing Cancer Hospital. FundingBeijing Talents Foundation (2016000021223ZK18), National Natural Science Foundation of China (81672696, 81402264). DisclosureAll authors have declared no conflicts of interest.

Primary malignant melanoma of esophagus: clinicopathologic characterization of 20 cases including molecular genetic profiling of 15 tumors

Primary malignant melanoma of esophagus is very rare, and its clinicopathologic and genetic features have not been extensively investigated. In this study, 20 tumors from 14 male and 6 female patients (40–79 years old) were evaluated. Dysphagia, chest pain, and weight loss were frequent symptoms. Thirteen melanomas, including two with multiple lesions, involved the distal third of esophagus. The median tumor diameter was 6 cm. Epithelioid morphology, moderate atypia, and pigmentation were typical findings. None of the patients had melanoma elsewhere, and all tumors exhibited a junctional peri-epithelial component consistent with a primary lesion. The median mitotic activity was 11 per 10 high-power fields (range, 0–31). Nine patients died of tumor within 4–22 months, however, two showed long-term (96 and 104 months) survival. In 15 cases, tissue for further immunohistochemical and molecular studies were available. BRAF, KIT, and NRAS mutation status was assessed by Sanger sequencing in all 15 tumors. The next-generation sequencing of 50 or 409 genes was performed in five and three cases, respectively. IGF1R expression indicating activation of the IGF axis was seen in 82% (9/11) of tumors. However, no BRAF mutations were identified. In 33% (5/15) of tumors, NRAS mutations were detected. KIT expression was seen in 50% (7/14) of melanomas including single KIT mutant. Two of three tumors evaluated with 409 genes panel revealed multiple driver mutations indicating sub-clonal expansion, whereas a single mutation (TSC1 p.H371Q) was the sole change in the third case. SF3B1 p.K666T and p.R625C mutations were detected in two cases. However, no co-occurrence of SF3B1 and GNAQ or GNA11 mutations, seen in uveal melanoma, was detected. FBXW7 p.R465C and p.R479G mutations, linked to cancer progression, were found in two of eight tumors. In summary, esophageal melanoma mutation profile indicates complexity of molecular mechanisms underlying its pathogenesis.

PS02.192: TWO CASES OF PRIMARY MALIGNANT MELANOMA OF ESOPHAGUS TREATED WITH SUBTOTAL ESOPHAGECTOMY

Abstract Background Malignant melanoma of the primary esophagus is rare, in general it has high malignancy and poor prognosis. We report two cases of early-stage primary malignant melanoma of esophagus (PMME) underwent subtotal esophagectomy. Methods Case presentation Results [Case 1]A 66-year-old man was pointed out a black legion on the lower esophagus by upper gastrointestinal endoscope for screening purposes. The lesion was diagnosed as malignant melanoma by biopsy. In addition, another black lesion was also found in the pharynx, but there was no malignant cell. Other examinations did not reveal any findings of lymph node metastasis and distant metastasis. We diagnosed PMME (T1aN0M0 Stage 0) and performed surgical resection. Pathologically it was pT1a (LPM), pN0. There is no recurrence, and it is under observation. [Case 2] A 51-year-old woman was conducted upper gastrointestinal endoscopy for the purpose of scarring epigastric pain, and a black lesion was pointed out in lower esophagus. Surgical resection was performed with diagnosis of PMME (T1bN0M0 Stage I). The pathological stage was pT1a (MM), pN0. Conclusion The 5 year survival rate of malignant melanoma of primary esophagus is poor with about 30 to 35%, and especially in cases with lymph node metastasis, the survival rate further decreases. The both cases were discovered accidentally by endoscopic examination, leading to early diagnosis and early treatment. Therefore, long survival is expected. There is also a report that melanosis is associated with melanoma, so case 1 requires careful follow-up observation. Disclosure All authors have declared no conflicts of interest.

Primary malignant melanoma of esophagus shared similar genetic characters with both cutaneous and oral mucosal melanoma

We read with interest of the letter to the editor by Dr. Krauthammer. We appreciate the author for sharing his experiences in melanoma genome research, especially his insights into different melanoma subtypes. Primary malignant melanoma of esophagus (PMME) is subtype of mucosal melanoma, just like other subtypes of mucosal melanoma, it was difficult to make sure whether it was a primary mucosal melanoma or a metastasis site which originated from a cutaneous site.

Clinicopathological characteristics, staging classification, and survival outcomes of primary malignant melanoma of the esophagus.

Primary malignant melanoma of esophagus (PMME) is a remarkably rare and highly aggressive tumor. Studies related with clinicopathological findings, staging classification, and clinical outcomes are lacking. We reviewed 21 cases of PMME at the Tianjin Medical University Cancer Institute and Hospital from January 2002 to February 2017. Nineteen patients (90.48%) presented a history of dysphagia for months, and two (9.52%) experienced retrosternal pain. Histologically, tumors were composed of atypical melanocytes with melanocytosis surrounding the tumor. The overall survival was 1-40 months, with the median time of 10 months. The mucosal staging classification for upper aerodigestive tract showed better distribution of overall survival with different stages than that of the American Joint Commission on Cancer staging classification for esophagus, but without statistical difference. Both the clinical and pathological characteristics were not highly consistent with overall survival. PMME is a considerably aggressive tumor with poor prognosis. The staging classification of mucosal melanoma of the upper aerodigestive tract may be a good option for PMME patients.

Melanoma maligno primario atípico de esófago y su manejo quirúrgico: a propósito de un caso clínico

Introduction: The Primary Malignant Melanoma of Esophagus is an uncommon and very agressive tumor. With controversial management, it predominates the surgical treatment in localized disease. Clinical case: We present the case of a young women with Primary Malignant Melanoma of Esophagus with atypical presentation and its surgical management using the Akiyama technique.

Primary Malignant Melanoma of the Esophagus

Introduction: Primary malignant melanoma of esophagus (PMME) accounts for 0.1%-0.5% of malignant tumors of esophagus. Since the first report of PMME, there have been about 300 cases. It occurs in the 6th and 7th decade with a 2:1 male to female ratio. It is assocaited with abnormal melanocytes and hyperplasia. Most commonly located in the middle and lower segments of esophagus. Case report: 73-year-old female with alcoholic cirrhosis presented with three months of fatigue, dyspepsia, regurgitation, dysphagia, diarrhea and vomiting. Denied significant weight loss. There were no skin lesions or lymphadenopathy. Abdomen was non-tender, but moderately distended with splenomegaly. CT chest/abdomen/pelvis demonstrated a large middle mediastinal mass measuring at 7.1 x 6.1 x 8.4 cm that extended to the posterior mediastinum inseparable from a markedly thickened esophagus. Esophagram revealed an irregular 5cm long stricture and soft tissue mass in the posterior mediastinum. Esophagoscopy revealed an 11cm ulcerating mass with malignant stricture originating 24cm from the incisors. Histopathology showed ulcerated necrotic debris and foci of tumor with chronic inflammation. The cells were polygonal with mild nuclear pleomorphism and mild to moderate amount of amphophilic cytoplasm. The tumor was positive for Vimentin, S100 protein and MART1. Consistent with malignant melanoma of the esophagus, T4N2N3Mx Stage IIIC. Due to the advanced stages and the patient's comorbidities, the patient was not a candidate for surgical resection or chemotherapy. The patient received palliative radiotherapy for dysphagia and tracheal compression. Discussion: PMME has high metastatic potential with 40-80% incidence of distant metastasis at diagnosis. Over 70% of the chief complaints are dysphagia and epigastralgia. The typical radiological finding on a barium esophagogram is lobular, polyploidy, or segmented tumor typically extending horizontally. The characteristic endoscopic finding is a pigmented polyploidy lesion. Definitive diagnosis is made by immuno-histochemical examination with positive S100 protein, HMB45 and neuron-specific enolase. Surgical resection is an effective treatment for early stage PMME. The postoperative 5 year survival rate is 37%. Postoperative adjuvant chemotherapy does not increase the survival, but is palliative. Recent studies show potential with immunotherapy. Patient with advanced inoperable PMME can benefit from the radiation therapy.

Primary Malignant Melanoma of Esophagus Treated with Endoscopic Mucosal Resection and Esophagectomy

A 74-year-old male with a long-standing history of chronic lymphocytic leukemia presented with dyspepsia. Upper endoscopy showed a subtle bluish 3–5-mm discoloration in the esophageal mucosa at approximately 20 cm from the incisors (Fig. 1). Biopsies demonstrated melanoma in situ and focal invasion into the superficial sub-mucosa, associated with melanosis, and consistent with primary esophageal melanoma (PMME, Fig. 2a, b). The cells stained positive for S-100 and MART-1a, which confirmed PMME. In an attempt to stage and treat the lesion, endoscopic mucosal resection (EMR) was done using the band and snare method. Pathology revealed an extensive in situ melanoma and a small cluster of invasive melanoma at one margin of excision within the sub-mucosa. A repeat EGD and biopsy demonstrated residual melanoma in situ at the margins of the resection. Repeat EMR was discussed; however, the patient wished to proceed with a transhiatal esophagectomy with cervical esophagogastric anastomosis. The surgical specimen revealed a 4.0×2.5-cm area of black–brown mucosal discoloration, located 1.5 cm form the proximal margin of resection. Microscopic sections showed extensive residual intramucosal melanoma involving the discolored area, the proximal cervical margin and random sections of mucosa away from the discolored area (Fig. 3a, b). Thirty weeks after the surgery, the patient is clinically stable except for cervical dysphagia for which he is treated with dilatations.

Primary malignant melanoma of esophagus: report of a case

患者女,64岁.因心窝部隐闷不适3个月,于2008年5月19日就诊于本院消化内科.患者既往无肿瘤病史,仔细检查体表皮肤、黏膜未见肿瘤生长,予以内窥镜检查.内窥镜下见食管上中段黏膜光滑,下段距门齿32～40 cm食管黏膜见散在蓝色斑点,靠贲门齿状线处黏膜颜色加深呈蓝黑色,贲门右侧壁黏膜小片状粗糙隆起,略呈结节状,活检6块,质地有弹性。

Primary malignant melanoma of esophagus: Report of four cases and review of the literatures

Objective: To investigate the clinical features and prognosis of the primary malignant melanoma of esophagus, to try to find out a rational therapy and to evaluate the value of surgical resection. Methods: Retrospective study was conducted for four cases with Primary malignant melanoma of esophagus hospitalized from May 1975 to April 1999. The relevant literatures of primary malignant melanoma of esophagus in recent years were also reviewed. Results: Four patients received multimodality therapy including surgical resection. The survival time is 16 years, 53 months, 5 months and 6 months, respectively. Conclusion: Primary malignant melanoma of the esophagus has a poor prognosis. Surgical resection plays an important role and is indispensable. The patterns of combination treatment modality need further investigation. Preoperative therapy combined with surgical resection and post-operative therapy may be a better management.

縦隔鏡補助下経食道裂孔的食道切除術を行った食道原発早期悪性黒色腫の１例

縦隔鏡補助下経食道裂孔的食道切除術を行った食道原発早期悪性黒色腫の１例