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Ependymomas can arise along the entire neuraxis; however, they possess site-specific unique molecular alterations and a methylome pattern which is directly related with the prognostic outcomes. Since 2016, when the updated fourth edition of World Health Organization (WHO) classification of tumors of the central nervous system was published, it has been emphasized to classify ependymomas by anatomic site and molecular signatures associated genetic alterations so that classification of the disease reflects its underlying biology. In continuation, the fifth edition of the WHO classification of CNS tumors introduces major changes, including site-specific molecular profiles as the basis of classifying ependymomas. Furthermore, an integrated tier system of reporting is recommended for better clinical correlation and predicting outcomes. WHO grading can still be included in a specific tier, along with molecular markers.

Low-grade gliomas are the most common primary central nervous system (CNS) neoplasms in the pediatric age group. The majority of these tumors are circumscribed, while diffuse low-grade gliomas are relatively rare. The pediatric type diffuse low-grade gliomas (pDLGG) have a distinctly different biological behavior, molecular profile, and clinical outcome as compared to their adult counterpart. In the 5th edition of World Health Organization (WHO) CNS classification, pDLGGs are subclassified into four distinct histomolecular entities, namely, (i) diffuse astrocytoma, MYB- or MYBL1-altered, (ii) angiocentric glioma, (iii) polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and (iv) diffuse low-grade glioma, MAPK pathway-altered. Although the molecular profile, to a great extent, aligns with the morphological features, it is not specific. Many of the molecular alterations described in pDLGG have therapeutic implications with the availability of newer targeted therapies. A wide range of testing platforms are available for routine assessment of these molecular alterations in clinical laboratories, though WHO does not recommend any particular method.

The latest fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) has been built on the prior WHO 2016 classification as well as recommendations put forward by seven updates of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT). Various new tumor types and subtypes have been recognized which are of clinical significance. Tumor groups have been restructured and the nomenclature of some tumor types has also been revised. The use of terms 'entity' and 'variant' have been replaced by 'type' and 'subtype'. Significant changes have been introduced in the grading of tumors viz. use of Arabic numerals, grading within individual tumor types and combined histological and molecular grading. The terms 'Not otherwise specified' and 'Not elsewhere classified' can now be used for all tumor types. WHO CNS5 also for the first time endorses the use of DNA methylation profiling for the diagnosis of some tumor types/subtypes. Finally, the importance of combining histology with molecular parameters is emphasized for the “layered reporting” and “integrated diagnosis”, which will provide valuable diagnostic, prognostic, and predictive information, as well as for some entities, suggest targeted therapies.

Introduction: Uterine tumors resembling ovarian sex cord tumor (UTROSCT) are a unique group of neoplasms with diverse morphology and immunophenotypic characteristics, coexpressing sex cord, epithelial, and smooth-muscle markers. To date, less than 100 cases have been reported and there is paucity of data concerning their clinical behavior. Materials and Methods: All cases of uterine body tumors diagnosed over a period of two and a half years (2016-2018) were retrieved. Histopathological features were reviewed and extended panel of immunohistochemistry was performed to identify cases of UTROSCTs. Results: Six cases of UTROSCTs were identified with a median age of 46.5 years. Four of them presented with menorrhagia, while two with postmenopausal bleeding including one with a history of carcinoma breast. Three of these cases were initially misdiagnosed as endometrial stromal sarcoma and adenocarcinomas. They all underwent hysterectomy with bilateral salpingo-oophorectomy. Conclusion: It is considered a tumor with low malignant potential; however, one out of six cases (16.7%) in our study showed metastasis, within 1 year of diagnosis. It is important to recognize this entity as it mimics a wide range of both benign and malignant tumors. Molecular pathogenesis and exact management protocols remain elusive due to rarity,hence, multi-institutional studies are warranted.

We report the case of a 5-year-old male child presenting with seizures for 4 months. Magnetic resonance imaging (MRI) revealed a cortical-based solid cystic lesion in the right parietal lobe. Histopathological examination showed a tumour comprised of spindled glial fibrillary acid protein (GFAP) positive neoplastic cells interspersed with bizarre pleomorphic cells showing nuclear pseudoinclusions and intermingled dysplastic ganglion cells variably immunopositive for synaptophysin, chromogranin, Neu-N and immunonegative for neuron filament protein (NFP). This report highlights the occurrence of the rare composite pleomorphic xanthoastrocytoma-ganglioglioma and the vagaries of immunohistochemical analysis in highlighting neuronal differentiation in such a case setting. In addition, to the best of our knowledge this is the youngest patient till date to present with this entity.

This study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases. Combinatorial assessment of MGMT and TERT emerged as independent prognostic markers, especially in the IDH1 wild-type GBMs. Thus, within the IDH1 wild-type group, cases with only MGMT methylation (group 1) had the best outcome (median PFS: 83.3 weeks; OS: not reached), whereas GBMs with only TERT mutation (group 3) had the worst outcome (PFS: 19.7 weeks; OS: 32.8 weeks). Cases with both or none of these alterations (group 2) had intermediate prognosis (PFS: 47.6 weeks; OS: 89.2 weeks). Majority of the IDH1 mutant GBMs belonged to group 1 (75%), whereas only 18.7% and 6.2% showed group 2 and 3 signatures, respectively. Interestingly, none of the other genetic alterations were significantly associated with survival in IDH1 mutant or wild-type GBMs. Based on above findings, we recommend assessment of three markers, viz., IDH1, MGMT, and TERT, for GBM prognostication in routine practice. We show for the first time that IDH1 wild-type GBMs which constitute majority of the GBMs can be effectively stratified into three distinct prognostic subgroups based on MGMT and TERT status, irrespective of other genetic alterations.

Background: Meningiomas are the most common benign central nervous system tumors. However, a sizeable fraction recurs, irrespective of histological grade. No molecular marker is available for prediction of recurrence in these tumors. Materials and Methods: We analyzed recurrent meningiomas with paired parent and recurrent tumors by fluorescence in situ hybridization for 1p36 and 14q32 deletion, AKT and SMO mutations by sequencing, and immunohistochemistry for GAB1, progesterone receptor (PR), p53, and MIB-1. Results: 18 recurrent meningiomas (11 grade I, 3 grade II, 4 grade III) with their parent tumors (14 grade I, 2 grade II and 2 grade III) were identified. Overall, 61% of parent and 78% of recurrent meningiomas showed 1p/14q co-deletion. Notably, grade I parent tumors showed 1p/14q co-deletion in 64% cases while 82% of grade I recurrent tumors were co-deleted. AKT mutation was seen in two cases, in both parent and recurrent tumors. SMO mutations were absent. GAB1 was immunopositive in 80% parent and 56.3% recurrent tumors. MIB-1 labeling index (LI), PR and p53 expression did not appear to have any significant contribution in possible prediction of recurrence. Conclusion: Identification of 1p/14q co-deletion in a significant proportion of histologically benign (grade I) meningiomas that recurred suggests its utility as a marker for prediction of recurrence. It appears to be a better predictive marker than MIB1-LI, PR and p53 expression. Recognition of AKT mutation in a subset of meningiomas may help identify patients that may benefit from PI3K/AKT pathway inhibitors, particularly among those at risk for development of recurrence, as determined by presence of 1p/14q co-deletion.

It is often difficult to establish confirmatory diagnosis in cases of extrapulmonary tuberculosis (TB) because of its paucibacillary nature and difficulty in accessing the involved organs. In several cases, empirical anti-tubercular treatment is started, and the patient is followed-up closely for response. In countries with high prevalence of TB, it is a reasonably good strategy and works most of the times. However, catastrophe may occur when aggressive lymphomas masquerade as TB.

Aims: To study, the effects of ipsilateral ureteric obstruction on contralateral kidney and the role of renin angiotensin system (RAS) blockade on renal recovery in experimentally induced unilateral ureteric obstruction. Materials and Methods: Unilateral upper ureteric obstruction was created in 96 adult Wistar rats that were reversed after pre-determined intervals. Losartan and Enalapril were given to different subgroups of rats following relief of obstruction. Results: The severity of dilatation on the contralateral kidney varied with duration of ipsilateral obstruction longer the duration more severe the dilatation. There is direct correlation between renal parenchymal damage, pelvi-ureteric junction (PUJ) fibrosis, inflammation and severity of pelvi-calyceal system dilatation of contralateral kidney with duration of ipsilateral PUJ obstruction. Conclusions: Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs has been found to significantly improve renal recovery on the contralateral kidney. It can, thus, be postulated that contralateral renal parenchymal injury was mediated through activation of RAS.

Background: The objective of the following study is to determine and to compare the different morphological parameters with duration of obstruction created experimentally in unilateral upper ureters of rats. Materials and Methods: Unilateral upper ureteric obstruction was created in 60 adult Wistar rats that were reversed after predetermined intervals. Rats were sacrificed and ipsilateral kidneys were subjected for analysis of morphological parameters such as renal height, cranio-caudal diameter, antero-posterior diameter, lateral diameter, volume of the pelvis and average cortical thickness: Renal height. Results: Renal height and cranio-caudal diameter of renal pelvis after ipsilateral upper ureteric obstruction started rising as early as 7 days of creating obstruction and were affected earlier than antero-posterior and lateral diameter and also were reversed earlier than other parameters after reversal of obstruction. Renal cortical thickness and volume of the pelvis were affected after prolonged obstruction (> 3 weeks) and were the late parameters to be reversed after reversal of obstruction. Conclusions: Cranio-caudal diameter and renal height were the early morphological parameters to be affected and reversed after reversal of obstruction in experimentally created ipsilateral upper ureteric obstruction.

Gastroesophageal reflux (GER) disease is a significant comorbidity of neuromuscular disorders. It may present as paroxysmal dyskinesia, an entity known as Sandifer syndrome. A 6-week-old neonate presented with very frequent paroxysms of generalized stiffening and opisthotonic posture since day 22 of life. These were initially diagnosed as seizures and he was started on multiple antiepileptics which did not show any response. After a normal video electroencephalogram (VEEG) was documented, possibility of dyskinesia was kept. However, when he did not respond to symptomatic therapy, Sandifer syndrome was thought of and GER scan was done, which revealed severe GER. After his symptoms got reduced to some extent, a detailed clinical examination revealed abnormal facies with flaccid quadriparesis. Muscle biopsy confirmed the diagnosis of a specific congenital myopathy. On antireflux measures, those episodic paroxysms reduced to some extent. Partial response to therapy in GER should prompt search for an underlying secondary etiology.

Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis of unknown aetiology. Multifaceted clinical manifestations, non-specific MRI findings, a broad range of differential diagnoses and diverse pathological appearances prove to be a diagnostic challenge. However, a prompt diagnosis and aggressive treatment are crucial to avoid permanent damage. Hence, we present the clinico-pathological spectrum of this entity and highlight the limitations of currently available diagnostic modalities. We describe in detail the histopathological findings of eight cases of PACNS diagnosed at the Department of Pathology, AIIMS, over a period of eight years. Eight cases of PACNS were identified during this period. Five cases (62.5%) showed features of granulomatous vasculitis, two (25%) showed lymphocytic vasculitis and one case (12.5%) showed a predominantly necrotizing pattern of vasculitis. Diagnosis of PACNS is a challenge and requires a high index of clinical suspicion. Appropriate work-up to exclude other conditions is mandatory. Brain biopsy is useful in making the diagnosis and ruling out mimicking conditions.