Malignant melanoma of the small bowel presenting with intussusception in a woman: a case report

Abstract

Primary malignant melanoma originating in the small bowel is very rare. We report the case of primary malignant melanoma of the small bowel with secondary intussusception in a 51-year-old female with no prior history of cutaneous melanoma. The patient was admitted to the hospital for clinical bowel obstruction after 6 months of varying symptoms of antecedent syncopal events secondary to profound anemia due to iron deficiency followed later by vomiting, abdominal pain and weight loss. A CT scan showed intussusception and she underwent a small bowel resection. Diagnosis of malignant melanoma was confirmed post-operatively following immunohistochemistry. The patient history and postoperative investigation excluded the existence of a primary lesion elsewhere. Our case represents an aggressive primary small bowel melanoma presenting as intussusception.

Practice points.

• Primary melanomas preferentially occur on the skin, retina and anus but can also occur occasionally at other locations like the esophagus, penis or inside the vagina.

• When a melanoma is found elsewhere, these locations should be assessed to determine the possibility of a previous primary melanoma.

• Malignant melanomas involving the GI tract are most commonly treated by surgical resection.

• High-risk features in the primary tumor and regional lymph node metastasis define patient subsets that are at increased risk for recurrent disease and therefore a candidate for adjuvant therapy.

• The few recorded cases of the long-term clinical outcome of patients with primary small bowel melanoma suggest a poor prognosis with surgery alone.

• The Eastern Cooperative Oncology Group is conducting a clinical trial to study the differences in outcome between two adjuvant therapies, ipilimumab and high-dose IFN-α-2b, in treating patients with high-risk stage III–IV melanoma that has been removed by surgery.

• It is not yet known whether ipilimumab is more effective than IFN-α-2b in treating patients with melanoma.

Malignant gastrointestinal melanomas are relatively rare and frequently metastasize from cutaneous primary sources. However, primary melanoma may also originate in regions of the GI tract such as the esophagus, small intestine, rectum and anus [1]. Only a limited number of cases have been reported in the literature [2]. The highest rates of primary gastrointestinal malignant melanoma are seen in the anorectum due to the presence of melanoctyes [3,4]. The small intestine is believed to have the highest predilection for the development of metastatic melanoma due to its abundant blood supply, allowing for metastasis from distant sites such as the skin [3,4]. Although small bowel involvement by malignant melanoma is most frequently metastatic, a primary mucosal origin at this site has been reported in rare cases. Diagnosis is difficult due to nonspecific symptoms and because tumors are often undetectable by endoscopy and colonoscopy.

Whether a metastatic melanoma of the GI tract originates from an unknown or regressed primary lesion or originated in the GI tract itself is difficult to distinguish. However, early diagnosis is important due to the malignant nature of melanoma. Median survival for patients with primary noncutaneous melanoma is 4–6 months. The 5-year survival rate for stage IV melanoma is less than 10% [4]. Despite poor prognosis, surgical resection alone remains the mainstay of treatment for patients with small bowel melanoma with little evidence confirming benefit of combining adjuvant immunomodulatory therapy. In this paper, a case of primary small bowel malignant melanoma presenting as intussusception is reviewed.

Case description

A 51-year-old Caucasian female presented to the emergency department (ED) on New Year’s Eve after having two episodes of syncope as well as having passed melena that day. She had never before experienced these symptoms. The patient’s past medical history included hypothyroidism, iron deficiency anemia and headaches, but no prior record of malignant melanoma. Her medications included with levothyroxine 75 mcg orally once a day and sumatriptan 50 mg orally once a day as needed. The patient underwent a hysterectomy more than 5 years earlier for menorrhagia and has not had a period since. She was a former smoker, admitted to occasional alcohol use and denied illicit drug use. Her family history revealed psoriatic arthritis, hypertension and Crohn’s disease. She was a Fitzpatrick type II skin type with fair skin and blonde hair. She had a history of blistering sunburns and subsequently used sunscreen regularly.

After arrival in the ED, rectal exam revealed melena in the rectal vault with a hemoccult-positive test. Otherwise, ENT, cardiovascular, pulmonary and abdominal exams were unremarkable. Vital signs were stable. Initially, her hemoglobin was 11.4 g/dl but trended down to 9.4 g/dl. Her labs revealed iron deficiency anemia. The patient was transfused 2 units of packed red blood cells and was evaluated by a gastroenterologist who recommended a panendoscopy. Esophagogastroduodenoscopy (EGD) revealed gastritis, esophagitis and a gastric polyp, which on pathology was just normal gastric mucosa with no significant histopathologic changes. Colonoscopy revealed no abnormal pathology. The patient was discharged and told to follow-up with her primary care physician to manage iron deficiency anemia. She was referred to a hematologist.

The patient later developed loss of appetite in the ensuing months. A video capsule endoscopy was performed which did not reveal any significant findings. The patient continued to experience extreme malaise and fatigue. Her blood counts were monitored and she was recommended to take oral iron, which brought her hemoglobin up to 12.3 g/dl, but she stopped taking it due to gastrointestinal intolerance. Thus, she was recommended and received a course of intravenous iron. This was tolerated well and her symptoms improved.

Approximately 6 months after initial presentation to the ED, the patient started to experience intermittent vomiting associated with evolving abdominal pain and a greater than 20 pounds unintentional weight loss. She was seen again by her gastroenterologist. A gastric emptying study suggested a diagnosis of gastroparesis. The patient was treated with ciprofloxacin 500 mg twice daily and metoclopramide 10 mg as needed with no relief of symptoms.

The patient followed-up with her primary care physician to discuss other potential causes of persistent vomiting and weight loss. The patient was told by her primary care physician to return to the ED for evaluation and was admitted for clinical small bowel obstruction. She was tachycardic (HR: 116 bpm) with borderline hypotension (97/66 mmHg). Physical exam revealed abdominal distention, tenderness in the epigastric and mid-abdominal region, and decreased bowel sounds throughout. A CT scan revealed distention of the stomach and small bowel secondary to a long segment of intussusception seen in the lower abdomen. Additionally on computed tomography, there was a suggestion of a mass in the small bowel just distal to the point of intussusception.

The patient was seen by a general surgeon and, upon review of the CT scan, believed to have intussusception secondary to the large intraluminal, hyperdense mass associated with the small bowel. It was unclear from the CT scan what the true size of the mass was, and so a decision was made to take the patient to the OR for an emergent laparoscopy, possible laparotomy and possible small bowel resection (Figures 1 & 2). Intraoperatively, the area of intussusception was found to be too large to reduce laparoscopically and a midline laparotomy was performed. A 40-cm-long segment was resected. A large heavily pigmented mass measuring 11.5 cm was present. The mucosal surface was ulcerated. Thirteen mesenteric lymph nodes showed no evidence of malignancy. No other abdominal pathology was seen. The postoperative course was uneventful.

Figure 1. . CT scan: transverse cut showing distension and intussusception of the small bowel.

Figure 2. . CT scan: coronal cut showing intussusception of the small bowel.

Pathology of the mass revealed markedly pleomorphic malignant cells with high mitotic rate involving the full thickness of the bowel wall. Immunostains were diffusely and strongly positive for HMB-45 and negative for S100 protein. These findings were diagnostic for metastatic malignant melanoma (Figures 3 & 4). The tumor did not harbor BRAF mutation and c-kit mutation was not found thereby ruling out gastrointestinal stromal tumor.

Figure 3. . H+E stain at 4× showing small bowel mucosa on the right and melanoma on the left.

Figure 4. . H+E stains at 40× zoomed in on the melanoma.

The patient’s medical history was carefully reviewed and no evidence of previous malignant melanoma was found. A thorough full-skin exam was performed by a dermatologist, which revealed a lesion on her anterior neck and one on her central back. Both were excised and found to be atypical-lentiginous compound nevi. There were no other findings suggestive of cutaneous melanoma. A dilated ocular exam did not reveal significant findings to suggest ocular melanoma. Fluorodeoxyglucose-PET-CT scan revealed increased metabolic activity at the liver border but follow-up MRI of her liver did not reveal metastatic lesions. The remainder of the PET scan was unremarkable.

The case was discussed at a multidisciplinary cutaneous oncology tumor board. Recommendation was for 1 year of adjuvant high-dose α-interferon with IFN-α (20 million units/m² 5 days per week for 4 weeks) followed by 10 million units/m² subcutaneously three-times weekly for an additional 11 months. She has no baseline psychiatric illnesses. At the time this case report was written, the patient was receiving subcutaneous interferon three-times a week and reported significant but tolerable side effects including dry mouth, fatigue, arthralgias, low-grade fever and occasional constipation.

Upon completion of 1 year of interferon treatment, the patient will receive a follow-up full-body PET scan. She also will follow-up with her gastroenterologist to periodically survey her GI tract. In the meantime, her dermatologist has been performing a full-body skin exam every 6 months.

Discussion

While it only accounts for 1–3% of all cancers, malignant melanoma has an unusual tendency to metastasize to the GI tract [5]. Interestingly, it has been reported that in only 1–4% of patients gastrointestinal involvement of malignant melanoma was found on imaging or endoscopy [6]. However, in up to 60% of these cases, gastrointestinal metastases were found during autopsy [7]. Among the malignant tumors that may metastasize to the small bowel, malignant melanoma is identified as the primary tumor in 50–70% of cases [6]. Because of these findings, it has long been believed by some that gastrointestinal involvement is generally metastatic. Nevertheless, an increase in the number of primary small bowel melanoma cases are being reported.

Clinical presentation of a small bowel melanoma is typically similar to that of other types of gastrointestinal tumors. Symptoms and findings may include abdominal pain, constipation, melena, anemia, weight loss and fatigue. Intestinal melanoma can present as single or multiple polypoid lesions and, as seen in our patient, can cause intestinal intussusception. Substantial lymphadenopathy indicates spread to the mesenteric lymph nodes. Because of the rich vascular and lymphatic supply of the intestinal mucosa, it is surprising that our patient did not have positive lymph nodes with a mass measuring 11.5 cm. In contrast, positive lymph nodes are certainly expected in metastatic malignant melanoma.

Primary melanomas preferentially occur on the skin, retina and anal canal but can also occur occasionally in other locations such as the esophagus, penis or inside the vagina [8]. Before making the diagnosis of primary melanoma of the small bowel, these potential primary locations need to be considered. There should be no history of prior removal of an atypical melanocytic skin tumor. Blecker et al. proposed the following criteria for the diagnosis of a primary melanoma of the small bowel: presence of a solitary mucosal lesion in the intestinal epithelium; absence of melanoma or atypical melanocytic lesions of the skin; and presence of intramucosal melanocytic lesions in the overlying or adjacent intestinal epithelium [9]. Furthermore, primary intestinal melanomas are usually single solitary pigmented tumors, in contrast to metastatic lesions which are usually multiple and may be pigmented or non-pigmented. We regard the diagnosis of primary small bowel melanoma in the above case because all of these features applied, even after thorough investigation of other potential sites. However, although a melanoma of a more common site could not be identified on multiple exams of our patient, we cannot completely exclude the possibility of a metastasizing melanoma from an unknown primary site that was not found or had regressed.

Malignant melanomas involving the GI tract are most commonly treated by surgical resection of the affected area when involving the small bowel [10]. The long-term clinical outcome of patients diagnosed with primary small bowel melanoma is not well documented but the few recorded cases suggest a poor prognosis with surgery alone [3]. The role of adjuvant therapy is continually evolving. The benefits of immunotherapy are not completely defined for primary malignant melanoma of the small bowel, but ongoing trials with long-term follow-up will determine the optimal adjuvant treatment for patients with this disease [11–13].

Ipilimumab is a monoclonal antibody that blocks a molecule known as CTLA-4. CTLA-4 may play a role in slowing down or turning off the body’s immune system, and affects its ability to fight off cancerous cells. It may work by allowing the body’s immune system to recognize, target and attack cells in melanoma tumors. A Phase III ECOG trial is comparing ipilimumab at two doses versus high-dose interferon as adjuvant therapy for patients previously treated with surgery for high-risk stage III–IV melanoma. This trial does not specifically look at treatment of primary melanoma found in locations other than the skin. The outcomes of those treated with ipilimumab are being compared with high-dose IFN-α-2b. Monoclonal antibodies may interfere with tumor cells ability to grow and divide. IFN-α-2b may interfere with the growth of tumor cells and slow the growth of melanoma and other cancers by interacting with the hosts cells rather than by direct effect on tumor cells [13]. It is not yet known whether ipilimumab is more effective than IFN-α-2b in treating patients with melanoma [14]. More research is needed in order to determine the efficacy of either of these treatments for primary small bowel melanoma.

Conclusion

Melanoma of the small bowel is a rare diagnosis that can cause small bowel intussusception. We report a case of a 51-year-old woman in whom a large solitary malignant melanoma of the small bowel was observed. She underwent resection of the tumor as well as of 13 mesenteric nodes, which were clear of cancer cells. Histopathologic reports confirmed that the tumor was a malignant melanoma and further workup neither detect a possible primary site nor metastatic lesions. At 3 months following surgery, the patient is undergoing immunomodulatory therapy and is, at the time this case was written, doing well.

Comments

Primary malignant melanoma of the GI tract is challenging and controversial to diagnose. Some authors believe that melanoma found outside of its most common location (skin) is metastatic, even if an outright primary site cannot be identified. However, this belief continues to be disputed by evidence and case reports. Due to this conflicting information, it is difficult to establish an appropriate plan of care for these patients outside of surgical resection and close follow-up. New clinical trials are currently in progress to determine optimal adjuvant immunotherapy after surgical resection. The results of these and future case reports will broaden our knowledge of how primary malignant melanoma, and in particular melanoma of the GI tract, can be treated successfully with optimal patient outcomes.