Contributed by Alejandro A Gru, MD1, Norman L Lehman, MD, PhD2, Jose Otero, MD, PhD,
1Divisions of Hematopathology and Dermatopathology and 2Division of Neuropathology. The Ohio State University Wexner Medical Center
A 59 year-old man with a past medical history significant for a renal transplant, secondary to hypertensive nephrosclerosis and diabetes, presented with a 3-4 week history of progressive mental status changes, including confusion, somnolence and personality changes. He also had 1-2 weeks of low-grade fevers and chills, with associated weight loss. One to two months prior to his presentation to the emergency room, he was diagnosed with monomorphous post-transplant lymphoproliferative disorder (PTLD) on an axillary lymph node biopsy. Focal areas compatible with diffuse large B-cell lymphoma were seen. His original PET scan revealed extensive lymphadenopathy both above and below the diaphragm.
Upon admission, he was noted to have EBV viremia (approximately 1.5 million copies). A brain MRI showed numerous hyperintense lesions seen in T2 and FLAIR (Figure 1) sequences with a periventricular distribution, and two areas with particular hyperintensity within the left medial temporal lobe (Figure 2), and posterior parietal and occipital lobes. With contrast enhancement there was an irregular enhancing lesion measuring 1.5 x 0.9 cm involving the amygdala on the left side. Many other small ring-enhancing lesions and partial crescents were seen (Figure 3). The corpus callosum was quite small and irregular. Radiologically the features were suspicious for a metastatic disorder, demyelination, an infectious process or lymphoma.
Additional laboratory findings revealed a mild leukopenia (WBC 3.4) and CNS viremia seen by a lumbar puncture. His CSF was negative for syphilis, legionella, Cryptococcus, histoplasma, toxoplasma, JC/BK viruses, CMV and HSV. Flow cytometric analysis of the CSF failed to reveal a clonal B-cell population. Because of his clinical deterioration, chemotherapy was held after the diagnosis of PTLD. In light of the clinical history, a stereotactic brain biopsy was performed.
Histologically, there were areas with brain infarction and associated gliosis (Figures 4 and 5). The most striking feature seen was the presence of a heterogeneous mononuclear cell infiltrate with a predominant perivascular distribution (Figures 6 and 7). The polymorphous infiltrate was composed of small to medium sized lymphocytes with coarse chromatin and variable nucleoli (Figures 8 and 9). Scattered admixed large cells were also present. The background cells also included plasma cells and histiocytes (Figure 10).
Additional immunohistochemical stains were performed: CD3 stained small T-cells in the perivascular areas (Figure 11). CD20 was positive in a much larger proportion of cells, including some of the very rare admixed larger lymphocytes (Figures 12 and 13). CD138 was positive in the plasma cells, which comprised approximately 10-15% of the infiltrate. MUM1 was also positive in the plasma cells, and scattered larger cells (Figure 14). BCL-6 was predominantly negative. In-situ hybridization for cytoplasmic kappa and lambda light chains revealed clonal lambda light chains restriction among the plasma cells (Figures 15 and 16). In-situ hybridization for Epstein-Barr Virus-encoded RNA (EBER) was positive in few scattered cells (Figure 17). The proliferation index labeled by Ki67 was low (approximately 10-15% of the cells, Figure 18). AFB, GMS, Gram stains and SV40 were all negative. What is your diagnosis?