Genetic insight into Birt-Hogg-Dubé syndrome in Indian patients reveals novel mutations at FLCN.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a rare monogenic condition mostly associated with germline mutations at FLCN. It is characterized by either one or more manifestations of primary spontaneous pneumothorax (PSP), skin fibrofolliculomas and renal carcinoma (chromophobe). Here, we comprehensively studied the mutational background of 31 clinically diagnosed BHDS patients and their 74 asymptomatic related members from 15 Indian families. RESULTS: Targeted amplicon next-generation sequencing (NGS) and Sanger sequencing of FLCN in patients and asymptomatic members revealed a total of 76 variants. Among these variants, six different types of pathogenic FLCN mutations were detected in 26 patients and some asymptomatic family members. Two of the variants were novel mutations: an 11-nucleotide deletion (c.1150_1160delGTCCAGTCAGC) and a splice acceptor mutation (c.1301-1G > A). Two variants were Clinvar reported pathogenic mutations: a stop-gain (c.634C > T) and a 4-nucleotide duplication (c.1329_1332dupAGCC). Two known variants were: hotspot deletion (c.1285delC) and a splice donor mutation (c.1300 + 1G > A). FLCN mutations could not be detected in patients and asymptomatic members from 5 families. All these mutations greatly affected the protein stability and FLCN-FNIP2 interaction as observed by molecular docking method. Family-based association study inferred pathogenic FLCN mutations are significantly associated with BHDS. CONCLUSION: Six pathogenic FLCN mutations were detected in patients from 10 families out of 15 families in the cohort. Therefore, genetic screening is necessary to validate the clinical diagnosis. The pathogenic mutations at FLCN affects the protein-protein interaction, which plays key roles in various metabolic pathways. Since, pathogenic mutations could not be detected in exonic regions of FLCN in 5 families, whole genome sequencing is necessary to detect all mutations at FLCN and/or any undescribed gene/s that may also be implicated in BHDS.

Diffuse parenchymal lung disease in a case of chronic arsenic exposure.

A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD). Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date.

Mature cystic teratoma of mediastinum with pleural effusion: An uncommon entity.

Teratomas are tumours composed of tissues originating from at least two of the three primitive germ layers, i.e., ectoderm, mesoderm and endoderm. A dermoid cyst, commonly known as benign cystic teratoma is a histological variant containing epidermis and its derivative (sebaceous material) within a lining of squamous epithelium. Mediastinum is the most common extragonadal site for germ cell tumours including mature teratomas. However, pleural effusion secondary to rupture of benign germ cell tumour is quite a rarity and the nature of pleural effusion in such ruptured cases has not been discussed in detail in literatures. Here, we are presenting a case of mature cystic teratoma coexistent with pleural effusion which is quite an uncommon entity making this case quite an interesting learning curve.

Silicosis in the form of progressive massive fibrosis: A diagnostic challenge.

Silicosis is a major occupational lung disease with a relatively fatal and irreversible outcome. Early diagnosis for shifting the potential candidates to safe modes of workplace as well as for prevention of further progression is the cornerstone of management. Here, we present a complicated case of silicosis in the form of progressive massive fibrosis, which was initially interpreted as tuberculosis; radiological images had resemblance with tuberculosis and cryptogenic organizing pneumonia. Radiology-guided trucut biopsy was imperative to confirm the diagnosis.

Role of DR-70 immunoassay in suspected malignant pleural effusion.

CONTEXT: A good proportion of patients with undiagnosed pleural effusion (PE) turn into malignancy over a period of time. Identification of positive biomarker may help in selecting the individuals who require close follow-up. AIMS: The aims of this study were to evaluate the role of DR-70 immunoassay in suspected malignant PE. SETTINGS AND DESIGN: We conducted a cross-sectional study among 89 patients of suspected malignant PE and 50 normal subjects (NS) were taken as control. MATERIALS AND METHODS: Patients with exudative PE; who had pleural fluid lymphocyte count greater than 50% and adenosine deaminase less than 30 U/L were taken as cases. We had selected NSs among relatives of patients having normal blood chemistry and radiological investigations. Sensitivity and specificity of the test to differentiate malignant and non-malignant PE and also to identify PE with underlying malignancy was analyzed. RESULTS: Mean value of DR-70 in NS was found to be 0.83 ± 0.273 mg/L without any significant difference between males (0.82 mg/L) and females (0.85 mg/L). Mean value of DR-70 in PE with underlying cancer was 5.03 ± 3.79 mg/L. Sensitivity (80%) and specificity (77.78%) of the test was maximum in PE with underlying cancer using cut-off value of 2 mg/L. Mean value DR-70 in malignant PE was 5.18 ± 3.75 mg/L and in non-malignant PE was 3.73 ± 3.74 mg/L without any statistically significant difference (P = 0.08). CONCLUSIONS: DR-70 assay has high sensitivity in detecting underlying lung cancer, but has no role in differentiating malignant PE from non-malignant PE.

Habitual physical activity score as a predictor of the 6-min walk test distance in healthy adults.

BACKGROUND: The 6-min walk test (6MWT) is a simple, inexpensive test of functional exercise capacity. The 6MWT distance (6MWD) in healthy adults varies geographically, emphasizing the need for population-specific reference equations. The purpose of the present study was to investigate the influences of the habitual physical activity (HPA) score and other anthropometric and demographic parameters on the variability of the 6MWD among healthy adults and to propose a reference equation. METHODS: This was a prospective, cross-sectional, observational study. The 6MWT was conducted in a 30-m hospital corridor on 201 healthy volunteers, 125 men and 76 women, aged 20-60 years. The HPA in the previous 6 months was assessed using Baecke's questionnaire. Univariate analysis followed by multiple regression analysis was performed to analyze the significance levels of different probable predictors. RESULTS: The 6MWD was significantly greater in more active than in less active subjects (663.8±55.4m vs. 599.9±67.8m, p<0.001). The regression analysis showed that the subject's age in years (p=0.017), gender (p=0.006), height in cm (p=0.004), weight in kg (p<0.001), total activity score (TS) (p<0.001), and absolute difference in heart rate before and after exercise (p<0.001) could explain 48.9% of the variability in the 6MWD in healthy adults. CONCLUSIONS: The HPA score is probably the most appropriate variable to include in the reference equation predicting the 6MWD in healthy adults from the Indian subcontinent.

Role of sputum examination for acid fast bacilli in tuberculous pleural effusion.

BACKGROUND: Sputum for acid fast bacilli (AFB) is seldom looked for in the etiological diagnosis of tuberculous pleural effusion usually due to the absence of any parenchymal lesion radiologically, but presence of tubercle bacilli in sputum may have important epidemiological and therapeutic implication. AIMS: This study aims to evaluate the role of sputum examination for AFB in the patients of tuberculous pleural effusion with no apparent lung parenchymal lesion radiologically. SETTINGS AND DESIGN: Forty-five consecutive indoor patients of suspected tuberculous pleural effusion having no apparent lung parenchymal lesion on chest radiography were selected for our study. It was a prospective and observational study conducted over a period of 1 year. MATERIALS AND METHODS: After confirming the etiology of pleural effusion as tuberculous by biochemical, cytological, histopahtological, and microbiological tests, emphasis was given on sputum examination for AFB by smear examination and culture for Mycobacterium tuberculosis. RESULTS: Sputum was bacteriologically (smear and /or culture) positive for tuberculosis in 10 out of 30 cases (33.33%) in which tuberculous etiology was confirmed by histology and /or bacteriology (definite tuberculosis). No sputum AFB (smear and culture) was found in 15 cases of probable tuberculosis where tuberculous etiology was established by indirect methods like Adenosine de aminase level more than 40 unit/l and other relevant investigations. Over all, sputum was bacteriologically smear and/or culture positive in 10 out of 45 cases (22.22%). CONCLUSION: Careful and thorough sputum examination in cases of tuberculous pleural effusion may help as a diagnostic tool and it has therapeutic and epidemiological implications.

Role of pleural biopsy in etiological diagnosis of pleural effusion.

BACKGROUND: Pleural effusion remains the most common manifestation of pleural pathology. Sometimes it is difficult to differentiate between tubercular and malignant pleural effusion in spite of routine biochemical and cytological examination of pleural fluid. AIMS: This study aims to evaluate the role of pleural biopsy to determine the etiology of pleural effusion and to correlate it with the biochemical and cytological parameters of pleural fluid. SETTINGS AND DESIGN: Seventy two consecutive patients of pleural effusion were selected from the out patient and indoor department of a tertiary hospital of Kolkata. It was a prospective and observational study conducted over a period of one year. MATERIALS AND METHODS: Biochemical, cytological and microbiological evaluation of pleural fluid was done in all cases. Those with exudative pleural effusions underwent pleural biopsy by Abram's needle. Subsequently, the etiology of effusion was determined. RESULTS: Malignancy was the most common etiology, followed by tuberculosis. Pleural biopsy was done in 72 patients. Pleural tissue was obtained in 62 cases. Malignancy was diagnosed in 24, tuberculosis in 20 and non-specific inflammation in 18, on histopathological examination. Out of 20 histological proven tuberculosis cases adenosine de-aminase (ADA) was more than 70 u/l in 11 cases. CONCLUSIONS: In our study, malignancy is more common than tuberculosis, particularly in elderly. When thoracoscope is not available, pleural fluid cytology and pleural biopsy can give definite diagnosis. Pleural fluid ADA ≥ 70 u/l is almost diagnostic of tuberculosis, where pleural biopsy is not recommended.

Pulmonary arteriovenous malformation: An uncommon disease with common presentation.

A 45-year-old male presented with massive hemoptysis, clubbing in all limbs, disproportionate hypoxia and persistent ill-defined shadow in left lower zone in chest radiograph since his childhood. The patient received empirical anti-tuberculosis treatment and the chest X-ray finding was misinterpreted as tuberculoma. Subsequently, CT pulmonary angiography proved it to be a case of a simple type solitary pulmonary arteriovenous malformation with a saccular aneurysm in left lower lobe.

It's easy to miss complicated hydatid cyst of lung.

A 60-year-old female presented with pneumonitis of right lower zone. CT scan revealed mass like lesion with multiple air pockets. FNAC and ultrasound confirmed the diagnosis as isolated active pulmonary hydatid cyst, which is not common finding in adult population.

Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis among asthma patients in eastern India.

To find out the clinicoradiomycopathological profile of allergic bronchopulmonary Aspergillosis (ABPA) and incidences of aspergillus hypersensitivity (AH) among asthma patients, 215 consecutive extrinsic asthma patients were screened with aspergillus intradermal test and those found positive for AH were investigated further for ABPA. Out of 215 asthma patients (124 males and 91 females), 54 were hypersensitive to AH and 15 of them fulfilled criteria for ABPA. On repeated culture of sputum and/or broncho-alveolar lavage fluid, A flavuswas the most common isolate (40%), followed by A fumigatus (26.67%). No species was isolated in 4 cases (26.6%). AH/ABPA is not very uncommon in this part of the country. Diseases similar to ABPA caused by other fungus might be diagnosed if allergen tests for other fungal antigens are made widely available. A strong clinical suspicion and proper laboratory backup is essential for diagnosing ABPA and related diseases.

Spindle cell sarcoma of foot with metastasis--a case report.

A 34-year-old male presented with right sided chest pain, shortness of breath and a swelling over his left foot. Chest radiology revealed a mass lesion in the right middle lobe which on CT guided biopsy showed features of spindle cell sarcoma. Surgical excision of both the lung and foot masses were done, both of which on histopathological examination proved to be spindle cell sarcoma.

Five-years experiences of the Revised National Tuberculosis Control Programme in northern part of Kolkata, India.

BACKGROUND: The Revised National Tuberculosis Control programme (RNTCP), India. AIM: To assess the impact of the expansion of the RNTCP in the case detection and treatment outcome. MATERIALS AND METHODS: Reports of patients with tuberculosis (TB) diagnosed and treated under RNTCP from 2001 to 2005 under Bagbazar TB unit (TU), Kolkata, reviewed retrospectively. RESULTS: Of 2814 cases registered between 2001 and 2005, 1268 were new smear-positive pulmonary TB (PTB), 308 were new smear-negative PTB and 536 were new extrapulmonary TB (EPTB). During that period, the new smear-positive case detection rate increased from 41 to 61 per lakh population, the annual total case detection rate increased from 87 to 142 per lakh and the treatment success rate reduced from 90% to 76%. The default and failure rates increased from 7% to 10% and from 3% to 10%, respectively. CONCLUSION: A steady increase was observed in the annual total case detection rate and annual new smear-positive case detection rate from 2001 to 2005, but the 3-month conversion rate and cure rate of new smear-positive patients were progressively decreased. Default rate and treatment failure rate of new smear-positive patients were also increased. So it needs extra attention and evaluation of this disappointing treatment outcome.

A young lady presented with limited pulmonary Wegener's granulomatosis.

A 19 year old female college student presented with fever, dry cough, chest pain, blood tinged sputum with subsequent development of polyarthralgia with radiological evidence of bilateral multiple unevenly distributed pulmonary nodular opacities with cavitation. There was no other systemic involvement and the patient was cytoplasmic antineutrophil antibody (c-ANCA) positive with more than four times the normal upper limit of anti PR3 antibody. Excellent response to oral steroid with antimicrobial agent "trimethoprim - sulphamethoxazole" was noted.

Testicular tuberculosis mimicking testicular malignancy.

A 22 years old male presented with right sided scrotal swelling of 5 months duration. On examination it was found to be of orange-sized, firm to hard in consistency with mild tenderness. Ultrasonography of testes failed to arrive at a diagnosis. However, fine needle aspiration cytology of the testicular swelling confirmed the diagnosis of testicular tuberculosis. Even conservative approach in the management gave satisfactory result.

Hyperviscosity syndrome with pulmonary involvement.

A 44-year-old male presented with dizziness, blurring of vision, unproductive cough, dyspnoea, heaviness of head, fever and hepatosplenomegaly along with reticulonodular infiltration in chest x-ray. His serum showed monoclonal IgM gammopathy. Peripheral blood smear, bone marrow examination and serum protein electrophoresis suggested it was a case of Waldenstrom's macroglobulinaemia. Chest x-ray and CT scan of thorax were suggestive of pulmonary involvement in the form of interstitial lung disease.