Childhood-Onset Myopathy With Preserved Ambulation Caused by a Recurrent ADSSL1 Missense Variant.

Background and Objectives: Distal myopathies are a heterogeneous group of primary muscle disorders with recessive or dominant inheritance. ADSSL1 is a muscle-specific adenylosuccinate synthase isoform involved in adenine nucleotide synthesis. Recessive pathogenic variants in the ADSSL1 gene located in chromosome 14q32.33 cause a distal myopathy phenotype. In this study, we present the clinical and genetic attributes of 6 Indian patients with this myopathy. Methods: This was a retrospective study describing on Indian patients with genetically confirmed ADSSL1 myopathy. Details were obtained from the medical records. Results: All patients presented in their first or early second decade. All had onset in the first decade with a mean age at presentation being 17.7 ± 8.4 years (range: 3-27 years) and M:F ratio being 1:2. The mean disease duration was 9.3 ± 5.2 years ranging from 2 to 15 years. All patients were ambulant with wheelchair bound state in 1 patient due to respiratory involvement. The median serum creatine kinase (CK) level was 185.5 IU/L (range: 123-1564 IU/L). In addition to salient features of ptosis, cardiac involvement, bulbar weakness, and proximo-distal limb weakness with fatigue, there were significant seasonal fluctuations and decremental response to repetitive nerve stimulation, which have not been previously reported. Muscle histopathology was heterogenous with the presence of rimmed vacuoles, nemaline rods, intracellular lipid droplets along with chronic myopathic changes. Subtle response to pyridostigmine treatment was reported. While 5 of 6 patients had homozygous c.781G>A (p.Asp261Asn) variation, 1 had homozygous c.794G>A (p.Gly265Glu) in ADSSL1 gene. Discussion: This study expands the phenotypic spectrum and variability of ADSSL1 myopathy with unusual manifestations in this rare disorder. Because the variant c.781G>A (p.Asp261Asn) is the most common mutation among Indian patients similar to other Asian cohorts, this finding could be useful for genetic screening of suspected patients.

Neuromuscular disease genetics in under-represented populations: increasing data diversity.

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.

A novel biallelic frameshift variant in C2orf69 causing developmental regression, seizures, microcephaly, autistic features, and hypertonia.

Combined oxidative phosphorylation deficiency type 53 (COXPD53) is an autosomal recessive neurodevelopmental disorder (NDD) caused by homozygous variants in the gene C2orf69. Here, we report a novel frameshift variant c.187_191dupGCCGA, p.D64Efs*56 identified in an individual with clinical presentation of COXPD53 with developmental regression and autistic features. The variant c.187_191dupGCCGA, p.D64Efs*56 represents the most N-terminal part of C2orf69. Notable clinical features of COXPD53of the proband include developmental delay, developmental regression, seizures, microcephaly, and hypertonia. Structural brain defects of cerebral atrophy, cerebellar atrophy, hypomyelination, and thin corpus callosum were also observed. While we observe strong phenotypic overlap among affected individuals with C2orf69 variants, developmental regression and autistic features have not been previously described in individuals with COXPD53. Together, this case expands the genetic and clinical phenotypic spectrum of C2orf69-associated COXPD53.

Gamut of Orbital Lesions in a Tertiary Neurocenter-A Clinicopathological Study of Lesions Seen Over a Period of One Decade.

Background: The orbital region is an anatomically complex area comprising crucial contiguous/adjacent structures. Since the eye has a neuroectodermal basis of embryogenesis, many of the lesions may be similar to those arising in the central nervous system. Objective: To record and describe the clinicopathological spectrum of orbital lesions presenting to a neurology center. Study Setting: The retrospective study included biopsy/resected specimens of patients with orbital/ophthalmic lesions referred to the Department of Neuropathology, between February 2007 and February 2018. Materials and Methods: : The demographic, clinical, and radiological details were retrieved from the departmental archives and the slides were reviewed. Results: There were 99 cases in the period of the study (2007-2018) with a peak in fourth and fifth decades (age range: 5 months to 68 years; mean: 37.2 years; M: F =1.06: 1). Eighty-six (86.8%) cases had epicenter in the orbit, whereas 13 (13.13%) cases were extraorbital with orbital extension. The benign neoplasms predominated (50/99, 50.5%) followed by malignant neoplasms (24/99, 24.24%), infective conditions (11/99, 11.11%) and tumor like conditions (7/99, 7.07%). The most common benign tumor was vascular tumor (17/50, 34%) followed by meningioma (12/50, 24%), while epithelial malignant tumor (6/24, 25%) was the most common malignancy. Fungal infection was the most frequent infective condition (6/11, 54.5%). Conclusion: The spectrum of ocular-orbital lesions varies with the geographic area and the nature of the institute catering to the needs of patients. The spectrum of lesions that we encountered from a neurological institute was vastly different from that reported from ophthalmic centers with very low frequency of retinoblastomas.

Basic requirements to establish a neuromuscular laboratory.

Histopathological analysis of muscle biopsy is a prerequisite in the evaluation of neuromuscular disorders, particularly inflammatory myopathies, metabolic myopathies, congenital myopathies, muscular dystrophies and differentiating myopathies and neurogenic disorders with overlapping clinically features. It not only provides useful information that helps in the diagnosis but also treatment and management. Fundamental skills and basic knowledge regarding handling, processing and analyzing a muscle biopsy are required in any specialized or a general pathology lab supporting neuromuscular clinical services. Care during transport of the muscle biopsy, sample receipt in the laboratory and grossing is very important. Standard operating procedure should be followed for the preanalytical steps (freezing and cryomicrotomy), routine and special staining (enzyme and non enzymatic) and immunohistochemistry. A well organized neuromuscular laboratory with good quality management system is necessary for the practice of myopathology. This article gives an overview of establishing such a laboratory.

Utility of multiparametric pre-operative magnetic resonance imaging in differentiation of chordoid meningioma from the other histopathological subtypes of meningioma-a retrospective study.

PURPOSE: To determine the magnetic resonance imaging (MRI) features which could pre-operatively differentiate chordoid meningioma (CM) from other histopathological subtypes of meningioma. METHODS: Retrospective analysis of pre-operative MRI of cases with histopathologically confirmed diagnosis of meningioma during the last 5 years at our institute was done. T1W, T2W, FLAIR sequences, and post-contrast enhancement were evaluated on a qualitative scale. Normalized ADC ratios (nADCR) and normalized fractional anisotropy ratios (nFAR) were derived. The intratumoral susceptibility score (ITSS), presence of sunburst pattern of vasculature, bone changes, tumour-parenchyma interface, and oedema-to-tumour ratio were also determined. RESULTS: A total of 81 lesions were analyzed out of which 15 were CM. CM showed a higher relative contrast enhancement as compared to all other subtypes except for angiomatous and microcystic meningioma. Relative signal intensity on FLAIR could differentiate CM from transitional meningioma. nFAR was found to be significantly higher in fibroblastic meningioma and significantly lower in microcystic meningiomas as compared to CM. Anaplastic meningiomas were remarkable for bone changes and an ill-defined tumour-brain interface in significantly higher proportion of cases as compared to CM. nADCR > 1.5 was found to be an independent predictor of CM with a sensitivity of 84.6%, specificity of 89.8%, positive predictive value of 64.7%, and negative predictive value of 96.4%. CONCLUSION: Routine pre-operative MRI may be able to differentiate CM from other meningioma subtypes and a cut-off value of greater than 1.5 for nADCR could be predictive of > 50% chordoid histology of meningioma with a high sensitivity, specificity, and negative predictive value.

Exploring immunoreactivity of TTF-1 and AVP in hypothalamic hamartoma.

INTRODUCTION: Hypothalamic hamartoma (HH) is a rare developmental disorder presenting with gelastic seizures or precocious puberty attributed to gonadotrophin-releasing hormone expression by the hamartoma. The histogenesis of HH is uncertain, and diagnosis of HH is difficult in small biopsies due to its close resemblance to normal hypothalamic nuclei. TTF-1 and arginine vasopressin (AVP) are associated with gonadotropin-releasing hormone release. MATERIALS AND METHODS: In this study, we explored the expression pattern of TTF-1 and AVP in HH and its utility, if any, in diagnosis. We reviewed the clinical, radiologic, and histopathological features of 23 HH diagnosed over the past decade at our Institute. RESULTS: The age at presentation ranged from 11 months to 34 years with gelastic seizures (82.6%), precocious puberty (17.4%), and developmental delay (8.7%) as presenting symptoms. On imaging, all the lesions (n = 9) involved the posterior and tuberal group of hypothalamic nuclei, while 5 cases involved the anterior hypothalamus. Anatomically, the lesions involved mammillary body, arcuate and periventricular nuclei. On histopathology, 52% cases revealed nodular arrangement of small neurocytic cells separated by glial stroma. TTF-1 and AVP immunoreactivity was absent in all the cases, whereas in normal hypothalamus, AVP was expressed in periventricular nuclei. CONCLUSION: Our results suggest that immunoexpression of TTF-1 is absent in HH, particularly in those arising from the posterior hypothalamus, and this can be used in small biopsies to distinguish from a normal hypothalamus as well as from posterior pituitary tumors.

Sellar atypical teratoid rhabdoid tumor in an adult: Clinical and pathological dilemmas.

An atypical teratoid rhabdoid tumor (ATRT) is a pediatric embryonic tumor of the central nervous system and is uncommon in adults. We report a case of a 33-year-old female who presented with multiple dural lesions that were diagnosed as ATRT. She had a past history of endoscopic transnasal transsphenoidal and subsequent transcranial decompression of suprasellar lesion 6 months prior, with a presumptive diagnosis of atypical pituitary adenoma, which on retrospective evaluation was confirmed as sellar ATRT. Adult sellar ATRT, though rare, has now been proposed as a distinct clinicopathological and genetic variant that is predominantly seen in middle-aged women. We discuss the uniqueness of this rare aggressive tumor with reference to the age, location, and the challenges faced in the clinical and pathological diagnosis.

Case of primary dural epithelioid angiosarcoma with review of literature and differential diagnosis.

The central nervous system (CNS) is an uncommon site for primary epithelioid angiosarcoma. We report a case of a 25-year-old male who presented with swelling over the head, headache, and weakness of the right side for 6 months. MRI revealed a heterogeneously intense large left parietal dural-based, extra-axial mass with dural tail infiltrating the brain parenchyma, overlying calvaria along with mass effect and vasogenic edema in the left parietal lobe. The patient underwent complete resection of the tumor with adjuvant radiotherapy. Histology revealed a mitotically active vasoformative neoplasm with epithelioid morphology which was immunoreactive for CD31, ERG, FLI-1, and variably for CK. Based on the histomorphological and immunohistochemical profile, a diagnosis of epithelioid angiosarcoma was rendered. The extreme rarity in this location and the highly malignant nature of this tumor makes the clinical diagnosis and management very challenging. These tumors are often considered as meningiomas on prebiopsy imaging due to dural location and dural tail. Further, the misconception may continue on histological examination if only EMA is utilized, since both meningioma and epithelioid angiosarcoma can be positive. There are only 10 previous reports of meningeal angiosarcoma reported in the literature.

Novel variants broaden the phenotypic spectrum of PLEKHG5-associated neuropathies.

BACKGROUND AND PURPOSE: Pathogenic variants in PLEKHG5 have been reported to date to be causative in three unrelated families with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and in one consanguineous family with spinal muscular atrophy (SMA). PLEKHG5 is known to be expressed in the human peripheral nervous system, and previous studies have shown its function in axon terminal autophagy of synaptic vesicles, lending support to its underlying pathogenetic mechanism. Despite this, there is limited knowledge of the clinical and genetic spectrum of disease. METHODS: We leverage the diagnostic utility of exome and genome sequencing and describe novel biallelic variants in PLEKHG5 in 13 individuals from nine unrelated families originating from four different countries. We compare our phenotypic and genotypic findings with a comprehensive review of cases previously described in the literature. RESULTS: We found that patients presented with variable disease severity at different ages of onset (8-25 years). In our cases, weakness usually started proximally, progressing distally, and can be associated with intermediate slow conduction velocities and minor clinical sensory involvement. We report three novel nonsense and four novel missense pathogenic variants associated with these PLEKHG5-associated neuropathies, which are phenotypically spinal muscular atrophy (SMA) or intermediate Charcot-Marie-Tooth disease. CONCLUSIONS: PLEKHG5-associated neuropathies should be considered as an important differential in non-5q SMAs even in the presence of mild sensory impairment and a candidate causative gene for a wide range of hereditary neuropathies. We present this series of cases to further the understanding of the phenotypic and molecular spectrum of PLEKHG5-associated diseases.

Cerebral small vessel disease with hemorrhagic stroke related to COL4A1 mutation: A case report.

Stroke is a major cause of mortality and morbidity with a wide variety of etiological risk factors. Cerebral small vessel disease (SVD) is an important cause of stroke in the young with several hereditary disorders affecting these small blood vessels. Mutations in the COL4A1 gene (COL4A1) have been shown to be associated with a broad range of disorders including hemorrhagic stroke, myopathy, glaucoma and others. We report a rare case of stroke in an intellectually disabled 18-year-old girl with radiological evidence of basal ganglia microbleeds, periventricular white matter signal changes and porencephalic cyst. Ophthalmic examination revealed bilateral microcornea and Axenfeld-Rieger anomaly. At autopsy there were hemorrhagic lesions at multiple sites within the brain. Histology revealed thickened small-caliber vessels which demonstrated disruption and fragmentation of the basement membrane by collagen type IV alpha 1 immunohistochemistry and by electron microscopy. A missense COL4A1 mutation involving glycine residue was detected in the patient. The present case illustrates the clinicopathological spectrum of COL4A1-related cerebral SVD presenting as hemorrhagic stroke in the young with porencephaly, intellectual disability, and Axenfield-Rieger anomaly and thus adds to the clinical heterogeneity of this genetic disorder.

Ossified Occipital Pseudomeningocele following Ventriculoperitoneal Shunt Malfunction.

Ossification of pseudomeningocele is a rare occurrence and is one of the rare complications of ventriculoperitoneal (VP) shunt malfunction. We report a case of 12-year-old boy who came with features of raised intracranial pressure following shunt malfunction which was placed as a treatment to the aqueductal stenosis. Computed tomography showed ventriculomegaly and hypodense collection in the occiput with posterior rim of calcification. The findings were confirmed on histopathology. Although ossified pseudomeningocele is a rare entity following VP shunt placement, it should be suspected if patients present with aggravated symptoms, especially if there is shunt malfunction as the treatment option varies with the presence or absence of resultant symptoms and ossification.

Intracranial fungal granuloma: a single-institute study of 90 cases over 18 years.

OBJECTIVE: Intracranial fungal granuloma (IFG) remains an uncommon entity. The authors report a single-institute study of 90 cases of IFG, which is the largest study until now. METHODS: In this retrospective study, all cases of IFG surgically treated in the years 2001-2018 were included. Data were obtained from the medical records and the pathology, microbiology, and radiology departments. All relevant clinical data, imaging characteristics, surgical procedure performed, perioperative findings, and follow-up data were recorded from the case files. Telephonic follow-up was also performed for a few patients to find out their current status. RESULTS: A total of 90 cases consisting of 64 males (71.1%) and 26 (28.9%) females were evaluated. The mean patient age was 40.2 years (range 1-79 years). Headache (54 patients) was the most common presenting complaint, followed by visual symptoms (35 patients), fever (21 patients), and others such as limb weakness (13 patients) or seizure (9 patients). Cranial nerve involvement was the most common sign (47 patients), followed by motor deficit (22 patients) and papilledema (7 patients). The mean duration of symptoms before presentation was 6.4 months (range 0.06-48 months). Thirty patients (33.3%) had predisposing factors like diabetes mellitus, tuberculosis, or other immunocompromised status. A pure intracranial location of the IFG was seen in 49 cases (54.4%), whereas rhinocerebral or paranasal sinus involvement was seen in 41 cases (45.6%). Open surgery, that is, craniotomy and decompression, was performed in 55 cases, endoscopic biopsy was done in 30 cases, and stereotactic biopsy was performed in 5 cases. Aspergilloma (43 patients) was the most common fungal mass, followed by zygomycosis (13 patients), chromomycosis (9 patients), cryptococcoma (7 patients), mucormycosis (5 patients), and candida infection (1 patient). In 12 cases, the exact fungal phenotype could not be identified. Follow-up was available for 69/90 patients (76.7%). The mean duration of the follow-up was 37.97 months (range 3-144 months). The mortality rate was 52.2% (36/69 patients) among the patients with available follow-up. CONCLUSIONS: A high index of suspicion for IFG should exist for patients with an immunocompromised status and diabetic patients with rhinocerebral mass lesions. Early diagnosis, aggressive surgical decompression, and a course of promptly initiated antifungal therapy are associated with a better prognosis.

Brain and Spinal Cord Lesions in Leprosy: A Magnetic Resonance Imaging-Based Study.

Neurotropism and infiltration by Mycobacterium leprae of peripheral nerves causing neuropathy are well established, but reports of central nervous system (CNS) damage are exceptional. We report CNS magnetic resonance imaging (MRI) abnormalities of the brain and spinal cord as well as lesions in nerve roots and plexus in leprosy patients. Eight patients aged between 17 and 41 years underwent detailed clinical, histopathological, and MRI evaluation. All had prominent sensory-motor deficits with hypopigmented and hypo/anesthetic skin patches and thickened peripheral nerves. All demonstrated M. Leprae DNA in affected peripheral nerve tissue. All received multidrug therapy (MDT). Two patients had brainstem lesions with enhancing facial nuclei and nerves, and one patient had a lesion in the nucleus ambiguus. Two patients had enhancing spinal cord lesions. Follow-up MRI performed in four cases showed resolution of brainstem and cord lesions after starting on MDT. Thickened brachial and lumbosacral plexus nerves were observed in six and two patients, respectively, which partially resolved on follow-up MRI in the two cases who had reimaging. The site and side of the MRI lesions corresponded with the location and side of neurological deficits. This precise clinico-radiological correlation of proximal lesions could be explained by an immune reaction in the gray matter corresponding to the involved peripheral nerves, retrograde axonal and gray matter changes, or infection of the CNS and plexus by lepra bacilli. Further study of the CNS in patients with leprous neuropathy is needed to establish the exact nature of these CNS MRI findings.

Intracranial Actinomycosis Manifesting as a Parenchymal Mass Lesion: A Case Report and Review of Literature.

BACKGROUND: Intracranial actinomycosis is a rare bacterial infection with no characteristic clinical or radiologic diagnostic features. The usual presentation is similar to pyogenic brain abscess or osteomyelitis with or without pachymeningitis. Intracranial actinomycosis rarely manifests as a parenchymal mass lesion. A high index of suspicion is warranted in a patient with immunosuppression or predisposing factors, such as dental procedure, sinusitis, cardiac septal defect, craniofacial trauma, cranial surgery, lung infection, or abdominopelvic infection. CASE DESCRIPTION: A young woman presented with a right parietal parenchymal lesion with involvement of the calvaria and pericranium. She had no predisposing factors for intracranial actinomycosis. She underwent complete microsurgical excision of the lesion followed by prolonged antibiotic therapy. She experienced a good functional recovery. CONCLUSIONS: Intracranial actinomycosis manifesting as a parenchymal mass lesion is extremely rare compared with abscess and pachymeningitis. Histopathologic examination remains the mainstay of definitive diagnosis, as culture may be negative in significant number of cases. Aggressive surgical excision with prolonged antibiotic therapy enhances the chances of a good functional outcome.

Pediatric Suprasellar Atypical Teratoid Rhabdoid Tumor Arising from the Third Ventricle: A Rare Tumor at a Very Rare Location.

Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant tumor of the central nervous system, commonly affecting children below 3 years of age, with around 300 cases reported in the literature. Suprasellar area is a very rare location for such tumor in the pediatric population, with technical difficulties in complete excision. Third ventricular ATRT is very rare. Here, we report the case of a 2-year-old male child who presented with lethargy and vomiting. He had features of raised intracranial pressure with reduced vision in both eyes. Magnetic resonance imaging of the brain revealed a heterogeneously enhancing lobulated giant lesion in the suprasellar location, occupying the third ventricle and hypothalamus with encasement of both carotids. He underwent pericoronal parasagittal craniotomy, interhemispheric transcallosal interforniceal approach and gross total excision of the lesion. Postoperatively, the child had altered sensorium and diabetes insipidus, both of which recovered over a span of 10 days. Histopathological examination of the specimen was consistent with the diagnosis of World Health Organization Grade IV ATRT. In spite of all our efforts, he succumbed to his illness 5 months postoperatively.

Primary Pediatric Intracranial Neuroblastoma: A Report of Two Cases.

Neuroblastoma is the most common pediatric extracranial solid malignancy. It has a high propensity for spread, especially to the bones and lymph nodes. The involvement of central nervous system is uncommon and most of the cases are restricted to the spine. Primary intracranial neuroblastoma is extremely rare and very few cases have been described in the available literature. We report two cases of primary intracranial neuroblastoma in pediatric age group.

Supratentorial Pure Cortical Ependymoma: An Unusual Lesion Causing Focal Motor Aware Seizure.

Ependymomas usually arise from the ependymal lining cells of the ventricular system and central canal of the spinal cord. Supratentorial ependymoma is a rare entity with the variable clinical course. In a small number of cases, ependymoma arises from supratentorial parenchyma. Only a few cases are reported in the literature. We report a case of 3-year-old girl with left frontal mass. Total removal of the mass lesion was performed without any neurological deficit. Pathological examination of the excised tumor was consistent with anaplastic ependymoma. We have discussed management strategy of this rare entity.

A simple algorithmic approach using histology and immunohistochemistry for the current classification of adult diffuse glioma in a resource-limited set-up.

AIMS: The WHO 2016 classification of diffuse gliomas combines histological and molecular parameters for diagnosis. However, in view of cost constraints for molecular testing, an economical working formula is essential to reach a meaningful diagnosis in a resource-limited setting. The aim of this study was to establish a practical algorithmic approach using histology and immunohistochemistry (IHC) in the classification of diffuse gliomas in such a set-up. METHODS: Diffuse gliomas of WHO grade II and III diagnosed in our institute in the year 2016 were analysed for histological and IHC features, using the markers isocitrate dehydrogenase 1 (IDH1R132H) and α thalassemia/mental retardation syndrome X-linked gene (ATRX). Fluorescence in situ hybridisation (FISH) for 1p/19q co-deletion was performed when requested. RESULTS: 449 diffuse gliomas (grades II/III) were included in the study. Integrating histology and IHC features, as per the WHO 2016 guidelines, we derived the following groups: Astrocytoma, IDH-mutant (A,IDH-mt, 37.2%); astrocytoma, not otherwise specified (A,NOS, 12.7%); oligoastrocytoma, NOS (OA,NOS, 4.5%); and oligodendroglioma, NOS (ODG,NOS, 45.6%). FISH was performed in a subset of ODG,NOS, OA,NOS and A,NOS gliomas. This revealed 1p/19q co-deletion in all cases of ODG,NOS, 15.8% of OA,NOS and 37.5% of A,NOS. Sequencing for rare IDH 1/2 mutations was not carried out in this study. CONCLUSION: In a resource-limited set-up, histology with IHC (IDH1(R132H) and ATRX) form the baseline to reasonably derive four histomolecular subgroups of diffuse glioma. Of these, we recommend, OA,NOS and IDH1(R132H)-non-mt ODG,NOS to be our priority for performing 1p/19q co-deletion studies in comparison to IDH-mt ODG,NOS, and it would not be mandatory for astrocytoma. Sequencing for rare IDH mutations is advised for A,NOS and OA,NOS groups, but not for the IDH1(R132H)-non-mutant diffuse gliomas with 1p/19q co-deletion.

LIN28A, a sensitive immunohistochemical marker for Embryonal Tumor with Multilayered Rosettes (ETMR), is also positive in a subset of Atypical Teratoid/Rhabdoid Tumor (AT/RT).

INTRODUCTION: CNS embryonal tumors comprise a group of highly malignant neoplasms with a wide spectrum of histomorphological entities that includes Medulloblastoma (MB), Atypical Teratoid/Rhabdoid Tumor (AT/RT), Neuroblastoma (NB), Ganglioneuroblastoma (GNB), Embryonal Tumor with Multilayered Rosettes (ETMR), and the embryonal tumor-Not Otherwise Specified (NOS). The entity ETMR includes previously described histopathologic patterns-Embryonal Tumor with Abundant Neuropil and True Rosettes (ETANTR), Ependymoblastoma (EBL), and Medulloepithelioma (MEPL). Based on the histopathological similarities (multilayered rosettes) among ETANTR, EBL, and MEPL, as well as uniform clinical behavior and common molecular genetic characteristics, the WHO revision has created a new entity, "ETMR." Immunoreactivity of LIN28A has been identified as a sensitive tool for the diagnosis of this entity. Since there is a paucity of literature regarding immunoreactivity of LIN28A across all embryonal CNS tumors, the present study was undertaken. MATERIALS AND METHODS: During the 5-year study period (2012 to 2016), all the embryonal tumors (MB, AT/RT, other embryonal tumors-ETANTR, MEPL, PNET) that had been earlier diagnosed in the department of neuropathology (cases operated in our institute as well as received as referral) were reviewed. The archived Hematoxylin and Eosin (H&E) and the available immunohistochemistry (IHC) sections were studied. Further, for the other embryonal tumors where the paraffin blocks were available, an extended panel of IHC was performed for confirming the diagnosis of embryonal tumor and only confirmed cases were included in the study. The demographic details of the study cohort were noted. IHC for LIN28A was performed on conventional sections. RESULTS: A total of 396 cases of embryonal tumors including 302 MB, 72 AT/RT, and 22 other embryonal tumors were diagnosed during the study period. Among these, 80 MB, 35 AT/RT, 4 ETANTR, 1 MEPL, 4 NB, 2 GNB, and 1 CNS embryonal tumor-NOS (total-127) were included for the study. LIN28A immunoreactivity was absent in all MB, GNB, NB, and CNS embryonal tumors-NOS whereas all cases of ETMR (4 ETANTR, 1 MEPL) and 8/35 (23%) of AT/RT showed immunopositivity for LIN28A, which was patchy and distinct in most of the cases of ETMR. CONCLUSION: Our study reiterates that LIN28A is a sensitive IHC marker for the diagnosis of ETMR. We also show that among CNS embryonal tumors, LIN28A is not specific to ETMRs and such immunoreactivity can also be seen in a proportion of AT/RTs.