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).