Spectrum of endoscopic gastric subepithelial lesions encountered on EUS-FNA: A single center experience.

BACKGROUND AND OBJECTIVES: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is a minimally invasive and reliable non-surgical technique for the diagnosis of gastrointestinal lesions. The present study aimed to evaluate the spectrum of lesions encountered in the gastric subepithelium on EUS-FNA at a tertiary care center. MATERIALS AND METHODS: Archival data of all patients undergoing EUS-FNA for gastric submucosal lesions over a period of 5 years was retrieved. Patient demographics, clinical presentation, and EUS findings were recorded along with the FNA results. RESULTS: A total of 78 EUS-FNA samples were analyzed. Material was adequate in 62 cases (79.48%) and inadequate in 16 cases (12.82%) patients due to scant cellularity. Of the adequate samples, 34 (43.5%) were reported as neoplastic while 20 (25.64%) were non-neoplastic, and 8 (10.25%) were reported as suspicious of a neoplasm. In the neoplastic category, the predominant diagnosis was of spindle cell neoplasm comprising gastrointestinal stromal tumor (13), benign neural tumor (03), leiomyoma (02), and spindle cell tumors (03). The latter could not be categorized further due to a lack of IHC material. The next common diagnosis was adenocarcinoma (06) followed by neuroendocrine tumor (02) and poorly differentiated carcinoma (01). The non-neoplastic lesions included non-specific pathology (15), inflammatory lesions (08), and one case each of tuberculosis, pancreatic rest, and Brunner gland hamartoma. Cell blocks for ancillary testing were available in 54 cases (65.23%) and follow-up was available in 42 cases (53.84%). CONCLUSION: EUS-FNA is a good modality for the diagnosis of gastric submucosal lesions with a high diagnostic yield.

Anaplastic (undifferentiated) carcinoma of pancreas, an uncommon variant: Diagnosed on endoscopic-guided fine needle aspiration.

Anaplastic carcinoma of pancreas (ACP) are rare pancreatic neoplasms. They are well known to be associated with more aggressive tumor behavior and less favorable prognosis than usual pancreatic ductal adenocarcinoma. Endoscopic-guided fine needle aspiration (EUS-FNA) is now a widely accepted modality in diagnosis of pancreatic lesions. However, only a few reports are available describing cytological features of anaplastic carcinoma. Here, we report two cases of ACP diagnosed on EUS-FNA.

Diagnostic Utility of Claudin4 and Comparison with BerEp4 as a Marker for Metastatic Adenocarcinoma in Serous Effusions.

INTRODUCTION: Fluid cytology for malignant cells is important for diagnosis and staging of malignancies. Morphological overlap between reactive mesothelial cells and adenocarcinoma poses challenges, for which many immunohistochemical markers like BerEp4 and MOC-31 have been used extensively. Claudin4 is a new marker with promising results; however, further studies are required to establish its role as a pan-carcinoma marker in serous effusions. This study aimed to determine the utility of Claudin4 in diagnosing metastatic adenocarcinoma in effusions and comparing its performance with BerEp4. METHODS: Claudin4 immunohistochemistry (IHC) was performed on effusion cell blocks (n = 60) reported as positive or suspicious for metastatic adenocarcinoma on cytology over a 1-year period and was scored for intensity (0-3) and percentage of positive cells (0-4). The results were compared with BerEp4 IHC and correlated with follow-up. Ten benign effusions were included as negative controls. RESULTS: Claudin4 IHC was positive in all 60 (100%) cases, irrespective of the primary site. BerEp4 IHC was positive in 58 (96.7%) fluids and negative in 2 (3.3%) cases. All 10 benign effusions were negative for Claudin4 and BerEp4. Claudin4 showed higher intensity and proportion scores as compared to BerEp4 in cases where tumor cells were predominantly singly scattered and was comparable to BerEp4 where tumor cells were arranged in groups. Sensitivity, specificity, PPV, and NPV of Claudin4 in our study was 100%. Sensitivity, specificity, PPV, and NPV of BerEP4 was 96.7%, 100%, 100%, and 83.3%, respectively. CONCLUSION: Claudin4 IHC staining results were comparable to BerEp4, irrespective of the primary site, and it performed better in cases where tumor cells were predominantly scattered singly.

Grading of pancreatic neuroendocrine tumors on endoscopic ultrasound-guided fine-needle aspiration using Ki-67 index and 2017 World Health Organization criteria: An analysis of 32 cases.

OBJECTIVES: Biological behavior of pancreatic neuroendocrine tumors (Pan NETs) is difficult to predict on morphology alone. The assessment of proliferation by the Ki-67 proliferation index (PI) is considered to be an important prognostic parameter in these tumors and has been endorsed by the 2017 World Health Organization (WHO) grading system for Pan NETs. Although widely accepted on surgical specimens, there is varied opinion on grading of these tumors on cytology samples. This study aimed at classification and grading of Pan NETs on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using the recent 2017 WHO criteria and assess the reliability of Ki-67 grading by comparing it with histology samples wherever available. MATERIAL AND METHODS: Search of cytopathology lab records over a 3-year period (June 2015-May 2018) revealed 33 cases of pancreatic NETs diagnosed on EUS-FNA specimens. Using the guidelines of 2017 WHO classification and grading of Pan NETs, retrospective grading of these Pan NETs was done. They were graded as Grades 1, 2, and 3 well differentiated Pan NETs and poorly differentiated Grade 3 neoplasms based on Ki-67 PI and cytomorphology. Cytomorphological features were compared across the three grades. The cytological grading was then compared with the histological grading where available. RESULTS: Ki-67 grading on cytology was done in 32 cases (22 on cell block and 10 on smears), of which 19 (59.4%) were Grade 1, 8 (25%) were Grade 2, and 5 (15.6%) were Grade 3 tumors. The most common cytomorphological features observed in Grade 1 tumors were small round uniform cells with granular chromatin and prominent plasmacytoid morphology. As the grade increased, tumor cells showed increased pleomorphism, angulated nuclei, and less frequent plasmacytoid cells. Histopathology (biopsy/resected specimens) was available in 11 of the 32 cases. Comparison of grading on cytology and histology showed concordance in ten of the 11 cases (k value = 0.862). CONCLUSION: Our data suggest that grading of Pan NETs by assessing Ki-67 PI on cytology samples collected by EUS-FNA shows good agreement with that measured on histology samples.

Role of EUS-FNA for gallbladder mass lesions with biliary obstruction: a large single-center experience.

Background and study aims Although endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) is an established modality for pathological sampling of pancreatic and biliary lesions, limited data are available on the diagnostic value of EUS-FNA for evaluation of gallbladder mass lesions, a common cause of obstructive jaundice. We aimed to evaluate the usefulness of EUS-FNA for diagnosis of gallbladder mass lesions presenting with biliary obstruction. Patients and methods This study was a retrospective analysis of data from patients who had undergone EUS-FNA for gallbladder mass lesions. FNA was performed on either a gallbladder mass, metastatic node or liver lesions. Outcome measures were diagnostic yield of EUS FNA and adverse events. Results From April 2011 to August 2018, 101 patients with gallbladder mass lesions with biliary obstruction underwent EUS-FNA. The final diagnosis was malignancy in 98, benign disease in one, and two patients were lost to follow-up. EUS-FNA confirmed the diagnosis in 89 of 98 patients with malignancy (sensitivity 90.81 %); was false negative in nine of 98 cases with malignancy; and was truly negative in the solitary patient with benign disease (specificity 100 %). Positive predictive value, negative predictive value (NPV), and accuracy were 100 %, 10 %, and 90.90 %, respectively. Two patients had self-limiting pain. Conclusion EUS-FNA is a sensitive tool for evaluation of gallbladder mass lesions presenting with obstructive jaundice. However, because of low NPV, lesions in which FNA is negative should be further evaluated.

Liquid-based and conventional cytology for bronchial washings/bronchoalveolar lavages in the diagnosis of malignancy - An institutional experience.

BACKGROUND: Liquid-based cytology (LBC) has been developed as an alternative for conventional cytology (CC) in cervical smears. It is now increasingly being used all over the world for cervical cancer screening. However, its role and diagnostic accuracy in bronchial wash (BW)/bronchoalveolar lavage (BAL) specimens remains undetermined. AIMS: To assess and compare the diagnostic performance and accuracy of LBC with CC for detecting malignancy in bronchial specimens. SETTINGS AND DESIGN: This was a retrospective analytical hospital-based study. MATERIALS AND METHODS: Bronchial specimens (BW/BAL) received over a period of 4.5 years were reviewed. The samples were processed by CC from June 2010 to September 2012 (2.25 years) and by LBC from October 2012 to December 2014 (2.25 years). Data were retrieved from the records of cytology laboratory and compared among both the groups. Detection rate for histologically or cytologically verified samples was calculated. RESULTS: A total of 559 cases verified by histological and cytological follow-up were evaluated. These included 247 CC cases and 312 LBC cases. The positive diagnostic rate for malignancy in CC was 28.6% whereas that for LBC was 32.9%. The negative diagnostic rates were 66.5% and 66.3% for CC and LBC, respectively. However, unsatisfactory rates had shown a good reduction from 4.4% in CC to 0.6% after LBC introduction. The smears showed more homogeneous distribution of cells with elimination of obscuring factors such as blood, inflammation, and mucus. CONCLUSIONS: The diagnostic accuracy of LBC was slightly better than CC. The unsatisfactory rates showed reduction in LBC preparation. Thus, LBC is a viable alternative to CC and has the advantages of standardization of preparation with decrease in unsatisfactory rates.

Endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing mediastinal lymphadenopathy.

CONTEXT: The diagnosis of mediastinal lymphadenopathy is always a challenge. There always a need of a technique that is highly accurate as well as safe for diagnosis the same. AIMS: The aim of the study is to assess the clinical usefulness and safety profile of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing the patients with mediastinal lymphadenopathy. SETTINGS AND DESIGN: This was an observational prospective study. SUBJECTS AND METHODS: One hundred adult patients with mediastinal lymphadenopathy who underwent EBUS-TBNA with aspirate obtained from the most hypoechoic lymph node (with a 22 gauge needle) and its cytopathological analysis were included in the study. Patients were observed for postprocedure complications. RESULTS: Out of 100, 92 cases were reported as adequate (diagnostic yield = 92%). Among these 92, there were 71 granulomatous lymphadenitis (tuberculosis [TB] = 41 [44.5%], sarcoid-like granuloma = 30 [32.2%]). Malignancy was reported in 16 (17.3%) patients, and 5 (5.43%) were reported to have reactive lymphadenopathy. There was one case each of Mycobacterium avium complex and Mycobacterium abscessus. Out of 16 cases of malignancy, six cases were adenocarcinoma, four cases of squamous cell carcinoma, and two cases of small cell carcinoma. There were three cases of Hodgkin's lymphoma and one case of non-Hodgkin's lymphoma. No major complications were noted, except fever (26), nausea (20), mild bleeding (4), bronchospasm (3), and transient intraprocedural hypoxia (2). CONCLUSIONS: EBUS-TBNA is highly accurate (diagnostic yield 92%) and safe procedure for diagnosing mediastinal lymphadenopathy. In our experience, granulomatous lymphadenitis was most common with TB as the main etiology.

Report: Stem cell applications in neurological practice, an expert group consensus appraisal.

INTRODUCTION: Neurologists in their clinical practice are faced with inquiries about the suitability of stem cell approaches by patients with a variety of acute and chronic (namely neurodegenerative) disorders. The challenge is to provide these patients with accurate information about the scope of stem cell use as well as at the same time, empowering patients with the capacity to make an autonomous decision regarding the use of stem cells. METHODS: The Indian Academy of Neurology commissioned an Expert Group Meeting to formulate an advisory to practicing neurologists to counsel patients seeking information and advice about stem cell approaches. RESULTS AND CONCLUSIONS: In the course of such counselling, it should be emphasized that the information provided by many lay websites might be unsubstantiated. Besides, standard recommendations for the stem cell research, in particular, the application of several layers of oversight should be strictly adhered in order to ensure safety and ethical use of stem cells in neurological disorders.

Clear cell neuroendocrine tumor of pancreas: Endoscopic Ultrasound-guided fine needle aspiration diagnosis of an uncommon variant.

The cytomorphologic features of clear cell neuroendocrine tumor of pancreas have been rarely reported in cytology literature. The cytomorphology of this rare variant mimics many primary and metastatic clear cell tumors of the pancreas. However, a precise cytological diagnosis can be rendered by awareness of this entity and judicious use of immunohistochemistry. We report one such case in a young woman diagnosed on endoscopic ultrasound fine needle aspiration. The tumor cells showed positive staining with synaptophysin, chromogranin, and also with inhibin.

Mediastinal Adenopathy in India: Through the Eyes of Endobranchial Ultrasound.

OBJECTIVE: Aetiology of mediastinal adenopathy is likely to vary with geographic location and socioeconomic status of a population. Whilst most of adenopathy in the West could be attributed to malignant disorders, causes of the same in a developing country like India has not been extensively studied earlier due to lack of less invasive tools to sample these nodes for cytological and microbiological analysis. Endobronchial ultrasound (EBUS) helps us reach these nodes as a minimally invasive procedure to take aspirations under real-time ultrasound guidance. The aim of the present study is to study the aetiology of mediastinal adenopathy in our population with the help of EBUS. METHODS: This was a retrospective analysis of all EBUS procedures done by the authors and the diagnosis thus obtained at Sir Ganga Ram Hospital, New Delhi, India between April 2010 and December 2011. RESULTS: A total of 300 patients underwent EBUS in the above period. Most common aetiology encountered in our population was a granulomatous disorder (53% cases) like tuberculosis and sarcoidosis whilst malignancy was third in order of diagnosis (17% cases). Lymph node enlargement due to anthracosis was another uncommon aetiology encountered in the study (5% cases). CONCLUSIONS: Benign granulomatous disorders like tuberculosis and sarcoidosis are the most common causes of mediastinal adenopathy in our population. EBUS is proving its worth for diagnosing mediastinal adenopathy.

Can cytomorphology of granulomas distinguish sarcoidosis from tuberculosis? Retrospective study of endobronchial ultrasound guided transbronchial needle aspirate of 49 granulomatous lymph nodes.

BACKGROUND: The differential diagnosis of tuberculosis (TB) and sarcoidosis on fine needle aspiration material is very challenging in tubercular endemic regions. We carried out a pilot study to explore cytomorphologic features of granulomas which could help in differentiation between sarcoidosis and TB. Final diagnoses in these patients were based on clinical, microbiologic and follow-up studies. MATERIALS AND METHODS: Endobronchial ultrasound guided transbronchial needle aspiration smears of 49 consecutive patients with a final cytologic diagnosis of granulomatous lymphadenitis were reviewed. Based on cytologic features two cytologic categories were enunciated and the results were correlated with microbiologic studies and/follow-up of minimum of 6 months. RESULTS: The cytologic categories did not correlate with the final clinical outcome of patients. CONCLUSIONS: Different patterns of granulomas observed in cytology smears do not help distinguish TB from sarcoidosis. The novel non-invasive techniques of mediastinal sampling though help in confirming granulomatous pathology, distinction between these entities and treatment decisions still depend upon correlating cytologic, microbiologic, clinical and radiological data in a large number of cases in tubercular endemic regions.

Nitric oxide (NO) counteracts cadmium induced cytotoxic processes mediated by reactive oxygen species (ROS) in Brassica juncea: cross-talk between ROS, NO and antioxidant responses.

Research on NO in plants has achieved huge attention in recent years mainly due to its function in plant growth and development under biotic and abiotic stresses. In the present study, we investigated Cd induced NO generation and its relationship to ROS and antioxidant regulation in Brassica juncea. Cd accumulated rapidly in roots and caused oxidative stress as indicated by increased level of lipid peroxidation and H2O2 thus, inhibiting the overall plant growth. It significantly decreased the root length, leaf water content and photosynthetic pigments. A rapid induction in intracellular NO was observed at initial exposures and low concentrations of Cd. A 2.74-fold increase in intracellular NO was recorded in roots treated with 25 µM Cd than control. NO effects on Malondialdehyde (MDA) content and on antioxidant system was investigated by using sodium nitroprusside (SNP), a NO donor and a scavenger, [2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide] (cPTIO). Roots pretreated with 5 mM SNP for 6 h when exposed to 25 µM Cd for 24 h reduced the level of proline, non-protein thiols, SOD, APX and CAT in comparison to only Cd treatments. However, this effect was almost blocked by 100 µM cPTIO pretreatment to roots for 1 h. This ameliorating effect of NO was specific because cPTIO completely reversed the effect in the presence of Cd. Thus, the present study report that NO strongly counteracts Cd induced ROS mediated cytotoxicity in B. juncea by controlling antioxidant metabolism as the related studies are not well reported in this species.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of mediastinal lymph nodes: experience from region with high prevalence of tuberculosis.

Utility of EUS-FNA in diagnosing granulomatous lesions of mediastinum in regions with high prevalence of tuberculosis has not yet been evaluated. In the present study, utility and limitations of EUS-FNA of mediastinal lesions from a tertiary care center with high prevalence of tuberculosis were studied. All cases where EUS-FNA had been performed to diagnose mediastinal lymphadenopathy from January 2006 to December 2008 were retrieved from the files of cytopathology laboratory. These were reviewed by the cytopathologist. Two hundred and eighty one EUS-FNA aspirates from 269 patients were evaluated. Satisfactory aspirates were available in 259 cases. A cytological diagnosis of granulomatous lymphadenitis was rendered in 206 cases. Of these, tuberculosis could be established as an etiology in 76 cases and sarcoidosis in 7 cases only. In remaining 123 cases the etiology of granulomatous lymphadenitis could not be established and clinical correlation was suggested. Malignancies were diagnosed or suspected in 24 and 5 cases, respectively. The study highlights that the dilemma of tuberculosis versus sarcoidosis persists in regions with high prevalence of tuberculosis. However, EUS-FNA is useful in diagnosing unsuspected malignancies and confirming the presence of granulomatous lymphadenitis.

Fine needle aspiration cytology of metastatic urothelial carcinoma: Study of seven cases with review of literature.

BACKGROUND: Metastatic urothelial carcinoma (UC) is rarely described in cytology literature. Appropriate cytological diagnosis is important in certain clinical scenarios to exclude a second primary. AIMS: To delineate cytological features that are helpful in diagnosing metastatic UC. MATERIALS AND METHODS: The study included seven male patients with age range of 48 - 72 years. These patients were diagnosed cases of UC and had now presented with lesions in liver, lungs, bones or lymph nodes. Computed tomographic (CT)/ultrasonographic (USG) guided fine needle aspiration cytology (FNAC) was available from one of these sites. RESULTS: Cercariform cells (CCs) could be identified in five out of seven cases. In four cases, multilayered papillary fragments (MPFs) were identified which were reminiscent of histopathologic appearance of UC. One of these two morphologic features was present in all the cases. However, both CC cells and MPFs were present only in two cases. CONCLUSION: Previous clinical history is indispensible while diagnosing metastatic UC. MPFs and CC cells are strong morphologic clues to urothelial origin. In poorly differentiated tumors, differentiation from other epithelial tumors may not be possible on the basis of morphology alone.

FNA diagnosis of CD99 positive neuroblastoma: A diagnostic dilemma.

Tissue diagnosis of small round cell tumors relies heavily on immunohistochemical staining. Two of the small round cell tumors, namely neuroblastoma and primitive neuroectodermal tumor, have considerable morphologic overlap. Many studies suggest that CD99 positivity virtually excludes the diagnosis of neuroblastoma. We report a case of poorly differentiated neuroblastoma in which aberrant CD99 positivity led to diagnostic dilemma.

Spontaneous ovarian hyperstimulation syndrome in a triplet pregnancy.

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication, usually iatrogenic after ovulation induction. OHSS is a very rare event in spontaneously conceived pregnancies. Only few cases have been reported in literature to the best of our knowledge. We report a very rare case of spontaneous critical OHSS (according to classification of severity of OHSS as mentioned in Greentop guidelines no. 5, 2006) associated with triplet pregnancy in a 26-year-old woman suffering from severe abdominal pain, distension, and dyspnea. Our case highlights the importance of a strong suspicion for OHSS when a clinical presentation could not be explained by common medical conditions.