Intracranial solitary fibrous tumor with atypical histologic features and distant bone metastases.
Solitary fibrous tumor (SFT) of the central nervous system (CNS) is rare and classified as a mesenchymal, non-meningothelial lesion (4). It would originate from CD34-positive fibroblasts localized to the dura and perivascular connective tissue. Intraventricular tumors would derive from the mesenchymal component of the choroid plexus (1). In the CNS, SFT occurs in adults without gender predilection. Symptoms and signs are non-specific and vary with tumor location. On neuroimaging, SFT is solid and shows diffuse enhancement. Dural attachment may be observed, however dural tail sign is not a feature. It may be mimicked by other discrete tumors, such as meningioma and hemangiopericytoma (HPC). Macroscopically, SFT is well circumscribed, solid, lobulated whitish mass. Local infiltration and necrosis may be found in aggressive lesions. Histologically, fusiform or ovoid cells with vesicular nuclei and scant cytoplasm occur in hypo- or hypercellular areas. Hyalinized and/or myxoid background may be found. Vascularization is variable and characterized by branching vessels, sometimes in staghorn-like pattern. Nuclear pleomorphism, necrosis and mitoses are absent or rare. Classically, SFT is strongly and diffusely immunopositive for vimentin, CD34, CD99 and Bcl-2. EMA, S-100 protein and cytokeratins are negative. Ki-67 index is often less than 2% (1, 6).
As regards differential diagnosis, most meningiomas show whorls and psammoma bodies. Such features are not prominent in the fibrous variant, which exhibits a spindled/storiform architecture. Unlike SFT, meningiomas are immunopositive for EMA and negative for CD34. Distinction between HPC and SFT may be difficult, as both show similar cytological and architectural findings, including staghorn-like vessels. In fact, it is debatable whether SFT and HPC are distinct entities or ends of a spectrum (2, 6). In this sense, it has been recently shown that both meningeal STF and HPC carry the NAB2-STAT6 fusion. NAB2 is a nuclear transcriptional modulator protein and STAT6 is a mainly cytoplasmic signal transducer and transcriptional activator. Such fusion may be identified through nuclear immunolabeling for STAT6 (3, 5). Although favoring a single genesis for both tumors, this cytogenetic finding may not help neuropathological differential diagnosis between SFT and HPC as both are expected to be immunopositive for STAT6. A possible use would be distinguishing STF and HPC from other mesenchymal tumors not showing that fusion, like meningioma (5). Currently, tumors showing no (or only focal) immunopositivity for CD34 are considered HPC, while those diffusely and strongly positive for CD34, as the case here reported, are diagnosed as SFT (1, 4, 6). Microscopic differentiation is relevant as HPC are WHO grade II (usual) or III (anaplastic) lesions tending to recur and/or metastasize more commonly than SFT. Even though the latter has not been assigned a WHO grading, it tends to behave as low grade tumor after total gross resection (1, 4).
Thus, our case illustrates an extremely rare presentation of an intracranial STF with atypical histologic features and distant bone metastases. The qualification of atypical is based on hypercellularity and mitotic index, according to a recent review (1). The authors found 220 cases of SFT of the CNS from 1996 to 2011, around 13% of which showed cytological atypia/pleomorphism, hypercellularity, > 4 mitoses/10 hpf and/or necrosis. Such findings were associated with tumors that locally recurred and/or originated distant metastases. Only 5 were complicated by extracranial metastases, just one in bone. The prognostic significance of spontaneous necrosis, high MIB1 index (>5%) and brain invasion are as yet undetermined (1).
Contributed by Fabio Rogerio, MD, PhD, Luciano de Souza Queiroz, MD, PhD