Female offspring gestated in hypothyroxinemia and infected with human Metapneumovirus (hMPV) suffer a more severe infection and have a higher number of activated CD8+ T lymphocytes.

Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71+ and FasL+) CD8+ T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV.

[Littoral cell angioma of the spleen. Report of one case]. / Angioma de células litorales del bazo. Un diagnóstico de lesión focal esplénica. Caso clínico.

Splenic vascular neoplasms are the most common form of spleen tumors. Among them, littoral cell angioma is rare and it is frequently an incidental finding in imaging studies. It has no specific clinical, laboratory or imaging findings. Splenectomy allows definitive diagnosis throughout a histopathological examination. We report a 52-year-old man presenting with asthenia and abdominal distension. Computed tomography with intravenous contrast showed multiple splenic hypodense masses and a prostatic enlargement. Presuming a lymphoma, a laparoscopic splenectomy was performed. Histopathologic examination diagnosed littoral cell angioma. During urological follow-up, a prostate adenocarcinoma was diagnosed.

Síndrome hematofagocítico como manifestación inicial de linfoma de Hodgkin clásico / Hemophagocytic syndrome as the initial manifestation of Hodgkin lymphoma

Introducción: las histiocitosis son un grupo heterogéneo de enfermedades; una de ellas es el síndrome hematofagocítico (SHF). Sus causas pueden ser infecciosas, neoplásicas, autoinmunes o relacionadas a inmunodeficiencias adquiridas; el linfoma de Hodgkin clásico (LHc) es una causa poco frecuente. Se reporta el caso de un hombre inmunodeprimido de 35 años que ingresa al hospital febril y con insuficiencia respiratoria grave.Métodos: se recopiló información clínica pertinente y se revisó material de biopsia estudiado con tinción de hematoxilina ­ eosina, técnica inmunohistoquímica e hibridación in situ cromogénica. Resultados: estudios de laboratorio muestran pancitopenia, altera-ción de pruebas hepáticas, hipertrigliceridemia, hipoalbuminemia e hiperferritinemia. El estudio de médula ósea hematopoyética con mielograma y biopsia muestran hallazgos compatibles con LHc, signos de hemofagocitosis e infección por virus Epstein-Barr (VEB). Se diagnostica SHF como primera manifestación de LHc e infección por VEB. Conclusiones: a la fecha, se describen 74 pacientes re-portados con SHF como manifestación de LHc; en el 84% fue su primera manifestación. Si bien la presentación clínica presentada es infrecuente, se ha propuesto una asociación en hombres con inmunodeficiencia, SHF, LHc e infección por VEB; por lo que se sugiere una sospecha diagnóstica alta.

Introduction: histiocytosis are a heterogeneous group of diseases; one of them is the hemophagocytic syndrome (HS). Its causes can be infectious, neoplastic, autoimmune or related to acquired immunodeficiencies; classic Hodgkin lymphoma (cHL) is a rare cause.We present the case of an immunosuppressed 35-year-old male who was admitted with fever and acute respiratory failure. Methods:pertinent clinical reports and biopsy material were reviewed; including hematoxylin-eosin stained slides from formalin-fixed and pa-raffin-embedded tissue blocks and immunohistochemical and chromogenicin situhybridisation studies. Results:laboratory studies revealed pancytopenia, abnormal liver functions, hypertriglyceridemia, hypoalbuminemia e hyperferritinemia. Bone marrow aspiration smear and biopsy showed a malignant lymphoid neoplasm consistent with cHL, signs of hemophagocytosis, and Epstein-Barr virus (EBV) infection. HS, as an initial manifestation of cHL, was diagnosed.Conclusions:to our best knowledge, there are 74 reported cases of cHL with HS; in 84% it was the initial clinical manifestation. Though this is an unusual presentation, an association between immu-nodeficiency, HS, cHL, and EBV infection has been proposed; so a high diagnostic suspicion is suggested.

Angioma de células litorales del bazo: un diagnóstico de lesión focal esplénica: caso clínico / Littoral cell angioma of the spleen: report of one case

Splenic vascular neoplasms are the most common form of spleen tumors. Among them, littoral cell angioma is rare and it is frequently an incidental finding in imaging studies. It has no specific clinical, laboratory or imaging findings. Splenectomy allows definitive diagnosis throughout a histopathological examination. We report a 52-year-old man presenting with asthenia and abdominal distension. Computed tomography with intravenous contrast showed multiple splenic hypodense masses and a prostatic enlargement. Presuming a lymphoma, a laparoscopic splenectomy was performed. Histopathologic examination diagnosed littoral cell angioma. During urological follow-up, a prostate adenocarcinoma was diagnosed.

Linfoma anaplásico de células grandes asociado a implantes mamarios diagnosticado mediante punción por aguja fina. Caso clínico

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin T-cell lymphoma, recently defined in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms. It occurs more commonly when textured implants are used and appears clinically as a late seroma. Cytologically, these lesions are composed of large atypical cells with pleomorphic nucleus and an immunophenotype positive for T cell markers and CD30, and negative for ALK1. We report a 56-years-old woman with breast implants who developed a periprosthetic seroma three years after surgery. A fine needle aspiration of the lesion was carried out. Cytology and the immunocytochemical study revealed cells compatible with BIA-ALCL. The flow cytometric study was negative. Excisional biopsy of the capsule was performed, observing that the neoplastic cells were confined to the inner surface of the capsule. Imaging studies did not find evidence of disseminated disease. The present case demonstrates the importance of the study of any late periprosthetic effusion, which can be performed using fine needle aspiration.

Transcriptomic profiles reveal differences in zinc metabolism, inflammation, and tight junction proteins in duodenum from cholesterol gallstone subjects.

Cholesterol Gallstone Disease (GSD) is a common multifactorial disorder characterized by crystallization and aggregation of biliary cholesterol in the gallbladder. The global prevalence of GSD is ~10-20% in the adult population but rises to 28% in Chile (17% among men and 30% among women). The small intestine may play a role in GSD pathogenesis, but the molecular mechanisms have not been clarified. Our aim was to identify the role of the small intestine in GSD pathogenesis. Duodenal biopsy samples were obtained from patients with GSD and healthy volunteers. GSD status was defined by abdominal ultrasonography. We performed a transcriptome study in a discovery cohort using Illumina HiSeq. 2500, and qPCR, immunohistochemistry and immunofluorescence were used to validate differentially expressed genes among additional case-control cohorts. 548 differentially expressed genes between GSD and control subjects were identified. Enriched biological processes related to cellular response to zinc, and immune and antimicrobial responses were observed in GSD patients. We validated lower transcript levels of metallothionein, NPC1L1 and tight junction genes and higher transcript levels of genes involved in immune and antimicrobial pathways in GSD patients. Interestingly, serum zinc and phytosterol to cholesterol precursor ratios were lower in GSD patients. A significant association was observed between serum zinc and phytosterol levels. Our results support a model where proximal small intestine plays a key role in GSD pathogenesis. Zinc supplementation, modulation of proximal microbiota and/or intestinal barrier may be novel targets for strategies to prevent GSD.

[Anaplastic large cell lymphoma associated with breast implants, diagnosed by fine needle aspiration. Report of one case]. / Linfoma anaplásico de células grandes asociado a implantes mamarios diagnosticado mediante punción por aguja fina. Caso clínico.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin T-cell lymphoma, recently defined in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms. It occurs more commonly when textured implants are used and appears clinically as a late seroma. Cytologically, these lesions are composed of large atypical cells with pleomorphic nucleus and an immunophenotype positive for T cell markers and CD30, and negative for ALK1. We report a 56-years-old woman with breast implants who developed a periprosthetic seroma three years after surgery. A fine needle aspiration of the lesion was carried out. Cytology and the immunocytochemical study revealed cells compatible with BIA-ALCL. The flow cytometric study was negative. Excisional biopsy of the capsule was performed, observing that the neoplastic cells were confined to the inner surface of the capsule. Imaging studies did not find evidence of disseminated disease. The present case demonstrates the importance of the study of any late periprosthetic effusion, which can be performed using fine needle aspiration.

Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.

Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.

Early-onset EBV-positive post-transplant plasmablastic lymphoma arising in a liver allograft: a case report and literature review.

We report a case of a 51-year-old man who received a cadaveric liver allograft for autoimmune and hepatopulmonary syndrome. The patient was admitted with symptoms of progressive vomiting and diarrhea 16 months after transplantation. Laboratory studies showed abnormal liver functions, and abdominal magnetic resonance imaging (MRI) showed a 76-mm heterogeneous mass in the liver. Histological examination showed a malignant lymphoid neoplasm with plasmablastic features. Plasmablastic lymphoma (PL) is rare in the post-transplantation period. To the best of our knowledge, only 25 well-documented cases of posttransplant PL, including ours, have been described.

Anatomic hepatectomy as a definitive treatment for hepatolithiasis: a cohort study.

BACKGROUND: Treatment requirements in hepatolithiasis may vary and may involve a multidisciplinary approach. Surgical resection has been proposed as a definitive treatment. OBJECTIVES: This study aimed to evaluate the clinical results of anatomic liver resection among Chilean patients with hepatolithiasis. METHODS: An historical cohort study was conducted. Patients who underwent hepatectomy as a definitive treatment for hepatolithiasis from January 1990 to December 2010 were included. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded. Preoperative, operative and postoperative variables were evaluated. RESULTS: A total of 52 patients underwent hepatectomy for hepatolithiasis. The mean ± standard deviation patient age was 49.8 ± 11.8 years (range: 24-78 years); 65.4% of study subjects were female. A total of 75.0% of subjects had a history of previous cholecystectomy. The main presenting symptom was abdominal pain (82.7%). Hepatic involvement was noted in the left lobe in 57.7%, the right lobe in 34.6% and bilaterally in 7.7% of subjects. The rate of postoperative clearance of the biliary tree was 90.4%. Postoperative morbidity was 30.8% and there were no postoperative deaths. Three patients had recurrence of hepatolithiasis, which was associated with Caroli's disease in two of them. Overall 5-year survival was 94.5%. CONCLUSIONS: Anatomic liver resection is an effective treatment in selected patients with hepatolithiasis and is associated with low morbidity and no mortality. At longterm follow-up, anatomic hepatectomy in these patients was associated with a lower rate of recurrence.

Florid reactive lymphoid hyperplasia (lymphoma-like lesion) of the uterine cervix.

Lymphoma-like lesion (LLL) of the female genital tract is an older term in the literature that describes a florid reactive lymphoid proliferation that can be misinterpreted as lymphoma. Multiple causes of LLL have been suggested but most cases remain unexplained. We describe the clinicopathologic features of 6 patients with LLL involving the uterine cervix. Five patients presented with abnormal Papanicolaou test (Pap smear), and 3 patients had a biopsy procedure performed prior to detection of LLL in a loop electrosurgical excision procedure (LEEP). In each specimen, surface epithelial erosion was associated with a superficial, polymorphous lymphoid infiltrate with numerous scattered large cells, without cellular necrosis or sclerosis. Squamous dysplasia was present in 4 patients. Immunohistochemical studies revealed a mixed population of B- and T-lymphoid cells. T-cells were more numerous but B-cells and formed aggregates or sheets in areas. The large cells were predominantly B-cells positive for CD20 and negative for CD3 in all cases. CD30 was positive 3 cases, and Epstein-Barr virus-encoded RNA was positive in 3 cases. Assessment for clonality in 1 patient using polymerase chain reaction (PCR) methods revealed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements. At last clinical follow-up there was no evidence of progressive or systemic disease. We conclude that LLL of the cervix has a number of etiologies and that a prior surgical procedure, present in 3 patients in this study, is another possible etiology. As has been reported by others, monoclonal IgH gene rearrangements can be detected in this entity which has a benign clinical course.

Leukocytoclastic vasculitis as early manifestation of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

Extensive necrotizing vasculitis (ENV) is a rare paraneoplastic phenomenon, and the majority of cases reported are associated with hematolymphoid neoplasms. Histologically, most cases of ENV represent leukocytoclastic vasculitis (LCV). Here we report the clinicopahological features of a 68-year-old man with ENV associated to a Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) of the elderly, a newly recognized lymphoproliferative disorder, most likely representing a paraneoplastic manifestation. The patient was treated with standard chemotherapy regimen for malignant lymphoma. Due to the extensive involvement of the extremities by ENV, surgical debridement was not feasible and a novel therapy based on CHITOSAN apposits was initiated with overall good response and subsequent re-epithelization of the skin lesions. The patient died of sepsis secondary to a Pseudomona pneumonia 17 months after diagnosis.

[Primary cerebral lymphomatoid granulomatosis in a HIV-positive patient. Case report]. / Granulomatosis linfomatoide cerebral primaria en paciente VIH positivo. Caso clínico.

We report a 34-years-old male, with a history of hepatitis B and human immunodeficiency virus (HIV) infection that was admitted to the hospital with malaise, weight loss, frontal behavior and chest pain. Imaging studies showed two frontal cortical/subcortical nodules. A stereotactic cerebral biopsy showed reactive gliosis and a prominent atypical angiocentric and angiodestructive lymphoid infiltrate containing large pleomorphic CD20 and EBV-positive cells consistent with Lymphomatoid granulomatosis. Other studies were negative. The patient was lost from follow up.

Granulomatosis linfomatoide cerebral primaria en paciente VIH positivo: Caso clínico / Primary cerebral lymphomatoid granulomatosis in a HIV-positive patient: Case report

We report a 34-years-old male, with a history of hepatitis B and human immunodeficiency virus (HIV) infection that was admitted to the hospital with malaise, weight loss, frontal behavior and chest pain. Imaging studies showed two frontal cortical/subcortical nodules. A stereotactic cerebral biopsy showed reactive gliosis and a prominent atypical angiocentric and angiodestructive lymphoid infiltrate containing large pleomorphic CD20 and EBV-positive cells consistent with Lymphomatoid granulomatosis. Other studies were negative. The patient was lost from follow up.

Overexpression of p73 as a tissue marker for high-risk gastritis.

PURPOSE: Histologic assessment of high-risk gastritis for the development of gastric cancer is not well defined. The identification of tissue markers together with the integration of histologic features will be required for this assessment. EXPERIMENTAL DESIGN: Matched tumor/nontumor adjacent mucosa (NTAM) of 91 early gastric cancer and 148 chronic gastritis cases were evaluated for histologic characteristics (atrophy, intestinal metaplasia, chronic inflammation, polymorphonuclear infiltration, and Helicobacter pylori) by the Sydney System. Atrophy risk assessment was also evaluated by the Operative Link on Gastritis Assessment (OLGA) staging system. Eight tissue markers (BRCA1, HSP90, STAT1, FHIT, EGFR, p73, p53, p16INK4a) and EBV were also evaluated by tissue microarray/immunohistochemistry/in situ hybridization platform. Data were analyzed by contingency tables (2 x 2) using Fisher's exact two-tailed test (P < 0.001) and integrated by Significance Analysis of Microarrays (SAM) and clustering analysis. RESULTS: Histologically, NTAM have severe intestinal metaplasia/chronic inflammation and severe atrophy assessed by Sydney and OLGA staging systems. H. pylori infection was similar in both groups, and EBV was found only in 5.5% of the tumor samples. Overexpression of p73 was higher in NTAM (50.5%) than in chronic gastritis (10.8%; P < 0.0001). Integration of histologic features and tissue markers showed that overexpression of p73, severe atrophy, and OLGA stage 4 were the most relevant features in NTAM. Clustering analysis correctly assigned NTAM and control cases (P < 0.0001). CONCLUSIONS: Overexpression of p73 should be considered for the assessment of high-risk chronic gastritis. SAM allows the integration of histology and tissue markers for this assessment.

[Cutaneous histiocytic sarcoma: report of one case]. / Sarcoma histiocítico cutáneo: reporte de un caso.

Histiocytic sarcoma (HS) is a rare hematologic malignancy with morphologic and immunophenotypic evidence of histiocytic differentiation. Previously known as "true histiocytic lymphoma", the tumor follows an aggressive clinical course. Involvement of lymph nodes, skin, and extranodal sites has been described. Among the latter, approximately 29 cases involving the skin have been reported. On pathology, the lesion shows a diffuse proliferation of large epitheloid histiocytes with marked pleomorphism. We report a 78 year-old male who presented with a nodular lesion in the forehead, involving the skin and son tissue. The pathological diagnosis was a HS. The patient was lost from follow up.

Sarcoma histiocítico cutáneo: Reporte de un caso / Cutaneous histiocytic sarcoma: Report of one case

Histiocytic sarcoma (HS) is a rare hematologic malignancy with morphologic and immunophenotypic evidence of histiocytic differentiation. Previously known as "true histiocytic lymphoma", the tumor follows an aggressive clinical course. Involvement of lymph nodes, skin, and extranodal sites has been described. Among the latter, approximately 29 cases involving the skin have been reported. On pathology, the lesion shows a diffuse proliferation of large epitheloid histiocytes with marked pleomorphism. We report a 78 year-old male who presented with a nodular lesion in the forehead, involving the skin and son tissue. The pathological diagnosis was a HS. The patient waslost from follow up.

Lymphomas involving the breast: a study of 106 cases comparing localized and disseminated neoplasms.

Lymphomas involving the breast account for approximately 2% of extranodal and <1% of all non-Hodgkin lymphomas. Our aim in this study was to classify breast lymphomas using the World Health Organization classification and then compare this classification with clinical, histologic, and radiologic findings as well as survival. The study group included 106 patients with breast lymphoma (105 women and 1 man). The neoplasms were divided into 2 groups based on extent of disease at initial diagnosis: localized disease (n=50) and disseminated disease (n=56). The follow-up period ranged from 4 to 252 months (median, 49 mo). Almost all (97%) patients presented with a palpable breast mass or masses. In the localized group, diffuse large B-cell lymphoma (DLBCL) was most frequent (n=32, 64%). In the disseminated group, follicular lymphoma was most frequent and exclusive to this group (P=0.0004). Mucosa-associated lymphoid tissue lymphomas occurred in both groups without a significant difference in frequency. A variety of other types of B-cell and T-cell non-Hodgkin lymphomas and classical Hodgkin lymphoma involved the breast at much lower frequency; most of these neoplasms involved the breast as part of disseminated disease. The clinical presentation correlated with radiologic findings: localized lymphomas presented as solitary masses, whereas disseminated lymphomas commonly presented as multifocal masses. There was a significant difference in the disease-free survival between patients with localized and disseminated DLBCL (P=0.003). In the disseminated group, patients with DLBCL had a worse disease-free survival compared with patients with mucosa-associated lymphoid tissue lymphoma or follicular lymphoma (P=0.01).