Progression of ocular melanoma metastasis to the liver: the 2012 Zimmerman lecture.

Abstract

To the best of my knowledge, this study demonstrates for the first time small, apparently dormant micrometastasis in the liver of patients with uveal melanoma. To evaluate the histological and immunohistochemical findings in metastatic uveal melanoma to the liver. Samples of liver were obtained at autopsy from patients who died of metastatic uveal melanoma to the liver. L. F. Montgomery Laboratory, Emory Eye Center, Atlanta, Georgia. A total of 10 patients who died of metastatic uveal melanoma to the liver. Sections of the liver were examined with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, or reticulin stains. The tumors' morphology, growth pattern, mean vascular density, and mitotic index were determined with the aid of immunohistochemical stains for S100, HMB45, CD31, and Ki67. Stage 1 metastases (defined as tumor clusters ≤50 μm in diameter) were identified in the sinusoidal spaces of 9 of 10 patients (90%). Stage 1 metastases were avascular and lacked mitotic activity. Stage 2 metastases (defined as tumors measuring 51-500 μm in diameter) and stage 3 metastases (defined as tumors measuring >500 μm in diameter) were found in all patients. Immunohistochemical stains were positive for S100 or HMB45 in all tumors. Overall, stage 1 metastases outnumbered stage 2 metastases (which outnumbered stage 3 metastases). The mean vascular density and mitotic index increased from stage 2 to stage 3 metastases (P < .05). The architecture of stage 2 metastases mimicked the surrounding hepatic parenchyma, whereas stage 3 metastases exhibited either lobular or portal growth patterns. Uveal melanoma that spreads to the liver can be categorized as stage 1 (≤50 μm in diameter), stage 2 (51-500 μm in diameter), or stage 3 (>500 μm in diameter) metastases. The later stage exhibits a lobular or portal pattern of growth. During this progression, tumors become vascularized and mitotically active.