Cribriform neuroepithelial tumour: novel clinicopathological, ultrastructural and cytogenetic findings

Abstract

Cribriform neuroepithelial tumour (CRINET) is a recently described tumour of neuroectodermal origin with distinct cribriform non-rhabdoid histological features and loss of INI1 protein expression [2]. The INI protein is encoded by the hSNF/INI1/BAF47 (SMARCB1) tumour suppressor gene, which is located on chromosome 22q.11.2 [4]. The gene product is a subunit of the adenosine triphosphate (ATP)-dependent SWI/SNF chromatin-remodelling complex, which normally regulates cell proliferation [7, 8]. Biallelic loss of SMARCB1 is seen in peripheral rhabdoid tumours, atypical teratoid/rhabdoid tumours (AT/RTs) of the central nervous system as well as familial schwannomatosis [1, 3, 10]. In contrast to AT/RTs, CRINETs lack rhabdoid tumour cells, and may be associated with a more favourable prognosis [2]. Here, we present a third case of CRINET with complete clinicopathological, ultrastructural and cytogenetic features. A 21-month-old boy presented with a 1-week history of imbalance, discoordination, recurrent falls and torticollis, as well as progressive nausea, vomiting and irritability. The family history was significant for possible ependymomas in the maternal great uncle and two maternal second cousins. Computed tomography (CT) and magnetic resonance (MR) imaging demonstrated a large heterogeneously enhancing mass within the fourth ventricle extending into the left cerebellopontine angle and associated with mild hydrocephalus and brainstem compression (Fig. 1a). The patient experienced an acute neurological deterioration and an urgent CT scan demonstrated haemorrhage into the tumour causing obliteration of the fourth ventricle and acute obstructive hydrocephalus (Fig. 1b). The patient underwent an urgent posterior fossa decompression and gross total tumour resection. Post-operatively, he underwent chemotherapy according to the Children’s Oncology Group (COG) 99703 protocol, which includes cisplatin, cyclophosphamide, etoposide and vincristine with stem cell rescue followed by the maintenance chemotherapy with tamoxifen and cis-retinoic acid. Fourteen months following the presentation, he remains in remission. On histology, the specimen showed a cellular neoplasm, in which mitotic activity was scattered and MIB-1 index was high. Cells were found to have oval nuclei with occasional notable nucleoli (Fig. 2a). Cuboidal to polygonal cells were arranged in sheets and chords occasionally forming tubule-like or rosette-like structures. The specimen contained punched out foci of necrosis. Typical rhabdoid cells were not appreciated. Immunohistochemistry showed neoplastic cells to be non-reactive for BAF47 (Fig. 2b). These cells were reactive for Vimentin, S100, beta-catenin (nucleus and cytoplasm), c-erbB2 and MAP2. Isolated cells reacted for p53, GFAP, cytokeratin (rare), EMA (scattered foci) and SMA (usually vasocentric). Studies for synaptophysin were negative. A summary of the current and previous immunohistochemical findings is presented in Table 1. Electron G. M. Ibrahim P. B. Dirks Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada