Atypical meningioma associated with reactive hyperplasia and colonization of meningeal melanocytes.
Based on histopathological features of the white-to-grayish lesion with spindle-shaped cells including intercellular collagen fibers, whorl formations, macronucleoli and brain invasion, the tumor was diagnosed as atypical meningioma according to the WHO classification of tumors of the nervous system (7, 9). However, we observed some areas exhibiting prominent accumulation of pigmented cells within the arachnoid membrane and subsequent infiltration of these cells from the arachnoid membrane to the interior of the meningioma tissue, which may be misleading in the diagnosis of melanocytic tumors, including primary melanocytic tumors (melanocytoma, malignant melanoma), melanotic progonoma and intracranial tumors of melanotic variants (melanotic schwannoma). These pigmented cells displayed no mitotic activity and negative immunoreactivity to Ki-67. No meningioma cells contained melanin pigments within their cytoplasm. Pigmented cells were immunopositive for S-100 protein but negative for EMA and HMB-45, and ultrastructural studies showed that they contained abundant secondary melanosomes (melanin granules), consistent with non-neoplastic, mature melanocytes (3). Histological, immunohistochemical and ultrastructural findings ruled out either possibility that these lesions were neoplasms of melanocytic origin or the presence of melanin-laden meningioma cells. We instead concluded that these marked proliferation and infiltration of melanocytes could be due to reactive hyperplasia and their colonization in the tumor tissue.
"Melanocyte colonization" was originally described by Azzopardi and Eusebi in a series of breast carcinomas, and was histologically defined as the presence of dendritic melanocytes in carcinomatous tissue (1). To date, melanocyte colonization has been reported in a variety of tumors, which are essentially non-pigmented and in most instances of epithelial origin. Association of this phenomenon with primary intracranial neoplasms is very rare, and to the best of our knowledge, only one case of a 70-year-old African-American woman who presented an atypical meningioma with melanocytic colonization has been reported by Nestor and colleagues (8). Although there have been several previous reports on "melanotic meningiomas", these cases are now considered to be meningeal melanocytomas (5, 6, 8) and thus are a different entity from a meningioma with melanocytic colonization. One interesting speculation made on the case of Nestor and colleagues was a racial factor; since the patient was African-American, the number of melanocytes in the leptomeninges might have been much greater than in general Caucasians (8). However, our case was a Japanese child, indicating that this phenomenon should be taken into consideration regardless of either race or age.
In the central nervous system (CNS), melanocytes are preferentially localized in the leptomeninges especially at the base of the brain (7). Since meningiomas usually have a long-standing, close association with the leptomeninges during tumor development, the source of the dendritic melanocytes seen in the previously-reported case of meningioma with melanocytic colonization was speculated to be leptomeningeal in derivation (8). Our case clearly showed unusual expansion of melanocytes in the arachnoid membrane and a continuous flow of melanocytes from there to the inside of the meningioma tissue, indicating that melanocytes colonizing the meningioma tissue in our case were derived from existing melanocytes normally residing in the leptomeninges.
For resident melanocytes to colonize into surrounding tissues and tumors, Azzopardi and Eusebi alluded to the necessity of melanocyte hyperplasia before they migrate towards the tumor tissue (1). A dense accumulation of non-proliferative, mature melanocytes in our case indicated that reactive hyperplasia of melanocytes relevant to their colonization could occur in the tumors of the CNS. In the practice of clinical pathology, it is necessary to differentiate tumors with melanocytic features from tumors of melanocytic origin such as malignant melanoma, because of the difference in their biological behavior, aggressiveness and clinical outcome. Therefore, it is important for surgical pathologists to recognize this phenomenon and differentiate a meningioma with reactive hyperplasia of melanocytes from primary pigmented tumors of the meninges (melanocytomas and malignant melanomas, 2), a metastatic malignant melanoma to a meningioma (10), and other intracranial tumors of melanotic variants, especially in frozen or small biopsy samples.
Contributed by Kenta Masui, MD, Satoshi O. Suzuki, MD, PhD, Akira Kondo, MD, PhD, and Toru Iwaki, MD, PhD