Contributed by Yuen Shan FAN, FRCPA, Philip C.W. LUI*, FRCPA, Fiona K.Y. TAM, MBBS, Kwan Ngai HUNG†, FRCS(Ed),
Ho Keung NG*, FRCPath, Suet Yi LEUNG, FRCPath
Department of Pathology, Queen Mary Hospital, The University of Hong Kong; *Department of Anatomical and Cellular Pathology,
Prince of Wales Hospital, The Chinese University of Hong Kong; †Department of Neurosurgery, Queen Mary Hospital, Hong Kong
A 33-year-old Chinese woman presented with intermittent slurring of speech, dysphasia together with right upper limb and facial weakness for two months with gradual worsening of the symptoms. Physical examination found decreased pin-prick sensation over right C6 to C8 dermatome and impaired proprioception in right hand. CT scan with contrast showed a well-demarcated contrast-enhancing left frontal tumor measuring 4.5 x 4.2 x 3 cm with perilesional edema and slight mass effect. Cystic changes were observed. The tumor was close to the cortical surface but not connected to the meninges (Figure 1). Surgical exploration found a non-encapsulated, well-circumscribed, vascularized tumor in the left frontal lobe. Tumor debulking under intraoperative cerebral function monitoring was performed. Around 95% of tumor was removed but complete excision could not be achieved due to significant decrease in amplitude of the brain motor evoked potentials. The patient recovered well after the operation with complete restoration of the function in the precentral and postcentral gyri as well as Broca's area.
Multiple pieces of soft greyish fragments altogether measuring 3 x 2 x 2 cm in aggregate were sent for pathological examination in fresh state. They were used in intraoperative cytologic smear, frozen section and subsequent histology as well as ultrastructural examination.
Intraoperative smears showed loose aggregates of polygonal and rhabdoid cells with eccentric nuclei and abundant cytoplasm. Intracytoplasmic inclusion bodies were occasionally seen. No significant cellular atypia or necrotic material was discerned. A glial fibrillary background was not evident (Figure 2). Neither psammoma bodies, intranuclear inclusions, nor papillary structures were found.
Histologic sections showed a malignant tumor arranged in sheets and pseudopapillary pattern (Figures 3 and 4). A distinct border was appreciated between the tumor and non-tumorous glial tissue. Most of the tumor cells displayed a rhabdoid appearance with uniform, eccentric nuclei and eosinophilic cytoplasm. Intracytoplasmic globules were observed in places (Figure 5). Some of the tumor cells showed very high nucleocytoplasmic ratio with small and markedly hyperchromatic nuclei, giving a primitive appearance (Figure 6). Perivascular pseudorosettes as characterized by stout cytoplasmic processes radiating towards central hyalinised blood vessel were easily found (Figure 7). No fibrillary matrix was seen in the stroma. Stromal hyalinization and calcifications were focally present (Figure 8). No palisaded necrosis was seen. Four mitotic Figures were identified per 10 high power fields (Nikon 22 mm eyepiece).
The rhabdoid tumor cells displayed a multilineage immunohistochemical profile. They were focal but strongly immunoreactive for glial marker glial fibrillary acidic protein (GFAP) (Figure 9), diffuse and strongly positive for neural marker S100-protein (Figure 10) and focal but strongly reactive for cytokeratin markers MNF116 and Cam5.2 (Figure 11). In addition, diffuse and strong membranous and cytoplasmic dot-like pattern was appreciated with epithelial membrane antigen (EMA) (Figure 12). The tumor cells were diffusely positive for vimentin. No neuronal differentiation was demonstrated with synaptophysin and neurofilament. There was no loss of INI-1 protein, a deletion seen in atypical teratoid/rhabdoid tumors (not shown). Dual-color FISH analysis was performed on paraffin sections with a target probe generated from BAC clone RP11-71G19 (22q11.23), which covers the entire SMARCB1 gene (associated with rhabdoid tumors), and the reference probe from RP11-494O16 (22q13.33). No deletion was discerned. The proliferation index was high as evident by approximately 10% of tumor cells were immunoreactive towards MIB-1 (Ki-67). The tumor cells were negative for HMB-45, actin and desmin.
Ultrastructural studies showed whorls of intermediate filaments in the cytoplasm of the rhabdoid cells (Figure 13). In addition, microvillous projections were observed on the cell surface (Figure 14). An occasional intercellular junction was identified. No cilia were seen.