Jacob M. Kusmak, Resident Physician, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD; Bradley C. Thaemert, General Surgeon, Surgical Institute of South Dakota, Sioux Falls, SD
Jacob M. Kusmak, MD, PharmD
Sanford School of Medicine
University of South Dakota
Sioux Falls, SD
Bradley C. Thaemert, MD
Surgical Institute of South Dakota
Sioux Falls, SD
Primary malignant melanoma of the esophagus (PMME) is an extremely rare disease, accounting for an estimated 0.1% of esophageal tumors.1,2 Prognosis for this disease is poor, with a 5-year survival rate of less than 5%.2 Approximately 240 cases of PMME have been reported in the medical literature, with only a minority of these presenting as the amelanotic type. We report a case of an amelanotic PMME in a 68-year-old woman, who was treated with esophagogastrectomy and chemotherapy. We also discuss the incidence, diagnosis, and treatment of these rare esophageal tumors.
A 68-year-old white woman presented to the emergency department with a 2- to 3-month history of chest pain and dysphagia that worsened upon consuming liquids. The patient was a nonsmoker and noted no changes in her weight. A cardiac investigation and a physical examination were unremarkable. Esophageal endoscopy demonstrated a 1-cm mass at the gastroesophageal junction. The initial biopsy was consistent with a malignant gastrointestinal spindle-cell tumor. Additionally, a colonoscopy revealed a small sessile polyp in the ascending colon, which was determined pathologically to be a benign tubular adenoma. The patient was referred for surgical consultation regarding the esophageal mass.
After discussing the risks and bene%uFB01ts of both surgical and nonsurgical therapeutic options, esophagogastrectomy was planned. An esophagogastrectomy via an Ivor-Lewis approach, pyloroplasty, and feeding jejunostomy were performed, and, macroscopically, the tumor-affected area was completely excised. The operation proceeded without complications.
Pathological evaluation of the surgical specimen revealed a 1.8 x 1.6 x 0.8-cm, %uFB01rm, homogenous, tan-white mass, arising at the gastroesophageal junction. Microscopically, the specimen was noted to have a zone of atypical cells with nuclear enlargement and prominent nucleoli. High magnification revealed spindle-shaped tumor cells with ill-de%uFB01ned cytoplasmic borders, nuclei with coarse chromatin pattern and nucleoli, and few mitotic %uFB01gures. The tumor demonstrated pushing borders and convergence towards the super%uFB01cial muscularis propria. Four lymph nodes were noted in the specimen, all with benign features. Immunohistochemical stains revealed the tumor cells were negative for AE1/AE3, CD34, CD117, actin, and chromogranin, but were positive for Melan-A (Figure 1). The %uFB01nal pathology report revealed a diagnosis of amelanotic PMME arising at the gastroesophageal junction and extending into the submucosa, with negative margins and benign lymph nodes.
Although the initial endoscopic biopsy indicated a gastrointestinal spindle-cell tumor, pathological examination of the surgical specimen was more accurate because a larger sample of tissue was examined and immunohistochemical stains were used. Due to the extremely rare incidence of PMME, an outside medical center was also consulted for a second opinion and con%uFB01rmed the diagnosis. Despite the fact that surgery was undertaken for a suspected spindle-cell tumor, the patient would still have undergone surgical resection had the initial biopsy indicated PMME.
Postoperative studies included plain radiographs and computed tomography (CT) scans of the chest, abdomen, and pelvis, which were unremarkable for primary or metastatic malignancy. The esophagus was determined to be the tumor's primary site after a thorough evaluation ruled out other sites, such as the skin, eyes, and anus. The patient's only postoperative complication was a slow return of gastrointestinal function, and she was discharged to home on postoperative day 18.
At 2-month follow-up, she still had signi%uFB01cant dysphagia to solids and liquids but noted some improvement in these symptoms, and tube feedings were used effectively and tolerated. A positron emission tomography (PET)/CT scan was performed for staging and did not reveal any metastatic disease. However, a 2-month postoperative esophageal endoscopy revealed a 3- to 4-mm tight stricture at the anastomosis site, and dilation was performed to expand the lumen to 15 mm. A repeat esophageal endoscopy 3 weeks later revealed another stricture, and subsequent dilation to 20 mm was performed. In addition, a mass was noted at the middle region of the esophagus, approximately 10 cm proximal to the anastomosis, of which biopsies were obtained. Pathological evaluation of these biopsies noted similarities to previous surgical specimens, which were consistent with recurrent amelanotic malignant melanoma (Figure 2). PET/CT scans were performed and again demonstrated no evidence of abnormal uptake.
After surgical evaluation and discussion, it was determined that the patient was not a candidate for a total esophagectomy. This conclusion was also reached after consultation with a thoracic surgeon at an outside facility. Additionally, a radiation oncology consultation determined that the patient was not a candidate for thoracic radiotherapy. Chemotherapy was then initiated, with temozolomide administered at 200 mg/m2 for 5 days, cycled every 28 days. After eight cycles of temozolomide, a repeat endoscopy and biopsies were negative for the disease, which indicated a complete response, and chemotherapy was stopped. An endoscopy 8 weeks later, however, yielded positive biopsies, and temozolomide was restarted. At the time of publication, this patient has survived 35 months after diagnosis of amelanotic PMME.
PMME is an extremely rare disease, accounting for approximately 0.1% of esophageal tumors.1,2 The esophagus usually lacks melanocytes, but research has indicated that they may be found occasionally in the esophagus because of aberrant migration and homing during embryogenesis.3 As with skin melanomas, PMME is thought to develop because of malignant degeneration of these preexisting melanocytes.4 Since the %uFB01rst report by Baur in 1906, there have been approximately 240 cases of PMME reported in the literature.5,6 In the United States, the incidence is estimated to be 8 new cases annually.3 The disease occurs twice as frequently in men as in women and usually affects individuals in their %uFB01fth through seventh decades of life, with a mean age of 59.6 years.2,7 There have been a few reports of PMME in the pediatric population, with Basque and associates reporting the %uFB01rst case in a 7-year-old child in 1970.2,8 Although some of the literature explains that there is no subpopulation at de%uFB01nite risk, other reports state that whites are almost exclusively affected, while still other sources indicate that there are more cases in Japan.2,6,9
At presentation, the most common symptoms of PMME include some form of dysphagia, vague retrosternal or chest pain, weight loss, hematemesis, or melena.2,6 PMME also has been an incidental %uFB01nding after routine radiological examination.10,11 Most often, esophageal endoscopy is performed and reveals an abnormal polypoid mass, of which biopsies are obtained and evaluated pathologically.7,12 In 90% of the documented cases, PMME was found in the distal two-thirds of the esophagus, where there is a greater concentration of melanocytes.2
Pathologically, melanomas of the esophagus are polypoid, may be multiple, and have a propensity for lateral spreading.3,9 They are classi%uFB01ed as primary if there is no evidence of melanoma in the skin, eyes, or internal organs. Microscopically, epithelioid, spindle-cell, and pleomorphic areas may be seen singly or in combination. In addition, pathology and gastroenterology sources state that in situ or junctional melanoma must be evident in the mucosa adjacent to the tumor.3,9 The amount of melanin that is present may be highly variable, with approximately 85% of the tumors presenting as pigmented and the remaining classi%uFB01ed as amelanotic.2,3 Con%uFB01rmation with immunohistochemical stains is needed for appropriate diagnosis of all melanomas of the esophagus. Most commonly, positivity with S100 and HMB45 are used in making the diagnosis, but research has also indicated the usefulness of Melan-A and tyrosinase positivity.3,9,13,14
Prognosis of PMME is poor. At the time of diagnosis, it is estimated that 30% to 50% of patients have lymph node or distant metastases to the mediastinum, liver, lungs, and brain.5,7,8,10 Treatment of PMME may incorporate many documented methods, including surgery, chemotherapy, radiotherapy, and immunotherapy. It is reported, however, that in approximately 33% of cases, only the symptoms were treated.2 The mean survival after diagnosis is 13.4 months, with only 4.2% of patients surviving for 5 years.2,15 Since the disease is so rare, no standard or recommended method of treatment is recognized, but in most cases esophagectomy is undertaken.6,16
In the few cases in which survival was reported as longer than 5 years, and even up to 12 years, patients underwent total or near-total esophagectomy.6,16 In an article by Volpin and colleagues, it is reported that the highest response rate (approximately 50%) is achieved using combined chemoimmunotherapy.6 In a case report by Matsutani and associates, a patient received an esophagectomy followed by postoperative chemotherapy and died 15 months after the operation.10 Sudhamshu and colleagues reported a case in which a trial of heavy-ion radiotherapy was performed after a patient refused surgery.11 Although endoscopic evidence of tumor was negative at 4-month follow-up, small metastatic lesions were noted in the lungs and liver at 5 months. Chemotherapy was initiated, but the patient died after 27 months of treatment. Other reports describe radiotherapy, with or without surgery, but the conclusion is that radiotherapy does not signi%uFB01cantly affect survival.6 Herman and associates describe a case in which endoscopic ablation and interferon therapy were used, which resulted in no signs of disease in the patient after 25 months.5
Because of the extremely low incidence of PMME, especially the amelanotic type, no treatment guidelines for this disease have been established. A thorough review of the literature indicates that most patients who experienced longer-term survival had undergone surgical esophagectomy as part of their treatment. In the case of our patient with amelanotic PMME, esophagogastrectomy combined with chemotherapy has yielded positive results. The patient is still alive 35 months after the condition was diagnosed. Although the prognosis is poor, surgical resection offers the best chance for extending survival in patients with PMME.