Metastatic Lymphoepithelioma-like Hepatocellular Carcinoma: a Potential Diagnostic Pitfall and Demonstration of Pd-l1 Expression

Abstract: Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare primary hepatic neoplasm with female predominance and relatively good prognosis. We report a 73-year-old female with chronic hepatitis B who developed metastatic lesions 5 years after underwent resection for LEL-HCC. The metastatic lesions showed a spectrum of morphologic findings, which could be mistaken for other entities such as lymphoma, particularly in lesions with single-cell infiltrative pattern and abundant tumor-infiltrating lymphocytes. Immunohistochemical study to confirm the origin of the neoplastic cells is important to make the diagnosis. We also highlighted the clinicopathologic correlation and potential therapeutic implication of programmed death ligand-1 expression in LEL-HCC.

Ocular disease in American crocodiles (Crocodylus acutus) in Costa Rica.

Beginning in early 2006, an ocular disease of unknown etiology was routinely observed in American crocodiles (Crocodylus acutus) inhabiting the highly polluted Tarcoles River in west-central Costa Rica. We examined the nature and incidence of ocular disease in Tarcoles crocodiles and assessed the possible association between the disease and accumulation of chemical pollutants in diseased individuals. During 12-15 September and 12-13 December 2007, crocodiles were captured and examined for ocular disease and sampled to determine environmental contaminant accumulation. Three of 11 (27.3%) crocodiles captured (all males) exhibited unilateral ocular disease, primarily characterized by corneal opacity and scarring, anterior synechia, and phthisis bulbi. Multiple pollutants were detected in crocodile caudal scutes (organochlorine pesticides [OCPs] and metals), crocodile blood (OCPs), and sediments (OCPs and metals) from the Tarcoles, but no associations were found between contaminant accumulation and the incidence of eye disease. On the basis of the limited number of diseased animals examined and the potential exposure of crocodiles to pathogens and other pollutants not targeted in this study, we cannot rule out infection or chemical toxicosis as causes of the eye lesions. However, circumstantial evidence suggests that the observed ocular disease is likely the result of injury-induced trauma (and possibly secondary infection) inflicted during aggressive encounters (e.g., territorial combat) among large adult crocodiles living at relatively high densities.

Surface water mitigates the anti-metamorphic effects of perchlorate in New Mexico spadefoot toads (Spea multiplicata) and African clawed frogs (Xenopus laevis).

Spea multiplicata (New Mexico spadefoot toad) larvae were exposed to 60, 110, and 1000 microg L(-1) perchlorate dissolved in natural surface water to determine risks associated with perchlorate exposure in desert-adapted anurans. Hind- and forelimb development and tail resorption were measured to identify effects of perchlorate exposure. No perchlorate-related effects on snout-vent length, hindlimb length, and proportion metamorphosed were observed in the highest treatment group (positive control; 1000 microg L(-1)) suggesting that either S.multiplicata are not sensitive to the effects of perchlorate at the concentrations tested or that unidentified constituents of natural surface water mitigated perchlorate toxicity. To identify whether surface water mitigated perchlorate toxicity, Xenopuslaevis were exposed to 20 and 60 microg L(-1) perchlorate in surface water and synthetic laboratory prepared water (i.e., FETAX media). X.laevis exposed to perchlorate dissolved in surface water exhibited no perchlorate-related anti-metamorphic effects, whereas X.laevis exposed to perchlorate in FETAX media experienced changes in percent metamorphosing (p<0.001), time to metamorphosis (p<0.001), snout-vent length (p<0.001), and hindlimb length (p<0.001) as compared to FETAX controls. These results suggest that natural surface water can mediate perchlorate effects at concentrations up to 60 microg L(-1) for X.laevis and greater than 1 mg L(-1) for S.multiplicata, potentially due to physicochemical properties of surface water. CAPSULE: This manuscript discusses the effects of perchlorate in natural surface water to S.multiplicata and X.laevis.

Plasma vitellogenin in Morelet's crocodiles from contaminated habitats in northern Belize.

Vitellogenin induction has been widely used as a biomarker of endocrine disruption in wildlife, but few studies have investigated its use in wild reptiles living in contaminated habitats. This study examined vitellogenin induction in Morelet's crocodiles (Crocodylus moreletii) from wetlands in northern Belize contaminated with organochlorine (OC) pesticides. Vitellogenin was measured in 381 crocodile plasma samples using a vitellogenin ELISA previously developed for this species. Vitellogenin was detected in nine samples, all from adult females sampled during the breeding season. Males and juvenile females did not contain detectable levels of vitellogenin; however, many of these animals contained OC pesticides in their caudal scutes, confirming contaminant exposure. The lack of a vitellogenic response in these animals may be attributable to several factors related to the timing and magnitude of exposure to endocrine-disrupting chemicals and should not be interpreted as an absence of other contaminant-induced biological responses.

Metals and organochlorine pesticides in caudal scutes of crocodiles from Belize and Costa Rica.

Despite high animal diversity in the Neotropics and the largely unregulated use and disposal of pesticides and industrial chemicals in Central America, few data exist regarding accumulation of environmental contaminants in Central American wildlife. In this study we examined accumulation of metals and organochlorine (OC) pesticides in caudal scutes of crocodiles from Belize and Costa Rica. Scutes from Morelet's crocodiles (Crocodylus moreletii) from two sites in northern Belize were analyzed for metals, and scutes from American crocodiles (C. acutus) from one site in Costa Rica were analyzed for metals and OC pesticides. All scutes (n=25; one scute from each of 25 individuals) contained multiple contaminants. Mercury was the predominant metal detected, occurring in all scutes examined from both species. Other metals detected include cadmium, copper, lead, and zinc. American crocodile scutes from Costa Rica contained multiple OC pesticides, including endrin, methoxychlor, p,p'-DDE, and p,p'-DDT, all of which occurred in 100% of scutes analyzed (n=6). Mean metal and OC concentrations varied in relation to those previously reported in crocodilian scutes from other localities in North, Central, and South America. OC concentrations in American crocodile scutes were generally higher than those previously reported for other Costa Rican wildlife. Currently, caudal scutes may serve as general, non-lethal indicators of contaminant accumulation in crocodilians and their areas of occurrence. However, a better understanding of the relationships between pollutant concentrations in scutes, internal tissues, and environmental matrices at sample collection sites are needed to improve the utility of scutes in future ecotoxicological investigations.

Widespread presence of naturally occurring perchlorate in high plains of Texas and New Mexico.

Perchlorate (CLO4-) occurrence in groundwater has previously been linked to industrial releases and the historic use of Chilean nitrate fertilizers. However, recently a number of occurrences have been identified for which there is no obvious anthropogenic source. Groundwater from an area of 155,000 km2 in 56 counties in northwest Texas and eastern New Mexico is impacted bythe presence of ClO4-. Concentrations were generally low (<4 ppb), although some areas are impacted by concentrations up to 200 ppb. ClO4- distribution is not related to well type (public water system, domestic, agricultural, or water-table monitoring) or aquifer (Ogallala, Edward Trinity High Plains, Edwards Trinity Plateau, Seymour, or Cenozoic). Results from vertically nested wells strongly indicate a surface source. The source of ClO4- appears to most likely be atmospheric deposition. Evidence supporting this hypothesis primarily relates to the presence of ClO4- in tritium-free older water, the lack of relation between land use and concentration distribution, the inability of potential anthropogenic sources to account for the estimated mass of ClO4-, and the positive relationship between conserved anions (e.g., IO3-, Cl-, SO4(-2)) and ClO4-. The ClO4- distribution appears to be mainly related to evaporative concentration and unsaturated transport. This process has led to higher ClO4- and other ion concentrations in groundwater where the water table is relatively shallow, and in areas with lower saturated thickness. Irrigation may have accelerated this process in some areas by increasing the transport of accumulated salts and by increasing the number of evaporative cycles. Results from this study highlight the potential for ClO4- to impact groundwater in arid and semi-arid areas through long-term atmospheric deposition.

Organochlorine contaminants in complete clutches of Morelet's crocodile (Crocodylus moreletii) eggs from Belize.

Seven complete clutches of Morelet's crocodile (Crocodylus moreletii) eggs were collected in northern Belize and examined for organochlorine (OC) pesticide residues. The primary OC detected, p,p-DDE, was found in every egg analyzed (n=175). Other OCs detected included p,p-DDT, p,p-DDD, methoxychlor, aldrin, and endosulfan I. Concentrations of individual OCs ranged from 4 ppb (ng chemical/g egg wet weight) to greater than 500 ppb. A statistical evaluation of p,p-DDE levels in three complete clutches was used to derive the minimum number of eggs needed from a clutch to precisely determine the mean p,p-DDE concentration representative of that clutch. Sample sizes of 8 (80% confidence level) and 11 (90% confidence level) were determined to yield an accurate estimate of contaminant levels in a full clutch of eggs. The statistically recommended sample size of 11 eggs (at 90% confidence level) was successfully tested on the four additional clutches.

Organochlorine pesticides in chorioallantoic membranes of Morelet's crocodile eggs from belize.

Recent studies examined the utility of the chorioallantoic membrane (CAM) as a nonlethal, noninvasive indicator of environmental contaminant exposure in oviparous wildlife. The CAM is a highly vascularized extraembryonic membrane that functions as a site for respiration, nutrient transport, and waste storage during embryonic development. After hatching, the CAM is usually discarded with the eggshell and can be used for chemical residue analysis. Chorioallantoic membranes have been used successfully to examine contaminant exposure and predict chemical concentrations in multiple species of birds and reptiles. In this study, we examined organochlorine (OC) pesticide concentrations in CAMs from eggs of Morelet's crocodiles (Crocodylus moreletii) from northern Belize. Multiple OCs were detected in crocodile CAMs, including aldrin, dieldrin, endrin, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethane, dichlorodiphenyldichloroethylene (DDE), heptachlor, lindane, and methoxychlor. Number and concentrations of OC compounds in CAMs were variable. The most prevalent contaminant detected was DDE, which occurred in 69% of CAMs, with concentrations ranging from 0.3 parts per billion (ppb) to 17.0 ppb. The OC burdens in crocodile CAMs confirm contamination of eggs and suggest exposure in embryos and maternal females. These results further support the use of CAMs as qualitative indicators of OC exposure in oviparous wildlife. The efficacy of this sampling technique in the field will depend on the logistics and cost associated with CAM collection and the specific life history traits of the wildlife species.

Organochlorine pesticides in elementary school yards along the Texas-Mexico border.

A reconnaissance study was undertaken to determine potential contaminant exposures to children through soil from elementary school playgrounds. Soil samples were collected from areas along the Texas-Mexico border, inland areas (soils from elementary school yards in cities/towns within the state of Texas), and three National Parks (one on the border, one in Tennessee, and one in Washington). The present study focused on organochlorine (OC) pesticides as the potential contaminants of concern because of their historical (and possibly current) use, and their importance as persistent organic pollutants (POPs). DDE and heptachlor were the most frequently detected OCs (69 and 63%, respectively), although heptachlor concentrations in soil never exceeded 5 ppb. Relatively higher concentrations of DDE were observed in agricultural areas along the border (50-60 ppb in soils from McAllen, Palmview, and San Benito) than in other soils. However, a school yard in Lubbock, TX had the highest OC concentration observed (70 ppb dieldrin). These results may be due to historical agriculture activity prior to the banning of OC pesticides such as DDT in the early 1970s, as well as the more recent use of DDT in Central and South America for malaria control.