Ranjana Gondal

High viral load and deregulation of the progesterone receptor signaling pathway: Association with Hepatitis E-related poor pregnancy outcome

BACKGROUND & AIMS Hepatitis E virus (HEV) infection is associated with high maternal and fetal mortalities. A prospective study was undertaken to evaluate the role of viral and host factors in HEV related pregnancy outcomes. METHODS The study included HEV infected pregnancy cases; acute viral hepatitis (AVH), n=100 and fulminant hepatic failure (FHF), n=43, and healthy pregnancy cases, n=50. HEV genotypes and viremia were studied by nucleotide sequencing and real time PCR, respectively. Progesterone receptor (PR) gene mutations (PROGINS) were studied by PCR, PR expression at the mRNA and protein levels in the placenta were studied by semi-quantitative RT-PCR and immunohistochemistry, respectively. Progesterone induced blocking factor (PIBF) expression was studied by RT-PCR in blood. Serum interleukin-10 (IL-10) and interleukin-12 (IL-12) levels were assayed by ELISA. RESULTS HEV viral load was significantly higher in FHF than AVH (p<0.001) and in cases with fetal mortality in AVH (p=0.001) and FHF (p=0.018). PROGINS were predominant in FHF compared to AVH (p=0.26) and showed reduced mRNA and protein expression. The risk of fetal mortality in AVH was two times higher (OR, 2.190; CI, 0.303-15.85) and maternal and fetal mortalities in FHF were 4-fold (OR, 4.0; CI, 0.363-44.113) increased in PROGINS carriers. PR and PIBF expression was lower in AVH and even lower in FHF compared to healthy controls. The higher IL-12/IL-10 ratio observed in FHF compared to other groups correlated with fetal mortality in AVH and FHF (p<0.001). CONCLUSIONS In conclusion, reduced expression of PR and PIBF, a higher IL-12/IL-10 ratio, and a high viral load results in poor pregnancy outcome in Hepatitis E.

Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters

BACKGROUND AND AIMS Hepatic steatosis (HS) is highly prevalent in chronic hepatitis C and is an important variable predicting progression of histological injury, insulin resistance, and reduced response to antiviral therapy. There are limited data on HS in patients with chronic hepatitis B (CHB). This is relevant since response to current antiviral therapies for CHB is rather limited. We investigated the spectrum and predictors of HS in CHB patients. MATERIALS AND METHODS Liver biopsies of consecutive patients of chronic Hepatitis B Virus (HBV) infection were studied and were categorized as: Group I - hepatosteatosis (>5%) and Group II - no steatosis (£5%). Anthropometric, histological, biochemical, virological, and metabolic determinants were compared. Logistic regression analysis was applied to identify variables that were independently associated with the presence of steatosis. RESULTS Of the 350 patients, 118 (33.7%) liver biopsies showed steatosis (Group I); 65 (55.1%) had mild (6 to <25%) and 53 (44.9%) had moderate to severe steatosis ((3)25%). Patients in group I, compared with group II, were older (35.5 ± 10.5 vs 27.9 ± 14.0 years, P < 0.01), predominantly male (M: F, 10.8: 1 vs 4.8: 1, P = 0.035), obese (75.0% vs 23.4%, P P < 0.01), with higher triglycerides (138.8 ± 62.1 vs 88.0 ± 27.9, P = 0.02), with higher cholesterol (171.9 ± 43.5 vs 139.3 ± 37.6, P = 0.017), and with higher serum insulin (13.1 ± 9.1 vs 9.1 ± 6.0, P < .027) levels. HBV DNA level was significantly lower in group I than group II; however, HBV genotype did not influence HS. By multivariate regression analysis, only high serum triglyceride level was independent parameter associated with HS. CONCLUSIONS Steatosis is seen in one-third cases with HBV-related chronic liver disease and is associated with host metabolic factors, especially serum triglyceride levels, whereas HBV DNA level negatively correlated with HS.

Apoptotic mechanisms in fulminant hepatic failure: Potential therapeutic target

IntroductionPathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF. MethodsLiver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes. ResultsImmunohistochemical analysis revealed high expression (P<0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P<0.001) higher in FHF in relation to AVH. ConclusionsEnhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.

Fine needle aspiration cytologic appearance of inflammatory pseudotumor of the liver. A case report.

BACKGROUND Inflammatory pseudotumor (IPT) is a rare space-occupying lesion of the liver that can be clinically confused with a malignant process. CASE REPORT A 28-year-old male presented with fever and a palpable, firm liver. Ultrasonography and computed tomography revealed a mass in the right lobe of the liver. Fine needle aspiration biopsy (FNAB) under ultrasonographic guidance showed inflammatory cells, fibroblasts and a few hepatocytes. A diagnosis of inflammatory pseudotumour was suggested and confirmed on a true-cut biopsy. CONCLUSION The cytologic appearance of IPT is characteristic. FNAB under ultrasonographic is a quick and easy technique for its diagnosis and differentiation from malignant space-occupying lesions.

Histological spectrum of chronic hepatitis in precore mutants and wild-type hepatitis B virus infection.

This study compares the histology of liver biopsies in precore mutant (PCM) and wild-type hepatitis B virus (HBV) infection. Thirty cases of PCM and 60 cases of wild-type HBV infection were included. Patients were diagnosed on the basis of serological profile and HBV DNA assessment. Liver biopsies in each case were assessed for histological activity and stage of fibrosis using a modification of Knodells scoring system. There was no statistically significant (P=0.14) difference in histological activity in the two groups. The difference in stage of fibrosis in the two groups was statistically significant (P=0.001). Quantitative estimation of viral load did not show any correlation with liver histology. PCM HBV showed greater stage of fibrosis compared with wild-type infection, and this may be related to disease progression and lack of response to therapy.

Benign signet ring cell change with multilayering in the gallbladder mucosa--a case report.

We describe a case of benign signet ring cell change in the gallbladder mucosa. On histopathological examination of H&E-stained sections, the gallbladder epithelium showed multilayering. The epithelial cells were large, columnar to polygonal with a small round basal or eccentric nucleus and vacuolated cytoplasm, giving them a signet ring appearance. There was no nuclear atypia, hyperchromatism or mitotic activity. The cells showed uniform positivity with mucicarmine, PAS and Alcian blue stains. The cytoplasmic vacuolations were negative for fat stains (Oil red O and Sudan IV). On immunohistochemistry, the cells showed positivity with antibodies for pancytokeratin (PCK) and epithelial membrane antigen (EMA). A diagnosis of benign signet ring cell change with multilayering in the gall bladder mucosa was made. Thoroughly reviewing the literature, we found only one case of benign signet ring cell aggregates in the gallbladder mucosa documented earlier. The lesion is hereby reported because of the unique histomorphology and the diagnostic dilemma which can occur as a malignant change in situ has to be excluded.

Florid xanthogranulomatous cholecystitis masquerading as invasive gallbladder cancer leading to extensive surgical resection.

Xanthogranulomatous inflammation of gallbladder wall can extend and infiltrate adjacent organs which can be mistaken for malignancy on preoperative investigations and, intraoperatively, often leads to extensive surgical resections. Only the histopathologic examination of the specimen allows correct diagnosis. We hereby review clinicopathologic findings of six cases which underwent extensive surgeries on clinical, radiological and intraoperative suspicion of gallbladder carcinoma which turned out to be xanthogranulomatous cholecystitis (XGC). There was no evidence of malignancy on histopathologic examination. Xanthogranulomatous inflammation extended into liver, duodenum, colon and stomach in case 1; liver and colon in case 2; liver, duodenum, colon in case 3; stomach, duodenum, colon in case 4; stomach and duodenum in case 5 and duodenum and colon in case 6. Lymph nodes in all the six cases showed reactive hyperplasia. We present here the clinico-radiologic findings of these cases, techniques which may help differentiate between an XGC and a gallbladder carcinoma and also discuss the management of these cases.

Primary Rhabdoid Tumor of the Gallbladder: Report of a Case

A 46-year-old man was operated on for cholelithiasis with chronic cholecystitis. On gross inspection of the resected gallbladder, a slight thickening in the body wall, in an area measuring about 1 × 0.5 cm, was noted. On light microscopic and immunohistochemical examinations, the lesion was diagnosed to be a rhabdoid tumor. After a thorough review of the literature we failed to find any reference to such a lesion in the gallbladder. This is the first known case report of a rhabdoid tumor of the gallbladder.

Making and using inexpensive manually constructed tissue micro-array: Experience of a tertiary care hospital in India

BACKGROUND Tissue micro-array enables the analysis of a large number of tissues simultaneously. Widespread use of this technology is hampered by the high cost of commercial array instruments. We describe our experience of constructing tissue micro-array in a simple method using easily available and inexpensive instruments. MATERIALS AND METHODS We used an 11-19 gauge (G) bone marrow trephine biopsy needle/ small sized slotted screwdriver to punch holes in the wax blocks. Cores were taken from donor tissue blocks using a bone marrow trephine biopsy needle and arrayed into host paraffin wax blocks. A detailed database was constructed for each array constructed. RESULTS The array blocks were used over a period of one year as internal control for immunohistochemistry (IHC), quality control and research. It took about 10 minutes to construct a nine-dot array and about one hour for a 56-dot array. During IHC, the average loss of control dots was less than one per cent. We did not see any loss of antigenicity in the control sections even after four weeks storage. DISCUSSION Tissue array construction by the technique described here is inexpensive and reliable alternative to automated instruments. Because it is easy to modify the arrays by varying the core size, it is easy to adapt this to individual labs and requirements. We recommend using blocks with cores in 3 x 3 to 5 x 4 grids as controls in IHC and for standardizing antibodies and array blocks with a larger number of cores for research.

Inflammatory myofibroblastic tumor appendix with concomitant mucosal dysplasia, simulating pseudomyxoma on preoperative aspiration cytology.

Inflammatory myofibroblastic tumor (IMT) has been described as a pseudosarcomatous proliferation of spindled myofibroblasts admixed with lymphoplasmacytic cells. The various terminologies like inflammatory pseudotumor, plasma cell granuloma, and inflammatory myofibrohistiocytic proliferation, used to describe this entity, highlight the controversial etiopathogenesis of this relatively indolent neoplasm. IMT has now been described in different anatomic locations. However, cases occurring in the gastrointestinal tract are rare with very few cases described in the appendix. We present a case of inflammatory myofibroblastic tumor appendix with mucosal dysplasia in a 41-year-old male, presenting with abdominal pain and lump in the right iliac fossa. Aspiration cytology yielded few atypical epithelial cells and spindle cells in a mucinous background, suggesting the possibility of pseudomyxoma peritonei. Awareness of IMT appendix with rare presence of mucosal dysplasia may help in preventing overzealous resection, especially in situations that on preoperative evaluation may suggest malignancy.