Plasmablastic lymphoma presenting as a large intracardiac mass and bilateral pleural effusions.

Plasmablastic lymphoma (PBL) is a rare aggressive lymphoma arising most frequently in the oral cavity of HIV-infected patients. Rare cases of PBL have been reported in extra-oral sites, as well as in HIV-negative patients. Cardiac involvement by lymphoma is very rare. The most common primary cardiac lymphoma is diffuse large B-cell lymphoma. We report an unusual case of PBL in a 49-year-old, HIV-positive man presenting with a large intracardiac mass and bilateral pleural effusions. Histological examination of the cardiac mass biopsy and cytological evaluation of the pleural fluid demonstrated large lymphoma cells with plasmablastic differentiation. By immunohistochemistry, the large lymphoma cells expressed CD30, CD45, CD138, MUM1, and kappa light chain, were weakly positive for EMA, and were negative for T-cell and B-cell markers, lambda light chain, and human herpes virus 8 (HHV8). In situ hybridization for Epstein Barr Virus-encoded RNA (EBER) was negative in large lymphoma cells. To our knowledge, in the English literature, this is the second reported case of PBL with cardiac origin and the first reported case of PBL that presents as a combination of intracardiac mass and pleural effusions.

Brca1 Mutations Enhance Mouse Reproductive Functions by Increasing Responsiveness to Male-Derived Scent.

We compared the gene expression profiles of ovarian granulosa cells harboring either mutant or wild type Brca1 to follow up on our earlier observation that absence of a functional Brca1 in these important regulators of menstrual/estrous cycle progression leads to prolongation of the pre-ovulatory phase of the estrous cycle and to increased basal levels of circulating estradiol. Here we show that ovarian granulosa cells from mice carrying a conditional Brca1 gene knockout express substantially higher levels of olfactory receptor mRNA than granulosa cells from wild type littermates. This led us to hypothesize that reproductive functions in mutant female mice might be more sensitive to male-derived scent than in wild type female mice. Indeed, it is well established that isolation from males leads to complete cessation of mouse estrous cycle activity while exposure to olfactory receptor ligands present in male urine leads to resumption of such activity. We found that Brca1-/- female mice rendered anovulatory by unisexual isolation resumed ovulatory activity more rapidly than their wild type littermates when exposed to bedding from cages where males had been housed. The prime mediator of this increased responsiveness appears to be the ovary and not olfactory neurons. This conclusion is supported by the fact that wild type mice in which endogenous ovaries had been replaced by Brca1-deficient ovarian transplants responded to male-derived scent more robustly than mutant mice in which ovaries had been replaced by wild type ovarian transplants. Our findings not only have important implications for our understanding of the influence of olfactory signals on reproductive functions, but also provide insights into mechanisms whereby genetic risk factors for breast and extra uterine Müllerian carcinomas may influence menstrual activity in human, which is itself an independent risk factor for these cancers.

Mechanism of hepatotoxicity due to black cohosh (Cimicifuga racemosa): histological, immunohistochemical and electron microscopy analysis of two liver biopsies with clinical correlation.

BACKGROUND: Consumption of herbal supplements in the developed world remains high. Cimicifuga racemosa (C. racemosa) extract, or black cohosh, is widely used as a hormone replacing and an anti-inflammatory agent, and has been shown to cause idiosyncratic hepatitis. The mechanism of acute liver injury in those cases is unclear. To date, hepatotoxic effects of C. racemosa have been studied mostly in vitro and in animal models. Data on human tissue is extremely limited, and mostly confined to histological findings of explanted livers. METHODS: We evaluated clinical data and examined surgical diagnostic liver biopsy specimens obtained from two female patients, who developed acute submassive liver necrosis, following consumption of C. racemosa. Both patients presented with acute elevation of liver enzymes, cholestasis, absence of reactivity to hepatitis A, B and C antibodies, and weak non-specific positivity for autoimmune serological markers. Initial histological interpretation of the biopsies, with focus on hepatic parenchyma and portal tracts, was done by light microscopy, followed by special stain series and immunohistochemical studies, including Cam 5.2, AE1/AE3, reticulin, α-actin, sirius red, and PAS with diastase. Areas of prominent lymphocytic infiltration of the periportal liver plate, observed microscopically, were further evaluated by electron microscopy (EM). 4HNE adduction study, an immunofluorescent assay, was performed to detect products of the oxidative damage and their localization in the liver parenchyma. RESULTS: Oxidative damage was evident by accumulation of 4HNE protein adducts in the cytoplasm of hepatocytes, secondary lysosomes and macrophages. We hypothesize that the adducted proteins, accumulated in the liver parenchyma, serve as autoantigens, which provoke an autoimmune response, and cause migration of lymphocytes to the affected regions. The formation of immunological synapses between hepatocytes and lymphocytes, predominantly T-lymphocytes, is demonstrated by electron microscopy. The autoimmune response induces piecemeal, or troxis necrosis of hepatocytes, a well described biological phenomenon, where lymphocytes gradually remove hepatocytes in a piecemeal fashion, slowly consuming them and leaving fragments of liver cells, or nubbins of anuclear cytoplasm of liver cell, at the interface between lymphocytes and hepatocytes. CONCLUSION: The pattern of pathological injury of liver cells in both patients, following consumption of black cohosh, is identical to troxis necrosis, seen during autoimmune hepatitis. Recognition of the possibility of the acute hepatic injury by the herbal supplement black cohosh is essential for early accurate diagnosis, and timely patient management.

Cytomorphological features of epithelioid hemangioendothelioma in ascitic fluid with radiological, clinical and histopathological correlations.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is an uncommon vascular soft-tissue tumor. Five cases of EHE in body fluids have been documented in the literature, all of them occurring in pleural effusions. This is the first description of cytomorphological features of EHE cells in ascitic fluid, accompanied by corresponding histopathological findings, clinical, and radiological data. CASE REPORT: Our patient presented with several liver masses, peritoneal involvement, bilateral pleural effusions, and massive ascites. EHE was suspected on cytological examination of the ascitic fluid and was confirmed by immunohistochemical studies. Simultaneously, a liver mass was identified and diagnosed on biopsy as EHE, affording accurate histopathological correlation. Cytologically, EHE cells appear relatively bland, often obscured by reactive mesothelial cells, and dispersed singly or clustered. They often possess intracytoplasmic vacuoles, referred to as 'blister' or 'signet ring' cells. High-power examination shows slightly misshapen mildly hyperchromatic nuclei with inconspicuous nucleoli. Immunohistochemically, EHE cells express strong positivity with vascular markers (CD31, CD34 and factor VIII). They are nonreactive with mesothelial markers (calretinin and WT-1). CONCLUSION: Recognition of the possibility of EHE cells in fluid by morphology should prompt proper immunohistochemical work-up to ensure an accurate diagnosis and timely patient management.

Alcoholic liver disease patients treated with S-adenosyl-L-methionine: an in-depth look at liver morphologic data comparing pre and post treatment liver biopsies.

BACKGROUND: The objective of this study is to assess if there were any changes in liver biopsies after treatment with S-adenosyl-L-methionine(SAMe) in alcoholic liver disease patients. METHODS: Liver biopsies of 14 patients were randomized for SAMe treatment at week 0 (biopsy #1) and at 24 weeks (biopsy #2). Patients received 1.2g of SAMe or placebo by mouth daily and stopped alcohol intake. Biopsies were semi-quantitatively scored for: steatosis, inflammation, necrosis, fibrosis, apoptosis by TUNEL stain, percent fibrosis per square field, smooth muscle actin stain, Kupffer cells, polymorphonuclear leukocytes, lipogranules, lymphocytes, balloon cell formation, Mallory-Denk bodies, and duct metaplasia. RESULTS: Comparing treatment arm to placebo arm, no significant difference was found between biopsy #1 and biopsy #2. However, when both study arms were grouped together, there was decrease in smooth muscle actin stain, where the P-value=0.027. CONCLUSION: Treatment with SAMe did not show a statistically significant difference in the characteristics studied. However, when both the treatment and placebo arm data were grouped together to increase the n and power, there was a decrease in the smooth muscle actin stain, reflecting a decrease in stellate cells activation, likely due to the alcohol abstinence. This study suggests that it may not be beneficial to wait for more definitive treatment, like liver transplant in alcoholic liver disease patients, since the liver tissue remained largely with the same degree of pathology six months out, regardless of treatment.