[Atypical renal cysts: a clinicopathological and molecular analysis of six cases].

Objective: To investigate the clinicopathological characteristics and molecular genetics of atypical renal cysts. Methods: Six cases of atypical renal cysts were collected from Zhejiang Provincial People's Hospital, Hangzhou, China, between February 2014 and February 2019. The clinicopathological characteristics and disease progression were analyzed. The 3p deletion and trisomy of chromosomes 7 and 17 were detected using fluorescence in situ hybridization (FISH). Results: All of the 6 patients were male, aged 43-63 years (median: 52 years). Preoperative Bosniak classification showed 4 cases of grade Ⅱ, 1 case of grade Ⅰ and 1 of grade Ⅲ. Histologically, atypical renal cysts appeared as unilocular or multilocular cysts, lined by multilayered flattened or cuboidal-shaped clear or eosinophilic cells. They often showed short papillary projections, and lacked solid or nodular growth of the lesional cells within the wall or septa of the cysts. Histologically, these cysts could be classified into three categories: acquired cystic disease-associated renal cell carcinoma (ACKD-RCC)-like (3 cases), clear cell type (2 cases), and eosinophilic papillary type (1 case). Two cases of ACKD-RCC-like atypical renal cysts were accompanied by clear cell renal cell carcinomas. On immunohistochemical staining, ACKD-RCC-like atypical renal cysts were focally CK7+/AMACR+/CD57+, the clear-cell type atypical renal cysts were CK7+/CAⅨ+, and eosinophilic papillary type atypical renal cysts were CK7+/AMACR+. FISH analyses showed that one case of ACKD-RCC-like atypical renal cysts had trisomy 17 and one case of clear cell type had 3p deletion, while no signal abnormality was detected in the other cases. The six patients were followed up for 13 to 70 months (median: 27 months), and no evidence of renal cell carcinoma was noted. Conclusion: Atypical renal cysts are a group of lesions that are heterogeneous in clinical, histological and immunophenotypical and molecular genetic features. FISH analyses suggest that a subset of the cases may be precursors of currently known renal cell carcinomas. Extensively sampling and careful observation of the histological characteristics of the cyst wall are important for distinguishing atypical renal cysts from extensively cystic renal cell carcinomas.

Wild rats as urban detectives for latent sources of asbestos contamination.

Based on a large body of evidence asbestos minerals have been classified as carcinogens. Despite the Italian ban on asbestos in 1992 and the subsequent remediation activities, latent sources of contamination may still represent a hazard where asbestos were particularly used. Using wild rats as sentinel animals, this study aimed at uncovering sites with the greatest potential for non-occupational exposure to asbestos in the city of Casale Monferrato (Piedmont Region, Italy), where the largest Italian manufacturing plant of asbestos-cement had been active. During the study period (2013-2015) a total of 40 wild rats were captured from 16 sampling capture points. The lungs of wild rats have been investigated by using scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS). The SEM-EDS detected the presence of asbestos fibers (tremolite/actinolite, amosite, and chrysotile) in rats' lungs from 11 sampling points. The hypothetical rats' home-range and the observed site-specific concentration of asbestos fibers per gram of dry lung tissue were used to identify areas to be targeted by additional search of latent sources of asbestos. In conclusion, our results showed that the use of wild rats as sentinel animals may effectively integrate the strategies currently in use to reduce the exposure to asbestos.

[Clinicopathologic and molecular characteristics of myxoid angiomatoid fibrous histiocytoma].

Objective: To investigate the molecular genetic and clinicopathologic characteristics, immunophenotypes, diagnostic and differential diagnostic features of myxoid angiomatoid fibrous histiocytoma (MAFH). Methods: Three cases of MAFH were collected from the archives of Zhejiang Provincial People's Hospital between January 2015 to August 2018. The clinical and radiologic features, histomorphology, immunohistochemistry, molecular genetics and prognosis were analyzed. Results: Patients consisted of 2 women and 1 man aged 37 years, 46 years, and 57 years, respectively. The clinical manifestations of 3 patients were presented as a painless, slowly-enlarged mass with a duration ranging of 2 weeks, 2 months and 50 years. These tumors were located at the deep somatic soft tissue of extremities or limbs (right hip, left forearm, left wrist, respectively) and 2 were preoperatively considered as ganglion cyst or giant cell tumor of tendon sheath by imaging examinations. The diameter of circumscribed mass lesion was ranged from 3.0 to 7.5 cm, which exhibited a gray white to tan and gelatinous cut surface. Extensive hemorrhage and cystic changes were observed in 2 cases. Under low magnification, all tumors showed a dense fibrous pseudo-capsule with a peritumoral lymphoplasmacytic cuff and a multi-nodular growth pattern. Blood-filled cystic spaces were observed in 2 tumors. The myxoid stroma occupied 60.0%, 80.0% and 90.0% area of the entire tumor, respectively. Within the myxoid areas, tumor cells were oval to stellate and arranged in cord-like, microcystic and reticular growth patterns. Transitions of myxoid tumor components to more solid areas with typical histology of angiomatoid fibrous histiocytoma (AFH) were observed at least focally in all the three cases. The tumor cells exhibited minimal atypia and scarce mitoses (1 to 2/50 HPF) without necrosis, and prominently focal intracytoplasmic vacuoles were identified in one case. The results of immunohistochemistry staining showed that, 2/3 cases focally expressed desmin, 2/3 focally expressed epithelial membrane antigen (EMA), and 1/3 focally expressed CD99. The positive index of Ki67 was approximately 1% to 5%. Fluorescence in situ hybridization analysis showed that EWSR1 gene rearrangement occurred in all of the three cases. During the period of follow-up, one case showed local recurrence at 15 months, one case showed postoperative recurrence at 24 months, and the recurrent tumor slowly grew for 120 months until the second resection, without recurrence at the following 2 months. The left case showed a disease-free survival at 32 months. Conclusions: MAFH is a rare subtype of AFH with a low-grade behavior and may lead to diagnostic confusions. Carefully searching for the typical AFH histomorphology and combining with EWSR1 gene rearrangement test can help to distinguish MAFH from other mimickers.

[Pigmented microcystic chromophobe renal cell carcinoma: a clinicopathologic analysis of five cases].

Objective: To investigate the clinicopathologic features, diagnostic and differential diagnostic aspects of pigmented microcystic chromophobe renal cell carcinoma (ChRCC). Methods: Five cases of pigmented microcystic ChRCC were collected at Zhejiang Provincial People's Hospital from January 2013 to January 2018. The clinical features, gross and histological appearances, immunohistochemistry and prognosis were analyzed and the relevant literature was reviewed. Results: There were 3 men and 2 women with age range of 45 years to 72 years (mean 57 years). All tumors were incidentally identified by imaging examinations. Grossly, the tumors were well-demarcated and showed diameters ranging from 1.8 cm to 4.0 cm(mean 2.9 cm). On cross section, the tumors were brown to gray tan with solid cut-surface mixed with multiple cysts of variable sizes. Hemorrhage was common, central scar was not seen. Microscopically, the tumors were composed predominantly of irregular and variable-sized microcystic or tubulocystic patterns, with extensive cribriform structures formation and focal adenomatous rearrangements seen in one case each, and focal pseudo-papillary structures (lacking true fibro-vascular cores) seen in two cases. Microscopic calcifications and psammoma bodies were present in all tumors. Four tumors composed mostly of eosinophilic cells whereas 1 predominated in plant-like cells. Brown pigmentations, either intracytoplasmic or extracytoplasmic, were noted in all five cases. The tumor cells had irregular, low-grade nuclei (Paner grade: 1) frequently with binucleation and perinuclar halos. Tumor necrosis or sarcomatous transformation was not seen. By immunohistochemistry, the tumor cells expressed CK, EMA, and E-cadherin diffusely and strongly in five cases; and CK7 and CD117 diffusely in four cases. They were negative for vimentin, CD10, CA9, AMACR/P504s, TFE3, HMB45, Melan A, S-100 protein, synaptophysin and chromogranin. Partial nephrectomies were performed for all five patients; there was no tumor recurrences or metastases at a follow-up of 2 to 55 months (mean, 17 months). Conclusions: Pigmented microcystic ChRCC is a rare histological variant of ChRCC with relatively indolent behavior, and shows morphologic heterogeneity which can elicit a wide range of differential diagnoses. Careful attentions to search for typical features of classic ChRCC with the use of immunohistochemistry can help to distinguish this tumor from its many mimickers.

[Clinicopathologic and molecular characterizations of Sertoli cell tumor, not otherwise specified of the testis].

Objective: To investigate the histomorpholgic spectrum, immunophenotypic, and molecular genetic features of Sertoli cell tumor, not otherwise specified (SCT, NOS) of the testis. Methods: Seven cases of SCT, NOS of the testis were analyzed(4 from Peking University Third Hospital and 3 from Zhejiang Provincial People's Hospital) between 2008 and 2017. The histopathologic features were examined based on HE staining, and EnVision method was used for immunohistochemistry staining of calretinin, inhibin, ß-catenin, cyclinD1, CD10, CKpan, neuroendocrine markers, WT1, Melan A, vimentin, SALL4, GATA3, PAX8, and S-100 protein. Mutational analysis of exon 3 of the CTNNB1 gene by polymerase chain reaction (PCR)-amplified sequences and direct sequencing was performed. Results: Patients ages ranged from 22 to 65 years (mean 43 years). The clinical manifestation in all was a slowly enlarging, painless testicular mass.The maximum diameter of the tumor ranged from 1.5 cm to 3.0 cm (mean 2.1 cm). Sectioning usually disclosed a tan-gray to white mass with vague lobular cut-surface. Microscopically, the tumors were well circumscribed and non-encapsulated; the tumor cells were rearranged in multiple growth patterns from diffuse solid sheets to trabeculae and cords, ribbon and solid or hollow tubules setting in variable amount of acellular fibrous stroma. Two cases showed acellular collagenous stroma constituted >50% of the tumor confirming to the diagnosis of sclerosing SCT. One case demonstrated a prominent myxoid stromal change. The tumor cells typically had moderate amounts of pale to lightly eosinophilic cytoplasm, 2 tumors had variable cells with abundant lipid-rich cytoplasm, and 1 other tumor showed scattered aggregates of multinucleated tumor cells. The tumor cells were bland-appearing without any evidence of atypia, mitoses were noted in 2 tumors (both were 1/50 HPF), but necrosis was absent. Immunohistochemical staining results as follows: vimentin (diffuse, 7/7), CD10 (diffuse membrane, 7/7); diffuse ß-catenin nuclear and cytoplasm staining in 5 of 7 cases, and all the 5 cases showed diffuse cyclin D1 nuclear staining, ß-catenin membrane staining in 2 of 7 cases, CKpan (5/7, focal or diffuse), calretinin (focal, 5/6), inhibin (focal, 3/7), synaptophysin (focal, 2/6), CD56 (focal or diffuse, 4/5), WT1 (diffuse nuclear, 4/5), and S-100 protein (diffuse, 3/7), and chromogranin A, Melan A, PAX8, GATA3 and SALL4 all were negative. Molecular genetic studies of PCR and direct sequencing showed CTNNB1 mutations in 4 of 7 (4/7) cases, 4 of the four mutation-carrying cases showed diffuse ß-catenin nuclear and cytoplasm immunoreactivity and diffuse cyclin D1 nuclear immunoreactivity in the tumor cells. Conclusions: SCT, NOS of the testis typically shows significant heterogeneities in both morphology and immunohistochemistry, thus causing differential diagnostic confusions. Molecular analyses showed mutations of exon 3 of CTNNB1 in more than half of these tumors, and nuclear accumulation of ß-catenin and over expression of cyclin D1 can be useful for the differential diagnosis of SCT, NOS.

Dioxin-like Compounds in Lake Fish Species: Evaluation by DR-CALUX Bioassay.

Fish consumption is the principal source of intake of organochlorinated compounds in humans. Compared with other types of foods of animal origin, fish contain the highest levels of polychlorinated biphenyls (PCBs), polychlorinated dibenzo- p-dioxins, and polychlorinated dibenzofurans, all of which are classified as highly toxic organochlorine compounds. Currently, lakes and fish farms in northern Italy are not regularly monitored for PCBs and dioxins in areas contaminated by industrial sources, partially because of the high costs of traditional analytical methods that limit the number of samples to be analyzed. The DR-CALUX cell bioassay is based on the uptake of the cellular aryl hydrocarbon receptor (AhR) for dioxins and dioxin-like compounds. The aim of this study was to assess the levels of dioxins and dioxin-like PCB contamination in Lake Maggiore and Lake Como, two lakes in northwestern Italy, and in nearby areas. The levels were quantified using the cell bioassay DR-CALUX and reference controls in two wild fish species, perch ( Perca fluviatilis) and roach ( Rutilus rutilus), and in a farmed species, rainbow trout ( Oncorhynchus mykiss). Tissue samples collected from the farmed rainbow trout were also submitted to immunohistochemical analysis of CYP1A expression as a marker for environmental pollutant-induced liver damage. The levels of dioxins, furans, and dioxin-like PCBs were all below the maximum levels and action limits set by European Union Regulation, suggesting no risk for human health associated with the consumption of the fish species caught or farmed in these areas.

Using multi-criteria risk ranking methodology to select case studies for a generic risk assessment framework for exotic disease incursion and spread through Europe.

We present a novel approach of using the multi-criteria pathogen prioritisation methodology as a basis for selecting the most appropriate case studies for a generic risk assessment framework. The approach uses selective criteria to rank exotic animal health pathogens according to the likelihood of introduction and the impact of an outbreak if it occurred in the European Union (EU). Pathogens were evaluated based on their impact on production at the EU level and international trade. A subsequent analysis included criteria of relevance to quantitative risk assessment case study selection, such as the availability of data for parameterisation, the need for further research and the desire for the case studies to cover different routes of transmission. The framework demonstrated is flexible with the ability to adjust both the criteria and their weightings to the user's requirements. A web based tool has been developed using the RStudio shiny apps software, to facilitate this.

A cross-sectional study to identify a set of risk factors for caprine herpesvirus 1 infection.

BACKGROUND: Caprine herpesvirus 1 (CpHV-1) causes neonatal mortality and reproductive failure in goats. Despite its impact on herd reproductive performance, few studies have investigated the risk factors associated with CpHV-1 infection. The aim of this cross-sectional study was to identify potential herd- and host-level risk factors associated with CpHV-1 prevalence in a goat population with heterogeneous seropositivity for CpHV-1. RESULTS: Blood samples and individual data from 4542 goats were collected from 255 herds in Piedmont, Italy. Enzyme-linked immunosorbent assay (ELISA) and serum neutralization tests were carried out to detect antibodies against CpHV-1. A mixed-effects model was applied to identify any statistical association between CpHV-1 seropositivity and a set of putative host-level and herd-level risk factors. A total of 630 samples tested were found positive by ELISA (prevalence = 13.9%; 95% confidence interval (CI) 12.9-14.9). Of the 255 tested herds, 85 were classified as positive for the presence of at least one gB-positive animal (herd prevalence 33.3%, 95% CI 27.5-39.2), with a within-herd prevalence between 0.7 and 100% (Q1 = 17.6%; median = 32.3%; Q3 = 50%) (Q = quartiles). The prevalence ratios showed a statistical association with the following risk factors: breeds other than Saanen, older age, larger herd size, meat and extensive herds, and co-existence of CAEV-infected animals. CONCLUSIONS: Results from this cross sectional study may help to elucidate the natural history of the infection and inform targeted strategies to control a disease with a potentially important impact on animal health and goat farming economy.

[Clinicopathologic features of atypical spindle cell lipomatous tumor].

Objective: To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Methods: Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People's Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. Results: All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, ß-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. Conclusions: ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.

[Extrapleural solitary fibrous tumor with uncommon histology: a clinicopathologic analysis of 7 cases].

Objective: To investigate the clinicopathologic characteristics, immunophenotypes, and differential diagnostic features of extra-pleural solitary fibrous tumor (SFT) with uncommon histology. Methods: Seven cases of extra-pleural SFT with uncommon histology were collected during January 2015 and December 2016 in Zhejiang Provincal People's Hospital; the clinical and radiologic features, histomorphology, immunophenotype and prognosis were analyzed. EnVision method was used for immunohistochemical staining of STAT6, CD34 and other differential diagnosis associated markers. Results: There were five male and two female patients, age from 23 to 54 years (mean=39 years). Three tumors were located in the soft tissue of head and neck, two in trunk subcutaneous soft tissue, one in sella region, and one in the kidney. Grossly the tumors ranged from 0.4 to 8.0 cm (mean=3.1 cm). Microscopically, all three head and neck cases resembled giant cell angiofibroma/giant cell subtype SFT, and one case showed sheet-like pattern of the multinucleated syncytial cells, creating a biphasic arrangement similar to myofibroma. Both truncal tumor resembled lipomatous type SFT, with one similar to dermatofibrosarcoma protuberans and the other to atypical spindle cell lipomatous tumor. The sella tumor showed morphology of a conventional SFT with high grade sarcomatous transformation. The renal tumor demonstrated a malignant SFT with entrapped benign renal tubules, mimicking a biphase synovial sarcoma or a malignant mixed epithelial and stromal tumor. By immunohistochemistry, all seven SFTs showed diffuse and strong nuclear reactivity to antibody against STAT6. Conclusions: Extra-pleural SFTs show a significant heterogeneity of morphology and biological behavior which could cause differential confusion.Careful attention to its characteristic histomorphology with the use of STAT6 immunohistochemistry can help distinguish this tumor from its many mimickers.

DISCONTOOLS: Identifying gaps in controlling bovine spongiform encephalopathy.

This article summarizes the 2016 update of the DISCONTOOLS project gap analysis on bovine spongiform encephalopathy (BSE), which was based on a combination of literature review and expert knowledge. Uncertainty still exists in relation to the pathogenesis, immunology and epidemiology of BSE, but provided that infected material is prohibited from entering the animal feed chain, cases should continue to decline. BSE does not appear to spread between cattle, but if new strains with this ability appear then control would be considerably more difficult. Atypical types of BSE (L-BSE and H-BSE) have been identified, which have different molecular patterns and pathology, and do not display the same clinical signs as classical BSE. Laboratory transmission experiments indicate that the L-BSE agent has zoonotic potential. There is no satisfactory conclusion regarding the origin of the BSE epidemic. C-BSE case numbers declined rapidly following strict controls banning ruminant protein in animal feed, but occasional cases still occur. It is unclear whether these more recent cases indicate inadequate implementation of the bans, or the possibility that C-BSE might occur spontaneously, as has been postulated for H- and L-BSE. All of this will have implications once existing bans and levels of surveillance are both relaxed. Immunochemical tests can only be applied post-mortem. There is no immunological basis for diagnosis in the live animal. All aspects of disease control are expensive, particularly surveillance, specified risk material removal and feed controls. There is pressure to relax feed controls, and concurrent pressure from other sources to reduce surveillance. While the cost benefit argument can be applied successfully to either of these approaches, it would be necessary to maintain the ban on intraspecies recycling and some baseline surveillance. However, the potential risk is not limited to intraspecies recycling; recycling with cross-species transmission may be an ideal way to select or/and modify properties of transmissible spongiform encephalopathies agents in the future.

[Clinicopathologic and molecular genetic characterizations of biphenotypic sinonasal sarcoma].

Objective: To investigate the clinicopathologic characteristics, immunophenotypes, molecular genetics, and diagnostic and differential diagnostic features of biphenotypic sinonasal sarcoma (BSNS). Methods: Three cases of BSNS were retrieved, the histomorphology, immunophenotype and molecular genetics were analyzed with review of literature. Results: There were 2 male and 1 female patient aged 45, 29 and 40 years, respectively.Computed tomography and magnetic resonance imaging examinations showed a large polypoid mass occupying the sinonasal cavity in all 3 patients. Microscopically, these tumors were un-circumscribed and composed of cellular spindle-shaped cells arranged in long and interlaced fascicles. A hemangiopericytoma-like growth pattern was frequently identified. The overlying hyperplastic respiratory epithelium invaginated down into the tumor forming a cystic (2 cases), glandular (1 case) structures and inverted in a papilloma-like (1 case)pattern, and foci of eosinophilic metaplasia were also noted in 2 of the three cases. The tumor nuclei were bland-appearing, mitoses were scarce and necrosis was absent. Immunohistochemically, the tumor cells showed co-expression of neural and myogenic markers in all the 3 cases, including that 3/3 showed diffuse and strong positivity of S-100 protein, 3/3 positivity of smooth muscle actin (1 diffuse and 2 focal), 1/2 diffuse positivity of calponin, 1/3 focal positivity of desmin, and 1/1 focal positivity of MyoD1.In addition, 1 detected for ß-catenin showed focal nuclear positivity. None of the 3 showed positivity to cytokeratin, CD34 or SOX10 in the tumor cells.Ki-67 showed an index <5%, 10% and <2%, respectively. Fluorescence in situ hybridization analysis showed rearrangements of PAX3 gene in all 3 cases. In case 3, reverse transcription polymerase chain reaction, followed by Sanger sequencing, demonstrated an in-frame fusion between PAX3 and FOXO1.Follow-up information (range 3-15 months)showed no evidence of local recurrence or distant metastasis in three cases. Conclusions: BSNS is a newly described entity which can be readily confused with a variety of benign and malignant spindle cell tumors encountered in the sinonasal cavity; immunohistochemistry co-expression of neural and myogenic markers and PAX3 gene rearrangement can help distinguish this tumor from its many mimickers.

[Clinicopathologic and molecular characteristics of malignant gastrointestinal neuroectodermal tumors].

Objective: To investigate the clinicopathologic and molecular characteristics, diagnostic, differential diagnostic and prognostic features of malignant gastrointestinal neuroectodermal tumor. Methods: Two cases of malignant gastrointestinal neuroectodermal tumor were retrieved; the clinical and radiologic features, histomorphology, immunophenotype, molecular genetics and prognosis were analyzed and the relevant literature reviewed. Results: Case 1 was a 57-year-old male, presented with recurrent abdominal pain and melena. Pelvic imaging showed a circumscribed thickening of the wall of a small intestinal segment, and a malignant lymphoma was favored. Case 2 was a 24-year-old male, presented with recurrent small intestinal malignancy. Imaging demonstrated multiple masses in the peritoneal and pelvic cavities, and a malignant gastrointestinal stromal tumor with multiple metastases was suspected. Grossly both tumors were located mainly in the muscularis propria of small intestine. Case 1 showed a single 5.5 cm tumor; and case 2 consisted of two tumors measuring 4 cm and 6 cm respectively. Microscopic examination of both tumors showed small round blue, but focally spindled or clear tumor cells in solid pattern. The tumor cells had scanty cytoplasm, indistinctive nucleoli and brisk mitoses. Osteoclast-like giant cells were dispersed within the stroma. In case 1 rosette-like and pseudo-papillary growth patterns were noted, and in case 2 there were variable-sized hemorrhagic cysts. By immunohistochemistry, both tumors showed strong and diffuse expression of SOX10 and S-100, and focal to diffuse expression of neuroendocrine markers (CD56 or synaptophysin). Case 2 exhibited focal reactivity to pan-cytokeratin. Both tumors lacked expression of markers associated with gastrointestinal stromal tumor, smooth muscle tumor, melanoma (HMB45 or Melan A), dendritic cell tumor and Ewing sarcoma. Fluorescence in situ hybridization analysis demonstrated EWSR1 rearrangement in both tumors and the next generation sequencing confirmed EWSR1-ATF1 gene fusion in case 2. At follow-up of 16 months, case 1 was recurrence or metastasis free; whereas case 2 showed multiple recurrences and metastases within 19 months although stable disease was transiently achieved when treated with combinations of multidrug and targeted chemotherapy. Conclusions: Malignant gastrointestinal neuroectodermal tumor is a rare and aggressive soft tissue sarcoma with a predilection for small intestine. It has distinctive morphologic, immunohistochemical and molecular characteristics and needs to be distinguished from other small blue round and spindle cell tumors that occur in the gut. Careful attentions to its characteristic histomorphology with the judicious use of immunohistochemistry and molecular genetics can help to distinguish this tumor from its many mimickers.

Familial hypercholesterolaemia with tuberous and tendinous xanthomas: case report and mutation analysis.

Xanthomas are important clinical manifestations of disordered lipid metabolism, which are mostly found in patients with familial hypercholesterolaemia (FH), an inherited disorder that is predominantly caused by mutations in the low-density lipoprotein receptor gene (LDLR). Tuberous and tendinous xanthomas with wide distribution and large size are rare; however, they may indicate the severity of FH, and tend to be found in homozygous FH. In this study, we investigated the clinical and genetic aspects of a young patient with FH presenting with multiple large masses in various locations. The lesions on the elbows and buttocks were locally excised and subsequently confirmed by biopsy to be xanthomas. Genetic analysis further confirmed that the patient was compound heterozygous for two mutations in both alleles of the LDLR gene. This rare case of compound heterozygous FH presenting with multiple large and widely distributed xanthomas provides a better understanding of FH and xanthomas.

Association of a specific major histocompatibility complex class IIß single nucleotide polymorphism with resistance to lactococcosis in rainbow trout, Oncorhynchus mykiss (Walbaum).

Major histocompatibility complex (MHC) loci encode glycoproteins that bind to foreign peptides and initiate immune responses through their interaction with T cells. MHC class II molecules are heterodimers consisting of α and ß chains encoded by extremely variable genes; variation in exon 2 is responsible for the majority of observed polymorphisms, mostly concentrated in the codons specifying the peptide-binding region. Lactococcus garvieae is the causative agent of lactococcosis, a warm-water bacterial infection pathogenic for cultured freshwater and marine fish. It causes considerable economic losses, limiting the profitability and development of fish industries in general and the intensive production of rainbow trout, Oncorhynchus mykiss (Walbaum), in particular. The disease is currently controlled with vaccines and antibiotics; however, vaccines have short-term efficacy, and increasing concerns regarding antibiotic residues have called for alternative strategies. To explore the involvement of the MHC class II ß-1 domain as a candidate gene for resistance to lactococcosis, we exposed 400 rainbow trout to naturally contaminated water. One single nucleotide polymorphism (SNP) and one haplotype were associated with resistance (P < 0.01). These results are promising for using MHC class IIß as a molecular marker in breeding rainbow trout resistant to lactococcosis.

Serological and virological survey of hepatitis E virus in wild boar populations in northwestern Italy: detection of HEV subtypes 3e and 3f.

Although rare in developed countries, most acquired human cases of hepatitis E virus (HEV) infection are associated with travel to developing countries where HEV is endemic. Increasingly, however, sporadic, non-travel-related HEV cases have been reported in developed countries. In Italy, only two studies to date have investigated the presence of HEV in wild boars. Here, we report a serological and virological survey of HEV in wild boar populations in northwestern Italy. During the hunting season, 594 serum and 320 liver samples were collected and screened for antibodies to HEV and HEV RNA. Overall, the seroprevalence was 4.9 %, and HEV RNA was detected in 12 liver samples (p = 3.7 %). No serum samples tested positive for HEV RNA. Phylogenetic analysis of the ORF2 region revealed that the isolates clustered within genotype 3, subtypes 3e and 3f, and were closely related to HEV strains previously detected in domestic pigs farmed in the same geographic area. Although the routes of viral transmission are still poorly understood, our data show that HEV genotypes 3e and 3f circulate in wild boars in northwestern Italy. Also, they provide evidence that autochthonous HEV infections in Italy could also be linked to wild boar populations, suggesting an increased risk for domestically acquired HEV infection in humans through wild animals. The HEV sequences determined in this study may be useful for comparing present and future human isolates to identify transmission events between wild boar, humans, and farmed pigs. Similarly to other more commonly known zoonotic agents, HEV should be included in national or regional disease surveillance programs for wild animals.