FINAL DIAGNOSIS: HIGH GRADE NON-HODGKIN'S B-CELL LYMPHOMA (NHL) INVOLVING THE PINEAL GLAND AND RETROPERITONEUM
NHL may involve the central nervous system (CNS) either as a primary tumor or hematogenously from a systemic lymphoma. The occurrence of malignant lymphoma in the pineal region is exceedingly rare. Only five cases of pineal gland lymphoma have been documented in the literature to date (1,4,6,8). The first reported case was that of a 21-year-old man in whom a T-cell lymphoma involved the pineal gland, suprasellar region and dorsal medulla oblongata (6). Another case report described an immunoblastic B-cell lymphoma of the pineal gland with subsequent metastasis to the cauda equina, despite chemotherapy and radiation (1). A further fatal case of a 52-year-old man presenting with headache, obtundation, apathy, Parinaud's syndrome and a homogenous enhancement on CT scan has been described (4). The other two documented cases were reported without clinical or pathological details (1,8). In addition to these five reported cases, another possible case of pineal lymphoma was that of a 21-year-old female in whom the tumor was originally described as a "large cell sarcoma" which involved the pineal gland, right ovary, adrenals, kidneys, lymph nodes and bone (7). Plasma cell tumors occurring as metastatic deposits within the pineal body of elderly individuals have also been noted (5,10). Our patient was an immunocompetent elderly woman, who was found to have a stage IV large B-cell NHL presenting initially as a pineal mass. At autopsy, the tumor had disseminated along the ventricular walls, as well as subarachnoid spread onto the local brain surfaces.
The differential diagnoses of a pineal region tumor with this cytology include pineoblastoma, some germinomas and metastatic small cell carcinoma. Pineoblastoma may rarely manifest in late adulthood (3). Like lymphomas, pineoblastomas are composed of poorly differentiated and discohesive cells having scant cytoplasm and pleomorphic nuclei. However, pineoblastomas usually display some secondary architecture, including rosette formation and aligning of their slightly elongated nuclei. Unlike lymphoma, they may also show nuclear molding. Most histologic features of pineoblastomas are shared with metastatic small cell carcinomas, although the former may show some tendency to differentiate into neurons or glia. In small biopsies, pineal germinomas may have an abundance of lymphocytes, also raising the possibility of a lymphoma or an inflammatory disease. These tumors can be readily distinguished by marker studies: metastatic small cell carcinomas display immunoreactivity for cytokeratins, and neither small cell carcinoma nor pineoblastoma exhibit lymphoid antigens. Lymphoglandular bodies characteristic of high grade lymphomas aided in the intraoperative smear diagnosis.
Metastases to the highly vascularized pineal gland presumably occur by hematogenous spread (7). The pineal gland, a circumventricular organ, has fenestrated capillaries and numerous sinusoidal vessels without perivascular glial sheeting; all structures that make up the blood brain barrier (BBB) elsewhere in the CNS. This exposes the pineal gland directly to the systemic circulation, including any pathogens or hematogenous tumor cells. In this patient who had widespread systemic disease at the time of her pineal lymphoma diagnosis, it is unclear if the peripheral disease preceded or co-occurred with the pineal tumor. At autopsy, this patient's lymphoma widely infiltrated the adjacent brain, which is typical of primary brain lymphomas, but uncharacteristic of their systemic equivalents. In contrast, primary brain lymphomas only very rarely spread outside the CNS (2). In either case, the pineal gland is an extremely unusual location for lymphoma. These findings suggest that this patient had an atypical lymphoma with characteristics between primary and secondary brain tumors. Finally, because the pineal gland lacks a BBB, involvement of this region by tumor may accordingly be successfully treated with chemotherapy (9). However, because the tumor in this case had spread into the brain, it apparently was no longer susceptible to the conventional systemic chemotherapy that reduced her retroperitoneal disease.
Contributed by Liron Pantanowitz, MD, Steven J Freedman, MD, PhD, Bruce J Dezube, MD and Jeffrey T Joseph, MD, PhD