Identification of a Novel Intronic Mutation in VMA21 Associated with a Classical Form of X-Linked Myopathy with Autophagy.

Introduction VMA21 -related myopathy is one of the rare forms of slowly progressive myopathy observed in males. Till now, there have been only a handful of reports, mainly from Europe and America, and two reports from India. Method Here, we describe a case of genetically confirmed VMA21 -associated myopathy with clinical, histopathological, and imaging features with a list of known VMA21 mutations. Results A 29-year-old man had the onset of symptoms at 18 years of age with features of proximal lower limb weakness. Muscle magnetic resonance imaging showed the preferential involvement of vasti and adductor magnus. A biopsy of the left quadriceps femoris showed features of autophagic vacuolar myopathy with vacuoles containing granular eosinophilic materials. In targeted next-generation sequencing, hemizygous mutation in the 3' splice site of intron 2 of the VMA21 gene (c.164-7 T > A) was identified and confirmed the diagnosis of X-linked myopathy with excessive autophagy. Conclusion This report expands the phenotypic and genotypic profile of VMA21 -related myopathy, with a yet unreported mutation in India.

Delineating the Spectrum of Pituitary Adenoma Based on the WHO 2017 Classification.

BACKGROUND: The WHO 2017 classification of endocrine tumors incorporates lineage-specific transcription factors (TF) and hormone expression for the classification of pituitary adenoma (PA). There is paucity of reports describing the spectrum of PA based on this classification. OBJECTIVE: The aim of this study was to delineate the spectrum of PA based on WHO 2017 classification of endocrine tumors. MATERIALS AND METHODS: PA diagnosed in the year 2018 were studied. H and E and hormonal immunohistochemistry (IHC) for GH, PRL, ACTH, TSH, FSH, LH, CK, T-Pit and MIB-1 were performed and the results were analyzed. RESULTS: The cohort included 88 cases. M: F ratio was 2:1. Clinically, 22 (25%) were functional and 66 (75%) were non-functional adenomas. Amongst the clinically functional adenomas, GH secreting adenomas were the commonest (68%). Majority (83%) of non-functional adenomas were hormone positive with gonadotroph adenomas being the commonest (72.7%). Eleven (12.5%) PA were clinically and hormonally silent. Three of these showed intense nuclear T-Pit positivity, classifying them under silent corticotroph adenoma. Lineage of the remaining eight adenomas remained undetermined, since, IHC for Pit-1 and SF-1 was not performed. The aggressive adenomas identified by IHC included sparsely granulated somatotroph adenoma, Crooke cell adenoma, silent corticotroph adenoma, densely granulated lactotroph adenoma in men and constituted 17% of the PA. Four (4/88) cases were clinically invasive. CONCLUSION: A large majority of PA including aggressive adenomas can be identified by IHC. Addition of T-Pit helped to identify silent corticotroph adenoma. Pit -1 and SF-1 TF would help identify plurihormonal Pit-1 PA and null cell adenomas.

Primary diffuse leptomeningeal primitive neuroectodermal tumor presenting as chronic meningitis.

Primary diffuse leptomeningeal primitive neuroectodermal tumor is a rare meningeal neoplasm which can masquerade as chronic meningitis. While the clinical presentation and radiological features may provide a clue to this condition, meningeal biopsy is essential to clinch the diagnosis. A high index of suspicion and a low threshold for re-evaluating cases of neuroinfection that do not respond to empirical therapy are essential in this scenario. We present the case of a nine year old boy who was initiated on antituberculous treatment for chronic meningitis with hydrocephalus. Meningeal biopsy revealed a primary diffuse leptomeningeal primitive neuroectodermal tumor.

Non-granulomatous inflammatory lesions of CNS: Approach to diagnosis.

Infections constitute an important and common category of diseases, particularly in less developed countries. Infections present with a broad spectrum of clinical and radiologic features dictated by the cell and tissue tropism and host response elicited, posing a considerable diagnostic challenge. Early diagnosis and treatment are crucial in preventing mortality and morbidity. Recourse is often made to biopsy for ascertaining the diagnosis, and hence the pathologist plays a vital role in patient management. Therefore, knowledge of the histopathologic changes is necessary to recognize the histological changes and guide the diagnostic workup and management. Each microbial agent elicits a distinctive pattern of inflammatory tissue response, which can serve as a clue to the etiological agent. Based on the causative organism, microbial, and host factors, the inflammatory response may be acute or chronic, necrotic or non-necrotic. The inflammation can be of varied patterns - lymphohistiocytic, granulomatous, inflammatory demyelinating, fibrosing, or showing minimal inflammation. The pattern of necrosis also differs based on the causative organism. Typically, pyogenic bacteria are associated with suppurative inflammation, tuberculosis with caseous granulomatous, and fungi with suppurative granulomatous inflammation. Viral infections are associated with lymphohistiocytic non-necrotizing inflammation and, based on cell tropism, can cause demyelination (e.g., JCV) and/or viral inclusions. Parasitic infections (protozoal or metazoal) display a broad spectrum of inflammatory changes that overlap with other types of infections. This review briefly describes pathological patterns and associated pathogens and provides an algorithmic approach based on pattern recognition that may be useful for the practicing pathologist.

Pathological Spectrum of Dura-Based Nonmeningothelial Lesions: 5 Years' Experience from a Tertiary Care Centre.

Introduction Nonmeningothelial lesions arising from the dura comprise a wide spectrum of pathologies ranging from neoplastic to infective etiologies. They have overlapping clinical and radiologic findings necessitating histopathological evaluation for the final diagnosis which in turn dictates management and prognosis. Therapeutic strategies are different for each of the lesion. There is scarcity of large case series detailing clinicopathological spectrum of dura-based nonmeningothelial lesions. Materials and Methods In this study, we analyzed the neuropathological spectrum of dura-based nonmeningothelial lesions diagnosed over a period of 5 years in our tertiary care center. Results There were 79 cases of dura-based nonmeningothelial lesions constituting 7.3% of all dura-based lesions (age range: 2-75 years; M:F = 2:3). Basal region was more frequently involved than the convexities. On histopathology, neoplastic lesions predominated (92.4%) and included in order of frequency solitary fibrous tumor/hemangiopericytoma (35.6%), gliomas (27.4%), metastasis (27.4%), mesenchymal tumors (4%), primitive neuroectodermal tumor (2.73%), and medulloblastoma (2.73%). Infective lesions were less frequent (7.6%), included fungal infections and Rosai-Dorfman disease. Conclusion Awareness of the spectrum of nonmeningothelial dural lesions is useful for pathologists as well as the treating surgeon.

Pilocytic astrocytoma with spontaneous malignant transformation with intracranial and skeletal dissemination: case report and review of the literature.

Pilocytic astrocytoma is a benign low-grade tumor with a favorable prognosis. We present a 47-year-old- lady with a posterior fossa pilocytic astrocytoma who underwent surgical decompression. She developed multiple early local recurrences Along with malignant transformation of the cranial lesion she developed skeletal dissemination within a very short time frame. There were no features or family history of neurofibromatosis 1. She did not receive radiotherapy or chemotherapy prior to the recurrences.

COVID-19-associated brain abscess caused by Trichosporon dohaense: A case report and review of literature.

We report the first case of Coronavirus Disease 2019 (COVID-19)-associated brain abscess caused by a rare Trichosporon species, T. dohaense. The patient was a known diabetic and had received systemic corticosteroids for the treatment of COVID-19. He underwent craniotomy and evacuation of abscess. The pus aspirate grew a basidiomycetous yeast, morphologically resembling Trichosporon species. The isolate was initially misidentified by VITEK® MS due to lack of mass spectral database of T. dohaense. Accurate identification was achieved by internal transcribed spacer-directed panfungal polymerase chain reaction. The patient had a favorable outcome following surgical intervention and antifungal therapy.

The risks factor of recurrence after skull base hemangiopericytoma management: A retrospective case series and review of literature.

OBJECTIVES: Skull base hemangiopericytomas are rare malignant meningothelial tumors involving anterior, middle, and posterior cranial fossa. The outcome of these tumors is inferior due to aggressive behavior and local recurrence. The study aimed to find out the factors affecting the early recurrence and the late recurrence. METHODOLOGY: A retrospective study was performed over 15 years, and patients were included from a single neurosurgical unit. A total of 35 patients were recruited for analysis. RESULTS: Twenty-five (71.4%) cases were in the posterior fossa, four (11.4%) cases in the middle cranial fossa, and three (8.6%) patients in the anterior cranial fossa. Fourteen (40%) cases underwent gross total excision, 21(60%) cases subtotal excision. Follow up available for 32 patients, and the median follow -up duration was 64 months (6-240 months). Progression-free survival for the gross total resection group was 104 months compared to 60 months for subtotal resection (p = 0.07). Nineteen (54.3%) cases had recurrence during follow- up period. Six (17.1%) cases recurrence at 1-year time, five (14.3%) cases at 3-year time, three (8.6%) at 5-yr time, four (11.4%) cases at 10- year time. Seventeen (48.6%) cases received radiotherapy, and 13 cases underwent re-exploration and excision of the tumor. Univariate ordinal logistic regression showed that the extent of resection was associated with 1-year, 3-year and 5-year recurrence. Multivariate ordinal logistic regression showed that only extent of resection (STR) was associated with both early and late recurrence. CONCLUSIONS: The extent of resection is the main predictor of early and delayed recurrence. Upfront radiation therapy has superior tumor control in skull base location.

Vogt-Koyanagi-Harada Syndrome - A Neurologist's Perspective.

Vogt-Koyanagi-Harada (VKH) syndrome is an immune-mediated granulomatous disease which affects melanin-rich organs like eyes, skin, nervous system, and ears. Neurological and auditory manifestations usually precede the involvement of other sites. Patients may manifest with "complete" or "incomplete" syndrome. We report two patients who presented with acute headache and impaired vision. Fundus examination revealed optic disc hyperemia and exudative retinal detachment which provided a clue for the diagnosis at the bedside. Fundus fluorescein angiogram (FFA) revealed abnormal dye leakage, whereas B scan showed choroid thickening. Cerebrospinal fluid (CSF) pleocytosis contrasted with unremarkable brain magnetic resonance imaging and lack of meningeal signs. Melanophagocytosis was evidenced by melanin-laden macrophages in CSF and skin biopsy. This finding is specific for VKH syndrome and helps to clinch the diagnosis even when the complete syndrome is not present cross-sectionally. VKH syndrome should be suspected in patients with aseptic meningitis if tests for common infectious and immune-mediated diseases are negative.

Consumption of spine by tuberculosis in the era of directly observed treatment, short-course and genomic diagnosis.

BACKGROUND: Extra Pulmonary Tuberculosis (EPTB) is a significant health problem in both developing and developed countries. Spinal tuberculosis (STB) is one of the significant forms of EPTB lacking epidemiological data. The present study was conducted to study the clinical, radiological, microbiological and histopathological features, treatment and outcome of Spinal tuberculosis. METHODS: This study was conducted for a duration of 19 years, from 2000 to 2018 at the department of Neuromicrobiology, NIMHANS, Bengaluru. It comprised of 252 patients with STB. All patients were diagnosed with the clinical features and confirmed by radiological, microbiological and histopathological findings. RESULTS: Results were tabulated and statistically studied. The most common age group is 30-40 years with male preponderance. Most patients presented with motor paraplegia/para paresis (99.6%). Thoracic spine was the most common vertebra affected (47.62%). The commonest imaging feature is soft tissue collection (81.74%). Most common histopathological feature was necrotising granulomatous inflammation (65.87%). Microbiology reports showed growth of Mycobacterium tuberculosis (MTB) in 29.76%, Ziehl Neelsen (ZN) smear showed acid fast bacilli (AFB) in 25.79%. Anti tubercular drugs and surgery were advised in 55.55% patients and only anti TB drugs for 39.28%. The entire course of anti tubercular treatment (ATT) was completed in 60.71% and 4.76% were defaulters. CONCLUSION: Spinal tuberculosis is a global disease, timely diagnosis with clinical, imaging, microbiological, histopathological features and complete course of anti-tubercular treatment along with symptomatic treatment appears to be safe and effective.

Central nervous system high grade neuroepithelial tumor with BCOR immunopositivity: Is there a molecular heterogeneity?

Central nervous system high grade neuroepithelial tumor - BCOR altered is a newly defined entity which is characterised by internal tandem duplication (ITD) in exon 15 of BCOR. These tumors resemble high grade glioma histologically and exhibit BCOR immunopositivity. However, recently fusions of BCOR are also described in CNS lower grade gliomas, thus questioning the sensitivity and specificity of BCOR immunohistochemistry for identification of BCOR-ITD. We describe four cases of high grade neuroepithelial tumor with BCOR immunopositivity which were diagnosed over a period of one year at our institute. Amongst these, only one tumor revealed BCOR-ITD on sequencing. SATB2 immunopositivity which is a sensitive marker of BCOR-ITD, BCOR fusions and YWHAE fusions was noted in three out of four cases. Our study suggests that BCOR immunopositive CNS high grade tumors are molecularly heterogeneous and could harbour genetic alterations other than BCOR-ITD.

Diagnostic Utility of CUSA Specimen in Histopathological Evaluation of Tumors of Central Nervous System.

INTRODUCTION: Cavitron Ultrasonic Surgical Aspirator (CUSA) is a technique used for the surgical treatment of tumors that aids the surgeon in highly selective tumor sampling with minimal injury to surrounding tissues. The utility of the tissue obtained from CUSA for histopathological diagnosis of central nervous system tumors is not as well-known as its surgical benefits. Even though a few studies have evaluated the diagnostic accuracy of CUSA specimen, these have dealt with very few cases. METHODOLOGY: In this study, we nil analysed 73 cases of CNS tumors (glial and non-glial) where CUSA specimen was available for histopathological examination and compared with findings on conventional samples as gold standard. RESULTS: Most frequent types of artefacts induced by CUSA included tissue breakdown resembling necrosis, empty spaces in tissues, and crush artefacts particularly in cellular tumors, that interfered with interpretation. CUSA samples were found optimal for diagnosis of non-glial tumors (45/73), (mainly mesenchymal), wherein the diagnostic utility was comparable to the conventional samples. Difficulties were encountered in glial neoplasms, medulloblastomas and meningiomas. In glial neoplasms (28/73), accurate grading was not possible (9/28, 32%) utilising CUSA samples alone as necrosis and mitosis were not represented. Similarly in meningiomas, mitosis and brain invasion, essential for grading, was not recognizable in CUSA samples. In medulloblastomas, extensive crush artefacts interfered with diagnosis and histological subtyping making it mandatory to examine conventional tissue samples and CUSA. Immunohistochemistry results were optimal with CUSA tissue, wherever performed. CONCLUSION: The greatest benefits of CUSA, is its ability to sample multiple areas enhancing the yield in heterogenous tumors like gliosarcomas and its utility in tumors at surgically inaccessible sites. As a policy, we recommend that it is beneficial that all surgically excised tissues including those from the CUSA bottle and suction be sent for histopathological analysis for optimising diagnostic accuracy.

Distal anterior cerebral artery aneurysm with bilateral fetal posterior cerebral arteries and trifurcation of anterior cerebral artery.

Developmental vascular anomalies of brain are non-modifiable risk factors for the development of aneurysms and are prone for rupture. We report one such association in a 44-year-old gentleman who succumbed to subarachnoid hemorrhage (SAH) secondary to ruptured distal anterior cerebral artery aneurysm associated with vascular anomalies in the anterior and posterior circulation that included trifurcation of anterior cerebral artery and bilateral fetal posterior cerebral arteries. We identified multiple anomalies in circle of Willis that could have contributed to the formation of aneurysm and early rupture. Knowledge of these variations is essential to plan early and optimum management with close follow-up.

Rare neurohypophyseal tumor presenting as giant pituitary macroadenoma with cavernous sinus invasion - A case report and review of literature.

BACKGROUND: Granular cell tumors (GCTs) of the pituitary are rare tumors of posterior pituitary that can present as giant pituitary macroadenoma due to the slow indolent growth of the tumor. We are reporting this case due to the rarity of GCT and usually these tumors are confined to the suprasellar region since they are arising from the pituitary stalk. GCTs that attain such giant size with cavernous sinus invasion are still rarer. CASE DESCRIPTION: A 38-year-old female who presented with progressive deterioration of vision and on evaluation by magnetic resonance imaging showed a giant pituitary macroadenoma with bilateral cavernous sinus invasion. The patient underwent pterional craniotomy and near-total excision of the lesion was done due to high vascularity and firmness of the tumor. Histopathology examination of the lesion showed spindle to globular cells with granular cytoplasm and was reported as GCT of the pituitary. CONCLUSION: GCTs are WHO grade1 non-neuroendocrine tumors arising from neurohypophysis and infundibulum. Complete excision is usually difficult due to the high vascularity, firm consistency, and local invasion of the tumor to the cavernous sinus and optic apparatus.

Clinicopathological Study of Extra-Axial Small Round Cell Tumors of the Cranium.

INTRODUCTION: The cranium is a host to a variety of neoplasms and includes small round cell tumors (SRCTs) as an important malignant subset. Although SRCTs are histomorphologically similar, they are histogenetically diverse comprising of malignancies of epithelial, hematolymphoid, neuroectodermal, and mesenchymal origin. OBJECTIVE: The study aimed to review the clinical and pathological profile of cranial SRCTs. MATERIALS AND METHODS: Study is a retrospective review (clinical, imaging, and histopathology) of cranial (extra-axial) SRCTs diagnosed on histology (period: 3.5 years). RESULTS: Study included 126 cases constituting 1.5% of all intracranial neoplasms and age ranging from 11 months to 82 years (mean: 34.3 years; M:F = 1.46:1). Peripheral primitive neuroectodermal tumors (pPNET-8.2%) was the commonest neoplasm followed by plasmacytoma (14.2%), poorly differentiated carcinomas (13.5%), lymphomas (9.5%), and sarcomas (8.7%). Rare tumors included glioma (undifferentiated) deposits, germ cell tumors, melanoma, neuroendocrine neoplasms, and embryonal tumor. Children constituted one-third of the total with PNETs, embryonal tumors, and round cell sarcomas being the common neoplasms. Elderly patients constituted 14% with plasmacytomas and epithelial neoplasms being common. Three percent of the tumors remained unclassified. Clinical symptomology was location dependent, headache being the commonest followed by visual symptoms. Radiopathological discordance was high (60%). CONCLUSION: SRCTs are unusual tumors with a wide spectrum of histogenesis, biology and clinical presentation. Their rarity in cranium, atypical localization, overlapping clinical, and imaging features pose significant difficulty for clinicians, radiologists, and pathologists. A combined algorithmic analysis of the clinical, radiological, and histolopathological findings, supplemented with immunohistochemistry can aid in specific diagnosis which is crucial for optimal management.