AMSA PremedFest 
University of Florida, 
Gainesville, FL
April 11-12, 2015


D. Metastatic melanoma

The patient’s imaging findings coupled with the past history of left orbital enucleation were the most important clues to the presumptive metastatic melanoma diagnosis. The melanoma likely stemmed from a previous ocular melanoma. This could not be verified, however, since the patient had lost all previous medical records. The characteristic histopathology of sheets of spindled-to-polygonal cells with frequent mitotic activity and dense cytoplasmic collection of brownish-black melanin pigment confirmed the clinical suspicion (Figure 4). The tumor cells were immunopositive for S-100 protein, HMB-45, and Melan-A. An MIB-1 labeling index of 38 percent was detected in the highest proliferating areas, where the immunohistochemical stains were performed after bleaching the melanin pigment on slides with KMnO4 solution. This combination of radiologic and histologic features is diagnostic. The characteristic T1- and T2-weighted MRI images with marked perilesional edema suggested a metastatic mitotic lesion. While assessing any extraor intra-axial, mitotically active lesions in the central nervous system (CNS), the possibility of a melanoma should be kept as a differential diagnosis, even in an apparent absence of pigmentation. Cytologic atypia, prominent nucleoli, and atypical mitotic figures are indicative of this lesion in the absence of melanin pigment. When such a lesion is detected, a diligent search for the melanin on histopathologic sections is necessary. Sometimes, the melanocytic nature of the lesions can only be established by immunohistochemical stains for S-100 proteins, Melan-A or HMB-45 stains, or by ultrastructural studies. The relative positioning and number of the lesions in the CNS sometimes help to differentiate the primary from the metastatic lesions. The metastatic lesions are usually intraparenchymal and multiple, but they can also be solitary. In this context, the importance of a detailed clinical history and physical examination should again be stressed. The differential diagnosis includes meningeal melanocytomas, pigmented meningioma, schwannoma, medulloblastoma, choroid plexus papilloma, astrocytoma, and pituitary tumors. Though sometimes difficult to distinguish with imaging, melanocytomas have less cytological atypia and mitotic activity, and the presence of a complete basal lamina around the tumor cells. Ocular or uveal melanoma is a malignant tumor of the eye involving the iris, ciliary body or choroid (collectively referred to as the uvea). It is regarded as a malignant tumor with a high recurrence rate, as more than 50 percent of primary ocular melanomas recur within 15 years of primary treatment. The prognosis for these tumors depends on several factors, such as tumor size, involvement of ciliary body, and age of the patient. Histologic factors, such as epithelioid morphology, high extracellular matrix production, or tumor-infiltrating lymphocytes, also play a role. Multiple studies, including the Collaborative Ocular Melanoma Study (COMS), have specified tumor size as the strongest indicator of metastasis and, therefore, survival. The gene expression profile of these tumors is very crucial in the prognosis of ocular melanomas. A gain on chromosome 6 or 8 and monosomy 3 are especially poor prognostic indicators. Metastasis to the liver has been documented, with a survival of only eight to 10 months following the identification of metastasis. Although metastases within the cortical parenchyma have been reported, these are relatively rare.

Metastatic melanoma in the CNS is almost incurable. Treatment is symptomatic and involves surgical tumor debulking and symptomatic relief. The use of steroids for perilesional edema is indicated for the reduction of intracranial pressure. Rare reports exist of metastasis from primary intracranial melanoma to the lungs, spleen, pancreas, and kidneys. The treatment options should be individualized for each patient based on the number of lesions and access to them, as well as the possibility of extracranial metastases. Radiation therapy, stereotactic radiosurgery, surgical resection, or immunologic therapies can be given.