Hans E Grossniklaus1. 1. L. F. Montgomery Laboratory, Emory Eye Center, Atlanta, GA 30322, USA. ophtheg@emory.edu
Abstract
IMPORTANCE: 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. OBJECTIVE: To evaluate the histological and immunohistochemical findings in metastatic uveal melanoma to the liver. DESIGN: Samples of liver were obtained at autopsy from patients who died of metastatic uveal melanoma to the liver. SETTING: L. F. Montgomery Laboratory, Emory Eye Center, Atlanta, Georgia. PARTICIPANTS: A total of 10 patients who died of metastatic uveal melanoma to the liver. INTERVENTION: Sections of the liver were examined with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, or reticulin stains. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.
IMPORTANCE: 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. OBJECTIVE: To evaluate the histological and immunohistochemical findings in metastatic uveal melanoma to the liver. DESIGN: Samples of liver were obtained at autopsy from patients who died of metastatic uveal melanoma to the liver. SETTING: L. F. Montgomery Laboratory, Emory Eye Center, Atlanta, Georgia. PARTICIPANTS: A total of 10 patients who died of metastatic uveal melanoma to the liver. INTERVENTION: Sections of the liver were examined with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, or reticulin stains. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: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.
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