Comparison of Primary and Metastatic Malignant Melanoma of the Esophagus: Clinicopathologic Review of 10 Cases

Archives of Pathology & Laboratory Medicine, Oct 2008 by Sanchez, Amy A, Wu, Tsung-Teh, Prieto, Victor G, Rashid, Asif, Hamilton, Stanley R, Wang, Huamin

Context.-Primary esophageal melanoma (PEM) is a rare disease and is difficult to distinguish from other esophageal malignancies and from metastatic melanoma.

Objective.-To develop diagnostic criteria for PEM, we compared the clinicopathologic features of 5 PEMs and 5 metastatic melanomas to esophagus.

Design.-Ten cases of esophageal melanoma, including 4 surgically resected specimens, 2 autopsy cases, and 4 cases reported on mucosal biopsies, were reviewed. The histologic parameters used in this study were well-characterized features for cutaneous melanoma, including junctional component (in situ melanoma), radial growth phase, modified Breslow thickness, depth of invasion, lymphovascular invasion, satellitosis, predominant type of cytology, and regional lymph node metastasis. Clinical and follow-up information was obtained by reviewing patients' medical records.

Results.-Previous history of cutaneous melanoma was present in all 5 cases of metastatic esophageal melanoma but was not present in the 5 patients with PEMs. In situ melanoma and/or radial growth phase were identified in all 5 PEMs but were not present in any of the metastatic cases. Among the 4 resected and 2 autopsy cases, melanocytosis and mixed epithelioid and spindle cell morphology was present in 2 (50%) of 4 PEMs but was not present in 2 (40%) of the metastatic melanomas. Melanin pigment was detectable in all cases. Patients with PEM had better survival than those who had metastatic melanoma to esophagus (P = .03).

Conclusions.-The presence of in situ melanoma, radial growth phase, melanocytosis, and mixed epithelioid and spindle cell morphology, in the context of no history of melanoma, distinguishes PEM from metastatic melanoma.

(Arch Pathol Lab Med. 2008;132:1623-1629)

It has been postulated that during early embryogenesis, melanoblasts migrate from the neural crest to various sites, including the epidermis, hair follicles, oral cavity, uvea, leptomeninges, and inner ear, which accounts for the development of primary malignant melanoma in these sites.1 The presence of esophageal melanocytes may be attributed to aberrant migration because the esophagus normally lacks melanoblasts.2-4 Primary esophageal melanoma (PEM), associated with melanocytosis of the esophagus, has been reported.5

Primary esophageal melanoma is an extremely rare tumor and accounts for only 0.1% to 0.2% of all primary esophageal malignancies.6-8 Similarly, esophageal metastasis of malignant melanoma is also uncommon. In 1964, Dasgupta and Brasfield9 reviewed 100 autopsy cases of metastatic melanoma to gastrointestinal tract and found only 4 patients who had esophageal metastases. Small bowel is the most common gastrointestinal site for metastatic melanoma, comprising 70% of all gastrointestinal metastasis.9 Because of the rarity of this disease, the literature on malignant melanoma of esophagus is limited, to our knowledge, to only a few small series and case reports that focused primarily on the clinicopathologic features of primary esophageal melanoma.10-13 There is no report in the literature that compares the distinguishing clinical and histopathologic features between PEM and metastatic melanoma of the esophagus. Thus, despite some of the established criteria based on the previous studies, the diagnosis of a primary esophageal melanoma remains challenging, and it is very difficult to definitively rule out a metastasis based on histology alone. For these reasons, we decided to study 10 cases of malignant melanoma of the esophagus, including 5 PEMs and 5 metastatic melanomas at our institution and to compare the clinicopathologic features between these 2 groups. The results from our study will help to further define the diagnostic criteria for PEM.

MATERIALS AND METHODS

Ten cases of esophageal melanomas, including 4 surgically resected specimens (3 primary and 1 metastatic), 2 autopsy cases (1 primary and 1 metastatic), and 4 cases reported on mucosal biopsies (1 primary and 3 metastatic), were identified in the files at the University of Texas, M. D. Anderson Cancer Center (Houston), covering a period of 49 years from 1957 to 2006. All 5 cases of PEM were reported based on clinicopathologic correlation with no history of melanoma. Formalin-fixed, paraffin-embedded tissue blocks were available from all cases except for 1 autopsy case of PEM (case 4). The institutional review board at the University of Texas M. D. Anderson Cancer Center approved this study.

Immunohistochemical studies for pancytokeratin, S100, and HMB-45 were performed on all cases except case 4. For case 4, melanin stain had been performed, and the tumor was positive for melanin pigment. The antibodies and dilutions used were S100 (1:40; 15E2E2, BioGenex, San Ramon, Calif) and HMB-45 (1: 50; HMB-45, Dako, Carpinteria, Calif). The pancytokeratin cocktail consisted of a mix of 4 different antibodies against cytokeratins: AE1/AE3 (1:50), CAM 5.2 (1:50), MNF116 (1:50), and 8/18 (SPM141, 1:25). Standard immunohistochemical staining techniques were used as described by Hsu et al.14 Appropriate positive and negative controls were used. The immunohistochemical staining results were categorized as positive or negative. All slides, including the hematoxylin-eosin and immunohistochemical-stained slides were reviewed jointly by a dermatopathologist (V.G.P.) and a gastrointestinal pathologist (H.W.). The gross features were obtained from pathology or autopsy reports. The following features were recorded: anatomic location, gross configuration, tumor size (centimeters), depth of invasion, predominant types of cytology (epithelioid, spindle, or mixed), modified Breslow thickness (millimeters), the presence or absence of an in situ component, radial growth phase, lymphovascular invasion, regional lymph node metastasis, and satellitosis. The radial growth phase was defined as the presence of intraepithelial proliferation of atypical melanocytes (in situ melanoma) beyond 3 epithelial ridges from the invasive component. The modified Breslow thickness was measured from the top of the mucosal surface to the deepest tumor cells.