Primary malignant melanoma of the esophagus

INTRODUCTION

Primary malignant melanoma of the esophagus is a rare, but aggressive tumor that accounts for <1% of all esophageal neoplasms.[1] Worldwide, approximately only 300 cases have been published in the English literature until date,[2] however, individual case reports have been described in the radiology literature.[34] We report a male patient with histopathologically confirmed primary malignant melanoma of the esophagus and describe the findings of fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT). Esophageal melanoma being an aggressive tumor is FDG avid and FDG PET/CT whole body scan can detect the disease burden with high sensitivity in this tumor subtype.

CASE REPORT

A 50-year-old male had been complaining of dysphagia to solids for about 2 months. His family history was unremarkable. No significant pigmented skin lesion and lymph node swelling were found on physical examination. Routine blood and urine profiles were also unremarkable. Endoscopy showed a large bluish colored intraesophageal lesion with luminal compromise in the entire esophagus. On endoscopic ultrasound, these lesions were heteroechoic, solid, without calcification with difficult to define layer of origin. Fine-needle aspiration cytology was suggestive of poorly differentiated carcinoma. Immunohistochemistry was done on biopsy specimen, which was positive for human melanoma black (HMB)-45, S-100 and vimentin and negative for cytokeratin and p53. CT chest revealed an esophageal mass with a 7 mm nodule in left upper lobe of the lung. No lymph nodes, liver, and skeletal lesions were seen. Based on histologic and immune-histochemical studies, the diagnosis of primary malignant melanoma was made.

Positron emission tomography and CT scan were asked for pre-treatment staging of the disease. PET/CT findings revealed a large, lobulated, expansile, intensely FDG avid, intraluminal, mural and extramural soft tissue mass lesion with exophytic component involving the upper, middle and lower thoracic esophagus [Figures 1 and 4] with FDG avid right supra clavicular and celiac lymph nodes and FDG avid lung [Figure 2] and skeletal metastases [Figure 3]. This patient was advised chemotherapy, but he refused.

Close

Figure 1 A large lobulated, expansile, intensely flurodeoxyglucose avid intra luminal, mural and extra mural soft tissue mass lesion with exophytic component involving the upper, middle and lower thoracic esophagus is seen on the positron emission tomography and computed tomography (PET/CT) and fused PET/CT images

Export to PPT

Close

Figure 2 Fluorodeoxyglucose avid metastatic lesion in left lung

Export to PPT

Close

Figure 3 Fluorodeoxyglucose avid skeletal metastases in posterior spine of dorsal vertebra, right ischium and trochanter of right femur

Export to PPT

Close

Figure 4 Maximum intensity picture image showing a large lobulated, expansile, intensely fluorodeoxyglucose avid intra luminal, mural and extra mural soft tissue mass lesion with exophytic component involving the upper, middle and lower thoracic esophagus

Export to PPT

DISCUSSION

Primary malignant melanoma most commonly originates from the skin; other less common extra cutaneous sites include squamous mucous membranes, uvea, retina, leptomeninges, genitourinary tract, digestive tract, biliary tract, and upper respiratory tract.[5] Primary melanoma of the gastrointestinal tract is exceedingly rare; conversely, cutaneous melanoma is the most common malignancy to metastasize to the gastrointestinal tract. Metastasis to the esophagus is extremely rare.[6] Primary malignant melanoma of the esophagus is a rare condition and has a reported prevalence of 0.1–0.5% of all esophageal malignancies.[1] Esophageal melanoma is twice as common in males than in females, occurring prevalently in the 6^th and 7^th decades of life. This malignancy is most commonly located in the middle or distal third of the esophagus, approximately in 90% of cases, probably because of the greater concentration of melanocytes in these regions.[2] The diagnostic criteria for accepting a melanoma as arising from the esophagus require the presence of melanin granules within the tumor cells as well as melanocytes in the overlying epithelial layer and areas of junctional activity within squamous mucosa and the adjacent epithelium. The more accurate diagnosis is confirmed by immuno-histochemical studies: Primary malignant melanoma of the esophagus typically reveals a positive antibody-specific cytoplasmic reactivity to HMB-45 and S-100 proteins with a negative reaction for cytokeratin or carcinoembryonic antigen. Ruling out a metastatic lesion is important if melanoma is found in the esophagus. Consequently, the diagnosis of primary esophageal melanoma can be accepted only in patients with no history of melanoma and no evidence at physical examination of melanoma involving the skin, eye, anus, or vagina. There is no significant risk factor of primary malignant melanoma of the esophagus. The most common symptoms are dysphagia, retrosternal or epigastric pain, hematemesis, and melena. Physical signs other than weight loss are uncommon. On endoscopy, these tumors usually appear as lobulated and darkly colored masses with intact mucosa or occasional ulceration. They are occasionally misdiagnosed as poorly differentiated carcinoma. The histopathologic diagnosis is usually confirmed after en bloc resection. CT of the thorax reveals a bulky esophageal mass compressing the adjacent mediastinal structures. Approximately, 40.9% of patients are reported to have metastases at the time of diagnosis. The most commonly involved sites are the paraesophageal lymph nodes (10.8%), supraclavicular lymph nodes (7%), liver (7%), lungs (6%), celiac lymph nodes (4%), and bones (2.9%)[7] CT might be useful in demonstrating mediastinal invasion, nodal enlargement, and distant metastatic disease. Magnetic resonance imaging shows high signal intensity masses in the esophagus on T1-weighted imaging due to paramagnetic scavenging by melanin, which helps preoperative diagnosis.

Role of FDG PET/CT has been established in the staging and follow-up of malignant melanoma. Studies have demonstrated that radiolabeled glucose analogs were preferentially taken up in murine melanomas and human melanoma xenografts, setting forth the rationale for the potential use of FDG in patients with melanoma. Owing to its high sensitivity for malignant lesions and the possibility of covering the whole body in one examination, it can supplement other staging tools. Because of the high tumor-to-background ratio, FDG/PET can highlight metastases at unusual sites that are missed with conventional imaging modalities. Furthermore, it provides information on the malignant potential of the detected lesion. Given the relative scarcity of primary melanomas of the esophagus little is known about its application for these tumors.

The radiological differential diagnosis of primary esophageal melanoma includes spindle cell carcinoma, leiomyosarcoma, esophageal lymphoma and Kaposi's sarcoma. The prognosis of primary malignant melanoma of the esophagus is dismal regardless of therapy in comparison with other common primary malignant tumors of the esophagus. The average overall survival is only 10–13 months, with the 5 years survival rate ranging from 0% to 4%.[7] Metastases are present at the time of diagnosis in 40.9% of cases. The most common sites involved at autopsy are the liver (39.3%), mediastinum (34.4%), lungs (24.6%), pleura (19.7%), supraclavicular lymph nodes (19.7%), peritoneum (14.8%), brain (13.1%), kidneys and adrenals (11.5%).[7] The treatment preferred for primary malignant melanoma of the esophagus is surgical resection. A total or near-total esophagectomy is mandatory as the tumor spreads longitudinally. Currently, radiotherapy, chemotherapy, and immunotherapy have not proved beneficial. However, these alternative therapeutic modalities play a palliative role if surgery is not possible.[2]

CONCLUSION

Primary malignant melanomas of the esophagus are rare, aggressive tumors with a fatal prognosis and should be considered in the differential diagnosis of bulky, polypoid masses that expand the esophagus on esophagograms and chest CT scan.