IDH1, ATRX, p53, and Ki67 Expression in Glioblastoma patients: Their Clinical and Prognostic Significance-A Prospective Study.

Context Glioblastoma multiforme (GBM) is a malignant and aggressive primary brain tumor with a poor prognosis. This adverse prognosis is due to the tumor's tendency for advancement and recurrence caused by highly intrusive nature of the persisting GBM cells that actively escape from the main tumor mass into the surrounding normal brain tissue. On the basis of biomarker illustration, it can be classified into molecular subgroups. Aims (1) To determine the expression of IDH1, ATRX, p53, and Ki67 by immunohistochemistry, in a cohort of GBMs. (2) To determine whether altered protein expression of any of these growth-control genes in GBM will show association with patient survival. (3) To establish prognostically distinct molecular subgroups of GBM, irrespective of histopathological diagnosis. Results In this prospective observational study, 35 histologically diagnosed cases of glioblastoma were enrolled. The mean age at the time of presentation was 43.46 ± 17.25 years with a male:female ratio of 1.3:1. Of the 35 cases, microvascular proliferation was seen in 23 cases. Large foci of necrosis (>50%) were seen in 10 cases and 27 cases had mitotic count ≥ 5/high power field (HPF). Of 35 cases, 5 (14.3%) cases showed IDH1 immunopositivity and 30 (85.7%) cases were negative for IDH1. ATRX was retained in 24 (68.6%) cases, while it was lost in 11 (31.4%) cases. The p53 immunoexpression was seen in 31 (88.6%) cases, whereas p53 was negative in 4 (11.4%) cases. The overall median survival (OS) was 6 months. In two protein pairs, the three compositions were IDH1-/p53+ (74.3%), ATRX +/IDH1- (62.9%), and ATRX +/p53+ (57.1%). Combined three-protein immunohistochemical analysis revealed five different molecular variants. Also, 8.6% (3/35) of the samples had aberrant protein expression of all three proteins, i.e., ATRX-/p53 +/IDH1 + , while 11.4% (4/35) were wild-type protein expression group, i.e., ATRX +/p53-/IDH1-. Conclusion In patients with single protein expression, Kaplan-Meier survival analysis showed statistically better OS in IDH1 mutant glioblastomas. In cases with double protein pairs, IDH1/p53 revealed statistically significant association with better median OS. The survival analysis of patients with IDH1/ATRX/p53 protein combinations also denoted a better OS. Hence, GBM can be grouped into prognostically relevant subgroups using these protein expression signatures individually, as well as the combined protein expression signatures.

Intraoral Basal Cell Carcinoma of Soft Palate: A Diagnostic Dilemma and Review of Literature.

Basal cell carcinoma is the most common cancer worldwide. Most of basal cell carcinoma can be detected in the early stages and are generally well controlled with local resection. Despite the high incidence of BCC, intramucosal BCC is a very rare clinical entity. We hereby present a rare case report of pigmented BCC on soft palate and review the literature of this entity.

Malignant solitary fibrous tumor of maxilla presenting as proptosis: A case report.

ABSTRACT: Solitary fibrous tumor (SFT) is a fibroblastic mesenchymal neoplasm that rarely metastasizes. SFTs was first described in relation to pleura. However, occurrence of this tumor type has been reported in other sites like peritoneum, liver, adrenal gland, meninges and oral cavity. In head and neck region, oral cavity is the most common site of involvement. Most of the solitary fibrous tumors are benign and present as an asymptomatic slow growing mass. Surgery remains the mainstay of treatment. Hereby, we describe a case of 71-year-old male with malignant solitary fibrous tumor arising from right maxilla invading the right orbit presenting as proptosis.

Demystifying COVID-19 lung pathology: A clinicopathological study of postmortem core needle biopsy.

BACKGROUND: Atypical presentation of coronavirus disease-19 (COVID-19) from classic acute respiratory distress syndrome needs to be extensively evaluated to understand the pathophysiology to optimize the management protocol for severely ill patients to abrogate the terminal event. METHODS: Autopsy core needle biopsies of lungs were obtained from 12 patients who died with COVID-19. Routine histopathological examination of lung tissue along with immunohistochemical analysis of C4d complement staining was studied. Formalin-fixed paraffin-embedded biopsy material was also subjected to real-time reverse transcription-polymerase chain reaction for severe acute respiratory syndrome - coronavirus (SARS-CoV2) gene. RESULTS: In the study, all the deceased patients were symptomatic with two-thirds suffering from isolated SARS-CoV2-related pneumonia while remaining one-third had secondary COVID-19 infection. Histopathological evaluation highlights diffuse alveolar damage as the predominant pattern; however, complement-mediated endothelial injury of septal microvasculature, and microthrombi was also distinctly observed with increased serum levels of D-Dimer and fibrinogen-degradation products. The patients who had extrapulmonary manifestations at the time of presentation also showed pulmonary vascular lesions on histopathologic examination. Our study confirms the presence of coagulopathy and immune-mediated microthrombi in pulmonary septal microvasculature in patients with severe disease. CONCLUSION: The results of our small series of patients highlight the possibility of immune-mediated pulmonary vascular injury and thrombosis which has the potential to evolve into large vessel thrombosis and pulmonary embolism in critically ill patients. Definitive therapeutic management protocol including thromboembolic prophylaxis and development of effective immune-modulatory target could possibly reduce mortality in severely ill patients.

A rare case of a solitary fibrous tumor of vulva, displaying NAB2ex6-STAT6ex17 fusion.

A solitary fibrous tumor (SFT), although ubiquitous, is rarely documented in the female genital tract, especially confirmed by STAT6 immunostaining and underlying NAB2-STAT6 gene fusion. A 24-year-old female presented with a gradually increasing vulvar swelling in her right labia, which rapidly increased in size over 1-year duration. Radiologically, a subcutaneous, predominantly solid, lobulated mass, measuring 10 cm in the largest dimension was seen involving her right labia majora and perineum. She underwent tumor resection, elsewhere, where it was reported as a pleomorphic sarcoma. Histopathologic review revealed a cellular tumor comprising spindle cells, displaying mild nuclear variation, arranged diffusely and focally, in a hemangiopericytomatous growth pattern, within a collagenous stroma. Interspersed were blood vessels with perivascular hyalinization and few giant cells. By immunohistochemistry, tumor cells showed patchy immunostaining for CD34 and diffuse immunostaining for STAT6. Furthermore, the tumor displayed NAB2ex6-STAT6ex 17 fusion by RT-PCR technique. This case constitutes one of the few reported cases of vulvar SFT, confirmed by STAT6 immunostaining and the second such case, displaying NAB2-STAT6 gene fusion. Diagnostic and treatment implications are discussed herewith.

Clinicopathological Correlation of Glioma Patients with respect to Immunohistochemistry Markers: A Prospective Study of 115 Patients in a Tertiary Care Hospital in North India.

BACKGROUND: With the incorporation of molecular subtyping in glioma patients in 2016 WHO classification, there is a need to understand the immunohistochemistry (IHC) marker expression in various glioma patients and to clinically correlate with various subgroups. OBJECTIVE: Aim of the study was to assess IHC marker expression profile in glioma patients and to clinically correlate them in various subgroups. MATERIALS AND METHODS: The prospective study included 115 glioma patients. IHC markers (isocitrate dehydrogenase [IDH] 1, ATRX, P53, Ki-67 antibody) were done in all patients. Patients received treatment as per the grade of tumor. The patients were followed in 3 monthly intervals, for a period of 12 months. SPSS software version 20.0 was used for statistical analysis. Tables were prepared in Microsoft Excel sheet. Kaplan-Meier method was used for survival analysis. RESULTS: There were 11 Grade 1, 33 Grade 2, 26 Grade 3, and 45 glioblastoma multiforme (GBM) patients out of which 10 patients were secondary GBM cases. IDH1 mutation is frequent in Grade 2 and Grade 3 tumors of both astrocytic and oligodendroglia tumors. Its mutation is also common in secondary GBM patients. ATRX mutation is specific to astrocytic lineage, Grade 2, Grade 3, and secondary GBM patients. CONCLUSION: Molecular nature of DA and AA cases can be accurately confirmed by combined IDH1 and ATRX IHC thereby avoiding costly investigations such as fluorescence in situ hybridization. In astrocytic tumors, p53 can act as a surrogate marker. IDH-mutant glioma patients have better prognoses than IDH wild gliomas.

Management of interstitial lung diseases: A consensus statement of the Indian Chest Society (ICS) and National College of Chest Physicians (NCCP).

BACKGROUND: Interstitial lung disease (ILD) is a complex and heterogeneous group of acute and chronic lung diseases of several known and unknown causes. While clinical practice guidelines (CPG) for idiopathic pulmonary fibrosis (IPF) have been recently updated, CPG for ILD other than IPF are needed. METHODS: A working group of multidisciplinary clinicians familiar with clinical management of ILD (pulmonologists, radiologist, pathologist, and rheumatologist) and three epidemiologists selected by the leaderships of Indian Chest Society and National College of Chest Physicians, India, posed questions to address the clinically relevant situation. A systematic search was performed on PubMed, Embase, and Cochrane databases. A modified GRADE approach was used to grade the evidence. The working group discussed the evidence and reached a consensus of opinions for each question following face-to-face discussions. RESULTS: Statements have been made for each specific question and the grade of evidence has been provided after performing a systematic review of literature. For most of the questions addressed, the available evidence was insufficient and of low to very low quality. The consensus of the opinions of the working group has been presented as statements for the questions and not as an evidence-based CPG for the management of ILD. CONCLUSION: This document provides the guidelines made by consensus of opinions among experts following discussion of systematic review of evidence pertaining to the specific questions for management of ILD other than IPF. It is hoped that this document will help the clinician understand the accumulated evidence and help better management of idiopathic and nonidiopathic interstitial pneumonias.

Management of interstitial lung diseases: A consensus statement of the Indian Chest Society (ICS) and National College of Chest Physicians (NCCP)

Interstitial lung disease (ILD) is a complex and heterogeneous group of acute and chronic lung diseases of several known and unknown causes. While clinical practice guidelines (CPG) for idiopathic pulmonary fibrosis (IPF) have been recently updated, CPG for ILD other than IPF are needed. Methods: A working group of multidisciplinary clinicians familiar with clinical management of ILD (pulmonologists, radiologist, pathologist, and rheumatologist) and three epidemiologists selected by the leaderships of Indian Chest Society and National College of Chest Physicians, India, posed questions to address the clinically relevant situation. A systematic search was performed on PubMed, Embase, and Cochrane databases. A modified GRADE approach was used to grade the evidence. The working group discussed the evidence and reached a consensus of opinions for each question following face-to-face discussions. Results: Statements have been made for each specific question and the grade of evidence has been provided after performing a systematic review of literature. For most of the questions addressed, the available evidence was insufficient and of low to very low quality. The consensus of the opinions of the working group has been presented as statements for the questions and not as an evidence-based CPG for the management of ILD. Conclusion: This document provides the guidelines made by consensus of opinions among experts following discussion of systematic review of evidence pertaining to the specific questions for management of ILD other than IPF. It is hoped that this document will help the clinician understand the accumulated evidence and help better management of idiopathic and nonidiopathic interstitial pneumonias.

Hypersensitivity pneumonitis: Clinical manifestations - Prospective data from the interstitial lung disease-India registry.

CONTEXT: Multiple environmental factors are associated with development of hypersensitivity pneumonitis (HP), and diagnostic algorithms for the diagnosis of HP have been proposed in recent perspectives. AIMS: We analyzed the data of patients with HP from interstitial lung disease (ILD)-India registry. The analysis was performed to (1) find the prevalence of HP, (2) reclassify HP as per a recently proposed classification criterion to assess the level of diagnostic certainty, and (3) identify the causative agents for HP. SETTING AND DESIGNS: This was a prospective multicenter study of consecutive, consenting adult patients with new-onset ILD from 27 centers across India (March 2012-April 2015). MATERIALS AND METHODS: The diagnoses were based on prespecified working clinical criteria and multidisciplinary discussions. To assess strength of diagnosis based on available clinical information, patients with HP were subclassified into definite HP, HP with high level of confidence, and HP with low level of confidence using a recent classification scheme. RESULTS: Five hundred and thirteen of 1084 patients with new-onset ILD were clinically diagnosed with HP and subclassified as HP with high level of confidence (380, 74.1%), HP with low level of confidence (106, 20.7%), and definite HP (27, 5.3%). Exposures among patients with HP were birds (odds ratios [OR]: 3.52, P < 0.001), air-conditioners (OR: 2.23, P < 0.001), molds (OR: 1.79, P < 0.001), rural residence (OR: 1.64, P < 0.05), and air-coolers (OR: 1.45, P < 0.05). CONCLUSIONS: About 47.3% of patients with new-onset ILD in India were diagnosed with HP, the majority of whom were diagnosed as HP with a high level of confidence. The most common exposures were birds, cooling devices, and visible molds.

COX-2 Expression in Breast Carcinoma with Correlation to Clinicopathological Parameters

Objective: Breast carcinoma is the most common malignant tumor and the leading cause of carcinoma deaths in women. Its etiology is multifactorial, implicating reproductive factors, hormonal imbalances and genetic predispositions. Studies have shown that Cycloxygenase-2 (COX-2) plays an important role in the carcinogenesis and increased expression has been regarded as a poor prognostic factor. The objective of our study is 1. To study COX-2 expression in normal breast tissue, DCIS and invasive breast cancer. 2. To determine COX-2 expression with clinicopathological prognostic parameters. Methods: Radical mastectomy specimens were studied for COX-2 expression by immunohistochemistry in 50 patients diagnosed as breast carcinoma. COX-2 expression is quantified as IHS Score and separately calculated for normal breast epithelium near the tumor, DCIS and invasive areas. Relationship between COX-2 expression with various clinicopathological parameters was evaluated. Result: The results of our study suggest an association of the expression of COX-2 to the factors associated with poor prognosis in breast cancer, such as larger tumor size, positive lymph node status, higher T stage and N stage and lymphovascular invasion. There was a higher COX-2 expression in the DCIS component as compared to the invasive ductal carcinoma component and the adjoining breast epithelium. Conclusion: Our study established the role of COX-2 in carcinogenesis and its association with adverse prognostic factors.

Intraoperative Squash Smear Cytology in CNS Lesions: A Study of 150 Pediatric Cases.

BACKGROUND: Tumors of the central nervous system in the pediatric age group occur relatively frequently during the early years of life. Brain tumors are the most common solid malignancies of childhood and only second to acute childhood leukemia. Squash cytology is an indispensable diagnostic aid to central nervous system (CNS) lesions. The definitive diagnosis of brain lesions is confirmed by histological examination. AIM: To study the cytology of CNS lesions in pediatric population and correlate it with histopathology. MATERIALS AND METHODS: One hundred and fifty cases of CNS lesions in pediatric patients were studied over a period of 2 years. Intraoperative squash smears were prepared, stained with hematoxylin and eosin, and examined. Remaining sample was subjected to histopathological examination. RESULTS: Medulloblastoma (24.0%) was the most frequently encountered tumor followed by pilocyctic astrocytoma (21.33%) and ependymoma (13.33%). Diagnostic accuracy of squash smear technique was 94.67% when compared with histological diagnosis. CONCLUSION: Smear cytology is a fairly accurate tool for intraoperative CNS consultations.

Malignant fibrous histiocytoma arising from renal capsule: An extremely rare entity.

Malignant fibrous histiocytoma (MFH) usually presents in the extremities or retroperitoneum. MFH arising from renal parenchyma or renal capsule is extremely rare, only few cases have been reported in literature and portend a poor prognosis. Renal MFH is differentiated from renal cell carcinoma, renal sarcoma, and sarcomatoid renal tumor only by histological and immunohistochemical studies. Since the therapeutic options for MFH are different, its early diagnosis is imperative. Herein, we report a case of a primary renal MFH in a 35-year-old male.

Intraoperative Squash Smear in Central Nervous System Tumors and Its Correlation with Histopathology: 1 Year Study at a Tertiary Care Centre.

BACKGROUND: Intraoperative squash smear cytology is a simple and reliable technique for rapid intraoperative diagnosis of neurosurgical specimens. The study was designed to assess the accuracy of intraoperative squash smear in the diagnosis of central nervous system (CNS) space-occupying lesions. MATERIALS AND METHODS: One hundred and fifty cases of CNS space-occupying lesion were studied in a period of 15 months. Smears were prepared from the biopsy sample obtained at the time of operation and were stained with rapid hematoxylin and eosin method. RESULTS: One hundred and forty-one cases showed complete correlation with histopathology, two cases showed partial correlation, and seven cases were discrepant. The overall diagnostic accuracy was found to be 94%. CONCLUSION: Intraoperative squash smear thus provides diagnosis with fair accuracy in brain tumors and is of great value in intraoperative consultation.

Interstitial Lung Disease in India. Results of a Prospective Registry.

RATIONALE: Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. OBJECTIVES: To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. METHODS: Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high-resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's κ was used to assess reliability of interobserver agreement. MEASUREMENTS AND MAIN RESULTS: A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's κ: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. CONCLUSIONS: Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide.

Dry cough in a middle-aged man.

Cough is often a distressing feature and may be caused due to varied reasons. A 39-year-old man presented with complaints of cough and had significant pigeon exposure. His chest X-ray revealed mediastinal enlargement and computed tomography chest revealed air trapping and mediastinal lymphadenopathy. Both endobronchial and transbronchial biopsies revealed granulomas. Thus, the patient was diagnosed as a case of sarcoidosis and started on steroids. Hypersensitivity pneumonitis may often mimic sarcoidosis; however, the presence of endobronchial granulomas will diagnose the latter condition.

Cryptococcal panniculitis in a renal transplant recipient: case report and review of literature.

BACKGROUND: Cryptococcosis is a deep fungal infection caused by Cryptococcus neoformans. The infection usually involves the lungs, the central nervous system as well as the skin, the bones and the urinary tract. Immunocompromised individuals, including solid organ transplant recipients, are at higher risk for cryptococcal infections. MAIN OBSERVATIONS: We present a 40-year-old renal transplant recipient who developed a slightly painful, erythematous, indurated plaque on his thigh several years after a kidney transplant. Histopathology revealed cryptococcal panniculitis and cryptococcus neoformans subsequently grew from the tissue culture. There was no other systemic involvement. CONCLUSION: The primary cutaneous form of cryptococcosis is extremely rare and early diagnosis and treatment is essential in view of possible dissemination and variable nonspecific clinical manifestations.