Clinical and pathological profile of gastric neuroendocrine tumors

Background: Gastric neuroendocrine tumors (G-NETs) are classified into well-differentiated NETs with three grades and poorly differentiated neuroendocrine carcinomas based on morphology and the Ki-67 index. Besides, G-NETs are broadly classified into four types based on clinical and pathophysiological features. Aim: To study clinical and pathological features of different types and grades of G-NET. Materials and Method: All G-NETs, diagnosed from January 2011 to December 2020, were included. Clinical presentation, peritumoral findings, lymph node status, and liver involvement were obtained and correlated with different grades and types of G-NETs. Results: NET was diagnosed in 88 cases. Tumors were graded as I, II, III, and carcinoma in 58, 14, 12, and 4 cases, respectively. Type I NET (49.2%) in the background of chronic atrophic gastritis was the most common type followed by type III (33.3%). Type I tumors were predominantly graded I (91.1%) and limited to the mucosa and submucosa. MEN-1-associated G-NET (type II) was seen in eight cases. All except one type II tumor was associated with ZES syndrome. Remarkably, peritumoral mucosa showed atrophy and intestinal metaplasia in 52.1% and 24.6% cases, respectively. Two cases were associated with adenocarcinoma. Lymph node metastasis was seen in all carcinoma and grade III cases. All carcinoma cases and 58.3% of grade III tumors showed liver metastasis. Conclusion: Biological behavior of G-NET varies with different types and grades of tumor. Typing and grading of G-NET should be done whenever possible to predict the aggressiveness of the tumor.

A clinicopathological study of persistent fetal vasculature

Purpose: To study the clinicopathological findings of Persistent Fetal Vasculature (PFV) in patients with congenital cataract and PFV. Methods: Six eyes with anterior or combined PFV with cataract underwent phacoaspiration with primary posterior capsulotomy with anterior vitrectomy with intraocular lens implantation followed by histopathological evaluation of the PFV stalk and membrane. Results: Four and two patients had combined and anterior PFV respectively. There was no postoperative hyphema, vitreous haemorrhage, glaucoma or retinal detachment in six months. Haematoxylin and eosin staining showed inflammatory cells predominantly with extramedullary hematopoeisis and vascularisation. Conclusion: We recommend IOL implantation in PFV, with early and aggressive amblyopia therapy.

Role of anti-tissue transglutaminase IgA+IgG antibodies in detection of potential celiac disease in patients with type 1 diabetes

Background & objectives: Celiac disease (CD) can exist in various forms in type 1 diabetes (T1D) patients and can remain undetected, leading to severe complications. This study was aimed to evaluate five commercially available anti-tissue transglutaminase (tTG) ELISA kits with distinct formats for the detection of CD and potential CD in T1D patients. Clinical and demographic profiles of the patients with different disease subsets were also studied. Methods: Fifty T1D patients with classical and non-classical symptoms of CD and 100 T1D patients without any symptoms of CD were included in this study. Anti-tTG autoantibody levels were estimated by five ELISA kits followed by histological examination of duodenal biopsy. HLA DQ2-DQ8 and DRB1-DQB1 typing was done, and serum levels for transforming growth factor (TGF)-?1 were also estimated. Results: Assay format detecting anti-tTG IgA antibodies against recombinant antigens along with neopeptides of gliadin was most efficient in the detection of CD in symptomatic patients, and assay format detecting IgA+IgG helped in the detection of potential CD in asymptomatic T1D patients. These findings were supported by histological examination and human leucocyte antigen analysis. Patients with potential CD were found to have markedly deranged glycaemic control parameters and also had significantly raised serum levels of TGF-?1, (P <0.05) compared to T1D patients. Interpretation & conclusions: Potential CD can be frequently seen in T1D patients. This can be attributed to the dietary patterns prevalent in the subcontinent and the genetic basis of the disease. Anti-tTG IgA+IgG antibodies can be useful in the detection of these potential CD cases in T1D patients. Early intervention with gluten-free diet can be considered in these patients for better disease management.

Primary gastrointestinal lymphomas - A study of 81 Cases from a Tertiary Healthcare Centre.

Purpose: Retrospective analysis of 81 routinely diagnosed gastrointestinal (GI) lymphoma to illustrate clinicopathological and immunohistochemical characteristics with predisposing condition. Materials and Methods: Age, sex, site, tumour stage, associated pathological features like lympho-epithelial lesion (LEL), atrophic gastritis (AG), intestinal metaplasia (IM) and enteropathy changes were analysed. Requisite immunohistochemical panel was applied wherever needed. Results: There were 55 male and 26 female patients with median age of 54.5 years. Site wise distributions were stomach 40, small intestine 22, colon 4, cecum 2, ileocecum 3, esophagus 1 and multiple sites 9. Histological subtypes were mucosa associated lymphoid tissue lymphoma (MALTOMA) 48, diffuse large B cell lymphoma (DLBL) 21, T cell lymphoma 9 [5 anaplastic large cell lymphoma (ALCL) and 4 enteropathy associated T cell lymphoma (EATL)], immunoproliferative small intestinal disease (IPSID) 2 and follicular lymphoma 1. LEL was present in 31 cases. Of the 19 AG, 8 had associated IM, and 1 case each had associated H Pylori infection and neuroendocrine tumor. Enteropathy was observed in 4 EATL, and one case each of DLBL and high grade MALTOMA. Giardia infection was present in 1 low grade duodenal MALTOMA. Of the 24 resected specimens, 16 were stage IE, 7 stage IIE and 1 stage IV (Mushoff's staging). Conclusion: Primary GI lymphoma was frequently observed in 6 th decade of life with male preponderance. Stomach was the commonest site and high grade MALTOMA being the commonest histological variant. Isolated colonic involvement and intestinal perforations were not infrequent. Rare variants like ALCL and follicular lymphomas were also observed.

Coexistent hepatic and pulmonary epitheloid hemangioendothelioma.

Epitheloid hemangioendothelioma (EHE) is a rare neoplasm of vascular origin known to arise in soft tissue, liver and lung. We describe a case of coexistent hepatic and pulmonary epitheloid hemangioendothelioma, proven on autopsy, and review the histological and radiological features of epitheloid hemangioendothelioma. The coexistence of hepatic with pulmonary EHE has been reported in only a few cases. Large confluent masses, peripheral location with capsular retraction, hypertrophy of uninvolved liver, invasion of portal and hepatic veins, enhancing margins and delayed enhancement and dense calcification are the typical features which provide a clue to diagnosis of hepatic EHE. In patients with both hepatic and pulmonary EHE it is difficult to say whether the tumor arose primarily in the lung or liver, or began simultaneously in both organs.

Utilization of antihepatocyte clone OCH1E5 (Hep Par 1) in histological evaluation of liver tumors.

Diagnosis of hepatocellular carcinoma (HCC) is not always easy on simple hematoxylin and eosin (H&E) stain. The diagnostic problems arise when tumor shows pseudoglandular, pleomorphic or clear cell differentiation. Various tumors markers have been described with varying sensitivity and specificity. Monoclonal antibody Hep Par 1 (OCH1E5) which is specific for hepatocytes offers great help in separation of these tumors. The aim of the present study was to determine utility of Hep Par 1 (OCH1E5) in differentiating HCC from metastatic tumors and cholangiocarcinoma. Total of 62 cases of liver tumors obtained from biopsies, resected or autopsy specimens were included in the study. Slides having representative sections were subjected to immunohistochemistry with monoclonal antibody Hep Par 1 (Dako Corp) using avidin biotin technique with primary antibody dilution of 1:40. Adjacent nontumorous hepatocytes were taken as positive control. Slides were examined by experienced pathologist without any information of clinical or H&E diagnosis. Cases were considered positive for Hep Par 1 if tumor cells showed cytoplasmic brown colored granules. The intensity and distribution (diffuse/ focal) of immunoreactivity was noted. Subsequently immunohistochemistry results were correlated with histology and clinical diagnosis. Hep Par 1 antibody was positive in 26 (42 %) and negative in 36 (58 %) liver tumors. On correlating with H&E sections, out of 26 positive cases, 25 (89.2%) were HCC and one was the case of metastasis of mucin secreting adenocarcinoma. From 36 tumors with negative staining 3 were cases of HCC, 27 metastatic adenocarcinomas and 6 cholangiocarcinomas. Only one case of liver metastasis of mucin secreting adenocarcinoma showed positivity. None of the cases of cholangiocarcinoma showed positivity for Hep Par 1. The three HCCs which did not take up staining for Hep Par 1 were 2 cases of moderately differentiated HCC having pseudoglandular pattern and a case of well differentiated HCC with trabecular arrangement. In 11(44%) cases staining was diffuse while in 14 (56%) it was focal but intense. Hep Par 1 is a useful marker in differentiating HCC from metastaic tumors and cholangiocarcinoma with sensitivity and specificity of 89 % and 97 % respectively and positive predictive value of 96 %. However one should be aware of limitations of immunohistochemistry.

Garlic hepatotoxicity: safe dose of garlic.

Information on the effect of garlic on the liver and optimal dose of garlic to avoid liver damage is not known. This study was planned to determine the safe dose of garlic. Male wistar rats (110-170g) were fed fresh garlic homogenate (FSH) orally in three different doses (1.0, 2.5 and 5.0 g/kg body weight/day) daily for 28 days. Liver histology, serum transaminases, bilirubin and alkaline phosphatase were estimated at 0, 14, 21 and 28 days in control and experimental animals. 1.0, 2.5 and 5.0 g/kg body weight/day of garlic showed significant (P<0.001) deterioration in liver function tests (LFT's) after 21, 14 and 7 days respectively. A 1.0 g/kg body weight/day dose of garlic was associated with marked histological damage in liver after 21 days. Therefore, three lower doses of garlic (0.1, 0.25 and 0.5 g/kg body weight/day) were given orally to another group of similar rats to determine the safe dose of garlic. LFT's were serially measured and animals were sacrificed on the 29th day of experiment. All three lower doses showed significant deterioration in the LFT's values of animals after 28 days of feeding the freshly prepared garlic homogenate. Both doses of garlic i.e. 0.1 and 0.25 g/kg body weight/day were associated with normal histology of liver, but 0.5 g/kg body weight/day dose of garlic showed morphological changes in the liver of one animal. Therefore, the present study suggests that garlic with high dose has the potential ability to induce liver damage and low doses (0.1 or 0.25 g / kg body weight/day) are safe doses of garlic.

Goblet cell status in idiopathic ulcerative colitis--implication in surveillance program.

Idiopathic ulcerative colitis (IUC) patients have higher incidence of dysplasia and malignancy. Close follow-up with biopsy at regular interval is mandatory. The study was done to correlate incidence of atypical epithelium, goblet cell hyperplasia (GCH) and disease duration (DD) with Ki67, AgNOR and p53 expression in IUC with disease for 5 or more years. Ki67 and AgNOR are good indicators of cellular proliferation and p53 tumour suppressor protein is a marker for neoplastic cell. Of 130 cases studied, 40 cases showed atypical epithelium and were selected for further study. DD in these 40 cases ranged from 60 to 228 months. All had GCH and showed histological features of chronicity. Low-grade dysplasia (LGD) was seen in 15 cases, indefinite for dysplasia (ID) in 8 and inflammatory atypia in 17 cases. Disease duration showed no influence in the type of atypical epithelium. A positive staining of lining epithelium by Ki67 and p53 was not restricted to dysplasia. LGD and ID showed stronger p53 nuclear staining. AgNOR appeared to be a more sensitive marker than Ki67. GCH showed a positive correlation with DD and AgNOR index. p53 expression correlated positively with goblet cell hyperplasia. Conclusion- goblet cell hyperplasia could indicate presence of epithelial cell dysplasia.

Association of ulcerative colitis with pulmonary sarcoidosis, subcutaneous lipomatosis and appendiceal adenocarcinoma.

We report a 52-year-old man with left-sided ulcerative colitis for 5 years and pulmonary sarcoidosis diagnosed 3 years back. He presented with subcutaneous lipomatosis and a right iliac fossa mass, which was diagnosed histologically as appendiceal adenocarcinoma. He was treated with right hemicolectomy, followed by chemotherapy.

Pneumobilia--clue to an unusual cause of diarrhea.

A 65-year lady presented with diarrhea and weight loss of six months duration. Initial evaluation suggested that malabsorption was the possible underlying mechanism for the diarrhea. Work up for the common etiologies of malabsorption was non-contributory. Presence of pneumobilia raised the suspicion of a bilio-enteric fistula, which was subsequently confirmed on barium enema and endoscopic cholangio-pancreaticography to be a cholecystocolic fistula. At surgery, a fistulous tract from the fundus of the gallbladder was found to be communicating with the hepatic flexure. Fistulectomy with cholecystectomy resulted in prompt relief of symptoms. Cholecystocolic fistula (CCF) is a rare biliary fistula with diverse presentation.

Exacerbation of ulcerative colitis by cytomegalovirus infection in an immunocompetent Indian patient.

A patient with typical features of idiopathic ulcerative colitis, in remission, developed an attack of severe colitis. Sigmoidoscopy showed submucosal black nodules in the sigmoid colon. Mucosal biopsies from the involved areas showed evidence of acute on chronic colitis with cytomegalic cells and intra-nuclear inclusions suggestive of cytomegalovirus (CMV) disease. The patient attained remission following subtotal colectomy and intravenous ganciclovir therapy for 3 weeks. The patient had another relapse five months later. The colonic biopsies during this relapse showed evidence only of idiopathic ulcerative colitis, with no CMV infection. The patient responded well to steroid therapy.

Soybean trypsin inhibitor confers protection against rotavirus infection in infant mice.

OBJECTIVE: To study the effects of soybean trypsin inhibitor (TI) on glycine uptake, glutathione (GSH) levels and morphological changes of intestine in rotavirus (RV) infected infant mice. METHODS: A total of 144 infant mice (7/8 days old) were divided in 3 groups (i.e. control, RV and RV + inhibitor). Infant mice were orally inoculated with the EB strain of RV and Trypsin protease inhibitor (TI) and 8 animals each were sacrificed on days 0,1,3,5,7 and 10 post infection (p.i). Glycine uptake (in vitro), GSH levels and histological changes were assessed in the jejunum, ileum and colon. RESULTS: Glycine uptake and GSH levels were significantly reduced on days 3 and 5 p.i in jejunum and ileum of RV inoculated animals, compared to the controls. Glycine uptake and GSH levels were maintained as in controls in the RV + TI inoculated animals on days 3 and 5 p.i in jejunum and colon but not in ileum where lesser values were recorded. Histology showed vacuolar degeneration in ileum towards the apical portion whereas normal morphology was observed in jejunum, similar to controls. No histological changes were observed in colon in any of the groups. Electron microscopic study confirmed the viral infection. CONCLUSION: Administration of Trypsin protease inhibitor along with RV reverted the effects of RV infection on amino acid uptake and GSH levels completely in the jejunum and partially in the ileum.

Gastrointestinal stromal tumors the assessment of malignant potential.

GISTS are the largest category of non-epithelial neoplasms of stomach and small bowel. Numerous immunohistochemical, ultrastructural and flow cytometry studies have been carried out for evaluation of prognostic factors which could predict malignant behaviour of these neoplasms. Tumor size of 5 cm and mitosis of 2/10 hpf were suggested as two important parameters which could predict the chances of recurrence and clinically aggressive course. The aim of this study is to examine predictive value of these two important parameters in assigning the tumors as high, intermediate and low risk groups. Using these two parameters we categorized 30 cases of GIST over a period of 6 years (1990-95) into low, intermediate and high risk groups and examined other features of these cases. Based on these two parameters alone we found that 4 cases each in low and intermediate group could be assigned to a higher risk group clinically as there were presence of adjacent organ infiltration, lymphatic emboli, serosal nodules, lymph node metastasis and transmural infiltration. Hence, other features like hemorrhage, necrosis and anaplasia should also be included in risk assessment. Metaplastic tissues like bone, cartilage and adipose tissues were seen only in high-risk categories.

Protection against rotavirus diarrhoea in mice by trypsin inhibitor.

To investigate the role of soyabean trypsin inhibitor (TI) during rotavirus (RV) diarrhoea, changes in enzyme activities of six relevant mucosal enzymes (lactase, sucrase, maltase, trehalase, glucoamylase and alkaline phosphatase) were assayed following inoculation of suckling mice with EB rotavirus (serotype 3) along with the TI and compared with the age-matched healthy control mice. The animals were divided into three groups i.e. group 1 (controls), group 2 (RV inoculated) and group 3 (RV + TI inoculated and sacrificed under light anaesthesia on 0, 1, 3, 5, 7 and 10 day post inoculation (dpi). Then intestines were excised and divided into two parts (jejunum and ileum). They were separately homogenized in 0.9% cold normal saline and activities of mucosal enzyme were measured. Alkaline phosphatase and disaccharidases were found to be decreased significantly in RV inoculated animals in both the anatomical portions of small intestine of mice. These enzyme levels were restored with the administration of TI i.e. in group 3 and became comparable to the controls in both intestinal portions. These studies suggest that activity of intestinal enzymes which are important in digestive absorptive functions of small intestine were restored with the addition of TI whengiven to infant mice showing its protective efficacy during rotavirus infection.

Alterations in duodenal disaccharidases in chronic smokers.

OBJECTIVE: To assess the effect of smoking on activity of intestinal disaccharidases. METHODS: The study was conducted on patients with non-ulcer dyspepsia who were smokers (n=20) or non-smokers (n=20). Smokers were classified according to smoking index into mild, moderate and heavy smokers. Biopsy specimens were taken from the second part of the duodenum at endoscopy and examined histologically, and for disaccharidase (lactase, sucrase, maltase and trehalase) activities. RESULTS: Mean duration of symptoms was more in smokers than in non-smokers. None of the smokers had endoscopic evidence of duodenal inflammation. Lactase and trehalase levels were significantly decreased in smokers. There was no difference in enzyme levels between mild smokers and non-smokers. Decreased lactase, maltase and trehalase activities were observed in moderate smokers compared to mild smokers. Duration of symptoms had no relation to enzyme activities. CONCLUSIONS: Intestinal disaccharidase levels are diminished by smoking.