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.

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.

Hereditary neuropathies: Genetics and utility of nerve biopsy.

Peripheral neuropathy is one of the most common neurological conditions of the nervous system. Hereditary neuropathies (HNs) form an important group with varying degrees of severity, causing a significant disease burden. Accurate diagnosis is essential for management, counseling, and preventing unnecessary extended workups for acquired etiologies and inappropriate treatment. Several hereditary neuropathies have characteristic or diagnostic histologic findings; however, in the era of molecular diagnostics, the role of nerve biopsy in the diagnosis of hereditary neuropathy has reduced significantly. Nevertheless, in sporadic cases, cases without a clear family history, clinical mimics, cases with rare mutations, and genetic variants of unknown significance, a nerve biopsy can confirm the diagnosis, provide an unexpected diagnosis, or direct a targeted molecular testing. HN may be non-syndromic, affecting predominantly the peripheral nervous system or syndromic where it is a part of more widespread neurological or multisystem involvement. This review summarizes the microscopic pathological features in a nerve biopsy in some of the more commonly encountered inherited peripheral neuropathies highlighting their utility in selected cases.

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.

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.

A Case of Ollier's Disease with P53 Mutation Positive and IDH1 (R132H) Negative Multicentric Gliomas.

Ollier disease is a rare nonhereditary disorder characterized by multiple enchondromas (enchondromatosis). To report a rare case of Ollier disease with gliomas and its mutation analysis. We hereby report a young lady who presented with seizures. She had a past history of multiple bony swellings in the right foot (operated) and swelling over the anterior chest wall for the past 15 years. MRI brain revealed multiple expansile T2/FLAIR hyperintense lesions in right superior and middle frontal gyri, left basifrontal lobe, and left precuneus in the cortical-subcortical location suggestive of glioma. She underwent biopsy which revealed left basifrontal anaplastic astrocytoma, not otherwise specified, WHO grade III, IDH1 (R132H) negative, P53 mutation positive, and ATRX loss of expression. We hereby report a rare case of Ollier disease with multicentric intracranial glioma-IDH1 (R132H) negative, P53 mutation positive, and ATRX loss of expression.

Cerebellar Liponeurocytoma: A Rare Fatty Tumor and its Literature Review.

Cerebellar liponeurocytoma is a rare oncological entity, and the knowledge about the treatment and outcome of these rare tumors is still evolving. Very few cases have been described in literature. We report a middle-aged male who presented with raised intracranial pressure features and gait ataxia. His imaging features revealed classical features of liponeurocytoma in cerebellar vermis, with abundant fat component evident in both computed tomography and magnetic resonance imaging. He underwent resection of the lesion and has been asymptomatic for 4 years. This report describes the classical radiological and immunohistochemical features of this rare entity with favorable outcome and reviews the existing literature.

L1CAM Immunopositivity in Anaplastic Supratentorial Ependymomas: Correlation With Clinical and Histological Parameters.

Supratentorial ependymomas (ST EPNs) are molecularly characterized, of which the RELA fusion positive tumors are the most common and aggressive subgroup. Moreover, histologically, anaplastic ST EPN (ST-AE) often mimic other central nervous system primary high-grade tumors resulting in a diagnostic dilemma. We aimed to study a cohort of ST-AE; evaluate the expression of two RELA fusion-associated markers-L1CAM and p65 (NF-κB); and correlate their expression with clinical and histological parameters. Cases of ST-AE diagnosed in our department from January 2011 to June 2016 (n = 72) were reviewed. A battery of immunohistochemical markers was employed. A total of 65 confirmed ST-AE were included in the study. Age ranged from 9 months to 60 years. There was a slight predominance in the pediatric population (57%). Male-to-female ratio was 1:1.16. Histomorphological features were varied and mimicked other high-grade tumors in several cases. L1CAM immunopositive tumors constituted 26% of cases and were predominantly seen in young children, in the frontoparietal location, and exhibited clear cell morphology with calcification. A consistent pattern of L1CAM immunopositivity was noted in paired primary and recurrent tumor samples. Our study portrays the varied clinical and histomorphological spectrum of ST-AE. The study emphasizes the association of L1CAM immunopositivity with a wide spectrum of histological parameters, literature on which is scant till date. Since ST EPN-RELA are tumors with aggressive behavior, such a correlation would be clinically relevant, particularly when there is limited access to molecular testing.

Transcriptome profiling reveals PDZ binding kinase as a novel biomarker in peritumoral brain zone of glioblastoma.

PURPOSE: Peritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT. METHODS: 17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells. Data was analysed using R Bioconductor software. Shortlisted genes were validated using qRT-PCR. Expression of one selected candidate gene, PDZ Binding Kinase (PBK) was correlated with patient survival, tumour recurrence and functionally characterized in vitro using gene knock-down approach. RESULTS: Unsupervised hierarchical clustering showed that TC and PT have distinct gene expression profiles compared to controls. Further, comparing TC with PT, we observed a significant overlap in gene expression profile in both, despite PT having fewer infiltrating tumour cells. qRT-PCR for 13 selected genes validated the microarray data. Expression of PBK was higher in PT as compared to TC and recurrent when compared to newly diagnosed GBM tumours. PBK knock-down showed a significant reduction in cell proliferation, migration and invasion with increase in sensitivity to radiation and Temozolomide treatment. CONCLUSIONS: We show that several genes of TC are expressed even in PT contributing to the vulnerability of PT for tumour recurrence. PBK is identified as a novel gene up-regulated in PT of GBM with a strong role in conferring aggressiveness, including radio-chemoresistance, thus contributing to recurrence in GBM tumours.

Occipital Intraosseous Hemangioma over Torcula: Unusual Presentation with Raised Intracranial Pressure.

BACKGROUND: Hemangiomas of the bone are benign, uncommon, slow-growing lesions accounting for <1.0% of all bony neoplasms. Intraosseous occipital hemangiomas are rare, and occipital hemangiomas presenting with features of raised intracranial tension are, with only 2 cases reported to date. CASE DESCRIPTION: In this case report, we describe the unique case of a 30-year-old male patient presenting with raised intracranial pressure due to venous obstruction at the torcula. The patient underwent excision of the lesion and became symptom free. CONCLUSIONS: Although these are benign lesions, they can have a varied clinical presentation. An understanding of the different clinical presentations and surgical nuances in excising such tumors can lead to early diagnosis and good patient outcome.

Rare pathologies in the posterior third ventricular region in children: case series and review.

Tumors of the pineal region in children often belong to 2 categories, namely germ cell tumors and pineal parenchymal tumors. Very rare pathologies have previously been reported in this region. Most of these tumors may be similar radiologically, while their management differs. The present series reports 2 children with pineal region tumors, each one being a rare pathological entity by itself, namely an embryonal tumor with abundant neuropil and true rosettes (ETANTR) and a rosette-forming glioneuronal tumor (RGNT). Very few such cases in each pathology have been reported in the literature for the pediatric age group up to now. Our series consists of 2 children, both presenting with a raised intracranial pressure of short duration. Imaging revealed lesions in the pineal region with similar radiological features. Both ETANTR and RGNT demonstrated mild enhancement. The 2 patients underwent surgical decompression either by Poppen's approach (n = 1) or a supracerebellar infratentorial approach (n = 1). The patient with ETANTR was advised radiotherapy, while the child with RGNT was advised a regular follow-up. This series presents some rare pathologies which can occur in the posterior third ventricular region with similar radiological features. Management differs based on the histology of the case.

Solitary juvenile xanthogranuloma in cervical spine: case report and review of the literature.

Solitary juvenile xanthogranuloma (JXG) in the spinal column is extremely rare. Here, we report and characterize the case of xanthogranuloma of the upper cervical spine. A 18-year-old male presented with neck pain for 3 months, along with progressive quadriparesis and sensory loss of 2 months duration with urinary retention. Motor examination revealed spastic quadriparesis with power of 2/5 in all the 4 limbs. Magnetic Resonance Imaging (MRI) spine with contrast showed a dorsally placed intradural extramedullary lesion at the level of C2-C4 vertebral body. The lesion, measuring 2.9x1.7x1.4 cm, was isointense on T1WI, hypointense on T2WI, and enhanced homogenously on contrast. He underwent an emergency C2-C4 laminectomy and complete excision of the lesion. At 3-month follow-up, he was asymptomatic except for mild neck pain. MRI scan of the cervical spine done at follow-up, revealed complete excision of tumor without any residual lesion. Histopathological examination of the mass revealed a polymorphous population of sheets of bloated pale foamy histiocytes (xanthoma cells), numerous admixed mature lymphocytes and several Touton giant cells. The cells were positive for CD68, a histiocytic marker, and negative for CD1a (excludes LCH) and S-100 (excludes RDD).

Primary intrasellar schwannoma.

Intracranial schwannomas commonly arise from the eighth cranial nerve in the cerebellopontine angle. Schwannoma arising in the sella and extending into the suprasellar region is very rare and is easily mistaken for pituitary adenoma. To our knowledge, there have been only 12 previous reports. We present a patient with primary intrasellar schwannoma that clinically and radiologically resembled a pituitary adenoma (PA). Intra-operative findings differed from a PA, as the tumour had a firmer consistency. Gross total excision of the lesion was done via a transethmosphenoidal approach. Post-operatively the patient improved in visual acuity and visual fields. We have reviewed the literature and described the characteristics of such lesions.

Rosette-forming glioneuronal tumor -- evidence of stem cell origin with biphenotypic differentiation.

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a new addition to the WHO classification of central nervous system tumors. To date, 72 cases have been described in literature. In the present study, we report the clinical and imaging features, with detailed histopathological and immunohistochemical profile, of eight cases. Confocal microscopic evidence of stem cell origin with biphenotypic, glial and neurocytic differentiation is presented with a comprehensive review of literature.

Intramedullary metastasis in a case of vermian medulloblastoma.

Medulloblastoma is one of the commonest primary CNS malignancies in children. Leptomeningeal dissemination and distant metastasis have been associated with medulloblastoma, but intramedullary metastases are very rare. CSF cytology and contrast-enhanced MRI are the main modalities used to diagnose leptomeningeal dissemination. However, intramedullary metastases are best picked up with contrast-enhanced axial sequences on MR imaging. In this report, a patient with medulloblastoma who developed intramedullary metastasis is described. The role of imaging and CSF cytology in diagnosing the spread along the CSF pathways is reviewed. Allusions are made to the possible mechanism of intramedullary metastasis in these tumors.

Clinical, neuroimaging and pathological features of 5-nitroimidazole-induced encephalo-neuropathy in two patients: Insights into possible pathogenesis.

We report two patients manifesting with involvement of central and peripheral nervous system with brain magnetic resonance imaging (MRI) changes and pathological features of neuropathy possibly due to harmful and chronic use of various nitroimidazole group of medications for recurrent diarrheal illness. Patient 1, a 21-year-old man with obsessive-compulsive disorder, impulsive behavior and harmful use of substance (tinidazole), had developed encephalopathy and biopsy-proven neuropathy with partial remission. The MRI of brain showed involvement of bilateral caudate, lentiform and dentate nuclei, and splenium, with contrast enhancement of the caudate and putaminal lesions and restricted diffusion of the splenial lesion. Patient 2 was a 50-year-old woman with irritable bowel syndrome and was on harmful use of tinidazole and metronidazole. She manifested with encephalopathy, ataxia, and neuropathy. Her MRI of brain revealed involvement of bilateral putamen, dentate nuclei and periventricular white matter with restricted diffusion. Sural nerve biopsy revealed evidence of vasculitic neuropathy. At follow-up, there was definite, though incomplete, recovery in both the patients. The MRI alterations improved completely in patient 2 and substantially in patient 1. Increasing awareness among the physicians may enable early recognition of potentially reversible neurotoxicity and avoid unwarranted prescription of such medications.

Spectrum of Neuro-Sjogren's syndrome in a tertiary care center in south India.

BACKGROUND: Neurological affection in Sjogren's syndrome (SS) can occur in the central and peripheral nervous system. Literature describing the neurological involvement in SS among Indian patients is lacking. MATERIALS AND METHODS: Six patients of SS fulfilling the histological or serological criteria of the American European Consensus Group for SS were studied prospectively. The patients underwent clinical examination and laboratory investigations. Their clinical and investigation features are described. RESULTS: The age of the patients ranged from 26 to 48 years, with a male to female ratio of 2:4. In our series, peripheral sensori-motor neuropathy and sensory ataxic neuropathy was seen in 3/6, mononeuritis multiplex in 2/6, cranial neuropathy in 2/6, autonomic neuropathy in 1/6, myelopathy in 4/6, optic neuropathy in 2/6, with presence of classical sicca features in 5/6 patients. Positive lip biopsy was seen in three, altitudinal field defect in one and positive Schirmer's test in five patients. Nerve conduction study abnormalities were seen in three and evidence of vasculitis was seen in nerve biopsy of one patient and chronic nonuniform axonopathy was seen in another. Antibody to Ro (SSA) or La (SSB) was positive in five patients. CONCLUSIONS: SS involves different parts of the nervous system with varied presentations. Clinical suspicion and adequate laboratory testing helps to diagnose and manage this disorder that is relatively rare in Indian patients.