Malignant melanoma is a relatively rare tumor comprising 1-3% of all tumors and exhibits an unusual tendency to metastasize to the GI tract . Although frequently seen in autopsy series in up to 50 to 60% of patients, only 2 to 5% of patients are diagnosed with metastatic malignant melanoma to the GI tract while they are still alive . It is because that there are no specific symptoms of early development, which are general and constitutional; and even if metastases do occur, they are usually accompany with symptoms such as abdominal pain (62%), hemorrhage (50%), nausea and vomiting (26%), mass (22%), intestinal obstruction (18%), or intussusceptions (15%), and are frequently diagnosed in an emergency situation . Metastasis to the GI tract is seen most frequently in the small intestine, followed by the colon, stomach, and rectum, but is rare in the esophagus. However, primary malignant melanoma originating in the small intestine and particularly in the duodenum is extremely rare, with only a few case reports [1, 6, 7].
There are different theories concerning the origin of primary malignant melanoma in the small bowel, though the controversy still exists over the presence of primary malignant melanoma in this area. Some proposes that malignant melanoma may originate from neural crest cells. These multipotential cells migrate through the body and can get to the bowel via the umbilical-mesenteric canal, where they later differentiate into specialized cells . Although not consistently confirmed, another theory suggests that malignant melanoma might potentially develop from amine precursor uptake and decarboxylation (APUD) cells . Besides, it is presumed that the small intestine normally contains melanoblasts, which may support the assumption of primary development of melanoma at this site.
Before making the diagnosis of primary malignant melanoma of the small bowel, thorough systemic examination must be done to rule out the possibility of metastasis from other sites, which may preferentially develop on the skin, retina, anal canal, or under the nail, and less frequently at other locations such as the esophagus, penis, or vagina. In addition, there should be no history of previous removal or spontaneous regression of any atypical melanocytic skin tumor . The following diagnostic criteria have been occasionally proposed. According to Sachs et al., primary malignant melanoma in the small bowel is diagnosed where there are: 1) biopsy-proven melanoma from the intestine at a single focus; 2) no evidence of disease in any other organs including the skin, eye and lymph nodes outside the region of drainage at the time of diagnosis; and 3) disease-free survival of at least 12 months after diagnosis. According to Blecker , it is diagnosed when there is lack of concurrent or previous removal of a melanoma or melanocytic lesion from the skin and lack of any other organ involvement and in situ change in the overlying or adjacent GI epithelium. In this case, one single focus located in the lateral of the descendant duodenum, and thorough postoperative investigation including a detailed history, clinical examination, endoscopic assessment, and radiologic imaging failed to reveal any evidence of a pre-existing primary tumor or any other metastatic lesion. Moreover, the patient has survived for more than 46 months with no evidence of loco regional recurrence or distant metastasis. Thus, we felt confident in supporting the diagnosis of PMMD.
Although the possibility of primary malignant melanoma in the small intestine does exist, the incidence is extremely low. In addition, melanoma by itself is a great mimicker of other neoplastic conditions . It is very easy to diagnose for the cases with obvious melanin pigment, but sometimes, the specimen only with little pigment or without any visible pigment, which may create a major diagnostic challenge, must be differentiated from other common intestinal tumors like lymphoma, carcinoma of poor differentiation, neuroendocrine tumor, leiomyosarcoma, GIST (Gastrointestinal Stromal Tumor), et al. More sections as far as possible and careful observation can help to find valuable diagnositic clues. Furthermore, immunohistochemical staining and electron microscope detection may play an important role for differential diagnosis. In our patient, the initial frozen sections revealed the tumor cells were relatively uniform with markedly cytologic atypia and abundant mitotic figures, so the pathologists favored lymphoma or carcinoma of poor differentiation, which were the most common malignancies of the duodenum. But further immunohistochemical stains provided no evidence for above diagnoses. By more careful observation, we found the discohesive tumor cells had one or more large eosinophilic nucleoli, which were one of the main features of melanoma apart from visible melanin pigment, so malignant melanoma - a very rare malignancy in this site should be taken into consideration. Expression of some specific markers such as HMB45, Melan-A and S-100 protein is required to confirm our conjecture.
Optical treatment for malignant melanoma is an extensive and curative surgery, if possible, because other methods including adjuvant radiotherapy, chemotherapy and immunotherapy cannot offer definite treatment outcome. The time of diagnosis and the presence of metastases are supposed to represent major determinants of prognosis [10, 12]. The median survival after curative resection of primary malignant melanoma of the small intestine is 49 months ; the longest reported survival is 21 years . To the best of our knowledge, our patient refused chemotherapy and just used Chinese traditional medicine intermittently. Now he has achieved disease-free survival of more than 46 months without any evidence of recurrence. The certain mechanism of Chinese traditional medicine is still unclear and always be regarded as complicated, sometimes even mysterious. Nowadays, one of generally accepted opinions is that it can enhance patients’ immunity efficiently. But melanoma is destined to behave aggressively, and widespread metastases may present as a late complication. Furthermore, the Ki-67 labeling index in this case was greater than 60% and the patient had one mesentery lymph node involved. This highlights the need for close and long-term follow-up.