RARE-23TWO CASES OF RARE INTRASPINAL POORLY DIFFERENTIATED NEUROENDOCRINE TUMOR WITH EXCELLENT RESPONSES TO RADIATION THERAPY

Abstract

We describe two unusual cases of poorly differentiated neuroendocrine tumor of the spinal cord and leptomeninges. A 61-year-old woman developed rapidly progressive lower extremity paraparesis and sensory deficits. MRI revealed an intradural extramedullary mass levels arising from the conus extending from T12-S3, in multiple foramina, with extensive craniospinal leptomeningeal dissemination. Debulking revealed a poorly differentiated neoplasm characterized by nuclear molding and a high mitotic rate with immunohistochemical positivity for neuroendocrine markers (CD56, chromogranin, synaptophysin). Hematopoietic markers, keratin, GFAP, S100, and CD99/MIC2 were negative, and EWSR1 gene was intact by FISH. She received craniospinal irradiation of 39.6Gy in 22 fractions with a 5.4Gy boost followed by temozolomide. She remains clinically stable nineteen months since presentation, and MRI shows dramatic improvement with small remnants of enhancement at the cauda equina and thoracic thecal sac. The second case is a 65-year-old man with two months of progressive lower extremity paraparesis. He became non-ambulatory with a KPS of 40. MRI revealed an expansile intramedullary cervical cord lesion and diffuse neuroaxial leptomeningeal enhancement. Biopsy revealed a small round blue cell tumor with a markedly elevated proliferative index. Immunostaining showed diffuse positivity for CD56 and CD99/MIC2, while stains for CD45 and keratin were negative. EWSR1 and FUS genes were intact. He received craniospinal irradiation with a boost to bulky disease. His exam improved greatly and he was ambulatory four weeks after radiation with a KPS of 90. One year after radiation, he has little residual radiographic disease with an unchanged examination. For both cases, no alternative primary source was identified. Cauda equine paragangliomas have been the principal intraspinal neuroendocrine tumors described to date; we have been unable to identify other reports of primary intraspinal high grade poorly differentiated neuroendocrine tumors. Remarkably, despite extensive disease and poor performance status both our patients had excellent responses to radiation.