Clinical Context

Metastases are the most common tumors in the central nervous system (CNS), accounting for more lesions than all primary tumors combined (1), and affecting just over half of the total number of brain tumor patients. Even these estimates are most likely low due to ascertainment bias among the terminally ill patients with cancer (2). The age distribution of patients with CNS metastases parallels the primary incidence of the most common metastasizing malignancies, increasing throughout adulthood. Although the presentation of metastatic disease in the CNS varies greatly, most patients present with sudden onset of mental status changes or seizures. Whereas many cancers are detected clinically when they interfere with function of the respective primary organ, a significant number of brain metastases are discovered before a primary diagnosis, adding to the importance of accurately classifying them (3,4).

Essentially all metastases reach the CNS by hematogenous spread, usually first establishing tumor in the lungs where malignant cells likely gain access to the systemic arterial circulation (2). Most often, the metastatic cells then lodge within the capillaries at the gray-white matter junction of the cerebral cortex, although metastatic lesions have been documented in every location in the CNS. Radiologically, suspicion for metastasis rises when there are multiple lesions (especially at the gray-white junction) or when the patient has a history of prior malignancy. Most metastases are approximately spherical with well-circumscribed, pushing borders and prominent adjacent edema, which appears on magnetic resonance imaging as T2-signal hyperintensity. Areas of necrosis and hemorrhage are common. Because of the paramagnetic qualities of melanin, intrinsic, bright T1 signal is characteristic of pigmented metastatic melanomas.

Only a few histologic types of cancer account for >90% of CNS metastases observed in practice, the majority of which are carcinomas, with melanomas making up most of the remainder. Lymphomas are considered systemic diseases, therefore not metastatic when involving the brain. The frequencies of metastases from particular organs do not reflect the rates of primary lesions in those sites. Pulmonary and mammary carcinomas account for roughly 60% of all brain metastases (5,6) but only
around 30% of all primary solid malignancies (6,7). In contrast, carcinomas of bladder, thyroid, and prostate are common as primaries but account for only a few percentage of all CNS metastases (2,5). Of bronchopulmonary carcinomas, adenocarcinoma is the most common (Figure 18-1), followed by neuroendocrine carcinoma, with only occasional metastases from squamous cell cancers. Renal cell and colorectal carcinomas also metastasize to the CNS but represent a small minority. Melanomas follow carcinomas in incidence among cerebral metastases, accounting for about 8% of all cases (5,8).

FIGURE 18-1 Pulmonary adenocarcinoma is the most common metastasis to the central nervous system, where it and other metastases form discreet sharply circumscribed lesions.

Only a few small series examine CNS metastases from sarcomas, emphasizing their relative rarity (9,10,11,12). Although still rare in pediatric populations, sarcomas account for a larger proportion of CNS metastases in those patients, from a third to half in two single-institution series (13,14). The most common histologic subtypes include osteosarcoma, pleomorphic undifferentiated sarcoma (malignant fibrous histiosarcoma), Ewing sarcoma, and leiomyosarcoma (9,11,12). Notable for its tendency to metastasize to the CNS is alveolar soft part sarcoma (Figure 18-2), which is represented among CNS-metastatic sarcomas far out of proportion to its primary incidence (9,10,11,12). It is rare for sarcomas to present with brain metastases, yet alveolar soft part sarcoma and synovial sarcoma have a greater propensity to do so.

Diffuse Leptomeningeal Metastasis (Meningeal Carcinomatosis, Carcinomatous Meningitis)

Some malignancies diffusely infiltrate the leptomeningeal space, spreading through the cerebrospinal fluid (CSF) and forming a sheet of malignant
cells over the pial surface. Although frequently referred to as “carcinomatous meningitis” because it usually originates from carcinoma and presents with symptoms similar to meningitis, melanomas and occasional sarcomas also diffusely involve the CSF space (15). Even with intrathecal chemotherapy and radiation treatment, the outlook for patients with diffuse leptomeningeal metastasis is grim, with a median survival of <6 months after diagnosis in one series (16). Malignant cells fill the subarachnoid space and often extend into the brain along the perivascular spaces (Figure 18-3).

FIGURE 18-2 Alveolar soft part sarcoma, composed of large cells with abundant granular eosinophilic cytoplasm and prominent nucleoli arranged in nests, is uncommon but shows a high rate of cerebral metastasis.

CNS Metastases in Children

Metastases are distinctly uncommon in the pediatric population, representing only about 2% of all pediatric brain tumors (13,14,17). Overall survival in children with CNS metastases is poor, with median survivals around a year or less (13,14). Some metastases in children may mimic primary CNS malignancies, including neuroblastoma, blastema-predominant Wilms tumor, alveolar rhabdomyosarcoma, and undifferentiated midline carcinoma (NUT1-related carcinoma).

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Oct 22, 2018 | Posted by in NEUROLOGY | Comments Off on Metastases
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