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1.
Zhonghua Bing Li Xue Za Zhi ; 49(1): 28-33, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31914531

RESUMO

Objective: To investigatethe clinicopathological features of stratified mucin-producing intraepithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) of the cervix with review of the literature. Methods: Sixteen patients with SMILE/ISMC components of the cervix were collected from files in the Department of Pathology at Xijing Hospital from January 2007 to March 2019. Clinicopathological data included age at diagnosis, clinical presentation, histological type, depth of invasion measurement, the status of lymphovascular space invasion (LVSI) and lymph node metastasis, FIGO staging and follow-up. Histochemistry AB and PAS-D staining and immunostaining for cytokeratin (CK) 7, p16, p63, p40, PAX8, MUC6, p53 were performed simultaneously. In addition, twelve cases with invasive endocervical adenocarcinoma were evaluated using three-tiered pattern-based system (also called Pattern Classification). Results: The average age at diagnosis for patients was 49.7 years (range, 33 to 65 years), and vaginal bleeding occurred in the majority of cases (13/16). The characteristic morphology of SMILE and ISMC was present as non-invasive and invasive stratified epithelium that the full-thickness cells contained different amount of cytoplasmic mucin, respectively. Five cases of SMILE coexisted with adenocarcinoma in situ (1 case), high-grade squamous intraepithelial lesion (1 case), and invasive adenocarcinoma (3 cases). Thirteen cases with ISMC components included pure ISMC (3 cases), mixed with usual-type endocervical adenocarcinoma (8 cases) or squamous cell carcinoma (2 cases). All pure ISMC had lymph vascular space invasion and depth of invasion exceeded 10 mm. All eleven cases of invasive adenocarcinoma with ISMC components belonged to Pattern C tumors, which typically showed diffusely destructive stromal invasion, solid or poorly differentiated components. The results of histochemical staining confirmed that SMILE/ISMC cells were rich in acidic and neutral mucin. The immunohistochemical staining for CK7 and p16 was diffusely strong positive in SMILE (4/4) and ISMC (8/8) components. The positive expressions of p63 and p40 was located in peripheral cells of stratified epithelial nests or merely in a few cells of SMILE (1/3) and ISMC (2/8) components. In ISMC tissues, there were partial expression of MUC6 (5/7), focal expression of PAX8 (2/8), and wild-type expression pattern (4/10) or completely negative expression (6/10) of p53 protein. All thirteen patients with follow-up data were alive (mean 50.5 months, range 4 to 140). Conclusions: As new tumor entities, SMILE is a rare and unique endocervical intraepithelial lesion, while ISMC belongs to an invasive leison. Given that the tumors with ISMC components may have aggressive behavior, it is important for clinicians and pathologists to fully understand the clinicopathological features of SMILE and ISMC.


Assuntos
Adenocarcinoma in Situ , Neoplasias do Colo do Útero , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Mucinas
2.
Int J Cancer ; 146(3): 617-626, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30861114

RESUMO

US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5-year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [CIN3]) after one, two and three negative cotests among 346,760 women aged 55-64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003-2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow-up. Five-year risks of CIN3 after one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%-0.046%), 0.041% (95% CI: 0.007%-0.076%) and 0.016% (95% CI: 0.000%-0.052%), respectively (ptrend < 0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks after one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5-year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harms versus benefits of continued screening. Ideally, this guideline should be informed by longer-term follow-up given that exiting is a long-term decision.


Assuntos
Adenocarcinoma in Situ/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma in Situ/patologia , California/epidemiologia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Detecção Precoce de Câncer/normas , Feminino , Humanos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Medição de Risco/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
3.
Int J Cancer ; 146(3): 810-818, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980692

RESUMO

Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population-based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high-risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9-valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21-24 year age group (annual percent change [APC] overall: -22.1%, 95% CI: -33.9 to -8.2; APC among screened: -16.1%, 95% CI: -28.8 to -1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.


Assuntos
Adenocarcinoma in Situ/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Adenocarcinoma in Situ/prevenção & controle , Adenocarcinoma in Situ/virologia , Adolescente , Adulto , Fatores Etários , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/isolamento & purificação , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Incidência , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/uso terapêutico , Lesões Pré-Cancerosas/prevenção & controle , Lesões Pré-Cancerosas/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
4.
Nat Commun ; 10(1): 5472, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784532

RESUMO

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.


Assuntos
Adenocarcinoma in Situ/genética , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Adenocarcinoma in Situ/imunologia , Adenocarcinoma in Situ/patologia , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Variações do Número de Cópias de DNA , Receptores ErbB/genética , Feminino , Perfilação da Expressão Gênica , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Perda de Heterozigosidade , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , MAP Quinase Quinase 1/genética , Masculino , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas de Ligação a RNA/genética , Receptor ErbB-2/genética , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos T/genética , Proteína Supressora de Tumor p53/genética , Sequenciamento Completo do Exoma
6.
Gynecol Oncol ; 155(2): 245-253, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604665

RESUMO

OBJECTIVE: We assessed whether human papillomavirus (HPV) viral load is an independent predictor of underlying cervical disease and its diagnostic accuracy by age. METHODS: The Biomarkers of Cervical Cancer Risk study was a case-control study from 2001 to 2010 in Montréal, Canada. Cases were histologically-confirmed cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), or cervical cancer cases. Controls were women presenting for routine screening with normal cytology results. We quantified HPV16/18/31/33/45 viral load from exfoliated cervical cells using a real-time PCR assay. Diagnostic accuracy of viral load was assessed using the area under the receiver operating characteristic curve (AUC). We restricted the analysis to the 632 cases and controls who were HPV16/18/31/33/45 positive. RESULTS: Geometric mean HPV16/18/31/33/45 viral load increased with severity of lesion grade, ranging from 0.7, 3.1, 4.8, 7.2, and 12.4 copies/cell in normal, CIN1, CIN2, CIN3&AIS, and cervical cancer respectively. The adjusted odds ratio of CIN1+ and CIN2+ increased respectively by 1.3 (95%CI 1.1-1.4) and 1.2 (95%CI 1.1-1.3) per log-transformed viral copy/cell increase of HPV16/18/31/33/45. This association was mainly driven by HPV16, 18, and 31 viral loads. The AUC of HPV16/18/31/33/45 viral load for discriminating between normal and CIN1+ women was 0.70 (95%CI 0.64-0.76) in HPV-positive women, and was 0.76 (95%CI 0.66-0.86) for women ≥30 years and 0.66 (95%CI 0.58-0.74) for women under 30 years. CONCLUSIONS: HPV viral load has lower diagnostic accuracy than has been reported for other HPV screening triage tests. However, it may be useful for triaging HPV tests in settings without cytology results such as HPV self-sampling.


Assuntos
Adenocarcinoma in Situ/virologia , Alphapapillomavirus/isolamento & purificação , Neoplasia Intraepitelial Cervical/virologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Quebeque , Carga Viral/fisiologia , Adulto Jovem
7.
PLoS One ; 14(8): e0221088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415639

RESUMO

OBJECTIVES: To investigate the use of imaging methods for predicting carcinogenesis in lobular endocervical glandular hyperplasia (LEGH). METHODS: We retrospectively analyzed preoperative images on transvaginal sonography and magnetic resonance imaging (MRI) in 23 cases with histologically diagnosed LEGH. RESULTS: Shape of cervical multicystic lesions on MR images could be divided into two types the flower-type with many small cysts surrounded by larger cysts, and the raspberry-type with many tiny, closely aggregated cysts. Six (46%) of 13 cases had raspberry-type lesions that were not detected on transvaginal sonography but were seen on MRI. Adenocarcinoma in situ (AIS) was identified in 4 postmenopausal women with raspberry-type lesions during the follow-up periods. In these cases, cytologic examination by targeted endocervical sampling using sonography enabled early detection of AIS. CONCLUSIONS: MRI and cytologic examination by targeted endocervical sampling may be very useful for predicting carcinogenesis in LEGH.


Assuntos
Adenocarcinoma in Situ/diagnóstico por imagem , Carcinogênese , Colo do Útero/diagnóstico por imagem , Imagem por Ressonância Magnética , Neoplasias do Colo do Útero/diagnóstico por imagem , Adenocarcinoma in Situ/patologia , Adulto , Idoso , Colo do Útero/patologia , Feminino , Humanos , Hiperplasia , Pessoa de Meia-Idade , Ultrassonografia , Neoplasias do Colo do Útero/patologia
8.
Eur J Obstet Gynecol Reprod Biol ; 240: 273-277, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352128

RESUMO

OBJECTIVE: to provide a practical tool for the evidenced-based management of adenocarcinoma in situ (AIS) of the uterine cervix, a challenging diagnosis encountered by colposcopists in their daily practice. METHODS: the proposed recommendations were drafted by the Italian Society of Colposcopy and Cervical Pathology (SICPCV) based on comprehensive reviews of previous guidelines, large uncontrolled studies, metanalysis, and sytematic reviews. The quality Level and the strength of the recommendations were graded and respectively expressed in Roman numbers (I-VI) and letters (A-E). RESULTS: Women with all subcategories of abnormal glandular cells and AIS on cervical citology should be offered colposcopy with endocervical sampling (Strength of recommendation: A). In women with cytological AIS and negative colposcopy or endocervical curettage, an excisional treatment under colposcopic guidance is recommended (Strength of recommendation: A). If immediate post-conization endocervical sampling is positive, further conization is indicated (Strength of recommendation: C). In women who desire to preserve fertility with positive cone margins, further conization should be performed (Strength of recommendation: B). If colposcopy is adequate, a cylindrical excision that includes the whole transformation zone and at least 1-1.5 cm of endocervix beyond the squamous-columnar junction should be performed (Strength of recommendation: B). If colposcopy is inadequate, it is recommended that conization includes the whole transformation zone with a depth of 20-25 mm (Strength of recommendation: B). Hysterectomy is the standard definitive treatment for AIS in women who do not wish to preserve fertility (Strength of recommendation: B). CONCLUSION: the proposed recommendations should enable clinicians to correctly diagnose, treat and follow AIS patients, avoiding mismanagement.


Assuntos
Adenocarcinoma in Situ/cirurgia , Colo do Útero/cirurgia , Colposcopia , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma in Situ/patologia , Colo do Útero/patologia , Feminino , Humanos , Neoplasias do Colo do Útero/patologia
9.
J Cancer Res Clin Oncol ; 145(8): 2061-2069, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31309301

RESUMO

PURPOSE: Cervical cancer metastases to the ovary may occur with advanced tumor stage, deep cervical stromal involvement and corpus involvement. Endocervical adenocarcinoma in situ (AIS) with ovarian involvement is exceptionally rare with about twelve reported cases. METHODS: Here we present a case of endocervical AIS with ovarian and pulmonary involvement 39 months after the initial diagnosis. The characteristics of that case were compared and summarized with the eleven previously published cases. RESULTS: The patients' age ranged between 30 and 40 years (median 37.4 years). The time interval between the diagnosis of AIS and ovarian involvement was 26.7 months (range 2-84 months). Majority of the patients are alive without evidence of disease after a median time of 63.4 months (range 9-156 months). All reported cases were positive for high-risk HPV which was associated with strong p16 expression on immunohistochemistry. CONCLUSIONS: The ovarian involvement by endocervical AIS suggests the concept of a transtubal spread of the neoplastic cervical cells with or without previous colonization within the endometrium without evidence of invasive growth, suggesting a seed and soil spread of the disease. In cases with ovarian involvement by the AIS and without additional extragenital spread, the prognosis may be favorable.


Assuntos
Adenocarcinoma in Situ/patologia , Suscetibilidade a Doenças , Neoplasias Pulmonares/secundário , Neoplasias Ovarianas/secundário , Neoplasias do Colo do Útero/patologia , Adenocarcinoma in Situ/virologia , Adulto , Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/patologia , Suscetibilidade a Doenças/virologia , Feminino , Humanos , Neoplasias Pulmonares/virologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/virologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia
10.
Diagn Interv Radiol ; 25(4): 270-279, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31295144

RESUMO

The tumor, node, metastasis (TNM) staging system approved by International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC) to stage lung cancer was recently revised. The latest revision is the 8th edition published in January, 2017. This new edition made some important changes to the previous edition, including modification of the T classification based on 1 cm increment, downstage of T descriptor including endobronchial tumor disregarding its distance from carina (T2), merging total and partial atelectasis/pneumonitis into the same T category (T2), upstage diaphragmatic invasion to T4, new classification concept of adenocarcinoma in situ and minimally invasive adenocarcinoma for pure and part-solid ground-glass nodules, and further division of extrathoracic metastasis into M1b and M1c based on the number and sites of extrathoracic metastases. Consensus is reached for debating situations not covered in the previous edition of staging system, such as the classification of pancoast tumor based on its invasion depth and staging tumors that extend directly across the fissure as T2a. Classification of multiple sites of pulmonary involvement, including multiple primary lung cancer, separate lung cancer nodules, multiple ground-glass or lepidic lesions, and consolidation, is also discussed. Even though the 8th edition of the TNM lung staging system provides us with more precise classification based on prognostic analysis of each TNM descriptors, there are still some potential limitations and clinical situations that have not yet been clarified in terms of clinical staging by imaging. It is important for radiologists to understand the major changes introduced in the 8th edition of TNM staging and to recognize the potential pitfalls and limitations of imaging interpretation to precisely classify the clinical stage of lung cancer.


Assuntos
Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias/métodos , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma in Situ/patologia , Idoso , Carcinoma/patologia , Feminino , Humanos , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Linfangite/diagnóstico por imagem , Linfangite/patologia , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias/tendências , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/patologia , Prognóstico , Radiologistas/educação , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Tórax/diagnóstico por imagem , Tórax/patologia
11.
Acta Cytol ; 63(5): 391-400, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216550

RESUMO

OBJECTIVE: The exfoliative cell analyzer, LC-1000 (Sysmex Corporation, Japan), is a medical device that presents the cell proliferation index and 23 research parameters as indicators of cellular proliferative potential. The objective was to evaluate the clinical usability of qualitative assessment by LC-1000 compared with cytology, the human papillomavirus (HPV) test, and histology as gold standard. STUDY DESIGN: Women that visited 3 sites between July 2015 and March 2017 were registered. The primary endpoint in this study was the comparison between LC-1000 measurement and HPV test for sensitivity and specificity for cervical intraepithelial neoplasia 2+ (CIN2+). A tree model algorithm was newly constructed by a statistical method and its relationship with histological results was evaluated. RESULTS: The sensitivity and specificity of LC-1000 were 78.3 and 74.1%, while those of the HPV test were 94.7 and 85.4%, respectively. A tree model comprising five categories was constructed. The proportion of advanced lesions was higher with the change in the rank classification results from 1 to 5. The positive predictive values of CIN2+ in the categories 4 and 5 were high. Despite the small number of subjects, cancer was undetected in categories 1 and 2. In addition, the comparison with follow-up results in 19 women assessed as CIN1 showed that the rate of progression in the categories 3-5 was 50% (7/14); progression in the categories 1 and 2 was 0% (0/5). CONCLUSIONS: LC-1000 may be useful for cervical cancer screening as an index to qualitatively evaluate CIN and cancer based on the changes in characteristics of cells.


Assuntos
Adenocarcinoma in Situ/patologia , Carcinoma/patologia , Proliferação de Células , Neoplasia Intraepitelial Cervical/patologia , Citodiagnóstico/instrumentação , Detecção Precoce de Câncer/instrumentação , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma in Situ/virologia , Automação Laboratorial/instrumentação , Biópsia , Carcinoma/virologia , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/genética , Árvores de Decisões , Diagnóstico Diferencial , Detecção Precoce de Câncer/métodos , Desenho de Equipamento , Feminino , Testes de DNA para Papilomavírus Humano , Humanos , Japão , Teste de Papanicolaou , Papillomaviridae/genética , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
13.
Histopathology ; 75(5): 649-659, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31107973

RESUMO

AIMS: The 2015 WHO classification for lung adenocarcinoma (ACA) provides criteria for adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (INV), but differentiating these entities can be difficult. As our understanding of prognostic significance increases, inconsistent classification is problematic. This study assesses agreement within an international panel of lung pathologists and identifies factors contributing to inconsistent classification. METHODS AND RESULTS: Sixty slides of small lung ACAs were reviewed digitally by six lung pathologists in three rounds, with consensus conferences and examination of elastic stains in round 3. The panel independently reviewed each case to assess final diagnosis, invasive component size and predominant pattern. The kappa value for AIS and MIA versus INV decreased from 0.44 (round 1) to 0.30 and 0.34 (rounds 2 and 3). Interobserver agreement for invasion (AIS versus other) decreased from 0.34 (round 1) to 0.29 and 0.29 (rounds 2 and 3). The range of the measured invasive component in a single case was up to 19.2 mm among observers. Agreement was excellent in tumours with high-grade cytology and fair with low-grade cytology. CONCLUSIONS: Interobserver agreement in small lung ACAs was fair to moderate, and improved minimally with elastic stains. Poor agreement is primarily attributable to subjectivity in pattern recognition, but high-grade cytology increases agreement. More reliable methods to differentiate histological patterns may be necessary, including refinement of the definitions as well as recognition of other features (such as high-grade cytology) as a formal part of routine assessment.


Assuntos
Adenocarcinoma in Situ/patologia , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/classificação , Adenocarcinoma in Situ/classificação , Adenocarcinoma de Pulmão/classificação , Citodiagnóstico , Histocitoquímica , Humanos , Neoplasias Pulmonares/patologia , Prognóstico
14.
Am J Obstet Gynecol ; 221(3): 241.e1-241.e6, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075244

RESUMO

BACKGROUND: Smartphones recently have been applied in the medical setting. However, the literature evaluating the utility of smartphones in gynecologic oncology is limited. OBJECTIVE: To evaluate the utility of a smartphone in the detection of uterine cervical lesions in patients with abnormal cervical cytology. STUDY DESIGN: Seventy-five women with abnormal cervical cytology were enrolled. Two doctors independently inspected the uterine cervix by using smartphone or colposcopy. Images were captured using acetic acid, and biopsies were taken as standard-of-care procedures. The diagnostic performance of the smartphone for cervical intraepithelial neoplasm 1 or worse and cervical intraepithelial neoplasm 2 or worse were evaluated, and the kappa value was calculated to determine the chance corrected agreement of the histologic diagnoses based on the smartphone and colposcopic findings. RESULTS: There was a substantial agreement between histologic diagnoses based on the smartphone and colposcopic findings, with a kappa value of 0.67 (95% confidence interval, 0.43-0.90). The sensitivity, specificity, positive predictive value, and negative predictive value of the smartphone in the diagnosis of cervical intraepithelial neoplasm 1 or worse were 0.89 (95% confidence interval, 0.79-0.96), 0.33 (95% confidence interval, 0.08-0.70), 0.91 (95% confidence interval, 0.81-0.97), and 0.30 (95% confidence interval, 0.07-0.65), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value in the diagnosis of cervical intraepithelial neoplasm 2 or worse were 0.92 (95% confidence interval, 0.81-0.98), 0.24 (95% confidence interval, 0.09-0.45), 0.71 (95% confidence interval, 0.58-0.81), and 0.60 (95% confidence interval, 0.26-0.88), respectively. CONCLUSION: We found that there was a substantial agreement between the histologic diagnoses based on the smartphone and colposcopic findings. The smartphone seems to be useful and may be an alternative to colposcopy.


Assuntos
Adenocarcinoma in Situ/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasia Intraepitelial Cervical/diagnóstico , Colposcopia , Smartphone , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma in Situ/patologia , Adulto , Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Centros de Atenção Terciária , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal
15.
Eur J Radiol ; 113: 238-244, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30927953

RESUMO

OBJECTIVE: To construct a predictive model to discriminate adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC) appearing as pure ground-glass nodules (pGGNs) using computed tomography (CT) histogram analysis combined with morphological characteristics and to evaluate its diagnostic performance. MATERIALS AND METHODS: Two hundred eighty-nine patients with surgically resected solitary pGGN and pathologically diagnosed with AIS, MIA, or IAC in our institution from January 2014 to May 2018 were enrolled in our study. Two hundred twenty-six pGGNs (79 AIS, 84 MIA, and 63 IAC) were randomly selected and assigned to a model-development cohort, and the remaining 63 pGGNs (11 AIS, 29 MIA and 23 IAC) were assigned to a validation cohort. The morphological characteristics were established as model A and histogram parameters as model B. The diagnostic performances of model A, model B, and model A + B were evaluated and compared via receiver operating curve (ROC) analysis and logistic regression analysis. RESULTS: Entropy (odd ratio [OR] = 23.25, 95%CI: 6.83-79.15, p < 0.001), microvascular sign (OR = 8.62, 95%CI: 3.72-19.98, p < 0.001) and the maximum diameter (OR = 4.37, 95%CI: 2.44-7.84, p < 0.001) were identified as independent predictors in the IAC group. The area under the ROC (Az value), accuracy, sensitivity and specificity of model A + B were 0.896, 88.1%, 79.4% and 91.4%, respectively, exhibiting a significantly higher Az value than either model A or model B alone (0.785 vs 0.896, p < 0.001; 0.849 vs 0.896, p = 0.029). Model A + B also conveyed a good diagnostic performance in the validation cohort, with an Az value of 0.851. CONCLUSION: Histogram analysis combined with morphological characteristics exhibit a superior diagnostic performance in discriminating AIS-MIA from IAC appearing as pGGNs.


Assuntos
Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma in Situ/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
16.
J Cancer Res Ther ; 15(1): 164-168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880774

RESUMO

Background: Radiofrequency ablation (RF) is already a viable alternative to surgical resection for focal liver tumors treatment. The use of RF ablation in combination with surgery or chemotherapy and the large panel of RF tools need new experimental models to develop new opportunities for this kind of therapy. Purpose: The purpose of this study was to identify the optimal RF parameters that will allow in situ colic cancer liver metastases destruction with minimal secondary effects. Materials and Methods: The CC531s colic cancer tumor cells were used to induce liver metastases in 30 synergic Wag/Rij rats. When metastases reached at least 1 cm in diameter, RF generator RITA 1500X, and expandable tip RF probe Starburst SDE (Angiodynamics, USA) was used for the RF ablation. The animal survival rate and the RF-induced lesions have been studied, while only the generator delivered power has been modified (90W, 20W, and 10W, respectively). Results: Survival was significantly low in the group with 90W-delivered power RF. Moreover, statistically significant differences were revealed between groups with high and low RF power, regarding the morphological changes of the liver parenchyma and the adjacent organs, without significant difference on the RF therapeutically effect. Conclusions: In an experimental setting, an increased RF generator power induces important lesions of the abdominal organs with subsequently important mortality rate, without improving the RF therapeutic efficiency.


Assuntos
Adenocarcinoma in Situ/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência/métodos , Adenocarcinoma in Situ/mortalidade , Animais , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Ablação por Radiofrequência/efeitos adversos , Ratos , Taxa de Sobrevida , Resultado do Tratamento
17.
Virchows Arch ; 475(1): 95-104, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30903272

RESUMO

The aim of this study was to evaluate the nuclear expression of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in endocervical neoplastic lesions such as invasive endocervical adenocarcinoma (ECA) and cervical in situ adenocarcinoma (AIS) in comparison with normal endocervix and non-neoplastic counterparts. A total of 54 consecutive neoplastic cases (37 ECA, 17 AIS) and 32 non-neoplastic endocervical lesions (15 reactive atypia, 9 microglandular hyperplasia, 3 tuboendometrioid metaplasia, 3 tunnel cluster, 2 endometriosis) were included in the study with adjacent normal endocervix if present. EZH2 immunoreactivity was evaluated semiquantitatively by three independent experts in lesions and adjacent normal glandular epithelium as well. EZH2 expression was defined robust if at least two of the three experts rated partial or diffuse positivity. Robust EZH2 expression was statistically compared among the neoplastic, non-neoplastic, and normal glandular epithelium samples. Diagnostic test capability of robust EZH2 expression was calculated. Fifty-three out of the 54 neoplastic cases (98%) showed robust EZH2 expression. Robust EZH2 expression was significantly less often (4 out of 32 cases, 12.5%) found in the non-neoplastic endocervical lesions (p < 0.0001) and never (0 out of 66 samples) in the adjacent normal glandular epithelium. Robust EZH2 overexpression had a sensitivity and specificity of over 95% in detecting neoplastic lesions versus non-neoplastic lesions or normal glandular epithelium. EZH2 may play a role in the pathogenesis of endocervical neoplasia, and the detection of robust expression of EZH2 might be a useful differential diagnostic tool in problematic endocervical lesions in histology and cytology as well.


Assuntos
Adenocarcinoma in Situ/enzimologia , Adenocarcinoma/enzimologia , Biomarcadores Tumorais/análise , Neoplasia Intraepitelial Cervical/enzimologia , Proteína Potenciadora do Homólogo 2 de Zeste/análise , Neoplasias do Colo do Útero/enzimologia , Adenocarcinoma/patologia , Adenocarcinoma in Situ/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/enzimologia , Núcleo Celular/patologia , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias do Colo do Útero/patologia
18.
Cancer Epidemiol Biomarkers Prev ; 28(3): 602-609, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30792242

RESUMO

BACKGROUND: The impact of human papillomavirus (HPV) vaccination has been observed in the United States through declining cervical precancer incidence in young women. To further evaluate vaccine impact, we described trends in HPV vaccine types 16/18 in cervical precancers, 2008-2014. METHODS: We analyzed data from a 5-site, population-based surveillance system. Archived specimens from women age 18-39 years diagnosed with cervical intraepithelial neoplasia grades 2-3 or adenocarcinoma in situ (CIN2+) were tested for 37 HPV types. We described the proportion and estimated number of cases of CIN2+ by HPV-type groups over time. Trends in HPV16/18-positive CIN2+ were examined, overall and by vaccination status, age, histologic grade, and race/ethnicity, using Cochrane-Armitage tests. RESULTS: In 10,206 cases, the proportion and estimated number of cases of HPV16/18-positive CIN2+ declined from 52.7% (1,235 cases) in 2008 to 44.1% (819 cases) in 2014 (P < 0.001). Declining trends in the proportion of HPV16/18-positive CIN2+ were observed among vaccinated (55.2%-33.3%, P < 0.001) and unvaccinated (51.0%-47.3%, P = 0.03) women; ages 18-20 (48.7%-18.8%, P = 0.02), 21-24 (53.8%-44.0%, P < 0.001), 25-29 (56.9%-42.4%, P < 0.001), and 30-34 (49.8%-45.8%, P = 0.04) years; CIN2 (40.8%-29.9%, P < 0.001) and CIN2/3 (61.8%-46.2%, P < 0.001); non-Hispanic white (59.5%-47.9%, P < 0.001) and non-Hispanic black (40.7%-26.5%, P < 0.001). CONCLUSIONS: From 2008-2014, the proportion of HPV16/18-positive CIN2+ declined, with the greatest declines in vaccinated women; declines in unvaccinated women suggest herd protection. IMPACT: The declining proportion of HPV16/18-positive CIN2+ provides additional evidence of vaccine impact in the United States.


Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/tratamento farmacológico , Vacinas contra Papillomavirus/administração & dosagem , Lesões Pré-Cancerosas/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/tendências , Adenocarcinoma in Situ/epidemiologia , Adenocarcinoma in Situ/prevenção & controle , Adenocarcinoma in Situ/virologia , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Feminino , Seguimentos , Humanos , Incidência , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/virologia , Prognóstico , Fatores de Tempo , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
19.
Lung Cancer ; 129: 16-21, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30797486

RESUMO

OBJECTIVES: The aim of this study was to investigate distinguishing clinicopathological features, in addition to histological invasiveness, in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) of the lung. MATERIALS AND METHODS: Patients with lung adenocarcinoma who underwent surgery at our hospital between 2007 and 2014 were reviewed, focusing on computed tomography (CT) images, operative procedures and clinical outcomes, histopathology, Ki-67 immunostaining, and EGFR-mutation status. EGFR mutations were examined using a peptide nucleic acid-locked nucleic acid PCR clamp method. Group comparisons were investigated by Mann-Whitney U or Fisher's exact tests. RESULTS: Of 629 patients with lung adenocarcinoma who underwent surgery, 91 (14%) of 103 AIS (n = 34) or MIA (n = 69) tumors were reviewed. The ratio of male to female patients with MIA compared to AIS was significantly higher (p < 0.02). Of 103 tumors, 99 (96%) were non-mucinous. By CT, 74% of AIS appeared as pure ground-glass nodules and 75% of MIAs as part-solid ground-glass nodules. Pathological tumor diameters and Ki-67 labeling index (LI) values were significantly greater for MIAs compared to AIS (p < 0.001 for both). A Ki-67 LI of ≥2.8% indicated the presence of an MIA rather than an AIS. EGFR mutations were more frequently detected in MIAs (33/69, 48%) than AIS (9/34, 26%; p = 0.055). The ratio of exon 19 deletions to exon 21 missense mutations in MIAs tended to be higher than those in AIS (p = 0.06). Patients did not experience a local recurrence or metastasis after AIS and MIAs were removed by wedge resection, segmentectomy or lobectomy. Five-year recurrence-free survival rates were 100%. CONCLUSION: Despite similar surgical outcomes for AIS and MIAs, we found differences in terms of gender, tumor diameters, CT findings, Ki-67 LI and a subset of EGFR mutations, highlighting the validity of classifying the two subtypes.


Assuntos
Adenocarcinoma in Situ/patologia , Adenocarcinoma de Pulmão/patologia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Pulmonares/patologia , Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Recidiva Local de Neoplasia , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X
20.
Asian Pac J Cancer Prev ; 20(2): 377-382, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30803195

RESUMO

Background: Adenocarcinoma in situ (AIS) of the uterine cervix is a preinvasive lesion of the invasive adenocarcinoma. We analyzed the cervical screening results leading to detecting the AIS lesions including the coexistence of AIS lesions with high-grade squamous intra-epithelial lesions (HSIL) and invasive carcinoma. Methods: Women who were diagnosed and received treatment for AIS at Chiang Mai University Hospital between January 1, 2007 and August 31, 2016 were retrospectively reviewed. The inclusion criteria were the women who had pathological diagnosis of AIS obtained from cervical punch biopsy or excisional cone biopsy with either loop electrosurgical excision procedure (LEEP) or cold-knife conization (CKC). The patient characteristics, diagnostic work-up and treatment details were reviewed, including the cervical screening results prior to the diagnosis of cervical AIS, pathologic results of excisional cone biopsy and hysterectomy specimens. Results: During the study period, 75 women with AIS pathology undergoing excisional cone biopsy with either LEEP (n=62) or CKC (n=13) were identified. The abnormal cytologic screening leading to detection of AIS was the squamous cell abnormality accounting for 57.3%. Abnormal glandular cytology accounted for 37.3%. The most common abnormal cervical screening results was HSIL cytology (n = 25) followed by AIS cytology (n = 13). Normal cytology was noted in 4 women in whom 3 were positive for HPV 18 and 1 had AIS on the endocervical polyp. AIS coexisted with HSIL and invasive carcinoma were detected in cone biopsy specimens in 21 (28%) and 29 (38.7%) patients, respectively. Conclusion: The majority of cervical screening results leading to detection of cervical AIS was the squamous cell abnormality accounting for 57.3% in which, HSIL cytology was the most common. Abnormal glandular cytology accounted for only 37.3%. Diagnostic cone excision is recommended if AIS lesion is noted in cervical biopsy specimen since nearly 40% have coexisting invasive lesions.


Assuntos
Adenocarcinoma in Situ/diagnóstico , Neoplasia Intraepitelial Cervical/diagnóstico , Citodiagnóstico/métodos , Detecção Precoce de Câncer/métodos , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma in Situ/cirurgia , Adulto , Idoso , Neoplasia Intraepitelial Cervical/cirurgia , Feminino , Seguimentos , Humanos , Histerectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Lesões Intraepiteliais Escamosas Cervicais/cirurgia , Neoplasias do Colo do Útero/cirurgia
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