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1.
Arch Virol ; 166(4): 1157-1161, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33550506

RESUMO

Numerous raised plaques were observed on the feet of a red-billed gull (Chroicocephalus novaehollandiae scopulinus) that had been found dead. The plaques consisted of thickened epidermis with cell changes indicative of papillomavirus (PV) infection prominent within affected areas. Evidence suggesting progression to neoplasia was visible in one lesion. A DNA sequence that was most similar, but only 68.3% identical, to duck PV type 3 was amplified from the papillomas, suggesting a novel PV type. Lesions containing PV DNA have only previously been reported in three avian species. This is the first evidence that PVs could cause neoplasia in birds.


Assuntos
Doenças das Aves/virologia , Carcinoma in Situ/veterinária , Charadriiformes/virologia , Papiloma/veterinária , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/veterinária , Animais , Doenças das Aves/patologia , Proteínas do Capsídeo/genética , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , DNA Viral/genética , Pé/patologia , Pé/virologia , Papiloma/patologia , Papiloma/virologia , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Filogenia
2.
Jpn J Clin Oncol ; 51(3): 434-443, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33420502

RESUMO

OBJECTIVE: The Japan Clinical Oncology Group 1505 trial is a single-arm multicentre prospective study that examined the possibility of non-surgical follow-up with endocrine therapy for patients with low-grade ductal carcinoma in situ. In that study, the eligible criteria included histopathological findings comprising low to intermediate nuclear grade and absence of comedo necrosis, and cases were entered according to the local histopathological diagnosis. Nuclear grade is largely based on the Consensus Conference criteria (1997), whereas comedo necrosis is judged according to the Rosen's criteria (2017). The purpose of this study was to standardize and examine the interobserver agreement levels of these histopathological criteria amongst the participating pathologists. METHODS: We held slide conferences, where photomicrographs of haematoxylin-eosin-stained slides from 68 patients with ductal carcinoma in situ were presented using PowerPoint. The nuclear grade and comedo necrosis statuses individually judged by the pathologists were analysed using κ statistics. RESULTS: In the first and second sessions, where 22 cases each were presented, the interobserver agreement levels of nuclear grade whether low/intermediate grade or high grade were moderate amongst 29 and 24 participating pathologists, respectively (κ = 0.595 and 0.519, respectively). In the third session where 24 cases were presented, interobserver agreement levels of comedo necrosis or non-comedo necrosis were substantial amongst 25 participating pathologists (κ = 0.753). CONCLUSION: Although the concordance rates in nuclear grade or comedo necrosis were not high in a few of the cases, we believe that these results could provide a rationale for employing the present criteria of nuclear grade and comedo necrosis in the clinical study of ductal carcinoma in situ.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Núcleo Celular/patologia , Oncologia , Carcinoma in Situ/patologia , Feminino , Humanos , Japão , Necrose , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes
3.
J Surg Oncol ; 123(4): 932-938, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33368336

RESUMO

BACKGROUND AND OBJECTIVES: Current management guidelines recognize the impact of hepatic versus peritoneal sided gallbladder cancers (GBC) on survival. However, no data exist regarding the significance of anatomic tumor location within the gallbladder. METHODS: We retrospectively analyzed all GBC that underwent surgical resection with curative intent in our health system from 2007 to 2017. We evaluated the effect of anatomic pathologic tumor location (fundus/body, neck, and multifocal) on clinicopathologic, perioperative, and oncologic outcomes. RESULTS: About 97 patients met criteria; 63% fundus/body, 22% multifocal, and 15% neck. Compared with fundus/body, neck tumors more frequently presented with preoperative jaundice (53% vs. 13%, p < .001), were smaller (20 mm vs. 30 mm, p = .068) and had significantly more biliary tree invasion (33% vs. 13%, p = .030) on histopathology. Although tumor characteristics (pTNM stage, liver invasion, lymphovascular invasion, prognostic nutritional index, and grade) were similar, neck tumors had significantly higher rates of R0 resection (53% vs. 11%, p < .001). Rates of adjuvant therapy were similar. Median PFS was similar between cohorts (p = .356). However, median overall survival (OS) was significantly shorter in neck (21 months) than fundus/body tumors (NR > 109 months), p = .015. CONCLUSIONS: Neck tumors were rare, small and more likely to result in jaundice secondary to biliary tree invasion. Despite higher R0 resection rates, these tumors had significantly worse OS.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Carcinoma in Situ/patologia , Neoplasias da Vesícula Biliar/patologia , Hepatectomia/efeitos adversos , Icterícia/patologia , Complicações Pós-Operatórias/patologia , Idoso , Carcinoma in Situ/cirurgia , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Icterícia/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Bull Cancer ; 107(11): 1148-1160, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33039132

RESUMO

Tumorigenesis has traditionally been considered as a multi-step process involving the activation of oncogenes as well as the inactivation of tumor suppressor genes. However, the mechanisms driving cancer initiation and progression are not restricted to molecular alterations and instead should be viewed as a complex process that interfaces with the entire organism. This didactic review provides an integrated and global view of the key fundamental principles of cancer development.


Assuntos
Carcinogênese , Apoptose , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma in Situ/patologia , Proliferação de Células , Progressão da Doença , Meio Ambiente , Inativação Gênica , Genes Supressores de Tumor , Instabilidade Genômica , Humanos , Inflamação/complicações , Mutação , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/irrigação sanguínea , Neoplasias/etiologia , Neoplasias/patologia , Células Neoplásicas Circulantes , Neovascularização Patológica/etiologia , Oncogenes , Lesões Pré-Cancerosas , Ativação Transcricional , Microambiente Tumoral
7.
Cancer Causes Control ; 31(8): 749-765, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32410205

RESUMO

PURPOSE: To investigate the association between mammographic density (MD) phenotypes and both clinicopathologic features of breast cancer (BC) and tumor location. METHODS: MD was measured for 297 BC-affected females using qualitative (visual method) and quantitative (fully automated area-based method) approaches. Radiologists' description, visible external markers, and surgical scar were used to establish the location of tumors. Binary logistic regression models were used to assess the association between MD phenotypes and BC clinicopathologic features. RESULTS: Categorical and numerical MD measures showed no association with clinicopathologic features of BC (p > 0.05). Participants with higher BI-RADS scores [(51-75% glandular) and (> 75% glandular)] (p < 0.001), and percent density (PD) categories [PD (21-49%) and PD ≥ 50%] (p = 0.01) were more likely to have tumors emanating from dense areas. Additionally, tumors were commonly found in dense regions of the breast among patients with higher medians of PD (p = 0.001), dense area (DA) (p = 0.02), and lower medians of non-dense area (NDA) (p < 0.001). Adjusted logistic regression models showed that high BI-RADS density (> 75% glandular) has an almost fivefold increased odds of tumors developing within dense areas (OR 4.99, 95% CI 0.93-25.9; p = 0.05. PD (OR 1.02, 95% CI 1-1.03, p = 0.002) and NDA (OR 0.99, 95% CI 0.991-0.997, p < 0.001) had very small effect on tumor location. Compared to tumors within non-dense areas, tumors in dense areas tended to exhibit human epidermal growth factor receptor 2 positive (p = 0.05) and carcinoma in situ (p = 0.01) characteristics. CONCLUSION: MD shows no significant association with clinicopathologic features of BC. However, BC was more likely to originate from dense tissue, with tumors in dense regions having human epidermal growth receptor 2 positive and carcinoma in situ characteristics.


Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Mamografia , Mama/patologia , Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/patologia , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Fenótipo , Receptor ErbB-2
8.
Am J Surg Pathol ; 44(7): e80-e86, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32235153

RESUMO

Penile cancer and its precursor lesions are morphologically and clinically heterogenous and they can be further characterized by immunohistochemical (IHC) and molecular genetic analyses. According to the current World Health Organization (WHO) classification, penile intraepithelial neoplasia (PeIN) and invasive penile carcinomas can be grouped into human papillomavirus (HPV)-related and non-HPV-related neoplasms. This distinction is clinically relevant for etiological and prognostic reasons. To gain insight into the current use of molecular testing and IHC in their diagnostics, a survey was held among the membership of the International Society of Urological Pathology (ISUP). About 250 pathologists from 51 countries answered the survey on the practice and use of IHC/molecular technique as aids in the diagnosis of penile squamous neoplasia. More than half (60%) of the respondents worked at an academic hospital. The questions focused on condylomas, precancerous squamous lesions, and squamous cell carcinoma (SCC). About 35% to 45% of the pathologists considered the use of IHC or molecular tests of value in the pathologic evaluation of precancerous and invasive neoplasms. The vast majority of the respondents do not use IHC for the diagnosis and subtyping of condylomas. There is emerging evidence that some condylomas may participate in the penile carcinogenesis process, especially the high-risk HPV-related atypical condylomas. We recommend the use of p16 in such cases. For most PeIN cases, about half of the responding pathologists make the diagnosis on hematoxylin and eosin slides only. For their subtyping, 50% to 55% of the pathologists use IHC in warty or basaloid PeINs and 40% in differentiated PeIN. To separate HPV-related PeIN from non-HPV-related PeIN, 80% reported using p16 and 20% Ki-67. On the basis of literature review and our practice, the ISUP working group recommends the use of Ki-67 to separate non-HPV-differentiated PeIN from squamous hyperplasia and the use of p16 to distinguish the pleomorphic variant of differentiated PeIN from HPV-related PeIN. With respect to SCCs, according to the survey, immunostaining is only applied in 15% of conventional invasive SCCs, the majority being diagnosed by hematoxylin and eosin. To separate HPV and non-HPV tumors, most (80%) would use p16 and 25% would use p53. For subtype classification, they consider IHC necessary to identify verrucous, papillary, warty, warty-basaloid, and basaloid carcinomas. p16 is used as a surrogate of polymerase chain reaction for the identification of high-risk HPV. We recommend the use of p16 immunostain in cases where the tumoral histologic features of the SCCs are not classical for HPV-related neoplasms, especially in poorly differentiated tumors. Because the majority of these neoplasms harbor high-risk HPV (HPV16), identifying the presence of the virus is rather more important than documenting its specific genotype.


Assuntos
Biomarcadores Tumorais , Carcinoma in Situ/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Penianas/diagnóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/genética , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Testes Genéticos/métodos , Humanos , Imuno-Histoquímica , Masculino , Mutação , Patologia Clínica , Patologia Molecular , Neoplasias Penianas/genética , Neoplasias Penianas/metabolismo , Neoplasias Penianas/patologia , Padrões de Prática Médica/estatística & dados numéricos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Sociedades Médicas , Urologia
9.
Hum Pathol ; 98: 81-88, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32142835

RESUMO

Flat urothelial lesions with atypia may pose significant diagnostic challenges. Given frequent increased proliferation rates in florid reactive urothelial atypia and limited studies on the interpretation of p53 stains in the urothelium (following current standard guidelines for correlation with P53 mutation status), we sought to further study the discriminatory value of Ki-67 and p53 for florid reactive urothelial atypia versus urothelial carcinoma in situ (CIS). Bladder specimens diagnosed as reactive urothelial atypia (n = 40) and CIS (n = 40) were assessed by immunohistochemical staining with antibodies for Ki-67, p53, CD44, and CK20. Immunoreactivity was scored based on percent cells positive for Ki-67 and pattern of reactivity with p53 (aberrant: diffuse strong positive or negative; normal: patchy/wild type). CD44 and CK20 reactivity patterns served as adjunctive internal validation controls for reactive urothelial atypia and CIS, as previously described. In reactive urothelial atypia, Ki-67 ranged from 0% to 90% (mean, 34% ± 26) with 30 cases (75%) having >10%. In CIS, Ki-67 ranged from 5% to 95% (mean, 50% ± 25) with 17 cases (43%) having >50%. In all 40 cases (100%) of reactive urothelial atypia, p53 expression had a wild-type pattern. In CIS, aberrant p53 expression was identified in 15 cases (37%): 3 cases (7%) were p53 negative (i.e. null phenotype) and 12 cases (30%) showed strong and diffuse nuclear reactivity (in >85% of cells). The remaining 25 cases (63%) of CIS had a p53 wild-type pattern of expression. Cytoplasmic CK20 immunoreactivity in umbrella cells was seen in 34 cases (85%) of reactive urothelial atypia, and 6 cases (15%) were negative. In addition, 35 cases (88%) of reactive urothelial atypia demonstrated full-thickness CD44 expression, while 5 cases (12%) had expression confined to the basal/parabasal layers of the urothelium. Strong and diffuse CK20 positivity was present in 39 cases (98%) of CIS, and patchy positivity was detected in 1 case (2%). None of the CIS cases overexpressed CD44: 16 cases (40%) showed focal expression in the nonneoplastic basal cell layer; 24 cases (60%) demonstrated no staining. In summary, Ki-67 has poor discriminatory value for reactive urothelial atypia versus CIS and adds little to the classic CK20/CD44 immunophenotype. While p53 sensitivity for CIS is relatively low (30%) and interpretation as either wild type or negative may be challenging in a small subset of cases, strong and diffuse nuclear reactivity was 100% specific in the distinction from florid reactive urothelial atypia in this cohort.


Assuntos
Carcinoma in Situ/química , Proliferação de Células , Imuno-Histoquímica , Antígeno Ki-67/análise , Proteína Supressora de Tumor p53/análise , Neoplasias da Bexiga Urinária/química , Urotélio/química , Carcinoma in Situ/patologia , Diagnóstico Diferencial , Humanos , Receptores de Hialuronatos/análise , Queratina-20/análise , Valor Preditivo dos Testes , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
10.
Radiology ; 295(2): 296-303, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32181727

RESUMO

Background The role of preoperative MRI for predicting surgical outcomes in patients diagnosed with ductal carcinoma in situ (DCIS) remains uncertain. Purpose To investigate the associations between preoperative MRI and surgical outcomes in DCIS confirmed by using US-guided core-needle biopsy (CNB) and to evaluate clinical-pathologic variables associated with a benefit from MRI. Materials and Methods Women with DCIS confirmed by using US-guided CNB between January 2012 and December 2016 were included in this retrospective study. Propensity score matching using 18 confounding covariates was used to create matched groups with MRI and without MRI, and surgical outcomes were compared. Clinical-pathologic variables were evaluated to determine women who benefited from MRI. Results A total of 541 women (mean age ± standard deviation, 50 years ± 10) were evaluated. Among 430 women who underwent MRI, 67 additional lesions (16%) were depicted, with 25 (37%) of the 67 additional lesions being malignant. Fifty-seven (13%) of the 430 women had a change in surgical plan because of their MRI findings; the change was appropriate for 31 (54%) women. In matched groups, the MRI group was associated with lower odds of positive resection margin (odds ratio [OR], 0.39; 95% confidence interval [CI]: 0.16, 0.93; P = .03) and repeat surgery (OR, 0.33; 95% CI: 0.12, 0.92; P = .03) compared with the non-MRI group. There was no difference in likelihood of initial mastectomy (OR, 1.2; 95% CI: 0.7, 2.0; P = .59) and overall mastectomy (OR, 0.93; 95% CI: 0.5, 1.6; P = .79). In the MRI group, low nuclear grade (90% [28 of 31] vs 69% [275 of 399]; P = .01), progesterone receptor positivity (81% [25 of 31] vs 61% [244 of 399]; P = .03), and human epidermal growth factor receptor 2 negativity (90% [28 of 31] vs 68% [270 of 399]; P = .01) were associated with a benefit from MRI versus no MRI. Conclusion Preoperative MRI depicted additional malignancy and reduced positive surgical margins and repeat surgery for ductal carcinoma in situ confirmed at US-guided biopsy without a higher mastectomy rate. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Pinker in this issue.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/cirurgia , Imagem por Ressonância Magnética/métodos , Adulto , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Biópsia Guiada por Imagem , Margens de Excisão , Mastectomia , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Ultrassonografia de Intervenção , Ultrassonografia Mamária
11.
J Pathol ; 251(2): 135-146, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32207854

RESUMO

Intestinal-type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (GPL: LGIN and HGIN), EGC, and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity-changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN, and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including five driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a five-gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease-free survival of GC patients (log-rank test: p < 0.0001), and the robustness was verified in an independent cohort (n > 300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer-like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Carcinoma in Situ/genética , Transformação Celular Neoplásica/genética , Perfilação da Expressão Gênica , Lesões Pré-Cancerosas/genética , Neoplasias Gástricas/genética , Transcriptoma , Carcinoma in Situ/imunologia , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/patologia , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Gradação de Tumores , Células-Tronco Neoplásicas/patologia , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/mortalidade , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Microambiente Tumoral
12.
Gynecol Oncol ; 157(2): 348-356, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32085863

RESUMO

OBJECTIVE: Our objectives were 1) to compare the efficacy of progestin therapy combined with metformin (Prog-Met) to Prog alone as primary fertility sparing treatment in women with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or early-stage endometrioid carcinoma (EC), and 2) to analyze the proportion of women achieving live birth following treatment. METHODS: A retrospective cohort study of all reproductive-aged women with AH/IN or EC treated with Prog ± Met from 1999-2018 was conducted. Complete response (CR) was assessed and Kaplan-Meier analysis used to calculate time to CR. Comparison of potential response predictors was performed with multivariable Cox regression models. RESULTS: Ninety-two women met criteria; 59% (n = 54) were treated for AH/EIN and 41% (n = 38) for EC. Their median age, body mass index, and follow up time was 35 years, 37.7 kg/m2, and 28.4 months, respectively. Fifty-eight women (63%) received Prog and 34 (37%) received Prog-Met. Overall, 79% (n = 73) of subjects responded to treatment with a CR of 69% (n = 63). There was no difference in CR (p = 0.90) or time to CR (p = 0.31) between the treatment cohorts. Overall, 22% experienced a disease recurrence. On multivariable analysis, EC histology was the only covariate associated with a decreased Prog response (HR 0.48; p = 0.007). Only 17% of the cohort achieved a live-birth pregnancy, the majority of which required assisted reproductive technologies (81%) and occurred in the Prog treatment group. CONCLUSIONS: Our study does not support the use of Prog-Met therapy for treatment of AH/EIN or EC. Additionally, fewer than 20% of women achieved a live-birth pregnancy during the study period, with most requiring ART.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma in Situ/tratamento farmacológico , Hiperplasia Endometrial/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Preservação da Fertilidade/métodos , Nascimento Vivo , Adulto , Carcinoma in Situ/patologia , Estudos de Coortes , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Metformina/administração & dosagem , Recidiva Local de Neoplasia/patologia , Gravidez , Resultado da Gravidez , Progestinas/administração & dosagem , Estudos Retrospectivos
13.
Eur Radiol ; 30(6): 3455-3461, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32086576

RESUMO

OBJECTIVES: To evaluate the diagnostic accuracy of unenhanced and contrast-enhanced MRI in the differentiation of mucosal high-grade neoplasia (MHN) from early invasive squamous cell cancer (EISCC) of the esophagus. METHODS: Between March 2015 and January 2019, 72 study participants with MHN (n = 46) and EISCC (n = 26) of the esophagus were enrolled in this prospective study. Postoperative histopathologic analysis was the reference standard. All participants underwent MRI (T2-multi-shot turbo spin-echo sequence (msTSE), diffusion-weighted imaging (DWI), and 3D gradient-echo-based sequence (3D-GRE)). Two radiologists, blinded to participants' data, independently evaluated MRI and assigned MR features including shape (mucosal thickening or focal mass), signal on T2-msTSE and DWI, enhancement degree (intense or slight), and enhancement pattern (homogeneous, heterogeneous, or heart-shaped). Diagnostic performance of the 5 features was compared using the chi-square test; kappa values were assessed for reader performance. RESULTS: Surgery was performed within 3.6 + 3.5 days after MR imaging. Inter-reader agreement on MR features was excellent (kappa value = 0.854, p < 0.001). All 8 mass-like MHN were "heart-shaped" in appearance. The degree of enhancement showed the best diagnosis performance in differentiating between MHN and EISCC of the esophagus. The combination of all 5 features had only borderline improved sensitivity, specificity, and AUC of 100%, 96.2%, and 0.999, respectively, which was not statistically significant compared with the degree of enhancement alone. CONCLUSIONS: MRI can differentiate MHN from EISCC in esophagus; the presence of "heart-shaped" appearance favors the diagnosis of MHN. KEY POINTS: • All 8 mass-like MHN showed a "heart-shaped" enhancement pattern which may help differentiating MHN from EISCC. • Degree of enhancement had the best diagnostic performance in differentiating between MHN and EISCC in esophagus. • The combined 5 features (shape, signal in T2-msTSE and DWI, enhancement degree, and enhancement pattern) provided sensitivity, specificity, and AUC of 100%, 96.2%, and 0.999, respectively, which was not statistically significant than tumor enhancement alone in distinguishing MHN from EISCC.


Assuntos
Carcinoma in Situ/diagnóstico por imagem , Diagnóstico Diferencial , Mucosa Esofágica/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Lesões Intraepiteliais Escamosas/diagnóstico por imagem , Idoso , Carcinoma in Situ/patologia , Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Células Epiteliais , Mucosa Esofágica/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Lesões Intraepiteliais Escamosas/patologia
14.
Hautarzt ; 71(4): 284-292, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-32065247

RESUMO

Anal intraepithelial neoplasia (AIN) and 89-100% of anal cancers are caused by persistent infections with high-risk (HR) human papillomaviruses (HPV). In HIV-positive patients, anal HPV infection and AIN are very common and these patients have a greatly increased risk of developing anal cancer. However, a continuous increase in the incidence of anal cancer has also been observed in the general population in recent decades. AIN can clinically present in diverse manners. In HIV-positive patients AIN can be hidden in condylomas. Furthermore, 3-14% of high-grade AIN progress to anal cancer within 5 years. Therefore, screening examinations should be offered to patients with an increased risk for anal cancer. The treatment options for AIN are similar to those for condylomas. HIV-positive patients with controlled immune status and HIV-negative patients with anal cancer respond comparably well to combined radiochemotherapy. A German-language AWMF S3 guideline for anal cancer will be available in 2020. In HIV-positive patients over 26 years of age, HPV vaccination showed no effect in a controlled phase­3 study. To prevent AIN and anal cancer in the future, HPV vaccination rates need to be increased in HPV-naïve girls and boys.


Assuntos
Neoplasias do Ânus/virologia , Carcinoma in Situ/virologia , Infecções por HIV/complicações , Soropositividade para HIV/complicações , Imunossupressão/efeitos adversos , Infecções por Papillomavirus/complicações , Adulto , Neoplasias do Ânus/patologia , Neoplasias do Ânus/terapia , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Papillomaviridae , Vacinas contra Papillomavirus
15.
Crit Rev Oncol Hematol ; 147: 102866, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32058913

RESUMO

The precursor lesion of vulvar squamous cell carcinoma (VSCC), namely vulvar intraepithelial neoplasia (VIN), is classified as: human papillomavirus (HPV)-related high grade squamous intraepithelial lesion (HSIL), and HPV-independent differentiated VIN (dVIN). Traditionally, histology and immunohistochemistry (IHC) have been the basis of diagnosis and classification of VIN. HSIL shows conspicuous histological atypia, and positivity on p16-IHC, whereas dVIN shows less obvious histological atypia, and overexpression or null-pattern on p53-IHC. For both types of VIN, other diagnostic immunohistochemical markers have also been evaluated. Molecular characterization of VIN has been attempted in few recent studies, and novel genotypic subtypes of HPV-independent VSCC and VIN have been identified. This systematic review appraises the VSCC precursors identified so far, focusing on histology and biomarkers (immunohistochemical and molecular). To gain further insights into the carcinogenesis and to identify additional potential biomarkers, gene expression omnibus (GEO) datasets on VSCC were analyzed; the results are presented.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , Papillomaviridae/isolamento & purificação , Neoplasias Vulvares/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Neoplasias Vulvares/virologia
16.
Oncol Rep ; 43(3): 877-885, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020221

RESUMO

Subjectivity in oral dysplasia grading has prompted evaluation of molecular­based tests to predict malignant transformation. Aneuploidy detected by DNA image­based cytometry (ICM) is currently the best predictor but fails to detect certain high risk lesions. A novel multiplex fluorescence in situ hybridization (FISH) panel was used to explore possible explanations by detecting aneuploidy at the single cell level. FISH was compared to reference standard DNA ICM in 19 oral lesions with epithelial dysplasia and used to characterize the cellular architecture. Copy number variation at 3q28, 7p11.2, 8q24.3, 11q13.3 and 20q13.12 and matched chromosome specific loci were assessed by dual­color FISH to assess numerical and spatial patterns of copy number increase and gene amplification. FISH revealed wide variation in copy number at different loci. Only low level copy number gain was present and often in only a small proportion of cells, although usually with all or all but one locus (9/12). Four cases showed gene amplification, one at two loci. Some probes revealed an internal presumed clonal structure within lesions not apparent in routine histological examination. Both methods produced similar diagnostic results with concordance in detection of aneuploidy by both methods in 17 out of 19 samples (89%). We have shown that oral dysplastic lesions may contain very few aneuploid cells at a cellular level, high copy number gain is rare and changes appear to arise from large chromosomal fragment duplications. Single stem lines are relatively homogeneous for loci with copy number gain but there is a subclonal structure revealed by gene amplification in some lesions.


Assuntos
Aneuploidia , Carcinoma in Situ/genética , Variações do Número de Cópias de DNA/genética , Neoplasias Bucais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Aberrações Cromossômicas/classificação , DNA de Neoplasias/genética , Células Epiteliais/patologia , Feminino , Citometria de Fluxo , Amplificação de Genes/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia
17.
J Gastroenterol Hepatol ; 35(8): 1372-1380, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32020670

RESUMO

BACKGROUND AND AIM: At present, there is no recognized diagnostic criteria for gastric low-grade intraepithelial neoplasia (LGIN). The purpose of this study was to determine whether an "endoscopic acanthosis nigricans appearance (EANA)" could be a useful endoscopic marker for distinguishing LGIN lesions from peripheral non-neoplastic tissues. METHODS: A retrospective study was conducted on 638 cases of suspected superficial lesions with endoscopic images from white light endoscopy and magnifying endoscopy combined with narrow band imaging. According to the pathological results of accurate biopsies, those lesions were divided into three groups: a control group, an LGIN group, and an early gastric cancer (EGC) group. RESULTS: According to the presence of EANAs, the sensitivity, specificity, positive predictive value, and negative predictive value for differentiating between the LGIN and control groups were 24.8%, 97.3%, 78.3%, and 76.6%, respectively. The sensitivity (84.1%) and negative predictive value (92.4%) were significantly improved by combining EANA with types IV-VI pit pattern. The intervening part and mean gray value of glands, representing microsurface features and microvascular variation, were significantly larger or higher in EANA lesions than in the surrounding non-neoplastic mucosa. LGIN with EANA was more likely to be present in lesions of type 0-IIa. In addition, the prevalence of EANAs in EGC was 16.7%. CONCLUSION: An EANA could be used as an auxiliary indicator for a diagnosis of LGIN in suspected lesions. It could also play a potential assistive role in the diagnosis of EGC lesions.


Assuntos
Acantose Nigricans/patologia , Biomarcadores Tumorais , Carcinoma in Situ/diagnóstico , Detecção Precoce de Câncer/métodos , Endoscopia/métodos , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Banda Estreita , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/patologia
18.
Virchows Arch ; 477(2): 269-277, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32034486

RESUMO

Carcinoma in situ (CIS) is believed to be a precursor of muscle-invasive carcinomas that may arise from these flat high-grade, superficial urothelial lesions. CIS accounts for approximately 10% of all bladder tumors. Therapeutic options for urothelial CIS are limited, and in order to inhibit disease progression and recurrence, current guidelines recommend transurethral resection (TURBT) followed by intravesical administration of Bacillus of Calmette-Guerin (BCG). Approximately 30-40% of patients fail the BCG therapy with recurrence and progression of disease. In the present study, we examined the expression of PD-L1 both in neoplastic epithelial cells and in stromal inflammatory cells in patients with diagnosis of CIS primary responders and not responders to BCG therapy, in order to verify if the PD-L1 expression could identify patients resistant to BCG treatment. Moreover, we analyzed on the same cases the immunoreactivities of anti-PD-L1 MoAbs such as SP263, C23, and SP142. Our results have showed that PD-L1 expression in tumor cells and in immune cell compartment is higher in BCG-unresponsive group than in BCG responders, but only the PD-L1 22C3 expression in tumor cells seems to be associated with recurrence of disease (p = 0.035; OR 0.1204; CI 95% from 0.0147 to 1.023). Hence, our data suggest that the PD-L1 22C3 expression could help to identify CIS that fail the BCG therapy, supporting the hypothesis that enhanced levels of intratumoral PD-L1 22C3 expressed by the tumor cells may explain the failure of BCG immunotherapy.


Assuntos
Recidiva Local de Neoplasia/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Bexiga Urinária/metabolismo , Neoplasias Urológicas/metabolismo , Idoso , Anticorpos Monoclonais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia
19.
Gynecol Oncol ; 157(2): 463-468, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32107046

RESUMO

PURPOSE: Colposcopy-guided punch biopsy is a cornerstone method for diagnosing vulvar diseases. The aim of this study was to evaluate the concordance rate of clinical findings in vulvar diseases during examinations, in comparison with colposcopy-directed punch biopsy. We also developed a new classification to simplify the categorization of vulvoscopic findings. METHODS: The concordance rate of the clinical findings was compared with the final histology results from punch biopsies. The data were collected between January 2014 and May 2017 at the Erlangen University Hospital. RESULTS: A total of 482 colposcopy-directed punch biopsies of the vulva were obtained in 420 women. The overall concordance rate of the clinical findings in comparison with the histological vulvar punch-biopsy findings was 53.9% for all entities - benign lesions, lichen, low- and high-grade squamous intraepithelial lesions (LSIL/HSILs), and vulvar carcinoma. The concordance rate for detecting LSILs was 64.3% (45/70). The concordance rate for detecting HSILs was 62.3% and for Vulvar carcinoma 65.2%. CONCLUSIONS: Punch biopsy of suspicious lesions continues to be a cornerstone in diagnosing HSILs and carcinoma of the vulva. Careful work-up of the vulva is recommended when patients have symptoms such as pruritus or pain. The new classification is more specific for diagnosing lesions in the vulva.


Assuntos
Carcinoma in Situ/diagnóstico , Neoplasias Vulvares/diagnóstico , Adulto , Biópsia/métodos , Carcinoma in Situ/patologia , Colposcopia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Vulvares/patologia
20.
Scand J Gastroenterol ; 55(1): 18-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31906741

RESUMO

Introduction: Endoscopic submucosal dissection (ESD) is extensively performed for the treatment of early gastric cancer (EGC) in the Eastern countries due to its favourable outcomes compared to gastrectomy in terms of lower complication rates, shorter hospital stays, better quality of life, with similar 5-year survival rate. Yet, its use is still limited in the UK.Aim: A long-term follow-up study to evaluate the outcome of ESD in the treatment of EGC in a Caucasian population at a tertiary referral centre in the United Kingdom.Methods: Data for the 35 Caucasian patients, who underwent ESD in a tertiary referral centre between May 2012 and June 2017 were collected. The selected patients were followed-up until May 2018. Curative resection (CR) and survival rates were used to measure the efficacy of ESD.Results: ESD was attempted on 46 lesions and completed on 37. En-bloc and CR rates of 57% and 19% were achieved, respectively. 24% of the lesions were non-CR and 57% were indefinite for non-CR/CR and 41% of the lesions showed change in histological grade post-ESD. Complete reversal of dysplasia/neoplasia was seen in 60% of the 'indefinite' group and 100% of the CR group at latest FU (18 months, mean). Recurrence was seen in 23% of the patients at latest FU. Seventy-one months' survival rate was 77%, while the disease-specific mortality was 0%.Conclusions: This study demonstrates the positive long-term outcome of ESD for gastric neoplasia in a UK Caucasian population, encouraging further development and implementation of ESD in the UK.


Assuntos
Carcinoma in Situ/cirurgia , Ressecção Endoscópica de Mucosa , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Grupo com Ancestrais do Continente Europeu , Feminino , Seguimentos , Mucosa Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Reino Unido
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