DIAGNOSIS AND DISCUSSION:
Diagnosis: Primary embryonal rhabdomyosarcoma of the brain.
Primary rhabdomyosarcoma within the central nervous system is rare. The majority of these present with a mass imbedded on the surface of the brain and are rarely entirely intraparenchymal (1). In addition, 72% of reported cases occur in children (4). Patient age at presentation ranges from 1-68 years and there is a slight male predominance (M:F ratio 1.6:1). Overall 55% of cases are supratentorial, however, in adults 82% of reported cases are supratentorial. This work describes an intraparenchymal primary rhabdomyosarcoma of the central nervous system located supratentorially in an adult. Essential for the diagnosis in this case was immunopositivity for desmin and myoglobin (Figure 4) and the ultrastructural features: the large cells contained myofilament bundles interrupted by Z-discs (Figure 5) and minute bundles of filament with dense bodies are seen in the cytoplasm of the small cells, attesting to their myogenesis and suggesting that the tumor is composed of a single cell type with maturation from anaplastic small cell to evolved rhabdomyoblast. Closer observation of the myofilament bundles and Z-discs in the large cells (Figure 6) reveals that most are not in register and there is an absence of thick filaments and A-bands, M-lines and H-zones in the sarcomeres. These features explain the lack of cross striations by light microscopy. Another important diagnostic feature in this tumour was the cytoplasmic bodies. These represent a degenerative abnormality of Z-bands and are a common non-specific finding in muscle biopsies (2). Despite their limited value in differentiating among muscle diseases, the characteristic eosinophilic, cytoplasmic inclusion (Figure 3) composed of a core of a dense feltwork of filaments surrounded by a lighter halo of randomly oriented finer filaments (Figure 5) is relatively specific for muscle itself. Thus their presence should be taken as equivalent to the demonstration of cross striations as a diagnostic clue for rhabdomyosarcoma. This feature is especially helpful in cases such as this where the cytoplasmic bodies but not the cross striations were identifiable by light microscopy.
The ultrastructural and immunohistochemical features described above clearly identify rhabdomyoblasts in this tumour. Other tumors in the central nervous system known to contain some primitive rhabdomyoblast elements include teratoma and medullomyoblastoma (3). However, the lack of teratomatous or neuroepithelial components and the absence of MYCN gene amplification by FISH analysis in our case clearly indicates that this is a primary rhabdomyosarcoma of the CNS and not a secondary cell line of differentiation in a primitive neuroectodermal tumour or teratoma.
Our studies lend support to the concept that some rhabdomyosarcomas can be segregated into a subset that a) affects adults, b) occurs supratentorially, and c) consists of pure embryonal rhabdomyosarcoma. The prognosis of primary embryonal rhabdomyosarcoma is poor with survival beyond 24 months being exceptional (1). Patients with the longest survival have received aggressive treatment consisting of radical gross removal, high dose (50-60 Gy) whole brain radiation followed by systemic chemotherapy (1). The debatable cell of origin of CNS rhabdomyosarcoma, primitive mesenchyme vs. neuroectoderm, makes the choice of most appropriate chemotherapeutic regimen difficult. Interestingly, the patient with the longest reported survival time (1) received a regimen based on agents used for systemic rhabdomyosarcoma and cerebral sarcomas. Although the evidence is very limited, this observation may provide support for a mesenchymal origin of primary CNS rhabdomyosarcoma.
Contributed by Cynthia Hawkins, MD, PhD, Paul Muller, MD, Juan M. Bilbao, MD