Intramedullary Spinal Cord Ependymoma and Astrocytoma: Intraoperative Frozen-Section Diagnosis, Extent of Resection, and Outcomes
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CLINICAL ARTICLE J Neurosurg Spine 30:133–139, 2019 Intramedullary spinal cord ependymoma and astrocytoma: intraoperative frozen-section diagnosis, extent of resection, and outcomes *Hiroki Hongo, MD,1 Keisuke Takai, MD, PhD,1 Takashi Komori, MD, PhD,2 and Makoto Taniguchi, MD, PhD1 Departments of 1Neurosurgery and 2Laboratory Medicine and Pathology, Tokyo Metropolitan Neurological Hospital, Fuchu, Tokyo, Japan OBJECTIVE The intraoperative differentiation of ependymomas from astrocytomas is important because neurosurgical strategies differ between these two tumor groups. Previous studies have reported that the diagnostic accuracy of intra- operative frozen sections of intracranial central nervous system (CNS) tumors is higher than 83%–97%, whereas that for spinal intramedullary tumors remains unknown. Herein, authors tested the hypothesis that intraoperative frozen-section diagnosis is the gold standard for a differential diagnosis of intramedullary spinal cord tumors. METHODS The clinical characteristics, intraoperative histological diagnosis from frozen sections, extent of tumor resec- tion, progression-free survival (PFS), and overall survival (OS) of 49 cases of intramedullary spinal cord ependymomas (n = 32) and astrocytomas (n = 17) were retrospectively evaluated. RESULTS The frozen-section diagnosis and final diagnosis with permanent sections agreed in 23 (72%) of 32 cases of ependymoma. Of the 9 cases of ependymoma in which the frozen-section diagnosis disagreed with the final diagnosis, 4 were incorrectly diagnosed as astrocytoma and the other 5 cases had a nonspecific diagnosis, such as glioma. None- theless, gross-total resection was achieved in 6 of these 9 cases given the presence of a dissection plane. The frozen- section diagnosis and final diagnosis agreed in 12 (71%) of 17 cases of astrocytoma. Of the 5 cases of astrocytoma in which the frozen-section diagnosis disagreed with the final diagnosis, 1 was incorrectly diagnosed as ependymoma and the other 4 had a nonspecific diagnosis. Gross-total resection was achieved in only 1 of these 5 cases. A relationship between the size of tumor specimens and the diagnostic accuracy of frozen sections was not observed. Ependymal rosettes and perivascular pseudorosettes were observed in 30% and 57% of ependymomas, respectively, but were absent in astrocytomas. Progression-free survival and OS were both significantly longer in cases of ependymoma than in cases of astrocytoma (p < 0.001). Gross-total resection was achieved in 69% of ependymomas and was associated with longer PFS (p = 0.041). In the astrocytoma group, gross-total resection was achieved in only 12% and there was no relationship between extent of resection and OS. Tumor grades tended to correlate with OS in astrocytomas (p = 0.079). CONCLUSIONS The diagnostic accuracy of intraoperative frozen sections was lower for intramedullary spinal cord ependymomas and astrocytomas in the present study than that for intracranial CNS tumors reported on in the literature. Surgical strategies need to be selected based on multiple factors, such as clinical characteristics, preoperative imaging, frozen-section diagnosis, and intraoperative findings of the tumor plane. https://thejns.org/doi/abs/10.3171/2018.7.SPINE18230 KEYWORDS intramedullary tumor; progression-free survival; overall survival; histopathology; tumor grade; surgical treatment; radiation; chemotherapy; oncology ABBREVIATIONS CNS = central nervous system; GTR = gross-total resection; ISCT = intramedullary spinal cord tumor; OS = overall survival; PFS = progression-free survival; PR = partial resection; STR = subtotal resection. SUBMITTED February 28, 2018. ACCEPTED July 10, 2018. INCLUDE WHEN CITING Published online October 19, 2018; DOI: 10.3171/2018.7.SPINE18230. * H.H. and K.T. contributed equally to this study and share first authorship. ©AANS 2019, except where prohibited by US copyright law J Neurosurg Spine Volume 30 • January 2019 133 Unauthenticated | Downloaded 09/30/21 04:23 PM UTC Hongo et al. NTRAMEDULLARY spinal cord tumors (ISCTs) are rela- TABLE 1. Subtype classification of ependymomas and tively rare neoplasms that account for only 2%–4% of astrocytomas central nervous system (CNS) glial tumors. In adults, WHO Ependymomas Astrocytomas Iependymomas are the most common ISCT, comprising Grade Type No. Type No. approximately 50%–60% of ISCTs.2,3 Most ependymo- mas are slow growing and well demarcated from the spi- I Subependymoma 3 Pilocytic astrocytoma 2 nal cord parenchyma.7 Accordingly, gross-total resection II Ependymoma 28 Diffuse astrocytoma 9 (GTR) is possible in most cases of ependymoma. Previ- III Anaplastic ependymoma 1 Anaplastic astrocytoma 5 ous studies have reported that the extent of resection is IV Not applicable 0 Glioblastoma 1 a strong predictor of progression-free survival (PFS).2,8,9 Intramedullary astrocytomas, the second most common ISCT, possess more infiltrative features than ependymo- mas.7,14 Because of this infiltrative characteristic, the re- lationship between GTR and PFS in astrocytoma is less istic features on MRI.6 Patient demographics, symptoms, clear,12 and adjuvant therapy such as radiotherapy and preoperative McCormick grades,11 symptom duration pri- chemotherapy is often combined with resection.1,14 Since or to diagnosis, tumor location, tumor size, extent of resec- neurosurgical strategies differ between these two tumor tion, adjuvant therapy, follow-up period, recurrence/pro- groups, the differentiation of ependymoma from astrocy- gression, and death were collected from medical charts. toma is important. Tumor size was indicated by the number of vertebral bod- One method employed to differentiate the two tumor ies the tumor involved. Extent of excision was assessed on types is an intraoperative frozen-section diagnosis.13,15 initial postoperative MRI and defined as follows: GTR, Previous studies have reported that the diagnostic accu- no residual tumor; subtotal resection (STR), 90%–99% racy of intraoperative frozen sections of intracranial CNS resection; partial resection (PR), 5%–89% resection; and tumors is higher than 83%–97%,3,4,13,15,16 whereas that for biopsy, < 5% resection. Recurrence and progression were ISCTs remains unclear. In the present study, we aimed to defined as an increased tumor size on follow-up MRI. The test the hypothesis that intraoperative frozen-section di- median follow-up period was 70 months (range 1–252 agnosis is the gold standard for a differential diagnosis of months). ISCTs. Surgical cases of intramedullary spinal cord ep- endymomas and astrocytomas were reviewed in order to Frozen-Section Diagnosis clarify how the results of a frozen-section diagnosis affect Diagnostic reports of a frozen-section diagnosis were microsurgical treatments and outcomes. classified into 1) agree, agreement between frozen-section and final diagnoses regardless of tumor grade; 2) disagree, Methods no agreement between frozen-section and final diagnoses; and 3) nonspecific diagnosis, frozen-section diagnosis is Patient Population and Clinical Data too wide to be classified, i.e., glial tumors. Sensitivities, The present study was approved by the institutional re- specificities, and positive and negative predictive values view board at the Tokyo Metropolitan Neurological Hospi- were calculated for the differentiation of ependymomas tal. All patients gave full written informed consent for fro- from astrocytomas. zen- and permanent-section diagnoses. Regarding study In 36 cases (23 ependymomas and 13 astrocytomas), participation, written informed consent was not obtained the presence of ependymal rosettes and perivascular pseu- because this was a retrospective study. A public notice that dorosettes and the largest diameter of each specimen were provided information on this study was instead provided re-reviewed using the surgical specimens for frozen sec- by the Tokyo Metropolitan Neurological Hospital. tions. The relationship between the accuracy of the frozen- We retrospectively reviewed the medical records of 49 section diagnosis and the maximum diameter of frozen consecutive patients with intramedullary spinal cord ep- sections was examined. In the remaining 13 cases, surgi- endymomas (n = 32) and astrocytomas (n = 17) for whom cal specimens for frozen sections were not available. intraoperative frozen-section diagnoses were made at To- At our hospital, the chief of the neuropathological de- kyo Metropolitan Neurological Hospital between January partment changed three times over a 23-year study period; 1993 and March 2016. Formalin-fixed paraffin-embedded therefore, three experienced neuropathologists engaged sections were diagnosed based on the 2007 WHO classi- in the pathological diagnosis of spinal intramedullary tu- fication of CNS tumors (Table 1). Ependymomas included mors. One of the three neuropathologists, a single neuro- WHO grade I subependymoma, grade II ependymoma, pathologist, examined each frozen and permanent section. and grade III anaplastic ependymoma. Astrocytomas in- The relationship between the accuracy of the frozen-sec- cluded WHO grade I pilocytic astrocytoma, grade II dif- tion diagnosis and each pathologist was examined. fuse astrocytoma, grade III anaplastic astrocytoma, and grade IV glioblastoma. One recent case of diffuse midline Preoperative MRI Diagnosis glioma H3 K27M-mutant (WHO 2016)10 was classified as Diagnostic reports on the MRI were retrospectively anaplastic astrocytoma in the statistical analysis. Cases reviewed in cases for which the frozen-section