| Japanese Journal of Clinical Oncology | Pages |
Introduction
Case report
Discussion
References
Primary Malignant Melanoma of the Esophagus: Report of a Case Successfully Treated with Pre- and Post-operative Adjuvant Hormone-Chemotherapy
INTRODUCTION
The concept of malignant melanoma of the esophagus as a primary disease was widely accepted in 1963, when De La Pava et al. (1) identified melanocites in the sub-mucosa of 4% of normal esophagus at autopsy examinations. In 1974, Tateishi et al. (2) confirmed these findings when they demonstrated an incidence of 8% in Japanese subjects. This malignant melanoma is very rare and accounts for 0.1-0.5% of all primary malignant neoplasms of the esophagus (3-5). Of the approximately 180 cases that have been reported to date (6), only about 30% of the patients survived more than 1 year after the initial diagnosis (7). The aggressive biological behavior of this disease, advanced stage at the time of the diagnosis and the lack of effective therapy have all contributed to its poor prognosis. In most cases, the correct diagnosis is revealed just after examination of the surgically resected specimen or at autopsy. However, with the development of specific antibodies and immunostaining techniques, an accurate pre-treatment diagnosis is possible. We present here the case of patient with long survival treated with hormone-chemotherapy during the pre- and post-operative period and radical esophagectomy with lymph node dissection.
Case report
The patient, a 45-year-old Japanese man, was referred to our hospital on the suspicion of esophageal cancer. A gastrointestinal barium examination had shown a filling defect of around 6 cm in the middle thoracic esophagus (Fig. 1). The patient was in good health without any complaint and underwent this examination as part of a routine medical check-up.
Figure 1. Esophagram showing a filling defect in the middle thoracic esophagus and an accessory lesion distal to the main lesion (arrow). There was no special history of family or past disease, but the patient had smoked about 40 cigarettes and drunk 1000 ml of sake (Japanese alcoholic beverage) every day for the prior 25 years. At the physical examination, no abnormality was encountered and the cervical lymph nodes were not palpable. The results of routine hematology and blood biochemistry tests were all within normal limits. The lung function test was compatible with a restrictive pattern. An upper endoscopy showed a polypoid, gray, ulcerated mass without bleeding beginning 28 cm from the incisors and extending to 34 cm (Fig. 2). Toward the anal end, 1-2 cm from the lower border of the tumor, a dark elevated intramural metastatic mass of around 1 cm was also visualized. The melanosis was not seen in the normal esophageal mucosa. Figure 2. Endoscopic examination revealed an ulcerated, dark, polypoid mass without bleeding. Microscopic examination of endoscopically biopsied specimens revealed that the tumor consisted mostly of spindle cells with vesicular nuclei, but in the junctional or subepithelial areas, the tumor cells were polyhedral, with an epithelioid appearance with large, irregular nuclei and prominent nucleoli (Fig. 3A and 3B). Numerous tumor cells had a large amount of melanin pigment in the cytoplasm (Fig. 3). These findings were compatible with melanoma and because no other foci of melanoma were found in any part of the body, the diagnosis of primary malignant melanoma was established.
Figure 3. Microphotograph of the resected specimen. (A) The tumor consisted of plump spindle cells with elongated cigar-shaped vesicular nuclei and staining revealed occasional Masson-Fontana-positive cells (×320). (B) The tumor cells showed multiple junctional changes (H.E., ×80). Computed tomography (CT) of the chest showed the mass located in the mild thoracic esophagus restricted to its wall. Enlargement of the pericardial lymph node was observed, which was probably secondary to tumoral dissemination, although no other metastasis was detected (Fig. 3). Pre-operative chemotherapy consisting of one course of dacarbazine (DITC) 1000 mg/m2, nimustine (ACNU) 100 mg/m2 and cisplatin (CDDP) 105 mg/m2 intravenously and tamoxifen (TAM) 20 mg orally once daily for 5 days was started. Twelve days later, the effect of the treatment was assessed by the esophagograms, and regression in tumor size of around 30% was observed. Two weeks after the chemotherapy, the patient underwent a subtotal esophagectomy and proximal gastrectomy via a right thoracotomy and laparotomy. The paraesophageal, right cardiac and left gastric artery lymph nodes were dissected. Reconstruction was performed by pulling up the stomach tube via the posterior mediastinal route. The patient's operative course was complicated by ileus, which was resolved with conservative treatment. During recovery, every 4 weeks starting 3 weeks after the operation, the patient received an additional three courses of chemotherapy with the same drugs and doses except for ACNU, which was given every other cycle. The patient has not suffered from severe side effects except for minor bone marrow suppression during these treatments. The resected specimen was a 4.2 × 3.7 cm ulcerated, dark polypoid mass. The accessory dark lesion was identified around 1 cm distal to the main tumor (Fig. 4). Microscopic findings confirmed the diagnosis of malignant melanoma with the intramural metastasis. The depth of invasion was to the submucosa layer and the infiltration of tumor cells was microscopically observed in the lymphatic vessels with the tumor but not in the vascular vessels. The surgical edges were free of microscopic invasion, but the pericardial and left gastric artery lymph nodes were positive for metastatic dissemination. Radiological and clinical evaluations during the post-operative 32 months of follow-up have not revealed evidence of recurrence or metastasis. The patient is alive and asymptomatic. Figure 4. Photograph of the resected specimen revealing a 4.2 × 3.7 cm, polypoid, ulcerated mass and a distal accessory dark lesion (intramural metastasis). The prognosis of patients with primary malignant melanoma of the esophagus is very poor. Undoubtedly, the aggressive nature of the disease is an important factor for its dismal evolution. The correct diagnosis is often made only at an advanced stage or at time of autopsy (7,8). Our patient was totally asymptomatic and the esophageal tumor was discovered only after a routine medical check-up. The endoscopic view of the gray, pigmented, polypoid tumor accompanied by a distal dark, apparently sub-mucosa accessory mass was highly suspicious of melanoma. However, in most cases, this tumor is mis-diagnosed; small cell carcinoma (8), carcinosarcoma (3,9), epidermoid carcinoma with prominent spindle-cell features, sarcomas or metastatic melanoma to the esophagus (10) are first considered. Often, endoscopic biopsies can be wrongly diagnosed as poorly differentiated squamous cell carcinoma (11), especially in amelanotic melanomas (12). The biopsied sample revealed the presence of histological features similar to those observed in malignant melanoma elsewhere in the body. Nevertheless, the presence of tumor cells around the basal layer of the squamous epithelium in the overlying mucosa of the tumor, termed junctional changes, that were initially developed by Allen and Spitz (13) and are present in only around 40% of reported cases (6,7,14), demonstrated the primary nature of the tumor. Moreover, with a meticulous physical examination and clinical history of our patient, metastatic origin was ruled out (15). However, the enlargement of pericardial lymph nodes observed by chest and abdominal CT suggested lymph node metastasis. In fact, at the time of diagnosis, around half of the patients with esophageal melanoma already have metastatic disease (16) and the routes of dissemination are both lymphatic and vascular (17). The thoracic, celiac and supraclavicular lymph nodes and liver, lung, pleura, peritoneum and brain are mainly affected (6). In primary esophageal cancer, other than melanoma, surgical resection is the standard treatment. Pre-operative chemotherapy alone or in combination with radiation has recently been demonstrated to induce pathological downstaging and increase survival (18,19). Regarding primary melanoma, this approach has not been attempted, probably because of the small number of pre-operative diagnosed cases and until now, if the condition of the patient is stable, surgery is considered the best treatment, with radical resection (8,11,14). The theoretical possibilities of downstaging of the tumor and of treating micrometastasis led us to consider the pre-operative chemotherapy approach. For melanomas, various drugs alone or in combination, including vinblastine, bleomycin, lomustine, vincristine and recently recombinant interferon-alpha and interleukin-2, have been used with varying results (20-23). The regimen of DITC, BCNN (carmustine), CDDP and tamoxifen, which produced promising results in melanoma patients with advanced disease as reported by Del Prete et al. (24), is a combination of drugs that has been widely studied. Several investigators (in particular, McClay and co-workers) have reconfirmed the suitability and good results of such chemo-hormone combinations and the modulatory effects that tamoxifen exerts over CDDP (25-28). Although this regimen had not been used against esophageal melanomas, we decided to administer one course during the pre-operative period (BCNN was replaced by ACNN, with a similar mode of action) and we observed considerable regression of the tumor size. Three additional courses after the operation completed this regimen. The dissection of regional lymph nodes that is routinely performed in patients with esophageal cancer has not been completely accepted with regard to esophageal melanoma (6). However, in the light of the high incidence of dissemination to lymph nodes (as in our patient) and the possibility of lymphatic recurrence, this approach has been advocated in some reports (5,8,29) and was also selected by us. In general, the prognosis of these patients is very poor, with asurvival of 2.2% at 5 years (1) and a median survival of about 10 months. Although our patient had advanced disease (lymph node metastasis), he is alive 32 months after surgery without evidence of recurrence or metastasis. The pre- and post-operative chemotherapy and radical surgical procedure with lymph node dissection probably contributed to his satisfatory outcome.
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References
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Last modification: 24 Nov 1998
Copyright©Japanese Journal of Clinical Oncology, 1998.
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