Histopathologic grading of medulloblastomas.

Abstract

We read with great interest the study by Eberhart et al. regarding the histopathologic grading of medulloblastomas.1 The authors concluded that pathologic grading with respect to anaplasia was associated with aggressive clinical behavior in patients with medulloblastomas. We wondered if some of these anaplastic tumors were atypical teratoid/rhabdoid tumors (AT/RT). This is because the illustrated photomicrographs in the second figure and the descriptions of the moderately anaplastic and severely anaplastic tumors were not different from that of a known pattern of AT/RT. Admittedly, the morphology of these anaplastic tumors is not very distinct and the tumor cells are not particularly rhabdoid; therefore, they are difficult to link to the diagnosis of AT/RT. However, it is known that, although AT/RTs are heterogeneous tumors in which rhabdoid (large) cells, small (primitive neuroectodermal tumor [PNET]) cells, mesenchymal (spindle cell) components and epithelial components are seen, in individual cases, except for the rhabdoid cells, the other components are not necessarily present.2-4 The morphology of the rhabdoid cells is also diverse. It varies from large, pale, bland cells to large cells with prominent nucleoli and small amounts of cytoplasm to large cells with vesicular nuclei, prominent nucleoli and esosinophilic intracytoplasmic inclusion having the appearance of classic rhabdoid cells known by general/anatomic pathologists.3-5 Among all these forms of rhabdoid cells, the classic rhabdoid cell is actually the rarest form encountered in AT/RT. Because AT/RT has a unique divergent differentiation, it is reactive to a wide range of immunohistochemical markers, such as epithelial membrane antigen (EMA), vimentin (VIM), smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), cytokeratin, S-100 protein, synaptophysin, neurofilament proteins, and desmin.2, 4 In our comparative study of AT/RT with PNET/medulloblastoma (MB), we systemically studied all our previously diagnosed PNET/MBs in order to identify the hidden AT/RTs.6 In this process, we used the combined immunohistochemical staining guidelines recommended by Rorke et al. (EMA, VIM, and SMA)2 and Burger et al. (EMA and GFAP),4 which included EMA, VIM, SMA, and GFAP as well as morphologic features to define AT/RT. Tumors that were reclassified/classified as AT/RT all had rhabdoid cells, and they were immunoreactive for at least two of the above four antibodies, while PNET/MB did not have any of these features. Further study including a wide variety of immunohistochemical markers (a total of 16) confirmed the striking polyphenotypic immunoreactivity of the AT/RTs that we examined.6 Histologically, most of the rhabdoid cells identified were large, pale, bland cells or large cells with prominent nucleoli and small amounts of cytoplasm, while classic rhabdoid cells were only encountered in 36% of tumors. The small cells, spindle cells, and epithelial components were only identified in 36%, 27%, and 18% of tumors, respectively. Embracing cells, a morphologic feature that had not been described previously, were noted in all our AT/RTs.6 However, this embracing cell was not seen in any of the PNET/MBs that we studied. Noticeably, the morphology of embracing cells appears to be identical to the cell wrapping in anaplastic medulloblastoma illustrated in Figure 2E of the current study. Furthermore, the illustrations of moderately and severely anaplastic tumors of the current study (Figs. 2C and 2E) were very similar to the illustration of AT/RT in Figure 1B of our report on the comparative study of AT/RT and PNET/MB.6 Because the morphology of the anaplastic medulloblastomas described in the current study was similar to some of the AT/RTs, it would be interesting to know the immunohistochemical staining patterns of these medulloblastomas. Donald Ming-Tak Ho M.D.* , Chih-Yi Hsu M.D., M.H.A.* , Hung Chiang M.D.* , * Department of Pathology and Laboratory Medicine Veterans General Hospital–Taipei, Department of Pathology National Yang–Ming University School of Medicine Taiwan, Republic of China.