Contributed by Gru AA1, Kolar G1, Wagner-Johnston ND2, Schmidt R1 , Yaseen NR1
1Dept of Pathology & Immunology and 2Division of Hematology and Oncology in Dept of Internal Medicine, Washington University School of Medicine. St. Louis, MO 63110
A 54 year-old man with past medical history significant for hypertension and gastro-esophageal reflux (GERD) presented with several months of sinus complaints (headaches, nasal drainage, sinus pain) requiring several courses of antibiotics and a right-sided tympanostomy tube placement. Over the last 2-3 months he developed bilateral eye pain with progressive vision loss, to the point of becoming blind in both eyes. He also had an unintentional weight loss of nearly 100 pounds. On physical examination no other motor, sensory, or cranial nerve deficits were seen. A CT scan of the brain showed a right frontoparietal subdural fluid collection, consistent with a hematoma, measuring up to 1 cm in thickness. This was associated with minimal midline shift and compression of the right lateral ventricle. A bilateral temporal artery biopsy and a turbinate biopsy showed no evidence of vasculitis. He underwent drainage of the hematoma without significant improvement of his symptoms. A brain MRI was performed. The T1 image revealed bilateral subdural collections, with associated diffuse meningeal thickening, (Figs 1, 2). There was a 1.5 cm lesion with restricted diffusion in the right parietal lobe and associated contrast enhancement, morphologically suspicious for a lymphoma. A FLAIR sequence showed no discrete mass corresponding to the area of restricted diffusion. In addition there was patchy mass-like effect, and mild herniation of the right parietal lobe into the burr hole.
A subsequent lumbar puncture showed a mildly elevated protein level and a negative cytology. The cell count was normal. A CT scan of the chest, abdomen and pelvis demonstrated no evidence of lymphadenopathy. A bone marrow biopsy was obtained (due to the concern for lymphoma), which showed normocellular marrow with multilineage hematopoiesis and no lymphoma (flow cytometry performed on the sample was also negative). Laboratory findings were significant for anemia and mild thrombocytosis (Hemoglobin 8.8 and Platelets 606). In addition, normal IgG levels with elevated IgG3 (108 mg/dl; nl range=18.4 - 106 mg/dl) and IgG4 (148 mg/dl; nl range=2.4 - 121 mg/dl) subclasses were seen. A biopsy of the putative enhancing lesion and the meninges was taken under MRI-guidance.
Histologically, the right dura was thickened and showed an infiltrate composed predominantly of small to medium-sized lymphocytes with clumped chromatin and abundant small, mature-appearing plasma cells (Figs 3, 4 and 5). In some areas the infiltrate appeared to be more pronounced around some blood vessels that were otherwise unremarkable. No vasculitis or necrotizing granulomatous inflammation was seen. By immunohistochemistry the lymphoid infiltrate was composed of a mixture of CD3+ T-cells (Fig.6) and CD20+ B-cells (Fig7). Rare larger CD20+ cells were occasionally seen, intermixed with the smaller lymphocytes. CD138 (Fig 8) showed an increased number of plasma cells, both singly scattered and clustered, which comprised approximately 30% of the cells in the infiltrate. In-situ hybridization for kappa and lambda revealed that the plasma cells were polytypic, with a kappa to lambda ratio of 3-4:1 (Figs. 9 and 10). An IgG4 immunostain (Fig.11) showed numerous positive plasma cells, comprising approximately 40% of that cell population. In several high-power fields there were over 10 IgG4+ cells (approximately 15-20 per HPF). IgG (Fig.12) stained relatively fewer plasma cells, representing 10-20% of the cells. The IgG4 to IgG ratio was markedly increased (>1). In-situ hybridization for EBER was negative. Molecular PCR studies were negative for IGH clonal rearrangement. What is your diagnosis?