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BACKGROUND: Collagenous sprue (CS) is a rare form of enteropathy that had been reported to be associated with celiac disease (CD) and collagenous colitis (CC). The aim of our study was to compare the clinical features, treatments, and outcomes of CS, CD, and CC. METHODS: All patients with histologic diagnosis of CS, CD, or CC with complete clinical data were extracted from our pathology database between 1990 and 2015. Demographic and clinical features were recorded along with treatments and outcomes. RESULTS: A total of 21 patients with CS were included. Overall CS patients were more symptomatic with 17 (81.0%) patients with diarrhea and 15 (71.4%) with unintentional weight loss. Positive celiac serology was noted in 5 (23.8%) CS patients. CS patients had higher rates for disease-related temporary total parenteral nutrition (TPN) use (38.1% vs. 1.1% vs. 1.0%, P < 0.0001) and disease-related hospitalization (52.4% vs. 3.3% vs. 8.2%, P < 0.0001) than that in CD and CC patients. Twenty CS patients received treatments, including the combination of gluten-free diet (GFD) and corticosteroids (n = 12), GFD only (n = 2), and corticosteroids only (n = 6). All CS patients showed symptomatic reliefs with treatment. Although CS patients had a higher rate for hospitalization and TPN use, disease-related death was not observed in all three groups. CONCLUSIONS: Collagenous sprue patients had more severe clinical presentation than patients with CD and CC and therefore had higher demand for temporary TPN and hospitalization. Nevertheless, a prompt use of steroids and/or GFD upon histologic diagnosis of CS may have contributed to an overall excellent prognosis.
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Doença Celíaca , Colite Colagenosa , Espru Colágeno , Corticosteroides/uso terapêutico , Idoso , Doença Celíaca/terapia , Colite Colagenosa/terapia , Espru Colágeno/terapia , Diarreia , Dieta Livre de Glúten , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral Total/estatística & dados numéricos , Prognóstico , Redução de PesoRESUMO
BACKGROUND AND AIMS: Mesenteric lymph nodes were usually removed during bowel resection surgery for Crohn's disease (CD). Mesenteric lymph node (MLN) granuloma predicted postoperative disease recurrence in patients with CD after ileocolic resection (ICR). This study was aimed to identify factors associated with MLN granulomas in a cohort of CD patients who underwent ICR. METHODS: The study group consisted of 18 patients with CD who underwent the index ICR between 2004 and 2012 and had MLN granulomas. The control group included 32 cases negative for MLN granulomas, which were randomly selected from the same period. Clinicodemographic and histological features were compared in these two groups. RESULTS: The presence of MLN granuloma was associated with younger age, perianal disease, and ileocolic disease. Gender, body mass index, smoking status, disease duration, extraintestinal manifestation, length of bowel resected, total number of nodes examined, medical treatment, and indications for surgery were not significantly different between the groups. The presence of MLN granuloma was associated with mural granuloma, transmural inflammation, mural abscess, hypertrophy of the muscularis propria, fibrosis of the muscularis propria, and serosal fibrosis in the small bowel. The multivariable analysis confirms that MLN granuloma was associated with age and transmural inflammation. CONCLUSIONS: In CD patients who underwent the index ICR, the presence of MLN granuloma was associated with younger age and transmural inflammation. Our current results suggest that the detection of MLN granulomas may be enhanced in patients at higher risk, that is, younger patients or those with transmural inflammation on imaging or histopathology.
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Fatores Etários , Doença de Crohn/etiologia , Doença de Crohn/cirurgia , Granuloma/etiologia , Linfonodos , Doenças Linfáticas/etiologia , Mesentério , Adulto , Idoso , Estudos de Coortes , Colectomia , Feminino , Granuloma/cirurgia , Humanos , Íleo/cirurgia , Inflamação , Doenças Linfáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Adulto JovemRESUMO
â¢Dedifferentiated endometrial carcinoma arising from serous carcinoma (null-type P53).â¢Differential diagnosis including carcinosarcoma, FIGO grade 3 endometrioid carcinoma.â¢Also need to rule out SMARCA4-deficient uterine sarcoma and other sarcomas.
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INTRODUCTION: Gastric glomus tumor (GT) is a rare submucosal tumor for which the preoperative diagnosis can be challenging. We report the cytomorphologic and immunohistochemical features of 4 gastric GTs diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology. MATERIALS AND METHODS: Files were searched to identify gastric GTs diagnosed by EUS-FNA between 2018 and 2021. A total of 4 cases of gastric GTs (3 men and 1 women; mean age, 60 years) were included. RESULTS: Three GTs were located in the gastric antrum and one in the gastric body. Their size ranged from 2 to 2.5 cm. Three patients presented with epigastric discomfort and one with chest wall discomfort. Rapid on-site evaluation was performed for 3 cases; the findings for all 3 were indeterminate. The smears were moderate to highly cellular and showed loose clusters of evenly distributed small- to medium-size bland tumor cells. The tumor cells had centrally located round to oval nuclei with inconspicuous nucleoli and scant to moderate amount of eosinophilic to clear cytoplasm. Examination of the cell blocks revealed branching small vessels surrounded by small- to medium-size cells. The neoplastic cells were positive for smooth muscle actin and synaptophysin and negative for AE1/AE3 and S-100. C-KIT and CD34 were variably positive. Ki-67 was <2% positive. In 1 case, the fusion panel-solid tumor (50 genes) revealed the MIR143HG-NOTCH2 fusion gene. CONCLUSIONS: Smears and cell block preparation revealed angiocentric sheets of uniform, small round to oval tumor cells with pale to eosinophilic cytoplasm, intermingled with endothelial cells. The differential diagnosis of gastric GTs on rapid on-site evaluation includes neuroendocrine tumors and epithelioid or spindled cell neoplasms. Immunohistochemical and molecular studies can be helpful in the preoperative diagnosis of gastric GT.
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Tumor Glômico , Neoplasias Gástricas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Tumor Glômico/diagnóstico por imagem , Tumor Glômico/genética , Células Endoteliais/patologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/genética , Diagnóstico Diferencial , Receptor Notch2RESUMO
This Letter presents a highly diastereoselective synthesis of C-hydroxymethine glycosides from glycal anomers using a chiral N-heterocyclic carbene-copper catalyst. The high diastereoselectivity was synergistically controlled by the stereocenter of the substrate and chirality of the N-heterocyclic carbene-copper complex without being interrupted by the stereochemistry of C5 and the anomeric position. This approach enables the production of a diverse array of C-hydroxymethine glycosides using synthetically versatile glycals and various functionalized aldehydes.
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Cobre , Glicosídeos , EstereoisomerismoRESUMO
BACKGROUND: Autoimmune pancreatitis (AIP) is a known mimicker of pancreatic ductal adenocarcinoma both clinically and radiologically. In this study, the authors present their institutional experience in diagnosing AIP on cytology and correlate results with the histologic findings. METHODS: A 14-year computerized search for patients who had histologically confirmed AIP with concurrent or prior cytology was performed. Clinical data, cytology findings, and surgical pathology results were reviewed for analysis. RESULTS: Eighteen patients were identified. The patients showed a male predominance, with a mean age of 59 years. Jaundice, weight loss, and abdominal pain were the most common clinical presentation. Five of 12 patients who were tested for serum immunoglobulin G4 had elevated levels. Cytologic findings of 16 cases that were available for review showed markedly inflamed fibrous stroma (54%) and cytologic atypia (50%). The final cytologic diagnoses were suspicious for adenocarcinoma (n = 1), atypical (n = 8), and benign/negative (n = 9). The corresponding surgical pathology diagnoses were classified as type 1 (n = 10), type 2 (n = 6), and AIP, not otherwise specified (n = 2). All type 2 AIP cases had at least atypical cytologic diagnoses, with one called suspicious for adenocarcinoma and another called adenocarcinoma at the time of rapid on-site evaluation. In contrast, eight of 10 type 1 AIP cases were negative/benign, and two of 10 were atypical. In these two atypical cases, the possibility of AIP was raised because of the presence of inflamed stroma. CONCLUSION: AIP is a pitfall in cytology because moderate-to-marked atypia can be present, especially in type 2 AIP. Because atypia can be severe, the presence of cellular fibrous stroma with lymphocytic stromal infiltrates and the integration of serum immunoglobulin G4 levels could be helpful in avoiding diagnostic overcall in AIP.
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Pancreatite Autoimune , Pâncreas , Humanos , Pancreatite Autoimune/complicações , Pancreatite Autoimune/diagnóstico , Pancreatite Autoimune/patologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Pâncreas/citologia , Adenocarcinoma/complicações , Adenocarcinoma/diagnósticoRESUMO
BACKGROUND: Interpretation of Hürthle cell-predominant cytologies (HCP) is very challenging as a majority is diagnosed as indeterminate. Prior studies have reported various cytologic features to help distinguish non-neoplastic (NN) from neoplastic and malignant lesions but had contradicting results. Our aim was to identify risk factors predictive of neoplasm and/or malignancy by correlating cytologic features with clinical and ultrasound findings. METHODS: Sixty-nine HCP cases with surgical follow-up were identified, including 35 NN, 20 adenomas, and 14 carcinomas. Ultrasound data were recorded utilizing Thyroid Imaging Reporting and Data System (TI-RADS) and American Thyroid Association (ATA) scoring systems. Sixteen cytologic criteria were evaluated and semi-quantitatively scored. Data were assessed by univariable, multivariable and stepwise logistic regression analysis; and statistical significance achieved at P-value <0.05. RESULTS: On univariable analysis, significant predictors of neoplasm were high cellularity, isolated single cells, absent colloid, non-uniform HC population (anisonucleosis), larger nodule size, and higher ATA score. Large-cell dysplasia and transgressing blood vessels were not found to be significant factors. Multivariable analysis identified a combination of four risk factors (high cellularity, anisonucleosis, absent colloid, and size ≥2.9 cm) that was associated with neoplasm in 10/11 patients. None of 15 patients with zero or 1 out of 4 risk factors had malignancy or neoplasm on follow-up. This model also significantly outperformed ATA and TI-RADS scoring systems. CONCLUSION: In the absence of four or three risk factors, the model excluded malignancy and neoplasm in all patients. The presence of all four factors predicted neoplasm and malignancy in 91% and 46% of cases, respectively.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Biópsia por Agulha Fina/métodos , Coloides , Humanos , Células Oxífilas/patologia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Nuclear protein in testis (NUT) carcinoma (NC) is an aggressive type of poorly differentiated carcinoma with a variable degree of squamous differentiation. NC is defined by the presence of BRD-NUT fusion oncogenes, the most common fusion form being the BRD4-NUTM1 gene. Variant rearrangements involving the BRD3 and NSD3 genes. Variant rearrangements involving the BRD3 and NSD3 genes occur in approximately one-third of the cases. AIMS: This is the first case regarding the study of cytological features of NC of the lung with BRD3-NUTM1 fusion. MATERIALS AND METHODS: A 36-year-old female with chest heaviness and shortness of breath was found to have a right-sided pleural effusion; she was non-smoker and denied any significant past medical illness. CT-chest revealed an 8.5 cm heterogeneous mass in the right and mid-upper lung. She underwent endobronchial ultrasound-guided (EBUS) transbronchial fine-needle aspiration (FNA) of the lung mass. Thoracocentesis was performed, and pleural fluid was sent to the laboratory for cytological evaluation RESULTS: The cytopathological findings showed atypical squamoid cells with variably prominent single or multiple nucleoli. Monotonous-looking cells with high nuclear to cytoplasmic ratio and hyperchromasia were also present. The atypical squamoid cells showed abundant clear to eosinophilic cytoplasm with rare individual cell keratinization and focal keratin pearl formation. The atypical cells were positive for CK7, p40, p63, mCEA and equivocal for NUT-specific antibody. The cytopathological findings were consistent with squamous cell carcinoma with focal keratinization. The Fusion Panel-Solid Tumor (50 genes) revealed BRD3-NUTM1 fusion gene. Diagnosis was amended to pulmonary NC. DISCUSSION: NC is a diagnostic challenge for pathologists as it can morphologically mimic undifferentiated carcinoma, squamous cell carcinoma, or neuroendocrine carcinoma. The challenge is not how to diagnose NC but rather determining when to include it in the differential diagnosis and perform the diagnostic molecular tests (FISH or NGS) or IHC study for NUT-specific antibody. CONCLUSION: When a specimen demonstrates a dual cell population of squamoid cells and primitive-looking tumor cells in the wrong clinical context (i.e., young patient with no smoking history), further molecular profiling is warranted to include the differential of a primary NC of the lung. The cytological features of NC itself have rarely been documented and moreover, that of a primary NC of the lung with BRD3-NUTM1 fusion has never been reported. We herein report cytological findings of a primary NC of the lung with BRD3-NUTM1 fusion gene.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Antígeno Carcinoembrionário/metabolismo , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Imunofenotipagem , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
BACKGROUND: The impact of implementing the Paris system (TPS) on the rate of discrepant cases in the negative for high-grade urothelial carcinoma (NHGUC) category that had a subsequent diagnosis of high-grade urothelial carcinoma (HGUC) on histology is not well studied. METHODS: We adopted TPS in May 2019. We searched discrepant cases with negative urine cytology 2017-2019 in our cyto-histo correlation database. The urine cytology and follow-up biopsy/resection were reviewed by a cytopathologist who also did Genitourinary (GU) Pathology subspecialty sign-out. Voided urine and instrumented urine were included in this study. RESULTS: There were total of 70 discrepant cases with negative cytology interpretation but HGUC on the subsequent biopsy or resected specimen. Following the TPS criteria, the rate of discrepant negative cytology cases increased from 6 cases between January 2017 and May 2019 to 64 cases after May 2019 when we adopted TPS. There were 2 discrepant negative cases in 2017, 3 cases in 2018, and 65 cases in 2019. Out of 65 cases in 2019, 64 cases were identified after May 2019. Additional 55 urine cytology slides were reviewed according to the TPS criteria, of which, the diagnoses remained unchanged in 45 (82%) cases and 10 (19%) cases were reassigned to either atypical or suspicious categories. The discrepancy was noted more on the instrumented urine and the upper tract urine. However, the false-negative rate rose faster in voided urine and lower tract urine. The risk of HGUC with the category of NHGUC was 0.03% in 2017, 0.05% in 2018, and 1.06% in 2019 at our institution. The increase in false-negative rate could not be attributed to a single cytopathologist. CONCLUSION: After adopting TPS for reporting urine cytology, there was an increase in HGUC from negative urine cytology which was subsequently confirmed on histology as cases of HGUC. The quality control of negative urines could be important monitoring the process when implementing TPS.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Carcinoma de Células de Transição/diagnóstico , Citodiagnóstico , Humanos , Neoplasias da Bexiga Urinária/patologia , Urina , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/patologia , Urotélio/patologiaRESUMO
The intestinal epithelium is subjected to repetitive deformation during normal gut function by peristalsis and villous motility. Such repetitive strain promotes intestinal epithelial migration across fibronectin in vitro, but signaling mediators for this are poorly understood. We hypothesized that integrin-linked kinase (ILK) mediates strain-stimulated migration in intestinal epithelial cells cultured on fibronectin. ILK kinase activity increased rapidly 5 min after strain induction in both Caco-2 and intestinal epithelial cell-6 (IEC-6) cells. Wound closure in response to strain was reduced in ILK small interfering RNA (siRNA)-transfected Caco-2 cell monolayers when compared with control siRNA-transfected Caco-2 cells. Pharmacological blockade of phosphatidylinositol-3 kinase (PI3K) or Src or reducing Src by siRNA prevented strain activation of ILK. ILK coimmunoprecipitated with focal adhesion kinase (FAK), and this association was decreased by mutation of FAK Tyr925 but not FAK Tyr397. Strain induction of FAK Tyr925 phosphorylation but not FAK Tyr397 or FAK Tyr576 phosphorylation was blocked in ILK siRNA-transfected cells. ILK-Src association was stimulated by strain and was blocked by the Src inhibitor PP2. Finally, ILK reduction by siRNA inhibited strain-induced phosphorylation of myosin light chain and Akt. These results suggest a strain-dependent signaling pathway in which ILK association with FAK and Src mediates the subsequent downstream strain-induced motogenic response and suggest that ILK induction by repetitive deformation may contribute to recovery from mucosal injury and restoration of the mucosal barrier in patients with prolonged ileus. ILK may therefore be an important target for intervention to maintain the mucosa in such patients.
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Mucosa Intestinal/enzimologia , Proteínas Serina-Treonina Quinases/fisiologia , Cicatrização , Animais , Linhagem Celular , Proteína-Tirosina Quinases de Adesão Focal/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Mutação , Cadeias Leves de Miosina/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/administração & dosagem , RNA Interferente Pequeno/fisiologia , Ratos , Quinases da Família src/antagonistas & inibidoresRESUMO
OBJECTIVES: Fine-needle aspiration (FNA) of thyroid bed lesions after thyroidectomy is challenging to evaluate. We determined the sensitivity, specificity, and positive and negative predicative value of thyroid bed FNA (TB-FNA) for detecting local recurrence of thyroid carcinoma. METHODS: A retrospective search was conducted for TB-FNAs from patients with a prior thyroid resection and subsequent ipsilateral FNA from the thyroid bed. Clinical and pathologic data were retrieved from the medical record. Patients were ultimately classified as "malignant" or "benign" based on the worst pathology identified and follow-up available. RESULTS: Forty-two cases were included, and the prior thyroidectomy pathology included 36 papillary thyroid carcinomas, two follicular carcinomas, one medullary carcinoma, and three benign cases. TB-FNA was adequate in 38 (90.5%) cases and interpreted as positive for malignancy (n = 22; 52.4%), suspicious for follicular neoplasm (n = 3; 7.1%), atypia of unknown significance (n = 2; 4.8%), and benign (n = 10; 23.8%). Twenty-seven patients had histologic follow-up, and 24 (87.5%) showed recurrent malignancy. The cytology sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 96%, 100%, 100%, 92.3%, and 97.4%, respectively, for identification of recurrent malignancy. CONCLUSIONS: Most TB-FNA cases ultimately were diagnosed with malignancy on follow-up, although there may be sampling bias, as not all clinically benign cases had surgical follow-up.
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Biópsia por Agulha Fina/métodos , Recidiva Local de Neoplasia/diagnóstico , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Citodiagnóstico/métodos , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
Monoterpene indole alkaloids, bearing a highly substituted piperidine ring, are a structurally diverse class of bioactive natural products, found in various parts of the world. Herein, we reported the construction of the key piperidine ring via palladium catalyzed reductive Heck coupling with a good syn selective manner, avoiding the usage of stoichiometric, highly toxic, air sensitive and moisture sensitive Ni(COD)2. To further showcase the value of this methodology, we realized the total synthesis of the structurally unique zwitterionic monoterpene indole alkaloid (-)-17-nor-excelsinidine in 9 steps, in which the key ammonium-acetate connection (N4-C16) of (-)-17-nor-excelsinidine was constructed via oxidative coupling in excellent yield and high regioselectivity under NBS/pyridine from the enolate of geissoschizine.
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The intestinal epithelium is subjected to repetitive deformation during normal gut function by peristalsis and villous motility. In vitro, cyclic strain promotes intestinal epithelial proliferation and induces an absorptive phenotype characterized by increased dipeptidyl dipeptidase (DPPIV) expression. Schlafen 3 is a novel gene recently associated with cellular differentiation. We sought to evaluate whether Schlafen 3 mediates the effects of strain on the differentiation of intestinal epithelial cell (IEC)-6 in the absence or presence of cyclic strain. Strain increased Schlafen 3 mRNA and protein. In cells transfected with a control-nontargeting siRNA, strain increased DPPIV-specific activity. However, Schlafen 3 reduction by siRNA decreased basal DPPIV and prevented any stimulation of DPPIV activity by strain. Schlafen 3 reduction also prevented DPPIV induction by sodium butyrate (1 mM) or transforming growth factor (TGF)-beta (0.1 ng/ml), two unrelated differentiating stimuli. However, Schlafen-3 reduction by siRNA did not prevent the mitogenic effect of strain or that of EGF. Blocking Src and phosphatidyl inositol (PI3)-kinase prevented strain induction of Schlafen 3, but Schlafen 3 induction required activation of p38 but not ERK. These results suggest that cyclic strain induces an absorptive phenotype characterized by increased DPPIV activity via Src-, p38-, and PI3-kinase-dependent induction of Schlafen 3 in rat IEC-6 cells on collagen, whereas Schlafen 3 may also be a key factor in the induction of intestinal epithelial differentiation by other stimuli such as sodium butyrate or TGF-beta. The induction of Schlafen 3 or its human homologs may modulate intestinal epithelial differentiation and preserve the gut mucosa during normal gut function.
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Células Epiteliais/citologia , Células Epiteliais/fisiologia , Mucosa Intestinal/citologia , Proteínas/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Indução Enzimática , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibronectinas , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas/genética , RNA Interferente Pequeno , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismoRESUMO
Primary effusion lymphoma (PEL) is a rare non-Hodgkin's lymphoma most commonly occurring in the context of human immune deficiency (HIV) infection. Herpes virus 8 (HHV-8) has been associated with PEL and considered to be the etiologic agent. In addition, most cases (60%-90%) also show evidence of Epstein-Barr virus (EBV) infection. We describe here an elderly man who was HIV seronegative and immunocompetent, and presented with worsening weakness and ascites. The diagnosis of PEL was rendered cytologically and supported by the results of flow cytometry. The presence of HHV-8 was demonstrated by immunohistochemistry, whereas EBV-associated genetic material was absent by EBER ISH. No lymphadenopathy or organ involvement with lymphoma was found. Systemic chemotherapy with lenalidomide was started given the poor prognosis and commodities of severe coronary artery disease; however, the patient did not respond and succumbed to his disease in 4 months. We present detailed cytologic and clinical findings of this very rare occurrence, and review literature of all reported PEL cases of HIV-negative, nontransplant, immunocompetent patients.
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Soronegatividade para HIV , Infecções por Herpesviridae , Herpesvirus Humano 8/metabolismo , Lenalidomida/administração & dosagem , Linfoma de Efusão Primária , Idoso , Evolução Fatal , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/tratamento farmacológico , Infecções por Herpesviridae/metabolismo , Humanos , Linfoma de Efusão Primária/diagnóstico , Linfoma de Efusão Primária/tratamento farmacológico , Linfoma de Efusão Primária/metabolismo , Linfoma de Efusão Primária/virologia , MasculinoRESUMO
Pneumocytic adenomyoepithelioma (PAM) was first described in 2007 and was included in the 2015 World Health Organization Classification of lung tumors as a variant of epithelial-myoepithelial tumor. This rare pulmonary neoplasm was reported to show both myoepithelial and duct-like components, with the latter exhibiting pneumocytic differentiation with TTF-1 expression. We present an index case and 6 additional retrospectively identified cases of pulmonary tumors with prototypical features of PAM. However, with additional clinicoradiologic, histologic, immunohistochemical and cytogenetic data, we were able to reclassify them as myoepithelial neoplasms-both primary and metastatic-with entrapped exuberantly hyperplastic alveolar structures lined by TTF-1 pneumocytes. We reviewed the available literature related to PAM and myoepithelial tumors. Our cases suggest that the entity referred to as PAM represents interstitial growth of myoepithelial neoplasms enticing marked proliferation of entrapped pneumocytes rather than a distinct biphasic neoplasm with pneumocytic differentiation.
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Adenomioepitelioma/classificação , Adenomioepitelioma/patologia , Células Epiteliais Alveolares/patologia , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Mioepitelioma/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: The presence of atypical endometrial cells in the Papanicolaou (Pap) test has been associated with an increased rate of endometrial malignancy, with reported rates ranging from 14% to 47%. However, most reported studies have focused on patients who were aged >40 years. The purpose of the present study was to investigate the clinical significance of identifying atypical endometrial cells in Pap test samples in women aged <40 years of age. MATERIALS AND METHODS: A search of the cytology Pap test database was performed from 2000 to 2014 using the keywords "atypical endometrial cells" or "atypical glandular cells favor endometrial origin" in women aged <40 years. The available ThinPrep slides were reviewed. The patients' clinical presentation, follow-up endometrial biopsy findings, treatment, and clinical follow-up data were recorded. Endometrial carcinoma tissue sections were screened for Lynch syndrome. RESULTS: The database search yielded 63 study cases. Of these 63 patients, 52 had subsequently undergone endometrial biopsy. Of the 52 patients with follow-up biopsy findings available, 9 (17.3%) had premalignant (5 with atypical hyperplasia) or malignant (4 with endometrioid adenocarcinoma) lesions. In addition, 16 patients (30.8%) had other endometrial pathologic features. The 9 patients with premalignant or malignant endometrial lesions (8 white, 1 black) were overweight or obese; 3 of the patients did not have any clinical symptoms. All 4 patients with endometrioid adenocarcinoma had negative Lynch syndrome screening findings. CONCLUSIONS: Our results suggest that it is important to recognize the presence of atypical endometrial cells in the Pap tests from young patients, given its association with the finding of premalignant and malignant pathologic features in subsequent endometrial biopsies.
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Carcinoma Endometrioide/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias do Endométrio/diagnóstico , Endométrio/patologia , Lesões Pré-Cancerosas/diagnóstico , Adolescente , Adulto , Carcinoma Endometrioide/complicações , Carcinoma Endometrioide/patologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Bases de Dados Factuais , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Obesidade/complicações , Teste de Papanicolaou/métodos , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Esfregaço Vaginal/métodos , Adulto JovemRESUMO
Altered transforming growth factor-beta (TGFbeta) expression may contribute to inflammatory bowel disease and modulate epithelial cell restitution. Interference with TGFbeta-mediated signaling inhibits excisional skin wound healing, but accelerates healing of incisional cutaneous wounds and wounds in some other tissues. Therefore, we sought to clarify the potential role of Smad3-dependent TGFbeta signaling in intestinal mucosal healing in Smad3 null mice. Jejunal serosal application of filter disks saturated with 75% acetic acid yielded a circumscribed reproducible ischemic mucosal ulcer 1 day later. We compared ulcer area at 3 and 5 days to day 1 in Smad3 knockout mice and syngeneic wild-type mice, and evaluated mucosal immunoreactivity at the ulcer edge for TGFbeta, phosphorylated (activated) focal adhesion kinase (pFAK), phosphorylated extracellular signal-related kinase (pERK), proliferating cell nuclear antigen and apoptosis by TUNEL. Ulcer healing in Smad3 null mice was 17% less at day 3 (n=14, P=0.022) and 15% less at day 5 (n=14, P=0.004) than in wild-type littermates. In wild-type mice, pFAK, pERK and TGFbeta immunoreactivity were elevated in epithelium immediately adjacent to the ulcer compared with more distant mucosa. However, this pattern of immunoreactivity for pFAK, pERK and TGFbeta was not observed in Smad3 null mice. Smad3 null mice exhibited increased epithelial proliferation and no differences in apoptotic cell death compared with wild types, suggesting that ulcer healing may reflect differences in restitutive cell migration. Thus, Smad3-dependent disruption of the TGFbeta signaling pathway impairs the healing of murine intestinal mucosal ulcers and alters patterns of activated FAK and ERK immunoreactivity important for cell migration at the ulcer edge. These studies suggest a significant role for Smad3-dependent TGFbeta signaling in intestinal mucosal healing.
Assuntos
Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/fisiologia , Proteína Smad3/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Cicatrização/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Jejuno/lesões , Jejuno/fisiologia , Masculino , Camundongos , Camundongos Knockout , Transdução de Sinais/fisiologiaRESUMO
Several genetic tools have been developed for use in Bacillus anthracis, but there is still a need for a more marker-free gene inactivation protocols. Thus, we report a method to generate unmarked mutations in B. anthracis. This approach was based on the counter-selectable pheS* gene with assistance by the I-SceI homing endonuclease. Using this strategy, the NprR gene, a transcriptional activator of B. anthracis, was deleted at an extremely high efficiency. Our study indicates that mutated pheS is a useful counter-selective marker to design a valuable genetic tool for in-frame and unmarked gene deletions of B. anthracis.
Assuntos
Bacillus anthracis/genética , Proteínas de Bactérias/genética , Genes Bacterianos , Marcadores Genéticos , Deleção de Genes , Engenharia Genética , MutaçãoRESUMO
Although substantial evidence has demonstrated that parity and 17ß-estradiol (E2) reduce mammary carcinogenesis, it is not clear how this protection is conferred. Thus, we examined the effects of parity and E2 treatment in the mammary glands of ovariectomized 15 week-old virgin mice, 15 week-old primiparous mice, and 9 month-old retired breeders. E2 treatment significantly increased lipid peroxidation, protein carbonylation, and protein nitrosylation in the virgin mice, but not in the age-matched primiparous mice or retired breeders. Mammary gland expression of the oxidative stress response protein Cu/Zn superoxide dismutase was consistently reduced in all of the E2-treated mice regardless of parity. Expression of the oxidative stress and DNA repair protein apurinic endonuclease (Ape1) was significantly increased only in the mammary glands of the E2-treated retired breeders. These findings suggest that E2 and parity help to reduce mammary oncogenesis by maintaining the structure and function of proteins, lipids, and DNA.