Amelanotic malignant melanoma of the esophagus: Report of two cases with immunohistochemical and molecular genetic study of KIT and PDGFRA

Abstract

The author reports herein two cases of amelanotic malignant melanoma of the esophagus. Case 1 is an 87-year-old woman who was admitted to our hospital because of nausea and vomiting. Endoscopic examination revealed an ulcerated tumor of the distal esophagus, and a biopsy was taken. The biopsy showed malignant polygonal and spindle cells. No melanin pigment was recognized. Immunohistochemically, the tumor cells were positive for melanosome (HMB45), S100 protein, KIT and Platelet derived growth factor receptor-α (PDG-FRA). The patient was treated by chemotherapy and radiation, but died of systemic metastasis 12 mo after the presentation. Case 2 is a 56-year-old man presenting with dysphagia. Endoscopic examination revealed a polypoid tumor in the middle esophagus, and a biopsy was obtained. The biopsy showed malignant spindle cells without melanin pigment. Immunohistochemically, the tumor cells were positively labeled for melanosome, S100 protein, KIT and PDGFRA. The patient refused operation, and was treated by palliative chemotherapy and radiation. He died of metastasis 7 mo after the admission. In both cases, molecular genetic analyses of KIT gene (exons 9, 11, 13 and 17) and PDGFRA gene (exons 12 and 18) were performed by the PCR direct sequencing method, which showed no mutations of KIT and PDGFRA genes. This is the first report of esophageal malignant melanoma with an examination of the expression of KIT and PDGFRA and the mutational status of KIT and PDGFRA genes.

Genetic aberrations in primary esophageal melanomas: molecular analysis of c-KIT, PDGFR, KRAS, NRAS and BRAF in a series of 10 cases

“…The presence of c-Kit mutations may contribute to response to specific tyrosin kinase inhibitor therapy, and therefore molecular screening for c-Kit mutations may be helpful for identifying alternative therapeutic options in esophageal melanoma. The occurrence of c-Kit mutations in esophageal melanoma has been reported recently in the literature, 11,12 but the studies analyzed only exons 11, 13 and 17, but not exon 9, where we could detect two mutations and which encodes for the extracellular domain of the c-Kit protein.…”

“…6,7 In both cutaneous and noncutaneous melanomas, various genetic aberrations occur and among them c-Kit, RAS-isoform and BRAF alterations are found at various frequencies. [8][9][10] However, molecular information about primary esophageal melanoma is scarce because of its rarity, and recent reports represent only small series or case reports with analysis of single or few molecular aberrations: most recently, Terada et al 11 have reported two cases from Japan where a PDGFR-A and a c-KIT mutation analysis was performed, without demonstrating a PDGFR-A and a c-KIT mutation in these tumors. Sekine et al 12 have described a larger series of 16 esophageal melanomas from Japan as well.…”

A tenebrous tale: malignant melanoma of the oesophagus

“…To diagnose melanoma of the oesophagus, a biopsy is taken11–13 and stained with the immunohistochemical stains used in the diagnosis of cutaneous melanoma. The presence of melanosome (HMB45), melan-A and S100 protein are obligatory for the diagnosis of melanotic melanoma 14. If an oesophageal melanoma is detected an extensive examination must be performed for synchronous melanoma at cutaneous and ocular sites 15.…”

Amelanotic malignant melanoma of the cervical oesophagus

“…It has been found that melanoblasts originate and further differentiate into melanocytes in the oesophageal wall after migrating from the neural crest cells 1 2 4 8. The role of NRAS and BRAF mutations with the presence of KIT and PDGFRA gene has been demonstrated in the pathogenesis of PMME 11. Allen and Spitz12 constructed a diagnostic criteria for PMME; however, it was noted that only 40% of oesophageal melanomas fulfilled these criteria 2 4 13…”