Contributed by Rachael A. Vaubel, MD, PhD and R. Ross Reichard, MD
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN
The patient is a 56-year-old woman with history of poorly differentiated squamous cell carcinoma of the esophagus, treated with neoadjuvant chemoradiation and esophagectomy. Approximately three years later, she presented with pancytopenia and was diagnosed with therapy-related myelodysplasia, consistent with refractory anemia with excess blasts-1 (RAEB-1). She was treated with induction (daunorubicin, cytarabine, and cladribine) and consolidation (daunorubicin and cytarabine) chemotherapy. She then received reduced intensity conditioning (fludarabine, cyclophosphamide, and total body irradiation) prior to undergoing double umbilical cord stem cell transplant. On day 35 post-transplant, she developed progressive bilateral loss of vision.
A thorough ophthalmologic work-up pinpointed no specific etiology; retinogram was normal while visual evoked potentials demonstrated severe bilateral conduction impairment. Brain MRI demonstrated mild to moderate FLAIR hyperintensities in the cerebral white matter, consistent with small vessel ischemic disease or treatment related changes. She then developed bilateral sensory loss in her lower extremities and was treated with plasmapharesis and corticosteroids, without improvement. She subsequently became encephalopathic, her pulmonary function deteriorated, and her family declined further intervention. Permission for a full autopsy was given.
On gross examination, the brain demonstrated prominent white matter pathology predominantly involving the left parietal lobe (Fig. 1a). Microscopic examination of this area demonstrated a relatively demarcated area of vacuolization (Fig. 1b) and myelin loss (LFB-PAS, Fig. 1c). Several small parenchymal lesions were also identified in the thalamus. Higher power images of the parietal lesion (Fig. 1d) showed frequent axonal spheroids, further highlighted by neurofilament (Fig. 1e) and APP immunostains. Numerous macrophages were present (CD68, Fig. 1f) along with a moderate number of reactive astrocytes (GFAP, Fig. 1g). In situ hybridization for JC virus was negative. What is the most likely diagnosis?