Contributed by Marie C. DeFrances, MD, PhD and A. Julio Martinez, MD FINAL DIAGNOSIS:
BRAIN, PINEAL REGION, STEREOTACTIC BIOPSIES: PINEOBLASTOMA
DISCUSSION:
Pineoblastomas are quite rare in adults. These neoplasms usually occur before age 20, are slightly more common in males, and account for approximately 45% of pineal region tumors. Patients such as the one in this case commonly present with the signs and symptoms of obstructive hydrocephalus and/or Parinaud's syndrome which is characterized by the following: upward gaze paralysis, normal vertical eye movement with doll's head maneuver, nystagmus with downward gaze associated with bilateral eye retraction, paralysis of accommodation, midposition of pupils, and light-near dissociation.
Radiologically, pineoblastomas are large lobulated ill-defined masses that are homogeneously hyperdense on CT following contrast and are hypointense on MRI. The tumors are often seen invading nearby structures and tracking along the leptomeninges, as was seen in this case. Grossly, the pineoblastoma is a soft, friable tumor often demonstrating hemorrhage and/or necrosis. Microscopically, the neoplastic tissue is hypercellular with tumor cells having large hyperchromatic nuclei with one discrete nucleolus and scant eosinophilic cytoplasm. The neoplastic cells grow predominantly in a diffuse pattern as was seen in this case, but rosette formation (Homer-Wright and Flexner-Winterstein rosettes) may be observed. Mitotic activity varies. The labeling index in the present case as determined by Ki-67 staining was about 30%. Immunostaining patterns demonstrate scattered positivity for synaptophysin, neuron specific enolase and retinal S-antigen. Immunostaining for glial fibrillary acidic protein is inconsistently positive. Our case demonstrated some positivity for synaptophysin and GFAP. Electron microscopy often reveals the presence of occasional cytoplasmic dense core granules, short immature cell processes, and occasional junctional complexes; however, no definite synapses are seen. This pattern of EM findings was observed in our case.
The cell of origin of the pineoblastoma is believed to be an immature, arrested or poorly differentiated pineocyte. During developoment, the normal pineal gland recapitulates the developmental program of the retina. Late in fetal development, cells in the pineal gland are ciliated and stain positively for melanin. However, by the first year after birth, these cells are replaced by mature pineocytes that contain photosensory apparatus and neuroendocrine granules.
Pineoblastomas may be somewhat difficult to diagnose histologically. The differential diagnosis includes pineocytoma, mixed pineoblastoma/pineocytoma, glial neoplasms such as glioblastoma multiforme, and primary central nervous system germ cell tumors. Some features of each of these malignancies may be useful to help distinguish between them. Pineocytomas can be differentiated from pineoblastomas based on the presence of small cells with a moderate amount of cytoplasm, rare to no mitoses, strong staining for synaptophysin, and obvious synapses on electron microscopy examination. Glial neoplasms tend to stain strongly with GFAP while pineoblastomas demonstrate inconsistent positivity. Primary germ cell neoplasms usually can be differentiated from pineoblastomas histologically, but special stains such as bHCG, PLAP and AFP that react positively with various types of germ cell neoplasms but negatively with pineoblastomas can be carried out to rule out the presence of pineoblastoma (Kleihues and Cavenee, 1997).
Therapeutic management of adults with pineoblastomas is controversial since such few cases exist in the literature. A combination of radiotherapy and chemotherapy is usually attempted. Prognosis is dismal regardless of therapy regimen. One series of adults with pineoblastoma had a median survival of 30 months (Chang et al., 1995). Another series showed a 49% five-year survival following various treatment modalities (Schild et al., 1997).
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Contributed by Marie C. DeFrances, MD, PhD and A. Julio Martinez, MD
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