1/8/2012 Case 3: High-grade glioneuronal tumor

Presented by: Dr. Sharer (from Dr. John Donahue - Rhode Island Hospital and Brown University, Providence)

Clinical History:

A 64-year-old man with a past medical history of low-grade astrocytoma, status post surgery x2 in 1985 and radiation approximately 20 years ago.  He was recently hospitalized for chest pain, and at that time a CT demonstrated mass effect in the left parietal lobe.  His wife had noted subtle word finding difficulty and memory changes for several months.  Subsequent MRI showed an enhancing mass in the left posterior parietal and occipital lobes.  Neurosurgery was consulted, and the patient returned for surgical intervention.

The original tumor was in the left frontal lobe.  He was biopsied here at R.I. Hospital on 4/10/85.  The official diagnosis was "well-differentiated astrocytoma (Grade 2).  The possibility of a mixed glioma cannot be ruled out.  There are minute and focal calcific deposits."

The tumor was resected at University of Massachusetts Medical Center on 6/18/85.  Diagnosis:  "Glioma with calcification, see note.  Note:  The tumor is moderately cellular and consists predominantly of cells with large round to oval hyperchromatic nuclei and an increased nuclear to cytoplasmic ratio.  Cellular pleomorphism is minimal, and mitotic figures are not observed.  In some areas, a distinct feltwork background of astrocytic glial processes is obvious on H&E stain, while in others PTAH stain is necessary to elucidate these fibers.  In these latter areas, microcalcification is prominent focally, and there is a suggestion of microcystic degeneration.  Occasional Rosenthal fibers are present.  Overall, the tumor has a histologic appearance suggestive of a low-grade astrocytoma, although occasional cells with apparent zones of perinuclear lucency reminiscent of oligodendroglial cells are present.  We have reviewed the biopsy from this patient's previous cranial surgery (Rhode Island Hospital).  There is some difference in the degree of nuclear pleomorphism, attempt at glial differentiation (along astrocytic/oligodendroglial/ependymal lines), and the extent of microcalcification between the two specimens.  In general, however, it seems that we are largely dealing with a fibrillary astrocytoma of intermediate grade (Grade 2) with a minor mixed glial component.  The material available for examination from both surgical procedures is very small."

Diagnostic Notes:

The present tumor was a cystic neoplasm in the left parietal-occipital lobe.

The 1985 biopsy and resection of the left frontal tumor showed perivascular pseudorosettes and was strongly GFA positive with a low MIB1/Ki-67. 

The 2011 material demonstrated in the presentation (not necessarily on the slides provided) showed a cellular atypical glial tumor with perivascular pseudorosettes with a small cell component and mitoses.  There was a microcystic region.  There were endothelial proliferation and necrosis.  GFA was expressed in the pseudorosettes but not in the small blue cell population.  The tumor expressed S100, was focally positive for EMA which was sometimes dot-like, and was positive for synaptophysin (dot-like). Some cells expressed neurofilaments.  MIB1/Ki-67 was focally seen in the pseudorosettes but was expressed in 90% of the small blue cells.

The differential diagnosis included mixed glioneuronal tumor, papillary glioneuronal tumor, astroblastoma and ependymoma.  It was called “Astroblastoma with malignant degeneration” as per the 2007 WHO classification, pp. 88-89 and Bruger PC (Smears and frozen section in Surgical Neuropathology, pp. 293-98. 

Dr. Rosenblum thought that this tumor did not have enough ependymal differentiation for the diagnosis of angiocentric glioma and that papillary glioneuronal tumor was not supported by the evidence.  EDH might be helpful; if positive, it would be in the diffuse glioma category.  Braf may be helpful for difficult pilomyxoid/pilocytic tumors.  He noted that “astroblastoma” is a pattern as per Bailey and Cushing and the term should be reserved for a tumor of children, that is well-circumscribed and showed astroblastic architecture in all areas, and that ‘astroblastoma is a diagnosis of exclusion, that is after one has ruled out astrocytoma and ependymoma. 

As per Dr. Donahue’s presentation, the parenchymal location and stout processes as well as the perivascular hyalinization are typical of astroblastoma, but the neuronal markers are disconcerting.  The 1985 tumor is best diagnosed as a “pilocytic astrocytoma.”  The patient developed an abscess in 12/11 and was re-admitted with this complication.

The consensus of the group was that the tumor is a high-grade glioneuronal tumor.