Uveal Melanoma Metastases: Clinico-Pathologic and Mutational Analysis of 21 Cases
Rajmohan Murali, Klaus Griewank, Johannes van de Nes, Richard Scolyer, John Thompson, Dirk Schadendorf. Memorial Sloan-Kettering Cancer Center, New York, NY; University Hospital Essen, Essen, Germany; Royal Prince Alfred Hospital, Sydney, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia
Background: Uveal melanoma is the commonest malignant tumor of the adult eye. It is often diagnosed at an advanced stage, and is associated with a poor prognosis (10-year survival ∼40%). Activating mutations of GNAQ or GNA11 occur in 80-90% of uveal melanomas. Metastases of uveal melanoma are generally hematogenous, and most commonly involve the liver. We investigated the clinico-pathologic and genetic features of metastases from uveal melanoma, with emphasis on their distinction from other melanocytic tumors in the differential diagnosis.
Design: From the clinical and pathology records of two institutions, 21 patients with metastases from primary uveal melanoma were identified. Pathologic features were evaluated by slide review in 19 cases, and all tumors were subjected to direct sequencing for exons 4 and 5 of GNAQ and GNA11.
Results: In 7 female and 14 male patients, median age at diagnosis of primary uveal melanoma was 59 years (range 14-73 years). The sites of metastasis were: liver (7), skin/subcutis (7), lung (1), brain (1), mediastinum (1), spleen (1), lymph node (1), and unknown (2). The tumors showed sheet-like, nested or lobular growth patterns, and were composed of exclusively epithelioid cells (14), exclusively spindle cells (2) or a mixture of epithelioid and spindle cells (3). Tumor cells contained moderate amounts of amphophilic cytoplasm in the majority of cases, and exhibited moderate to marked nuclear pleomorphism. Melanin pigment was present in 15 cases (moderate to marked in 7), and melanophages were seen in 9 tumors. Tumor necrosis was present in 5 cases. GNA11 mutations were detected in 11 (52%) cases (exon 4 in 2 cases and exon 5 in 9 cases), and GNAQ exon 5 mutations were seen in 4 (19%) cases.
Conclusions: Metastases from uveal melanomas show predilection for liver and skin, predominance of epithelioid cells, and conspicuous melanin pigment – features that should prompt consideration of the diagnosis and clinico-pathologic correlation when evaluating melanocytic tumors. The common occurrence of GNAQ/GNA11 mutations is particularly helpful in distinguishing them from metastases of cutaneous melanomas, in the vast majority of which these mutations are absent.
Monday, March 4, 2013 8:45 AM
Proffered Papers: Section H1, Monday Morning