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.