Pulmonary Spindle Cell Carcinoma: As Rare as a Hen's Teeth.

This case is about a 70-year-old man who presented with symptoms and laboratory reports that indicated differentials toward an infectious disease (pneumonia and tuberculosis). A lung mass was found in his chest X-ray and in the computerized tomography (CT) scan of his thorax. A biopsy was taken from the lung mass, and histopathological examination and immunohistochemical staining of the biopsy were done. The results revealed the presence of spindle cell carcinoma (SpCC) with vimentin and cytokeratin positivity. Spindle cell lung cancer is a rare type of non-small cell lung carcinoma, for which all available research indicates a poor prognosis. Due to the rarity of diagnosis, there is a dearth of information about the epidemiology and overall survival of affected patients.

A Rare Case of Primary Adenocarcinoma of the Gallbladder With Lymphoid Stroma.

Adenocarcinoma of the gallbladder is the most common gallbladder carcinoma. But lymphoid stroma in gallbladder carcinoma is one of the rarest presentations. A unique case of gallbladder adenocarcinoma with lymphoid stroma in a 47-year-old female is presented in this report. The surgically resected gallbladder demonstrated invasive adenocarcinoma with lymphoid stroma, though it was radiologically diagnosed as xanthogranulomatous cholecystitis. Adenocarcinoma was immunohistochemically positive for pancytokeratin (AE1/AE3), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and carcinoembryonic antigen (CEA). Lymphoid stroma was positive for CD45, where B-cell zones were CD20 and CD79a positive, and T-cell zones were CD3 positive, with a larger T-cell subset being positive for CD4 than CD8. This is the fourth reported case of gallbladder adenocarcinoma with lymphoid stroma, which needs to be studied for pathogenesis, prognosis, and future therapy, if any.

Synchronous Adenocarcinoma Stomach With Marginal Zone Lymphoma: A Sporadic Occurrence and Review of Literature.

Synchronous adenocarcinoma of the stomach with lymphoma is extremely rare. We report a case of a 65-year-old male patient with synchronous adenocarcinoma of the stomach with nodal marginal zone lymphoma. Initial endoscopic biopsy suggested invasive moderately differentiated adenocarcinoma and a locoregional disease, per contrast-enhanced computed tomography (CECT) scans. The patient was started on neo-adjuvant chemotherapy with the 5FU, leucovorin, oxaliplatin, docetaxel (FLOT) regime and, after response evaluation, underwent radical gastrectomy. Histopathology and immunohistochemistry suggested synchronous adenocarcinoma of the stomach with marginal zone lymphoma in perigastric lymph nodes. This case is probably the first such synchronous malignancy case reported from India. The prognosis of multiple primary malignancies is usually poor because no standard guidelines are available regarding optimum treatment and sequencing of available treatment modalities. The frequency of synchronous primary cancers has been increasing in recent years, probably due to better diagnostic modalities, and second primary in patients with cancer should be considered as one of the differential diagnoses.

Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Utility of tru-cut biopsy in diagnosis of palpable pediatric soft tissue neoplasms.

Context: Soft tissue neoplasms are infrequent in children with sarcomas accounting for approximately 7% of all pediatric malignancies. Morphologic diagnosis is challenging due to overlapping features. Subtyping and categorization of these lesions are difficult on fine-needle aspiration cytology (FNAC) alone owing to tumor heterogeneity and limited material in some cases. Tru-cut biopsies obtain adequate tumor tissue for ancillary studies besides conventional histology. Aim: The study aims to explore the role of tru-cut biopsy to arrive at a definitive diagnosis. The study also highlights the correlation between FNAC and histopathology on tru-cut biopsy besides explaining the significance of a panel of immunohistochemistry (IHC) markers for histological categorization and subtyping. Materials and Methods: A total of 61 children from infancy to 18 years were included in the study. Closed biopsy procedures like FNAC and tru-cut biopsy were performed, and the tru-cut biopsy specimen was subjected to a panel of immunohistochemical markers. Results: Fisher's exact test for sensitivity and specificity towards detection of malignancy was 83% and 86%, respectively for FNAC. For tru-cut biopsy, sensitivity was 94% and specificity was 91%. The two-sided P value (<0.0001) was extremely significant. Cohen's Kappa coefficient value for tru-cut biopsy was 0.772 suggesting a substantial strength of agreement. Tru-cut with IHC had a Kappa value of 0.866 suggesting greater agreement with histopathology. Conclusion: Tru-cut biopsy is a simple, safe, and reliable adjunct to the FNAC. Instead, immunohistochemistry enhances the diagnostic accuracy.

Paraganglioma of Urinary Bladder: An Uncommon Entity in Uropathology.

Paraganglioma of the urinary bladder is a rare neoplasm. It may be functional, secreting catecholamines, or nonfunctional. Clinically and histopathologically, it has the potential to be misdiagnosed as a more common urothelial carcinoma, especially in nonfunctional cases. A high index of suspicion on the part of pathologist can help in identification of characteristic histopathologic feature which coupled with immunohistochemistry can help in establishing the correct diagnosis. We present a case of paraganglioma in a 78-year-old male patient presenting with haematuria. Clinical provisional diagnosis rendered based on cystoscopic findings and radiology was urothelial carcinoma; however, was confirmed to be a case of paraganglioma of bladder on histopathological and immunohistochemical evaluation. A long follow-up is warranted. Herein, we also briefly review the relevant literature.

Diagnostic Yield of Closed Pleural Biopsy in Undiagnosed Exudative Pleural Effusions.

Introduction: In our practice, etiological diagnosis of pleural effusion is sometimes difficult despite cytological, biochemical and microbiological tests. The aim of the present study was to make an etiological diagnosis by means of closed pleural biopsy in undiagnosed pleural effusions. Methods:The study group consisted of patients with exudative pleural effusion where etiology was not determined by means of conventional cytological, biochemical and microbiological investigations. Pleural tissue was obtained by Abrams pleural biopsy needle. Pleural biopsy was subjected to histopathology, Ziehl-Neelsen (Z-N) staining and mycobacterial culture. Results:Four hundred fifty eight patients with pleural effusion were screened over three years and 82 of them were found to have undiagnosed exudative effusion after investigations, as mentioned in the Method section. The age of the 82 subjects [56 (68.29%) men and 26 (31.71%) women] ranged from 15 to 65 years (mean 32.6). Histopathology showed epitheloid granuloma with caseation necrosis in 50 (60.9%) patients and non-specific chronic inflammation in 14 (17.1%) subjects. Ziehl-Neelsen stain was positive for acid fast bacilli (AFB) in 10 (12.2%) patients and culture of pleural tissue showed the presence of Mycobacterium tuberculosis in 18 (21.9%) patients. Conclusion:In the era of thoracoscopy, percutaneous closed needle pleural biopsy still holds a significant role in cases of undiagnosed exudative pleural effusions where thoracoscopy is not available, being also a cost effective approach for developing countries. It can achieve specific diagnosis among 86.6% of cases with undiagnosed exudative pleural effusions.

Structural disruption of exonic stem-loops immediately upstream of the intron regulates mammalian splicing.

Recognition of highly degenerate mammalian splice sites by the core spliceosomal machinery is regulated by several protein factors that predominantly bind exonic splicing motifs. These are postulated to be single-stranded in order to be functional, yet knowledge of secondary structural features that regulate the exposure of exonic splicing motifs across the transcriptome is not currently available. Using transcriptome-wide RNA structural information we show that retained introns in mouse are commonly flanked by a short (≲70 nucleotide), highly base-paired segment upstream and a predominantly single-stranded exonic segment downstream. Splicing assays with select pre-mRNA substrates demonstrate that loops immediately upstream of the introns contain pre-mRNA-specific splicing enhancers, the substitution or hybridization of which impedes splicing. Additionally, the exonic segments flanking the retained introns appeared to be more enriched in a previously identified set of hexameric exonic splicing enhancer (ESE) sequences compared to their spliced counterparts, suggesting that base-pairing in the exonic segments upstream of retained introns could be a means for occlusion of ESEs. The upstream exonic loops of the test substrate promoted recruitment of splicing factors and consequent pre-mRNA structural remodeling, leading up to assembly of the early spliceosome. These results suggest that disruption of exonic stem-loop structures immediately upstream (but not downstream) of the introns regulate alternative splicing events, likely through modulating accessibility of splicing factors.

Bronchiectasis in India: results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry.

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0·0001]) and more likely to be men (1249 [56·9%] of 2195). Previous tuberculosis (780 [35·5%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13·7%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1·17, 95% CI 1·03-1·32; p=0·015), P aeruginosa infection (1·29, 1·10-1·50; p=0·001), a history of pulmonary tuberculosis (1·20, 1·07-1·34; p=0·002), modified Medical Research Council Dyspnoea score (1·32, 1·25-1·39; p<0·0001), daily sputum production (1·16, 1·03-1·30; p=0·013), and radiological severity of disease (1·03, 1·01-1·04; p<0·0001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation.

Synchronous Bilateral Wilms Tumor: Five-Year Single-Center Experience with Assessment of Quality of Life.

CONTEXT: Synchronous Bilateral Wilms tumor (sBWT). AIMS: This study aimed to assess the outcome of patients with sBWT treated on SIOP protocol. SETTINGS AND DESIGN: Retrospective and prospective randomized study. SUBJECTS AND METHODS: SIOP 93-01 protocol was used to study nine patients of sBWT in a single center and followed up over a period from 2 to 5 years. STATISTICAL ANALYSIS USED: Unpaired t-test and Mann-Whitney U-test were used for analysis. RESULTS: Of nine patients, six were included in the study as three patients lost to follow-up. Among the six patients, there were four girls and two boys with a median age of 2 years. Mean regression in the size of tumor was 87% in four out of six patients. Tumor with unfavorable histology showed 32% response (ratio of favorable: unfavorable histology 2:1). Event-free survival rate was 81.3% and overall survival was 90% over 2-5 years. Recurrence was seen in two patients of whom one had Denys-Drash syndrome. Mean DTPA glomerular filtration rate was 91.4/ml/min/1.73 m2 preoperatively and that of 3 months after completion of treatment was 84/ml/min/1.73 m2. Health-related quality of life (HRQOL) using Pediatric Quality of Life Inventory and Lansky Play Performance Scale revealed significant improvement results of all functioning domains such as physical, social, emotional, and school subscales with P < 0.05 and performance scale (P < 0.04). CONCLUSIONS: We suggest SIOP protocol for sBWT and bilateral nephron-sparing surgery in two stages. However, long-term follow-up is required to assess the ultimate renal function outcome. HRQOL is an essential guide in improving the conditions of pediatric cancer survivors.

Demographic Study and Management of Colonic Atresia: Single-Center Experience with Review of Literature.

CONTEXT AND AIM: The aim of this study is to highlight the rarity of this disorder and its associated anomalies and our objective was to review our experience in the management of colonic atresia (CA) with respect to staged surgery versus one-step procedure for a better outcome of the disease. SETTINGS AND DESIGN: A randomized, controlled, single-center study conducted over a period of 4 years from October 2013 to 2017. SUBJECTS AND METHODS: Nine cases were operated for CA of which three underwent primary anastomosis and six underwent initial colostomy followed by definitive surgery. Age, sex, body weight, clinical presentation, type of atresia, site, time interval of operation, associated anomalies, initial procedure, postoperative complications, final procedure, biopsy, hospital stay, and outcome were noted. STATISTICAL ANALYSIS USED: Microsoft Excel was used for statistical analysis. RESULTS: Out of 9 patients, 6 were males and 3 were females, 7 patients survived and 2 patients died (mortality 22.2%), of which one patient with primary anastomosis had leak and sepsis and one patient with primary anastomosis had associated Hirschsprung's disease (HD). Mean time gap for operation was 12.8 h and mean hospital stay was 3.5 days for initial colostomy and 21 days for primary anastomosis. Wound dehiscence occurred in 4 patients. Malrotation was found in 3 patients, HD in 2 patients, cardiac anomaly in 2, Meckel's diverticulum in 1, and cleft lip in 1 patient. Type IIIa atresia was found in in 6 patients, Type I in 2, and Type II in 1 patient. The most common site was transverse colon (n = 5). CONCLUSION: Diagnosis and management of CA is a challenge. Early presentation and diagnosis should be prompt. Staged procedure with initial colostomy followed by definitive procedure is the preferred choice. Associated anomaly HD must be ruled out.

Primary undifferentiated pleomorphic sarcoma of the breast in a young female: a case report.

BACKGROUND: Undifferentiated pleomorphic sarcoma is a rare entity and requires extensive immunohistochemical markers to differentiate it from other tumors of the breast. CASE PRESENTATION: We present a 29-year-old female with a left breast lump for 2 months. Initial diagnosis of malignant spindle cell tumor was done on core biopsy following which total mastectomy was done. After extensive sampling, on histology, highly pleomorphic spindle cells palisading the area of geographic necrosis with very high atypical mitosis were seen. As there was diagnostic difficulty, immunohistochemical antibody panel was used and diagnosis of undifferentiated pleomorphic sarcoma of the breast was made by exclusion. CONCLUSIONS: Core biopsy with immunostaining is possibly superior to FNA as an initial diagnostic modality for breast masses with atypical features.

Evaluation of Preoperative Serum Levels of CA 125 and Expression of p53 in Ovarian Neoplasms: A Prospective Clinicopathological Study in a Tertiary Care Hospital.

OBJECTIVES: To assess the preoperative serum levels of CA 125 with its diagnostic role and to evaluate the p53 expression in patients of primary ovarian neoplasms. We also wished to judge their relationship with other parameters like clinical staging and histopathologic tumor type. MATERIALS AND METHODS: The present study was conducted on 86 patients during the study period of 2.5 years. Preoperative CA 125 levels were evaluated by an automated immunoassay analyzer. p53 expression was judged immunohistochemically with pre-diluted monoclonal antibody. An objective scoring was done depending on distinct nuclear immunopositivity. RESULTS: Median value of preoperative CA 125 levels was 32 U/mL in benign surface epithelial-stromal tumors (BSEST), 53 U/mL in borderline surface epithelial-stromal tumors (BOT), 346 U/mL in malignant surface epithelial-stromal tumors (MSEST) and 560 U/mL in serous adenocarcinomas (SAC). Most of ovarian tumors were in the FIGO stage I (64 cases, 74.4%), but higher stages (II, III, IV) were observed mostly in MSESTs. SACs displayed the maximum p53 expression. Considering the cut-off value of more than 35 U/mL in CA 125 levels, the sensitivity to diagnose MSESTs was 94.7%. Preoperative CA 125 levels strongly and positively correlated with FIGO staging and p53 expression. Similarly p53 expression strongly and positively correlated with FIGO staging and histopathological categories. CONCLUSION: Higher values of preoperative CA 125 levels and higher expression p53 are associated with MSESTs and BOTs especially of serous type. They strongly correlate with each other and with tumor stage. But there is no serum CA 125 concentration that can clearly differentiate benign and malignant ovarian masses.

Expression of COX-2 and p53 in juvenile polyposis coli and its correlation with adenomatous changes.

INTRODUCTION: Gastrointestinal polyps commonly affect the pediatric population. The commoner variety amongst these is the solitary rectal polyp. Juvenile polyposis coli (JPC) is rare, characterized by multiple polyps occurring throughout the gut. AIM: The role of cyclooxygenase-2 (COX-2) has been implicated in gastrointestinal tumorigenesis. We aimed to look at the clinicopathological spectrum of solitary vs juvenile polyposis and compare their differences in expression of COX-2 and p53. MATERIALS AND METHODS: We studied 38 polyps from eight cases of JPC, collected over the past 10 years along with 40 solitary rectal polyps (SRP). RESULTS: The size of polyps was significantly more in cases of JPC compared to SRP. Adenomatous change was observed significantly more often in JPC. COX-2 expression was also significantly higher in the JPC group compared to SRPs. All cases of JPC polyps with adenomatous change showed strong COX-2 expression. There was no significant difference in expression of p53 in the JPC and SRP groups. CONCLUSION: We observed significantly higher COX-2 expression in JPC. Establishment of the role of COX-2 in JPC will help us formulate chemopreventive therapies as an adjunct to its surgical management.

Fine needle aspiration cytology of dermatopathic lymphadenitis in an asymptomatic female: A case report.

Dermatopathic lymphadenopathy usually presents as enlarged superficial lymph nodes, most often involving the axillary or inguinal regions. Most patients have a chronic dermatopathy that precedes the development of dermatopathic lymphadenopathy. This condition can be confused with lymphoma in adults. There are very few case reports on cytological features of this disease in literature. We describe a case of dermatopathic lymphadenopathy in a 50-year-old female without any skin disease.