Hepatoid adenocarcinoma of lung: A diagnostic challenge - Series of six cases with histopathological, predictive molecular and PD.L1 assessment.

Hepatoid adenocarcinoma of lung is a rare entity, accounting for 5% of all hepatoid adenocarcinoma. Distinguishing it from metastatic hepatocellular carcinoma is essential, but occasionally can be very challenging, especially with concurrent liver mass. A judicious immunohistochemical panel is warranted for accurate diagnosis and subsequent preservation of tissue for molecular testing. There is limited data on the mutational status, behavior and management strategies of this type of lung adenocarcinoma. We report largest series of six cases of hepatoid adenocarcinoma of lung citing the clinical, histopathological, immunohistochemical and molecular parameters including PD-L1 immunoexpression as a predictive biomarker for immunotherapy. None of the evaluated cases showed targetable mutation; however, four out of six cases showed significant PD-L1 expression. All the cases presented with advanced stage and received chemotherapy, however overall prognosis was dismal. In view of significant PD-L1 expression in these tumors and poor response to conventional chemotherapy, these cases might be considered for upfront immunotherapy.

A/H1N1/09 Influenza is Associated With High Mortality in Liver Cirrhosis.

BACKGROUND/AIMS: A/H1N1/09 influenza is associated with a high risk of complications in patients with chronic diseases. In view of patients with cirrhosis being recognized as another high-risk group for influenza morbidity and mortality, we report a cluster of suspected A/H1N1/09 infection in 110 patients admitted to a hepatology intensive care unit. METHODS: The pattern of spread, clinical outcome, and respiratory parameters of A/H1N1/09 of 22 positive cirrhotic patients were compared with those from a control group of 88 patients with chronic liver disease (CLD) with influenza-like pneumonia who tested negative for A/H1N1/09. RESULTS: A/H1N1/09 infection was confirmed in 22 (20%) patients. Eighteen of 22 (81.8%) CLD patients with A/H1N1/09 died of pneumonia and acute respiratory distress syndrome despite timely antiviral treatment. In contrast, only 35 (40%)of the control group of cirrhotic patients without A/H1N1/09 died. On univariate analysis, age > 45 years [OR 1.3; 95% CI 1.1-5.7, (P = 0.054)], encephalopathy > grade 2 [OR 5.4; 95% CI 2.8-12.3, (P = 0.042)], serum bilirubin >8 mg/dl [OR 2.1; 95% CI 1.8-12.3, (P = 0.052)], serum creatinine >1.8 mg/dl [OR 2.8; 95% CI 1.9-9.2, (P = 0.042)], PaO2/FiO2 ratio <200 [OR 4.5; 95% CI 3.1-18.5, (P = 0.026)] and INR > 2.5 [OR 2.2; 95% CI 1.8-6.7, (P = 0.032)] were risk factors for mortality at presentation. However, on multivariate analysis only PaO2/FiO2 ratio <200 and serum creatinine >1.8 mg/dl remained predictors of mortality. Secondary infections, whether fungal or bacterial, were noted to be independent risk factors for disease severity in patients with cirrhosis. CONCLUSION: Early detection and referral, and early antiviral treatment with a strict control of nosocomial spread is essential in patients with cirrhosis during epidemic influenza.

Impact of 2013 ASCO/CAP HER2 reporting guidelines in breast cancer: An assessment study from Indian oncology centre that primarily performs HER2 IHC testing with special emphasis on IHC equivocal category.

The ASCO/CAP guidelines for HER2 reporting in breast cancer published in 2007 and were updated in 2013 to assure that the right patient receives the targeted therapy. The updated guidelines have lowered the threshold for HER2 positivity criteria and altered the equivocal category for both IHC and FISH. This first study from India addresses the impact of these updated guidelines in the various reporting categories at a tertiary care centre. We compared the trend of HER2 IHC reporting 1 year before (Period A) and 1 year after (Period B) the implementation of updated 2013 ASCO/CAP guidelines. All HER2 equivocal IHC cases of post 2013 guidelines were reclassified as per 2007 guidelines to detect additional number of cases that have been put into equivocal category. Reflex FISH correlation was also assessed to detect any additional cases eligible for anti HER2 therapy with implementation of these updated guidelines. With implementation of updated 2013 guidelines, there was significant decrease in the number of cases scored as 1+ (from 30.7% to 20.6%; P value: .0001) while significant increase in number of 2+ cases (from 20.2% to 27.3%; P value: .004). Post 2013 guidelines, 39% (64 cases) of tumors were additionally put into the equivocal category which would have been considered as negative (score 1+) as per 2007 guidelines. The reflex FISH testing in these equivocal cases resulted in detection of only 1.5% of additional cases eligible for anti HER2 therapy. With implementation of updated 2013 guidelines, there is no significant increase in HER2 positivity trend. However, there is appreciable increase in IHC equivocal cases which subsequently led to increased reflex FISH testing without significantly contributing to the detection of additional eligible cases for anti HER2 therapy, but resulted in delaying of definite HER2 status along with financial implications.

Study of association of Epstein-Barr virus in lymphomas by Epstein-Barr virus-encoded RNA in situ hybridization: An Indian perspective from a tertiary care cancer institute.

BACKGROUND: The Epstein-Barr virus (EBV), also called human herpesvirus 4, is a virus of the herpes family. The EBV-associated lymphomas include Burkitt lymphoma, classic Hodgkin lymphoma (HL), lymphomas arising in immunocompromised individuals, peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphoma, extranodal nasal-type natural killer/T-cell lymphoma, and other rare histotypes. OBJECTIVE: The present study evaluated the role of EBV as an etiologic agent in various lymphomas and determined an Indian perspective in a tertiary care cancer center compared to that of Western literature. MATERIALS AND METHODS: Clinicopathological spectrum was studied in 184 cases of lymphomas using a standard immunohistochemistry panel and in situ hybridization for Epstein-Barr virus-encoded RNA (EBER) expression. RESULTS AND CONCLUSIONS: The prevalence of EBV was described in various HL and non-HL's and was found similar to that of Western literature. EBER expression was also observed in the nonneoplastic bystander cells in the studied cases which need further evaluation on larger scale studies.

Primary Hepatic Amyloidosis Presenting as Acute-on-Chronic Liver Failure.

Systemic amyloidosis of amyloid light chain associated protein (AL), also called primary amyloidosis, frequently involves the liver, but rarely causes clinically apparent liver disease. The more common presentation is with acute renal failure. Hepatomegaly and mild elevation of alkaline phosphatase are the most common clinical and biochemical findings, respectively. We report a case of systemic amyloidosis of AL that clinically presented as acute-on-chronic liver failure and resulted in a fatal clinical course in a 56-year-old man.

Cholangicarcinoma Presenting as a Sister Mary Joseph Nodule.

Sister Mary Joseph nodules represent metastatic cancer of the umbilicus. More than half of these cases are attributable to gastrointestinal malignancies including gastric, colonic, and pancreatic cancer. In addition, gynecologic (ovarian, uterine cancer), unknown primary tumors, and, rarely, bladder or respiratory malignancies may cause umbilical metastasis. We report the case of a Sister Mary Joseph nodule originating from a hilar cholangiocarcinoma. Umbilical nodules should prompt clinical evaluation, as these tumors are usually associated with poor prognosis.

Hepatobiliary IgG4 Cholangiopathy: Case Series and Literature Review.

IgG4 cholangiopathy is a recently described distinctive type of hepatobiliary manifestation of IgG4-related disease. This is often misdiagnosed as a malignancy of the hepatobiliary system on clinical presentation and imaging. Accurate diagnosis is crucial for appropriate management. Histopathology provides crucial information and is characterized by IgG4-positive lymphoplasmacytic infiltration with storiform fibrosis and obliterative phlebitis. We present the clinicopathological spectrum of a retrospective series of 6 cases of IgG4 cholangiopathy that clinically masqueraded as hepatobiliary malignancies.

Expression of estrogen receptor ß and Ki 67 in benign & malignant human prostate lesions by immunohistochemistry.

Estrogen regulates the growth of prostate through two receptors Estrogen receptor α & ß of which ERß is proposed to be antiproliferative. There is a wide variation in the results of various studies regarding the localisation, level of expression of ERß in benign & malignant lesions of prostate and its relation to the grade of tumor emphasizing the need for additional studies to standardize the distribution of this receptor in prostate. This was a prospective study conducted in Department of Pathology, UCMS, Delhi, evaluating ERß & Ki 67 immunoexpression in 60 cases of benign and malignant lesions of prostate (30 each). Tissue for study included prostatic core biopsy and TURP chips. After histomorphological diagnosis, immunohistochemical staining was performed using a monoclonal antibody. Nuclear expression of ERß & Ki67 was evaluated and compared between the two study groups (benign & malignant lesions) using Pearson chi square test. ERß was predominantly localized to nuclei of secretory epithelium of prostatic glands. Expression of ERß was higher in benign glands compared to carcinoma. However, majority of carcinomas retained ERß expression though at much lower levels. Expression of Ki 67 was higher in carcinoma than benign hyperplasia. There was no correlation between the ERß status, Ki 67 expression & grade of tumor. Expression of ERß is downregulated in carcinoma compared to benign hyperplasia and is consistent with its chemopreventive role in prostate. It might have a therapeutic implication as agonists' targeting this receptor could be a part of treatment protocol for those patients of carcinoma who retain this receptor at significant levels.

Spectrum of Histomorphologic Findings in Liver in Patients with SLE: A Review.

Collagen vascular diseases (CVDs) like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren syndrome (SS), and scleroderma are immunologically mediated disorders that typically have multisystem involvement. Although clinically significant liver involvement is rare, liver enzyme abnormalities are common in these patients. The reported prevalence of hepatic involvement in SLE, histopathologic findings, and its significance is very variable in the existing literature. It is important to be familiar with the causes of hepatic involvement in SLE along with histomorphological features which aid in distinguishing hepatitis of SLE from other hepatic causes as they would alter the patient management and disease course. Histopathology of liver in SLE shows a wide morphological spectrum commonly due to a coexisting pathology. Drug induced hepatitis, viral etiology, and autoimmune overlap should be excluded before attributing the changes to SLE itself. Common histopathologic findings in SLE include fatty liver, portal inflammation, and vascular changes like hemangioma, congestion, nodular regenerative hyperplasia, arteritis, and abnormal vessels in portal tracts.