Granular Cell Astrocytoma.
Patient received "Stupp's protocol" chemotherapy and radiation, but he died a few months after diagnosis.
Granular cell astrocytoma (GCA) is a rare morphologic variant of infiltrative astrocytoma with distinct morphologic features and aggressive clinical behavior. Few cases have been reported in the literature, almost all located in the cerebral hemispheres, or occasionally in the cerebellum (6) and one case in the spinal cord (5). The tumor shows male predominance and affects patients aged 29 to 75 years (mean 56 years). Presenting symptoms include new onset seizures, headache, aphasia, visual disturbances, hemiparesis, personality changes and cognitive decline. In most cases, neuroimaging studies show a solitary solid or partially cystic mass (1).
In terms of histological and immunohistochemical assessment, even though this case showed the typical features described in other reports, it is important to highlight the differential diagnoses considered. Granular cells (GC) resemble macrophages, therefore lesions such as cerebral infarct and demyelinating disease need to be ruled out. GCs are larger than macrophages, with coarsely granular cytoplasm packed with eosinophilic PAS-positive lysosomes (9); whereas macrophages show finely granular or foamy cytoplasm (2). GCs show significant nuclear enlargement, atypia and prominent eosinophilic nucleoli, features not typical of macrophages in central nervous system lesions. Both granular cells and macrophages are CD68 positive (7) and, in GCAs there is a "targetoid pattern" described for that immunostaining (4). GCA tumor cells on the other hand tend to be GFAP positive, a marker which is usually negative in macrophages. The caveat is that since GFAP immunostaining in GCA can be focal, weak, or even negative GFAP staining is not always helpful in establishing diagnosis (1). Another differential diagnosis that should be considered is metastatic carcinoma. In our case this was the main differential diagnosis because of the presence of more than one lesion. Absence of cytokeratin in granular cells and atypical astrocytes ruled out this diagnosis (3). Another defining feature in this type of lesion (therefore distinguishing it from the differential diagnoses) is the presence of areas of conventional astrocytoma. However, this component is not always present, making the distinction difficult in small biopsies lacking identifiable areas of conventional astrocytoma (1).
Even after adjusting for grade, clinical course of GCAs is more aggressive (8) than that of ordinary infiltrative astrocytomas, although at present, no explanation exists for this behavior. Perhaps granular cells are a morphologic marker of a separate, distinctly aggressive form of infiltrating astrocytoma. Granular cells in GCAs are significantly less proliferative than co-existing conventional astrocytoma cells. Thus, GCAs are similar to gemistocytic astrocytomas, an aggressive morphologic form of infiltrating astrocytoma in which, the gemistocyte, exhibits low MIB-1 labeling index (1).
In conclusion, we report a case of GCA, an uncommon morphologic variant of infiltrative astrocytoma, to emphasize the importance of considering the diagnosis. It's relatively low frequency means it may easily go undiagnosed; however diagnostic accuracy is of prognostic significance as well, since this is a highly aggressive brain tumor. To date there is no effective treatment, making publication of more case reports necessary.
Contributed by Gustavo Sevlever, MD, PhD; Naomi Arakaki, MD; María Asunción Beña, MD; Andrés Cervio, MD; Miguel A. Riudavets, MD