Macroscopically, the esophageal tumors were scattered distributed, the biggest tumor was 7.5 × 3.0 × 0.8 cm in dimension. The cut surface was reddish brown, solid, and tough. Scattered black nodules (the diameter was around 0.2–1.0 cm; Fig. 3A) were observed in the surface of the esophageal mucosa. The gastric body near the lesser curvature showed a 2.0 × 1.5 × 0.4 cm anabrosis, and the cut surface was light brown, solid, and tough (Fig. 3B). Microscopic examination of the gastric body showed poorly differentiated mucinous adenocarcinoma; signet ring cells could also be seen. Superficial muscularis propria was invaded, but metastasis of lymph node was not observed (Fig. 4A). Malignant melanoma infiltration was seen in the esophagus and submucosa was invaded with no lymph node involved (Fig. 4B). Both were primary malignant tumors. Immunohistochemistry staining of the stomach showed CK-pan (+), Ki-67 (+50%), P53 (+<5%), and Her-2 (+) (Fig. 5A), as well as S-100 (±) for the lymph nodes. Immunohistochemistry staining of the esophagus demonstrated Ki-67 (+40%), Melan-A (+) (Fig. 5B), HMB45 (+) (Fig. 5C), CD117 (+), S-100 (+) (Fig. 5D), CK-pan (-), CK5/6 (−), P63 (−), Vimentin (−), and Dog-1 (−). The patient was diagnosed with esophageal malignant melanoma and poorly differentiated gastric mucinous adenocarcinoma. The stage of gastric adenocarcinoma was classified as IB (pT2N0M0), according to the American Joint Commission on Cancer (AJCC) Cancer Staging Manual (8th Edition). The stage of PMME is uncertain because there is no standard staging for PMME as far as we know, and using TNM stage of esophageal cancer or cutaneous melanoma is not accurate in such case. One week after surgery, results of abdominal CT and esophagography were consistent with postoperative changes without any other abnormalities. Two weeks after surgery, chest drainage, mediastinal drainage, and gastric tube were removed, and the patient could start to eat a small amount of liquid food. The patient was discharged with good condition 3 weeks after surgery. Neither radiotherapy nor chemotherapy was performed after surgery, and the patient died after 3 months of follow-up. The patient and his family provided informed consent for this case report. On the contrary, our case does not need ethical approval from ethics committee or institutional review board.
Melanoma is a highly aggressive malignancy that mainly occurs at skin. As a noncutaneous melanoma, PMME has been occasionally reported since 1906. To date, about 337 cases of esophageal melanoma have been published,[4,8] whereas copresentation with gastric cancer has not been reported.
Little has been discussed about the etiology of PMME. Over 80% of the PMME located in the lower and middle thirds of the esophagus because a large number of melanocytes gathered in the location, which was consistent with our observation in this case. It has been indicated that the esophageal melanocytosis is a precancerous lesion of PMME,[9,10] and esophageal melanocytic dysplasia will eventually develop into PMME.[8,11]
The diagnosis of esophageal melanoma is often difficult because it mainly depends on clinical manifestations, endoscopy, and pathology. The clinical manifestations of PMME are not significantly different from other tumors of the esophagus. The most common symptoms is progressive dysphagia as well as, in our case, other symptoms include antiacid, heartburn, retrosternal pain, hematemesis, black stool, and weight loss, whereas a few patients are asymptomatic at diagnosis.[3,12–14] The shape of the tumor can be polypoid, nodular, beaded, or cauliflower-like. In 85% of cases, the lesions had pale, brown, blue, black, or dark-brown pigmentation. Gastroscopy always showed that the lesions were accompanied by ulceration or satellite nodules, which were fragile and easily bled. These were all in consistency with our findings. Although the accuracy rate of diagnosis by biopsy is approximately 80%, we did not perform biopsy in our case because endoscopic ultrasonography showed abundant blood flow signals and biopsy might lead to bleeding. Besides, sometimes the tumors are amelanotic with no melanin granules, concentrated in foci or covered by normal squamous epithelium, which might influence the accuracy of endoscopic biopsy and lead to misdiagnosis.[2,5,17] If histological diagnosis is uncertain, immune-related markers such as S-100 protein, HMB-45, and Melan-A should be performed to improve the accuracy of the diagnosis[3,18] owing to the high sensitivity of S-100 and high specificity of HMB-45 and Melan-A in melanomas. The pathological results in our case confirmed our diagnosis.
There is no standard strategy for the treatment of PMME. The studies on the effects of radiotherapy, chemotherapy, and immunotherapy were inconsistent; some cases reported survival benefits[19–23]; and others did not reach the same conclusion.[2,5,24] Currently, the main treatment for PMME is surgical excision. Radical resection is also the main treatment for early poorly differentiated stomach adenocarcinoma. Although 2 malignant tumors were treated by surgical resection in our case, the patient died 3 months after surgery. The most important prognostic factor noted in the literature is lymph node metastasis, which correlates with worse prognosis. However, based on our experience with this case, lymph node metastasis is not a decisive factor in prognosis, the double malignancy may have significantly reduced the survival time.
In conclusion, the cooccurrence of poorly differentiated gastric adenocarcinoma greatly worsens the prognosis and reduces survival time. Comprehensive examinations should be performed to make the accurate diagnosis. Endoscopic ultrasonography might be useful to diagnose PMME and avoid unnecessary bleeding. The clinical features, endoscopic examinations, and pathological diagnosis of this case may provide important clinical guidance for clinicians developing individualized treatment plans for specific patients.
We thank Editage (www.editage.cn) for English language editing.
XWM and XS designed the study; JL was the major contributor in writing the manuscript; XS performed the histological examination and immunohistochemistry; BW and YL collected the patient data. All authors read and approved the final manuscript.
Methodology: Bin Wang, Xun Sun.
Resources: Yan Liu.
Writing – original draft: Ji Li.
Writing – review & editing: Xun Sun, Xiangwei Meng.
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Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
gastric mucinous adenocarcinoma; multiple primary malignant neoplasms; primary malignant melanoma of the esophagus