Contributed by Ari Breiner, MD1, William Dubinski, MD2, Bruce Gray, MD3, David G. Munoz, MD, FRCPC2
1Neurological Institute of New York, Columbia University Medical Center - New York, New York, USA.
2 Division of Pathology, St. Michael's Hospital, University of Toronto - Toronto, Ontario, Canada
3Division of Diagnostic Imaging, St. Michael's Hospital, University of Toronto - Toronto, Ontario, Canada
A 63-year-old woman, with a history of polycythemia vera, chronic splenomegaly, and osteoporosis, was admitted to our institution for investigation of progressive neurological and gastrointestinal symptoms. Eleven months prior, she noted pitting edema of the lower extremities, chronic watery diarrhea, and hypoalbuminemia. She underwent extensive gastrointestinal investigations, which revealed only hepatosplenomegaly. Ten months prior, she noted progressive neurological symptoms, including gait ataxia, generalized weakness, and episodic rotational vertigo. Brain MRI revealed multiple non-enhancing T2-hyperintense lesions in the periventricular white matter. Five months prior to admission to our hospital, she suffered a right thalamic lacunar stroke, causing left hemibody numbness. CT angiography demonstrated a dissection of the right vertebral artery.
On admission to our hospital, the patient complained of severe abdominal tenderness, with peritoneal signs, and underwent urgent laparotomy. There were no abnormal intraoperative findings, and biopsies taken from the stomach, duodenum, and rectum were normal. Gastroscopy and colonoscopy were performed, and were unrevealing. Post-operatively, the patient was encephalopathic, and minimally responsive. MRI of the brain again demonstrated abundant T2/FLAIR hyperintense (non-enhancing) lesions in the periventricular white matter and corpus callosum (Fig 1A; axial FLAIR sequence), consistent with central nervous system (CNS) demyelination. A small focus of enhancing T2/FLAIR signal hyperintensity in the right thalamus was suggestive of chronic thalamic stroke. The dura was diffusely thickened, and uniformly enhancing, following administration of gadolinium (Fig 1B; axial T1 gadolinium sequence). The differential diagnosis of this new dural process included infectious, malignant, and autoimmune causes. Clinically, the patient continued to deteriorate, and expired three days later.
GROSS AND MICROSCOPIC PATHOLOGY
Open dural biopsy was performed prior to the patient's death, and revealed a polymorphic inflammatory cell infiltrate, consisting principally of sheets of large, epithelioid histiocytes with foamy cytoplasm. Many histiocytes contained intact lymphocytes or plasma cells within their cytoplasm, a phenomenon known as emperipolesis (Fig. 2; scale bar = 100 µm; inset, scale bar = 25 µm).
At autopsy, gross examination of the brain revealed a discoloured and thickened dura. Microscopically, the entire dura mater was infiltrated by foamy histiocytic cells demonstrating emperipolesis, as described above. The right vertebral artery was focally thickened, with aneurysmal dissection at the site (Fig. 3). Microscopically, the artery (Fig. 4; scale bar = 500 µm; inset scale bar = 25 µm) showed vessel wall infiltration and destruction by inflammatory cells. There was a 3mm infarct in the right thalamus. Samples obtained at the time of autopsy demonstrated mutation in the JAK2 tyrosine kinase, confirming a diagnosis of polycythemia vera.
Coronal gross sections of the cerebral hemispheres revealed multiple, small (0.1-1.4 cm), sharply demarcated lesions in the subcortical white matter (Fig. 5). Microscopic brain examination revealed that these subcortical lesions were due to a second, distinct pathological process, consisting of plaques of demyelination, located in the subcortical white matter, corpus callosum, periventricular regions, and multiple brainstem segments (Fig. 6; Luxol fast blue stain; scale bar = 1000 µm). These plaques demonstrated complete demyelination, with preservation of axons (Fig. 7; neurofilament stain; scale bar = 1000 µm), and an absence of active inflammation.