|Contributed by Liron Pantanowitz, MD1, Steven J. Freedman, MD, PhD2, Bruce J Dezube, MD2 and Jeffrey T Joseph, MD, PhD1|
|Departments of (1) Pathology and (2) Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School|
|Published on line in November 2002|
CLINICAL HISTORY AND IMAGING STUDIES:
A 72-year-old diabetic woman presented with a two-week history of progressive confusion, disorientation, short-term memory loss and shuffling gait. A general physical examination was unremarkable. Neurological examination demonstrated sluggishly reactive pupils, loss of upward gaze, bilateral pseudo-abducens nerve palsies, difficulty in performing finger-to-nose exercises on the right and a mild right facial paralysis. A MRI scan of her brain confirmed a T2 hypointense, slightly ill-defined, gadolinium enhancing 1.5cm mass in the pineal region, resulting in compression of the superior colliculus, effacement of the cerebral aqueduct and moderate obstructive hydrocephalus (Figure 1). CSF examination identified 190 erythrocytes, a single neutrophil, 77 lymphocytes, 22 macrophages and no microorganisms. She underwent a biopsy of the pineal lesion. Post-operatively she had persistent aphasia and diplopia. A whole body CT scan identified a large retroperitoneal mass and significant lymphadenopathy. Following four cycles of systemic chemotherapy, the patient returned to hospital three weeks later obtunded. A follow-up abdominal CT scan noted significant reduction of her retroperitoneal mass. A repeat MRI scan of her brain showed gadolinium enhancement in the pineal region, now with extension into contiguous brain parenchyma and the subependymal region. The patient died shortly afterward; four months after her initial presentation. An autopsy restricted to the brain was performed.
MICROSCOPIC DESCRIPTION AND AUTOPSY FINDINGS:
An intraoperative smear prepared from fragments of the pineal mass showed it to be composed of discohesive clusters of basophilic staining cells (Figure 2A, bar = 50 Ám). The cells were of moderate size, had only scant cytoplasm and an increased nuclear to cytoplasmic ratio. The anaplastic nuclei had complex nuclear membranes, were hyperchromatic and contained prominent nucleoli. Mitotic figures, apoptotic and lymphoglandular bodies were frequent (arrows). Occasional plasma cells and smaller reactive lymphocytes were also noted on the smear. A gliofibrillary matrix and multinucleated giant cells were absent. Blood vessels were also inconspicuous. Paraffin sections of the biopsy showed mitotically active, pleomorphic malignant cells infiltrating and almost completely replacing the residual pineal gland. These were arranged in sheets having a prominent "starry sky" pattern (Figure 2B, bar = 100 Ám). Rosettes were absent. There was strong immunoreactivity of the tumor cells for LCA and CD-20 (Figure 2C, bar = 100 Ám). Scattered CD3 and UCHL-1 positive cells were found interspersed among the larger malignant cells.
Dissection of the brain demonstrated wide encasement of the pineal region by firm white tumor (Figure 3A). The normally glistening lateral and third ventricular walls were obscured by a milky ivory-colored layer having multiple pinpoint red nodules. The fornix was markedly thickened and adherent to underlying structures. The internal cerebral veins (arrows) were entirely encased by tumor (Figure 3A). Microscopically, the infiltrating tumor along the ventricle had a prominent perivascular distribution (Figure 3B, bar = 1 mm) and was cytologically indistinguishable from that described in the biopsy. The white masses and fornix contained extensive tumor. A few residual laminated calcifications were present in the region of the pineal gland.