LETTER TO THE EDITOR Spinal Cord Pilocytic Astrocytoma With FGFR1-TACC1 Fusion and Anaplastic Transformation Elena V. Daoud , MD, PhD 1 , Akshat Patel 1 , Jeffrey Gagan, MD, PhD 1 , Jack M. Raisanen, MD 1 , George J. Snipes, MD, PhD 2 , Emmanuel Mantilla, DO 3 , Ramya Krothapally 1 , Kimmo J. Hatanpaa, MD, PhD 1 , and Edward Pan, MD 4 1 UT Southwestern Medical Center, Department of Pathology, Dallas, Texas 2 Baylor Medical Center, Department of Pathology, Dallas, Texas 3 John Peter Smith Health Network, Department of Oncology, Fort Worth, Texas 4 UT Southwestern Medical Center, Department of Neurology and Neurotherapeutics, Dallas, Texas Correspondence to: Elena V. Daoud, UT Southwestern Medical Center, Department of Pathology, 5323 Harry Hines Blvd, Dallas, TX 75390; E-mail: elena.daoud@phhs.org The authors received no financial support for the research, authorship, and publication of this article. The authors have no duality or conflicts of interest to declare. To the Editor: Pilocytic astrocytoma (PA) is a WHO grade 1 primary neoplasm that accounts for 5.4% of all gliomas, occurs pre- dominantly in childhood and adolescence, and usually arises in the cerebellum or cerebral midline structures (1, 2). The treatment of choice is surgical resection and the prognosis is excellent, with survival over 95% at 10 years (3). If a gross total resection (GTR) is achieved, postoperative radiation therapy or chemotherapy is not warranted, with low reported recurrence rates (4, 5). Development of anaplastic features is extremely uncommon, and many such tumors are associated with prior radiation therapy (6–8). However, little is known about the mechanisms and driver mutations associated with PA anaplasia (7). The majority of sporadic PAs harbor alterations leading to MAPK/ERK pathway activation, which include aberra- tions affecting the BRAF gene. The most common abnormal- ity (67%) is tandem duplication of 7q34, resulting in a transforming KIAA1549-BRAF fusion gene, in which BRAF lacks its auto-inhibitory domain and becomes constitutively active (9). However, the remaining 33% of PAs, although his- tologically similar, have less easily identifiable molecular aberrations. Other alterations that have been studied involve FGFR1 receptor tyrosine kinase (RTK) gene and include hot- spot point mutations, fusions, domain internal duplication and internal tandem duplication of the gene itself. While the KIAA1549-BRAF fusion is common in the cerebellum, FGFR1 alterations are more common in extracerebellar mid- line structures (10). Interestingly, the FGFR1-TACC1 fusion was recently described as the signature genetic alteration in a histologically defined subset of cerebellar PAs (11). We re- port the first case of a PA harboring the FGFR1-TACC1 fu- sion in an uncommon spinal location, which recurred 15 months following surgical resection and exhibited anaplas- tic transformation. CLINICAL CASE A 22-year-old female patient presented with left shoul- der numbness and weakness followed by left leg weakness and worsened gait. Cervical spine magnetic resonance imag- ing (MRI) with contrast demonstrated an enhancing intrame- dullary mass involving the brainstem and cervical spine, measuring 8.8 cm craniocaudally (Fig. 1A). A GTR was per- formed, no adjuvant therapy was provided, and the patient was observed. The mass was a histologically classic PA, a bi- phasic tumor comprised of loose oligodendroglioma-like areas in a myxoid and microcystic stroma with hyalinized blood vessels (Fig. 1C), with more solid areas containing densely fibrillar cellular arrangements with Rosenthal fibers (Fig. 1D, arrows). The immunohistochemical studies sup- ported glial lineage with strong, diffuse positivity for GFAP (Fig. 1F). There was no detectable mitotic activity and no in- filtration on H&E and neurofilament stains, while MIB-1 in- dex was 0.5%. Although extraventricular neurocytoma was considered, the biphasic architecture, diffuse expression of GFAP (Fig. 1F) and absence of expression of the neural anti- gens Neu-N, chromogranin and neurofilament supported PA. A next-generation sequencing (NGS) panel detected a loss- of-function mutation (p.A2451fs) in the tumor suppressor SETD2 and an FGFR1-TACC1 fusion. FISH was negative for 1p/19q codeletion, effectively ruling out oligodendroglioma. Although the canonical KIAA1549-BRAF fusion and V600E 283 V C 2020 American Association of Neuropathologists, Inc. All rights reserved. J Neuropathol Exp Neurol Vol. 80, No. 3, March 2021, pp. 283–285 doi: 10.1093/jnen/nlaa122 Downloaded from https://academic.oup.com/jnen/article/80/3/283/5992387 by guest on 27 May 2023