Neuropathology for the Neuroradiologist: Fluorescence in Situ Hybridization

Representative FISH studies in tumors of the nervous system—central neurocytoma (A–C), oligodendroglioma (D–F), small cell glioblastoma (G), and Ewing sarcoma/peripheral primitive neuroectodermal tumor (H). Note that marked histologic similarities are seen between central neurocytomas (A) and oligodendroglioma (D) (hematoxylin-eosin, 200×). However, FISH revealed normal copy numbers (ie, 2 signals in most cells) of chromosomal markers 1p32 (green signals) paired with 1p42 (red signals) in the central neurocytoma (B), with similar findings by using probes against 19p13 (green) and 19q13 (red) (C). In contrast, the oligodendroglioma showed evidence of both 1p (E, 1 green signal intensity in most tumor nuclei) and 19q (F, 1 red signal intensity in most tumor nuclei) deletions by using the same probes. The presence of numerous EGFR signals represents gene amplification and provided support for the diagnosis of small cell glioblastoma in this example (G; EGFR in red, chromosome 7 centromere in green). The diagnosis of Ewing sarcoma/peripheral primitive neuroectodermal tumor was supported in this case by the presence of the Ewing sarcoma gene rearrangement by FISH (H). In this hybridization, the green and red probes flank the Ewing sarcoma translocation breakpoint, such that normally, they are in close proximity and all cells contain 2 yellow or red-green fusion signals. In this case, 1 pair of red and green signals are split, indicating the presence of a translocation.