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Article ; Online: Overview of recent advances in the classification of ependymomas in WHO CNS5 classification: Simplified approach to their integrated diagnosis.

Gupta, Rakesh K / Sharma, Agrima / Sharma, Mehar C

Indian journal of pathology & microbiology

2022 Volume 65, Issue Supplement, Page(s) S68–S72

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Central Nervous System Neoplasms/diagnosis ; Central Nervous System Neoplasms/genetics ; Ependymoma/diagnosis ; Ependymoma/genetics ; Humans ; Prognosis ; Supratentorial Neoplasms/genetics ; Supratentorial Neoplasms/pathology ; World Health Organization
Language	English
Publishing date	2022-05-13
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	197621-7
ISSN	0974-5130 ; 0377-4929
ISSN (online)	0974-5130
ISSN	0377-4929
DOI	10.4103/ijpm.ijpm_1212_21
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Article ; Online: Congenital Myasthenia Syndrome Due to a Novel DPAGT1 Gene Mutation - An Error of Glycosylation Masquerading as a Congenital Myopathy.

Mahesan, Aakash / Kamila, Gautam / Tiwari, Richa / Das, Sumanta / Sharma, Mehar C / Jauhari, Prashant / Chakrabarty, Biswaroop / Gulati, Sheffali

Neurology India

2024 Volume 72, Issue 1, Page(s) 175–177

MeSH term(s)	Humans ; Glycosylation ; Myasthenic Syndromes, Congenital/diagnosis ; Myasthenic Syndromes, Congenital/genetics ; Muscular Diseases ; Myotonia Congenita ; Mutation/genetics
Language	English
Publishing date	2024-02-29
Publishing country	India
Document type	Journal Article
ZDB-ID	415522-1
ISSN	1998-4022 ; 0028-3886
ISSN (online)	1998-4022
ISSN	0028-3886
DOI	10.4103/neurol-india.Neurol-India-D-23-00582
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Zs.A 698: Show issues

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Article ; Online: Primary intradural extramedullary spinal Burkitt's lymphoma mimicking a nerve sheath tumor: a case report.

Bansal, Tungish / Sahu, Saumya / Sharma, Mehar C / Borkar, Sachin

Spinal cord series and cases

2022 Volume 8, Issue 1, Page(s) 53

Abstract: Spinal involvement in lymphomas is often associated with advanced disease. Primary spinal non-Hodgkin's lymphoma is a rare entity. A 47-year-old male presented with a history of neck pain followed by progressive quadriparesis and bowel bladder ... ...

Abstract	Spinal involvement in lymphomas is often associated with advanced disease. Primary spinal non-Hodgkin's lymphoma is a rare entity. A 47-year-old male presented with a history of neck pain followed by progressive quadriparesis and bowel bladder involvement over a 5-month period. The magnetic resonance imaging was suggestive of an intradural extramedullary lesion at the C1-C2 vertebra level. A surgical excision was done and the histopathology revealed atypical lymphoid cells, which are immunopositive for CD45, CD20, MUM-1, and BCL6, while negative for BCL2, EBV (LMP-1 and CISH), Cyclin D1 and confirmed the diagnosis of Burkitt's lymphoma. The patient received chemotherapy in the form of CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, high-dose cytarabine) regimen. Primary spinal intradural extramedullary Burkitt's lymphoma is a rare diagnosis that may often be difficult to differentiate radiologically from other causes of intradural extramedullary lesions. A thorough histological examination is warranted in such cases.
MeSH term(s)	Burkitt Lymphoma/diagnosis ; Burkitt Lymphoma/drug therapy ; Burkitt Lymphoma/pathology ; Cytarabine/therapeutic use ; Humans ; Ifosfamide/therapeutic use ; Male ; Middle Aged ; Nerve Sheath Neoplasms/drug therapy ; Treatment Outcome
Chemical Substances	Cytarabine (04079A1RDZ) ; Ifosfamide (UM20QQM95Y)
Language	English
Publishing date	2022-05-14
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	2058-6124
ISSN (online)	2058-6124
DOI	10.1038/s41394-022-00520-y
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Article ; Online: A Genetically Confirmed Case of Laminopathy: Clues from the Clinical Picture and Muscle Biopsy.

Badal, Sachendra / Sharma, Mehar C / Chakrabarty, Biswaroop / Jauhari, Prashant / Gulati, Sheffali

Neurology India

2023 Volume 71, Issue 2, Page(s) 390–391

MeSH term(s)	Humans ; Biopsy ; Laminopathies/pathology ; Muscles
Language	English
Publishing date	2023-05-06
Publishing country	India
Document type	Case Reports ; Journal Article
ZDB-ID	415522-1
ISSN	1998-4022 ; 0028-3886
ISSN (online)	1998-4022
ISSN	0028-3886
DOI	10.4103/0028-3886.375391
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Article ; Online: World Health Organization Classification of Tumors of the Central Nervous System 5

Mahajan, Swati / Suri, Vaishali / Sahu, Saumya / Sharma, Mehar C / Sarkar, Chitra

Indian journal of pathology & microbiology

2022 Volume 65, Issue Supplement, Page(s) S5–S13

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Central Nervous System/pathology ; Central Nervous System Neoplasms/diagnosis ; Histological Techniques ; Humans ; Prognosis ; World Health Organization
Language	English
Publishing date	2022-05-13
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	197621-7
ISSN	0974-5130 ; 0377-4929
ISSN (online)	0974-5130
ISSN	0377-4929
DOI	10.4103/ijpm.ijpm_48_22
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Article ; Online: Pediatric-type diffuse low grade gliomas: Histomolecular profile and practical approach to their integrated diagnosis according to the WHO CNS5 classification.

Purkait, Suvendu / Mahajan, Swati / Sharma, Mehar C / Sarkar, Chitra / Suri, Vaishali

Indian journal of pathology & microbiology

2022 Volume 65, Issue Supplement, Page(s) S42–S49

Abstract: 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 ... ...

Abstract	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 5
MeSH term(s)	Astrocytoma/pathology ; Brain Neoplasms/diagnosis ; Brain Neoplasms/pathology ; Child ; Glioma/pathology ; Humans ; Mutation ; World Health Organization
Language	English
Publishing date	2022-05-13
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	197621-7
ISSN	0974-5130 ; 0377-4929
ISSN (online)	0974-5130
ISSN	0377-4929
DOI	10.4103/ijpm.ijpm_1043_21
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Article ; Online: The evolution of pleomorphic xanthoastrocytoma: from genesis to molecular alterations and mimics.

Mahajan, Swati / Dandapath, Iman / Garg, Ajay / Sharma, Mehar C / Suri, Vaishali / Sarkar, Chitra

Laboratory investigation; a journal of technical methods and pathology

2022 Volume 102, Issue 7, Page(s) 670–681

Abstract: Pleomorphic xanthoastrocytomas (PXAs) are rare tumors accounting for less than 1% of astrocytomas. They commonly occur in young patients and have relatively favorable prognosis. However, they are well known to have heterogenous morphology and biological ... ...

Abstract	Pleomorphic xanthoastrocytomas (PXAs) are rare tumors accounting for less than 1% of astrocytomas. They commonly occur in young patients and have relatively favorable prognosis. However, they are well known to have heterogenous morphology and biological behavior with the potential to recur and disseminate throughout the central nervous system, especially their anaplastic counterparts. Recent advances in the molecular characterization have discovered BRAFp.V600E mutations in conjunction with CDKN2A/B deletions and TERTp mutations to be the most frequent alterations in PXAs. These tumors can present a diagnostic challenge as they share overlapping histopathological, genomic as well as methylation profile with various other tumor types, particularly epithelioid glioblastomas (eGBs). This review provides the spectrum of evolution of PXAs from their genesis to recent molecular insights and attempts to review pathogenesis and relationship to other tumors that they mimic especially eGB. It is postulated based on evidence from literature that PXA and eGB are possibly related and not distinct entities, being two ends of a continuous spectrum of malignant progression (grade 2-grade 4) with anaplastic PXA (grade 3) lying in between. Future WHO classifications will have to possibly redefine these tumors using more confirmatory data from larger studies.
MeSH term(s)	Astrocytoma/genetics ; Astrocytoma/pathology ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Glioblastoma ; Humans ; Mutation ; Prognosis ; Proto-Oncogene Proteins B-raf/genetics
Chemical Substances	Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2022-01-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80178-1
ISSN	1530-0307 ; 0023-6837
ISSN (online)	1530-0307
ISSN	0023-6837
DOI	10.1038/s41374-021-00708-0
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Article ; Online: PD-L1 expression in rare and aggressive thyroid cancers: A preliminary investigation for a role of immunotherapy.

Boruah, Monikongkona / Gaddam, Pranitha / Agarwal, Shipra / Mir, Riyaz Ahmad / Gupta, Ranjan / Sharma, Mehar C / S Deo, Suryanarayana V / Nilima, Nilima

Journal of cancer research and therapeutics

2023 Volume 19, Issue 2, Page(s) 312–320

Abstract: Background and aim: Programmed cell death ligand-1 (PD-L1) immunoexpression status determines the response to immunotherapy in many cancers. Limited data exist on PD-L1 status in aggressive thyroid tumors. We investigated PD-L1 expression across thyroid ...

Abstract	Background and aim: Programmed cell death ligand-1 (PD-L1) immunoexpression status determines the response to immunotherapy in many cancers. Limited data exist on PD-L1 status in aggressive thyroid tumors. We investigated PD-L1 expression across thyroid cancers and correlated it with their molecular profile. Materials and methods: Sixty-five cases of differentiated thyroid carcinoma, poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC) were assessed for PD-L1 expression (clone SP263, VENTANA). The differentiated cases encompassed the aggressive hobnail and tall cell subtypes of papillary thyroid carcinoma (PTC) besides classical PTC and follicular thyroid carcinoma (FTC). Ten nodular goiters (NG) were also evaluated. Tumor proportion score (TPS) and H-score were calculated. BRAF Results: Most PTC (87%) and ATC (73%) cases were PD-L1 positive (TPS ≥1%), with significantly higher positivity rates than NG (20%). TPS >50% was seen in 60% ATC and 7% PTC cases. The median TPS and H-score of ATC were 56 (0-96.6) and 168 (0-275), respectively, and of PTC were 9.6 (4-16.8) and 17.8 (6.6-38.6), respectively. The scores were similar across the PTC subtypes. Only one case each of FTC and PDTC was PD-L1 positive. PD-L1 expression correlated significantly with BRAF Conclusions: ATC showed intense and diffuse PD-L1 staining. Although most PTCs were PD-L1 positive, the expression was weaker and patchy, irrespective of the histological subtype. Results of this pilot study indicate that ATC is most likely to respond to immunotherapy. PTC, FTC, and PDTC may be less amenable to immunotherapy. PD-L1 expression correlated significantly with BRAF
MeSH term(s)	Humans ; B7-H1 Antigen/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Pilot Projects ; Thyroid Neoplasms/genetics ; Thyroid Neoplasms/therapy ; Thyroid Neoplasms/metabolism ; Thyroid Carcinoma, Anaplastic/genetics ; Thyroid Carcinoma, Anaplastic/therapy ; Thyroid Carcinoma, Anaplastic/pathology ; Adenocarcinoma, Follicular/pathology ; Thyroid Cancer, Papillary ; Mutation ; Immunotherapy
Chemical Substances	B7-H1 Antigen ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; prolinedithiocarbamate (135467-92-4)
Language	English
Publishing date	2023-04-01
Publishing country	India
Document type	Journal Article
ZDB-ID	2187633-2
ISSN	1998-4138 ; 0973-1482
ISSN (online)	1998-4138
ISSN	0973-1482
DOI	10.4103/jcrt.jcrt_1471_22
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Article ; Online: Macrofollicular Architecture in Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Pitfall in Thyroid Practice.

Yadav, Sujata / Kandasamy, Devasenathipathy / Damle, Nishikant / Goel, Rashi / Chumber, Sunil / Sharma, Mehar C / Boruah, Monikongkona / Agarwal, Shipra

Head and neck pathology

2023 Volume 17, Issue 4, Page(s) 899–909

Abstract: Background: Predominantly macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC-MF) is rare and often a cause of misinterpretation during pre-operative work-up and histopathology evaluation. We ... ...

Abstract	Background: Predominantly macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC-MF) is rare and often a cause of misinterpretation during pre-operative work-up and histopathology evaluation. We comprehensively evaluated the radiological, cytological, gross, microscopic, molecular and follow-up characteristics of four such cases, intending to increase its recognition and add our experience to the limited literature available. Methods: All such histopathologically-proven cases of IEFVPTC-MF were retrieved from the departmental archives. The clinical details, thyroid ultrasound, cytology and thyroid scan findings were reviewed. Allele-specific PCR for BRAF p.V600E, KRAS, NRAS, and HRAS mutations, and FISH assays for ETV6::NTRK3 fusion and RET fusions were performed. Results: There were four cases of IEFVPTC-MF diagnosed between 2021 and 2022, involving two males and two females. The median age at presentation was 27 years, and the duration of the disease was 1-10 years. Thyroid ultrasound was TR1 (benign; n = 1), TR2 (not suspicious; n = 2), or TR4 (moderately suspicious; n = 1). Cytology was categorized as nondiagnostic (n = 1), benign (n = 1), and atypia of undetermined significance (n = 1). The three nodules with available cytology smears showed abundant colloid. Cells were arranged as sheets/microfollicles/clusters. Nuclei were predominantly round with minimal/focal elongation, membrane irregularity, and cellular crowding. On gross examination, cut surfaces of the tumors showed variable amounts of colloid. The tumors were solid-cystic. Histopathology revealed partially encapsulated multinodular tumors. There were prominent pseudopapillae projecting into the lumina of macrofollicles. Nuclei were predominantly round with variable nuclear atypia, including chromatin clearing and multifocal presence of nuclear grooves. Pseudoinclusions were identified in two. Molecular analysis revealed NRAS codon 61 mutation and ETV6::NTRK3 fusion in one case each. Two patients had cervical lymph node and hematogenous metastases. Post-radio-active iodine, the response was structurally incomplete (n = 2), indeterminate (n = 1) and excellent (n = 1). Conclusions: Macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma is a major pitfall in thyroid oncology practice. Long-standing disease, and ultrasonographic and cytological features that overlap with benign disease, often lead to underdiagnosis during pre-operative evaluation. As patients may consequently develop distant metastases and have inadequate treatment response, there is a need for more vigilant understanding of the spectrum of macrofollicular thyroid disease for accurate diagnosis. ETV6::NTRK3 or other fusions, when found, present opportunities for targeted therapy.
MeSH term(s)	Male ; Female ; Humans ; Thyroid Cancer, Papillary/genetics ; Carcinoma, Papillary/pathology ; Thyroid Neoplasms/genetics ; Thyroid Neoplasms/pathology ; Adenocarcinoma ; Colloids ; Adenocarcinoma, Follicular/pathology
Chemical Substances	Colloids
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2407834-7
ISSN	1936-0568 ; 1936-055X
ISSN (online)	1936-0568
ISSN	1936-055X
DOI	10.1007/s12105-023-01584-4
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Article: Current status of DNA methylation profiling in neuro-oncology as a diagnostic support tool: A review.

Singh, Jyotsna / Sahu, Saumya / Mohan, Trishala / Mahajan, Swati / Sharma, Mehar C / Sarkar, Chitra / Suri, Vaishali

Neuro-oncology practice

2023 Volume 10, Issue 6, Page(s) 518–526

Abstract: Over the last 2 decades, high throughput genome-wide molecular profiling has revealed characteristic genetic and epigenetic alterations associated with different types of central nervous system (CNS) tumors. DNA methylation profiling has emerged as an ... ...

Abstract	Over the last 2 decades, high throughput genome-wide molecular profiling has revealed characteristic genetic and epigenetic alterations associated with different types of central nervous system (CNS) tumors. DNA methylation profiling has emerged as an important molecular platform for CNS tumor classification with improved diagnostic accuracy and patient risk stratification in comparison to the standard of care histopathological analysis and any single molecular tests. The emergence of DNA methylation arrays have also played a crucial role in refining existing types and the discovery of new tumor types or subtypes. The adoption of methylation data into neuro-oncology has been greatly aided by the development of a freely accessible machine learning-based classifier. In this review, we discuss methylation workflow, address the utility of DNA methylation profiling in CNS tumors in a routine diagnostic setting, and provide an overview of the methylation-based tumor types and new types or subtypes identified with this platform.
Language	English
Publishing date	2023-07-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2768945-1
ISSN	2054-2585 ; 2054-2577
ISSN (online)	2054-2585
ISSN	2054-2577
DOI	10.1093/nop/npad040
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