It's Deja Vu All Over Again

X-rays of the femur showed sclerosis. CT showed peri-aortic soft-tissue thickening. A left orbital biopsy revealed diffuse xanthogranulomatous inflammation, fibrosis, and lymphoplasmacytosis, consistent with Erdheim-Chester Disease (ECD). The patient underwent 6 cycles of doxorubicin, cyclophosphamide, and vincristine, with subsequent azathioprine for 14 years. In December 2012, he developed a left middle cerebral artery (L MCA) stroke with residual right homonymous hemianopia (R HH). Immunosuppresion was discontinued. Bone pain recurred. In April 2013, VA was 20/60 OD, 20/25 OS; Ishihara color vision was 10/11 OU. There was no RAPD. Automated perimetry showed R HH. Head CT revealed a new ring-enhancing right frontal lobe lesion, enhancing orbital lesions, and L MCA encephalomalacia. CT showed new perirenal infiltration and fascial thickening. Despite great debate regarding the etiology of his brain lesion, the patient declined further evaluation. He died 5 months later. Aside from orbital ECD, autopsy revealed pericardial (CD68+/CD1a-) and perirenal foamy histiocytic infiltrates with myxoid changes alternating with hyalinized fibrosis. There were other hypercellular intracerebral lesions aside from the right frontal mass on autopsy, with pleomorphic cells, mitoses, and necrosis, diagnostic of glioblastoma multiforme (GBM). There are no reported ECD cases with GBM. GBM may have developed secondary to chance mutation. Our other potential theories regarding GBM development in this long-standing case of ECD are:1. BRAF proto-oncogene mutations are seen in many ECD patients, gliomas, and GBM's. This patient may have the genetic architecture to develop both ECD and GBM. 2. Chronic azathioprine use may increase neoplasm risk. In this case, azathioprine induced ECD remission, but possibly led to GBM development. Some azathioprine-treated patients have developed BRAF-mutation-associated tumors. Since 1999, interferon-alpha has significantly improved survival for ECD patients. Vemurafenib, an BRAF-mutant inhibitor, has been used with promising results.