Medulloblastomas with systemic metastases: Evaluation of tumor histopathology and clinical behavior in 23 patients

To review the clinical behavior and histopathologic features of medulloblastomas that metastasize outside the central nervous systems (CNS). The authors studied 23 cases of medulloblastomas that metastasized outside the CNS. The patients included 15 males and 8 females, ages 1 to 40 years at initial diagnosis (median 8.5). Five of the patients were over 20 years of age at diagnosis. The histologic grade of anaplasia was determined for each case. Extra-CNS metastases were identified at initial presentation in four individuals and up to 11 years later in the remaining cases. Metastatic sites included bone/bone marrow (21 cases), soft tissue/lymph nodes (3 cases), and lung (1 case). In seven cases, multiple extra-CNS metastatic sites were documented. Of the patients with available clinical follow-up after metastasis, 10 died of their disease 1 to 39 months after detection of extra-CNS metastases (median 9 months), while 5 are alive 16 to 120 months after extra-CNS metastasis (median 45 months). Moderate or severe anaplasia was detected in 8 of 20 intracranial specimens (40%) and in 4 of 6 extra-CNS metastases (66%); these frequencies are higher than observed in medulloblastomas overall. Tissue from both the initial resection and subsequent recurrence or metastasis was available in six cases. The anaplasia grade was higher upon recurrence or metastasis in four of these six, consistent with tumor progression. Metastasis of medulloblastomas outside the CNS can occur after long periods of clinical remission and is associated with anaplasia in some cases. Medulloblastomas can show histologic progression on recurrence or metastasis.