Case Presentation:
A 59-year-old gentleman, with a past medical history of hypertension, hyperlipidemia, chronic immune thrombocytopenia (ITP) not requiring therapy (diagnosed seven years prior), and coronary artery disease status post percutaneous intervention/drug-eluting stent two months prior, presented to the emergency department after a fall.
Physical examination was unremarkable with the exception of a left facial droop. Laboratory evaluation showed mild thrombocytopenia (94 x 109/L).
Magnetic resonance imaging (MRI) revealed a 4.5 x 5.4 x 3.3 cm heterogenous, peripherally T1 post-contrast enhancing mass lesion involving the right frontal lobe with significant vasogenic edema (Figure 1A). This was concerning for primary CNS neoplasm like glioblastoma multiforme.
Pathologic analysis after stereotactic biopsy of the right frontal mass showed an angiocentric polymorphous lymphoid infiltrate composed of numerous small T-cells admixed with histiocytes and scattered intermediate-to-large, atypical, EBV (+) B-cells. The remainder of the lesion showed areas of lymphocytic vasculitis, angiodestruction, hemorrhage, and large areas of central necrosis (Figure 2A-F). The number of EBV (+) B-cells was variable, but overall, less than 5 per high-power-field (hpf). After multi-disciplinary discussion, the lesion was classified as an EBV-LPD with features suggestive of low-grade (grade I) lymphomatoid granulomatosis (LYG).
His platelet count dropped after the brain biopsy to 30 x109/L.  There was evidence of significant platelet dysfunction on whole blood impedance platelet aggregometry consistent with ITP. He received intravenous immunoglobulin (IVIG) and romiplostim along with a steroid taper. Clinical course was further complicated with vesicular rash over right arm and multiple dermatomes suggestive of disseminated zoster necessitating antiviral therapy.
Staging CT scans did not show any pulmonary or nodal involvement of LYG, but incidentally detected sub-massive pulmonary embolism for which therapeutic anticoagulation was started. Bone marrow aspiration/biopsy showed 30-40% involvement by low-grade CD5(-)/CD10(-) B-cell lymphoma. In-situ hybridization for EBV-encoded small RNA (EBER) was negative. Immunologic studies showed borderline low total IgG (681 mg/dL) and slightly decreased amounts of CD3(+)/CD8(+) T-cells. Serum protein electrophoresis did not show evidence of monoclonal gammopathy. EBV PCR was detectable but non quantifiable. HIV, hepatitis C and hepatitis B serologies were negative. Anti-nuclear and platelet antibodies were negative. Genetic testing for primary immunodeficiency and next-generation sequencing of the brain biopsy did not reveal any pathologic mutations.
The patient was started on rituximab 375 mg/m2 weekly for 4 weeks. This was immediately followed by ultra low-dose radiation therapy (ULD-RT) to the right frontal brain mass at a total dose of 4 Gray in 2 fractions (2 Gray/fraction). The patient had an excellent clinical and radiologic response to therapy with serial imaging showing significant decrease in size of the brain mass (Figure 1B). Platelet count normalized with rituximab, allowing discontinuation of romiplostim.
The patient remains on maintenance Rituximab every 2 months for a planned 2 years of therapy. He has tolerated the therapy well with continued response noted on imaging, 20 months after treatment initiation (Figure 1C).