Clinicopathological characteristics and outcomes in Embryonal tumor with multilayered rosettes: a decade long experience from a tertiary care centre
Abstract :
Background : Embryonal tumor with multilayered rosettes (ETMR) are a heterogenous group clinically, pathologically and topographically. Due to limited cases, data regarding its molecular genetics, pathology and prognostic factors is evolving. We retrospectively analysed our cohort of ETMR over last decade in order to study their clinicopathological characteristics and outcome. Methods : Our cohort consisted of patients diagnosed with Embryonal tumor with abundant neuropil and true rosettes (ETANTR)/Ependymoblastoma (EBL)/ Medulloepithelioma (MEPL) over the past decade. Clinical details, including outcome and imaging data was retrieved. Histological analysis including immunohistochemical work-up was performed. Results : Cohort included 15 patients with age range between 1-28 years and M:F ratio of 1.5:1. Supratentorial location predominated in comparison to tumors arising in posterior fossa. ETANTR and EBL patterns were equally distributed (40% each), followed by one case each of mixed pattern (EBL+ETANTR), MEPL and embryonal tumor, unclassified. All tumors readily expressed LIN 28A and INI-1 was retained. Recurrence with evidence of glial and rhabdoid differentiation was noted in a single patient 9 months following resection. Follow-up period ranged from 1-31 months, with overall median survival of 6.4 months. Eight patients were planned for adjuvant treatment following surgery, of which only four could complete it. All patients, except for one, succumbed to the disease. Conclusions:ETMR have a heterogenous morphology and gathers ETANTR, EBL, MEPL within its spectrum. Following treatment, the recurrent tumor may feature glial/rhabdoid differentiation. LIN28A is expressed in all cases, however should be interpreted in context of histology. Prognosis of ETMR remains dismal despite multimodal therapy.
Introduction :
Embryonal tumor with multilayered rosettes (ETMR) are aggressive, WHO grade 4 tumors which were defined by a distinct histological pattern about two decades ago.1-3 Previously, these tumors were classified under the broad umbrella of central nervous system-primitive neuroectodermal tumors (CNS-PNET).4Pfister and colleagues discovered a novel miRNA amplification of C19MC at chr19q 13.42 that was later considered as the genetic hallmark of ETMR.5 These tumors are highly heterogenous in terms of location and histology. The spectrum of histology described under ETMR includes embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL).6,7 The unifying features of these is amplification of C19MC of which LIN 28A is a surrogate marker.7,8 Recently, DICER mutations have been identified in C19MC negative tumors.9,10 Complete surgical resection which is attempted for patients with localised disease is associated with survival advantage similar to other pediatric brain tumors. These tumors have been conventionally treated with high-risk medulloblastoma protocols. Due to limited cases and its recent recognition, no specific treatment strategy using chemotherapy or adjuvant radiotherapy has been prospectively evaluated in ETMR patients so far.
We present our experience with this uncommon tumor diagnosed over the past decade and discuss the morphological features, treatment details and clinical outcome. Due to limited number of cases reported in the literature and since the molecular diagnosis is not routinely performed, the information regarding clinical, pathological features, favourable prognostic factors, optimal treatment options are still evolving; our cohort adds observational data to the existing knowledge regarding this tumor.
Material and methods : Our cohort comprised of 15 cases of ETMR diagnosed over past 10 years. Demographics, treatment and survival details were retrieved from neurosurgery and radiotherapy records. Haematoxylin and eosin (H&E) stained sections were evaluated and tumors were further characterized with an immunohistochemical panel consisting of antibodies to glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament protein (NFP), Neu N, LIN 28A, INI-1 and Ki67.