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1.
Int J Gynecol Pathol ; 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30059454

RESUMO

There is a controversy about whether endometriosis-associated ovarian cancer (EAOC) might represent a different entity from the corresponding ovarian cancer occurring de novo, in the absence of endometriosis. This study investigated the clinical-pathologic characteristics and outcome of EAOC compared with other ovarian carcinomas that are not associated with endometriosis (non-EAOC) in a large cohort. Seven hundred two patients meeting the inclusion criteria were further subclassified as group I when patients had ovarian carcinoma associated with or arising within endometriosis (EAOC) and group II when patients had non-EAOC. Age, gross features, histologic type, International Federation of Gynecology and Obstetrics stage, and disease-free survival (DFS) were compared between the groups. One hundred sixty-eight (23.9%) patients had EAOC, whereas 534 (76.1%) patients had non-EAOC. EAOCs were mostly endometrioid and clear cell type. Patients with EAOC were younger, present early, and had a lower rate of recurrence when compared with patients with non-EAOC, P<0.001. Patients with EAOC had longer DFS time, 51.9 mo (95% confidence interval, 44.9-58.8) versus 30.5 mo (95% confidence interval, 27.7-33.3) in non-EAOC patients. The 5 yr Kaplan-Meier estimate of DFS rate was 70% in 166 patients of group I and was 39.3% in 532 patients of group II, P<0.001. On multivariate analysis, International Federation of Gynecology and Obstetrics staging, histologic type, and treatment were the only significant factors affecting the hazards of recurrence. Patients with tumors associated with endometriosis are usually, younger, present early, have lower rate of recurrence, longer DFS, and their tumors are of lower grade and are more likely endometrioid or clear cell carcinoma.

2.
Neoplasia ; 20(7): 697-709, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29852322

RESUMO

Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed epithelial ovarian cancer histotype. Other identified risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation, during which the FTE cells become transiently exposed to follicular fluid (FF). To test whether mtBRCA1 or mtBRCA2 nonmalignant FTE cells respond differently to periovulatory FF exposure than control patient FTE cells, gene expression profiles from primary FTE cultures derived from BRCA1 or BRCA2 mutation carriers or control patients were compared at baseline, 24 hours after FF exposure, and 24 hours after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Gene set enrichment analysis revealed increased NFκB and EGFR signaling at baseline in mtBRCA1 samples, with increased interferon target gene expression, including members of the ISGylation pathway, observed after recovery from FF exposure. Gene set enrichment analysis did not identify altered pathway signaling in mtBRCA2 samples. An inverse relationship between EGFR signaling and ISGylation with BRCA1 protein levels was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1 cDNA. Suppression of ISG15 and ISGylated protein levels by increased BRCA1 expression was found to be mediated by decreased NFκB signaling. These studies indicate that increased NFκB signaling associated with decreased BRCA1 expression results in increased ISG15 and protein ISGylation following FF exposure, which may be involved in predisposition to HGSOC.


Assuntos
Células Epiteliais/metabolismo , Tubas Uterinas/citologia , Tubas Uterinas/metabolismo , Líquido Folicular/metabolismo , Genes BRCA1 , Mutação , NF-kappa B/metabolismo , Transdução de Sinais , Adulto , Biomarcadores , Células Cultivadas , Receptores ErbB/metabolismo , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Genes BRCA2 , Humanos , Pessoa de Meia-Idade , Filogenia , Transcriptoma
3.
Int J Surg Pathol ; 26(4): 306-317, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29338553

RESUMO

The distinction of primary mucinous ovarian carcinoma (PMOC) from other primaries or secondaries is essential for selecting therapeutic options and prognostication. We aimed to characterize the immunohistochemical profile of 36 PMOCs using an extended immunohistochemical panel, with clinicopathologic features and outcome. PAX8 was negative in 30 (83.3%), and SATB2 was negative in 32/35. HNF1B, AMACR, and napsin-A were detected in 33 (91.7%), 35 (97.2%), and 0 (0%), respectively. MMR proteins and ARID1A were retained in 100%; PTEN was lost in 4 (11.1%). P53 was aberrant in 10 (27.8%); none overexpressed p16. HER2 was positive in 6/35 (17.1%). Most PMOCs had a favorable outcome. However, recurrence is usually fatal. The typical tumor profile was CK7+, CK20+/-, CDX2+/-, PAX8-, ER-, PgR-, and SATB2-. HER2 positivity suggests a possible target for therapy in advanced disease.


Assuntos
Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/análise , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Carcinoma Epitelial do Ovário , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
4.
Acta Cytol ; 60(3): 225-31, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27442040

RESUMO

OBJECTIVES: Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon premalignant lesion of the uterine cervix. A detailed examination of preinvasive SMILE cases including a comparison of the cytologic features with usual-type adenocarcinoma in situ (AIS) and human papillomavirus (HPV) genotyping was performed. STUDY DESIGN: Excisions and preceding Papanicolaou (Pap) tests were retrieved from the files of 2 tertiary care centers. Histologic review estimated the lesional SMILE proportion. Pap tests were reviewed and assessed for architectural, cellular and background features. Cobas® HPV test was performed. RESULTS: 13 cases were identified. Mean/median patient age was 35/33 years (range 23-51 years). Concurrent high-grade squamous intraepithelial lesion was found in 10/13 (77%) and AIS in 8/13 (62%) cases. In 6 cases, SMILE was dominant (≥50%) and represented in 5/6 corresponding Pap tests. Cytology interpretations differed more often in the SMILE-dominant group (p < 0.05). SMILE and AIS had overlapping features. Feathering and prominent nucleoli were absent in SMILE. HPV DNA was detected in all 12 cases tested. HPV 18 was most common (7/12). Excisions with positive/suspicious margins were reported in 5/6 SMILE-dominant versus 3/7 nondominant cases. CONCLUSION: SMILE is best considered as an AIS variant for cytologic, etiologic and management purposes. Cytologic features overlap with AIS, but are more subtle and easily missed. HPV testing may play a role in facilitating SMILE detection.


Assuntos
Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/metabolismo , Colo do Útero/patologia , Mucinas/metabolismo , Lesões Intraepiteliais Escamosas Cervicais/metabolismo , Lesões Intraepiteliais Escamosas Cervicais/patologia , Adenocarcinoma in Situ/metabolismo , Adenocarcinoma in Situ/patologia , Adenocarcinoma in Situ/virologia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/virologia , DNA Viral/genética , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou/métodos , Papillomaviridae/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos , Adulto Jovem
6.
Int J Gynecol Pathol ; 34(5): 424-36, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26107560

RESUMO

Studies on the immunophenotypes of early forms of serous carcinoma arising from female genital tract are limited. We aimed to examine p53, p16(Ink4a), estrogen receptor (ER), progesterone receptor (PR), ERBB2, WT1, and Ki-67 protein expression in endometrial intraepithelial carcinoma (n=29), serous tubal intraepithelial lesion (n=4) and carcinoma (STIC, n=10), and the putative precursor p53 signature (n=11). Among endometrial intraepithelial carcinoma, 80% demonstrated p53 overexpression and 10% were consistent with a null phenotype. p16(Ink4a) immunostaining were observed in all endometrial intraepithelial carcinoma cases. ER, PR, ERBB2, and WT1 were positive in 54%, 25%, 11%, and 18% of cases, respectively. STIC cases demonstrated p53 overexpression and null phenotype in 90% and 10%, respectively. All STIC cases were p16(Ink4a) and WT1 positive, whereas ER and PR were positive in 70% and 20%, respectively. All STICs were negative for ERBB2. Among serous tubal intraepithelial lesion cases, 75% demonstrated p53 overexpression and 25% a null phenotype. p53 was positive in all 11 p53 signature cases, whereas p16(Ink4a) was universally negative. Finally, ER and PR were positive in 100% and 73% of p53 signature cases, respectively. These results suggest that p16(Ink4a) has a role in early Müllerian serous carcinogenesis but is absent in the earliest noncommitted lesion. p16(Ink4a) immunohistochemistry can be used as an adjunct confirmatory tool in p53-null cases with limited surface area.


Assuntos
Cistadenocarcinoma Seroso/classificação , Neoplasias dos Genitais Femininos/classificação , Carcinogênese/patologia , Carcinoma in Situ/patologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Neoplasias das Tubas Uterinas/patologia , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Neoplasias Ovarianas/patologia , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Proteína Supressora de Tumor p53/análise , Proteínas WT1/análise
7.
Int J Gynecol Cancer ; 23(7): 1205-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23835504

RESUMO

UNLABELLED: The question whether the appendix should be removed at the time of surgery for apparent early-stage ovarian cancer is controversial. Removal of the appendix in the setting of mucinous histologic type is primarily driven by the existing challenge to distinguish between primary ovarian mucinous neoplasm and metastatic appendiceal carcinoma to the ovary. OBJECTIVES: To evaluate the value of an appendectomy at the time of surgery for ovarian mucinous borderline tumors or carcinoma. METHODS: A retrospective single institute-based study was conducted. We identified patients who were operated on by a gynecologic oncologist for an abnormal pelvic mass, which was diagnosed as mucinous adenocarcinoma or mucinous borderline tumor between January 2000 and December 2010. Cases were included in the study if an appendectomy was performed at the time of initial surgery. RESULTS: Seventy-seven cases meeting the inclusion criteria were identified. The ovarian mass of 11 patients (14%) was diagnosed as metastatic appendiceal carcinoma involving the ovary. Evidence of metastatic disease, abnormal-looking appendix, or pseudomyxoma peritonei, were identified at the time of surgery for all of these cases. The condition of 30 patients (39%) and 36 patients (47%) were diagnosed as mucinous borderline ovarian tumor and invasive or microinvasive mucinous ovarian carcinoma, respectively. Evidence of metastasis from the ovary to the appendix was not identified in any of the cases. CONCLUSIONS: Our data suggest that in cases of apparent early-stage mucinous ovarian borderline tumors and cancer, adding an appendectomy at the time of surgery is not warranted in the absence of a grossly abnormal appendix or evidence of metastatic disease.


Assuntos
Adenocarcinoma Mucinoso/cirurgia , Apendicectomia , Neoplasias Ovarianas/cirurgia , Adenocarcinoma Mucinoso/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico , Fatores de Tempo
8.
Int J Gynecol Pathol ; 31(1): 57-65, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22123724

RESUMO

Undifferentiated carcinoma of the endometrium is a rare neoplasm, which, when involving the cervix, raises a question about its origin. Diffuse p16 positivity of uterine cancers is usually interpreted as a surrogate marker for high-risk human papilloma virus and favors cervical origin. In this study, we investigated the expression of cytokeratin 7 (CK7), monoclonal carcinoembryonic antigen (mCEA), estrogen receptor (ER), vimentin, and p16 in 28 cases of undifferentiated endometrial carcinoma, 20 high-grade endometrioid adenocarcinomas, and 50 cervical adenocarcinomas. Staining was considered positive when it was cytoplasmic for CK7, mCEA, and vimentin, nuclear for ER, and both nuclear and cytoplasmic for p16. Percentages of cells staining were recorded as follows: negative (0%-5%), 1+ (6%-25%), 2+ (26%-50%), 3+ (51%-75%), and 4+ (>75%). P16 was considered positive if it stained more than 75% of the tumor cells. Diffuse/strongly positive staining for p16 was seen in 40/50 (80%) cases of cervical adenocarcinoma and 14/28 (50%) cases of undifferentiated endometrial carcinoma. In high-grade endometrioid adenocarcinoma, staining was mainly patchy. CK7, mCEA, ER, progesterone receptor, and vimentin staining in undifferentiated endometrial carcinoma was as follows: 10/28 (36%), 4/28 (14%), 21/28 (75%), 23/28 (82%), and 26/28 (93%), respectively; for high-grade endometrioid carcinoma: 20/20 (100%), 1/20 (5%), 17/20 (85%), 18/20 (90%), and 19/20 (95%); for endocervical adenocarcinoma: 50/50 (100%), 45/50 (90%), 9/50 (18%), 8/50 (16%), and 6/50 (12%), respectively. Our data indicate that p16 may play a role in the tumorigenesis of a subset of undifferentiated endometrial carcinoma. In the setting of p16 positivity, undifferentiated endometrial carcinomas are more likely to be ER, progesterone receptor, and vimentin positive and mCEA negative when compared with endocervical adenocarcinomas. Distinction between undifferentiated endometrial carcinoma and endocervical adenocarcinoma, both of which can share diffuse p16 expression, should rely on detection of human papilloma virus in the latter.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Endometrioide/diagnóstico , Carcinoma/diagnóstico , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias do Endométrio/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/metabolismo , Adulto , Idoso , Anticorpos Monoclonais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma Endometrioide/metabolismo , Diagnóstico Diferencial , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/metabolismo
9.
Int J Gynecol Pathol ; 31(1): 80-90, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22123727

RESUMO

Adult granulosa cell tumors are usually diagnosed at an early stage. However, most patients with advanced or recurrent disease will die of the disease due to limited treatment options. Data on the immunohistochemical characteristics of recurrent granulosa cell tumors are limited. The aim of this study was to compare the immunohistochemical profile of primary and recurrent adult granulosa cell tumors. Special emphasis is given to epidermal growth factor receptor expression because it represents a potential marker for targeted therapy with monoclonal antibodies.Inhouse granulosa cell tumor cases accessioned between 1999 and 2008 were retrieved and reviewed according to the WHO classification. Cases were studied by immunohistochemistry using a panel of 11 antibodies. Immunostaining was semiquantitatively recorded.We have studied 20 cases of primary and 20 cases of recurrent adult granulosa cell tumors from 31 patients. Immunohistochemistry showed that primary tumors were positive for inhibin in 100%, calretinin 100%, CD56 90%, CD99 40%, D2-40 35% and low molecular weight keratin 30%. Recurrences were positive for inhibin 90%, calretinin 85%, CD56 95%, CD99 65%, D2-40 55% and low molecular weight keratin 10%. Recurrences were positive for inhibin 90%, calretinin 85%, CD56 95%, CD99 65%, D2-40 55%, and low molecular weight keratin 10%. All primary and recurrent tumors were negative for melan-A, CD10, and epithelial membrane antigen. Epidermal growth factor receptor was positive in 65% of primary tumors and 85% of recurrences. Ki67 index was higher in recurrence specimens. The immunoprofile of primary and recurrent adult granulosa cell tumors is highly concordant. Similar to primary tumors, almost all recurrent cases exhibited evidence of sex cord lineage. The lack of specific markers emphasizes the need for evaluation using a panel of antibodies. Special attention should be paid when low molecular-weight keratin is used as part of a panel differentiating granulosa cell tumors from carcinomas, as a significant proportion of the former are positive. Although targeted therapies directed against epidermal growth factor receptor have not been tested yet in the setting of advanced or recurrent granulosa cell tumors, the high level of epidermal growth factor receptor expression is important as we step to an era of advanced biolabeled imaging techniques.


Assuntos
Biomarcadores Tumorais/metabolismo , Tumor de Células da Granulosa/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Feminino , Tumor de Células da Granulosa/metabolismo , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Neoplasias Ovarianas/metabolismo , Estudos Retrospectivos , Adulto Jovem
10.
Int J Gynecol Pathol ; 29(4): 386-93, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20567154

RESUMO

There are limited data evaluating the significance of lymphatic vessel density (LVD) as a prognostic marker in cervical adenocarcinoma. In this study, we investigated intratumoral and peritumoral LVD, using the lymphatic marker D2-40, as a prognostic marker in endocervical adenocarcinoma. Surgical specimens from 50 consecutive patients with endocervical adenocarcinoma treated with complete staging surgical procedures were reviewed. Selected tumor blocks were immunostained for D2-40 and CD31. Positively stained microvessels (MVs) were counted in densely vascular/lymphatic foci (hot spots) at 400x field in each specimen (0.17 mm). Results were expressed as the highest MV count identified within any single field. Both intratumoral CD31 MV and peritumoral D2-40 LVD showed significant correlation with depth of invasion (r=0.39, 0.37, respectively), percentage of circumferential involvement (r=0.36, 0.48, respectively), and lymphovascular invasion detected by D2-40 (r=0.45, 0.51, respectively; P<0.01). Only peritumoral D2-40 LVD showed a significant correlation with lymph node metastases (r=0.40; P<0.01), disease-free and overall survivals. Using univariate analysis, peritumoral D2-40 LVD showed significant correlation with lymphovascular invasion detected by D20-40 and lymph node metastases (P<0.05), which was maintained on multivariate analysis. D2-40 detected lymphovascular invasion in 16 of 50 (32%) cases, and showed a significant correlation with depth of invasion, lymph node metastases, involvement of parametrium (r=0.41, 0.38, 0.32, respectively; P<0.01), and disease-free survival. Our study showed that both angiogenesis and lymphangiogenesis play an important role in the progression of endocervical adenocarcinoma, and that peritumoral D2-40 LVD is an independent predictor of lymph node metastasis.


Assuntos
Adenocarcinoma/patologia , Linfangiogênese/fisiologia , Vasos Linfáticos/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/irrigação sanguínea , Adulto , Anticorpos Monoclonais , Anticorpos Monoclonais Murinos , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Vasos Linfáticos/irrigação sanguínea , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Neoplasias do Colo do Útero/irrigação sanguínea
11.
Appl Immunohistochem Mol Morphol ; 18(1): 80-5, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19625948

RESUMO

High-risk human papilloma virus (HPV) seems to play a role in the pathogenesis of cervical squamous neoplasia and adenocarcinomas of the mucinous and endometrioid cell types. Cervical serous, clear cell, and small cell carcinomas differ from the conventional endocervical adenocarcinoma in their clinical characteristics. The data on the role of HPV in their pathogenesis are limited. In this study, we examined the presence of high-risk HPV-DNA in rare types of cervical carcinoma using polymerase chain reaction-based test. In-house cervical serous, clear cell, and small cell carcinoma cases accessioned between 2000 and 2008 were tested for HPV by polymerase chain reaction amplification of DNA extracted from deparaffinized sections using Roche AMPLICOR HPV Amplification Detection and Control Kits. The kit detects all 13 high-risk HPV-DNA genotypes. The positive cut-off point for AMPLICOR HPV Test was A450 = 0.2. We identified 4 serous, 3 clear cell, 1 mixed clear cell and serous, and 5 small cell carcinomas. High-risk HPV-DNA tested positive in 3 out of 4 serous carcinomas, 2 out of 3 cervical clear cell carcinomas, and all 5 cases of small cell carcinoma and the mixed cell type. Our report documents HPV status in a series of archival unusual types of adenocarcinoma of the uterine cervix. It suggests a robust association between high-risk HPV and these rare subtypes. Despite their unique clinical setting and morphologic appearance, the majority of these tumors likely share a common HPV-mediated carcinogenic pathway. Our observation is particularly significant in cervical cancer prevention as we enter the HPV vaccination era.


Assuntos
DNA Viral/análise , Papillomaviridae/isolamento & purificação , Neoplasias do Colo do Útero/virologia , Feminino , Fixadores , Formaldeído , Humanos , Papillomaviridae/genética , Inclusão em Parafina , Reação em Cadeia da Polimerase/métodos , Kit de Reagentes para Diagnóstico
12.
Am J Clin Pathol ; 132(4): 531-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19762530

RESUMO

We studied the expression of cytokeratin (CK) 7, CK20, CDX-2, and p16 in 119 cervical adenocarcinomas (65 usual type [50 invasive; 15 in situ], 37 intestinal type [21 invasive; 16 in situ], 10 endometrioid, 5 adenosquamous, and 2 signet-ring carcinomas) in comparison with 55 cases of rectal adenocarcinomas. The percentage of cells staining was considered negative if 0% to 5% stained; more than 5% was considered positive. For p16, staining of more than 50% was considered positive. CK7 was expressed in all cervical cases and in 12 rectal adenocarcinomas (22%). CK20 was expressed in 17 cervical adenocarcinomas (14.3%) and in 48 rectal adenocarcinomas (87%). CK20 immunostaining was diffuse in the majority of rectal tumors but focal in most cervical tumors. CDX-2 was expressed in all cases of rectal adenocarcinoma and in 46 cervical adenocarcinomas (38.7%): usual type, 10 (15%); intestinal type, 31 (84%); endometrioid type, 5 (50%); adenosquamous and signet-ring types, 0 (0%). CDX-2 is a marker for intestinal differentiation irrespective of a rectal or cervical origin. Therefore, it should not be used as the sole basis to confirm the colorectum as the primary origin in metastatic cases.


Assuntos
Adenocarcinoma/fisiopatologia , Proteínas de Homeodomínio/biossíntese , Transativadores/biossíntese , Neoplasias do Colo do Útero/fisiopatologia , Adenocarcinoma/patologia , Fator de Transcrição CDX2 , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Feminino , Humanos , Neoplasias Intestinais/fisiopatologia , Queratina-20/biossíntese , Queratina-7/biossíntese , Neoplasias Retais/fisiopatologia , Neoplasias do Colo do Útero/patologia
13.
Int J Gynecol Pathol ; 28(5): 480-8, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19696621

RESUMO

Vaginal radical trachelectomy (VRT) is a fertility-sparing surgical technique used as an alternative to radical hysterectomy in early stage cervical carcinoma. With the advent of VRT, preoperative evaluation of the surgical margin has become imperative, because if the tumor is found within 5 mm of the endocervical margin, additional surgical resection is required. In a study published earlier from our center, we came to the conclusion that a frozen section should be conducted only when a cancerous lesion is grossly visible, and that it could be omitted in normal-looking specimens or VRT with nonspecific lesions. Since then, 53 VRT have been performed in our center, and frozen sections were conducted according to these recommendations. Fifteen VRT were grossly normal, 24 had a nonspecific lesion and 14 showed a grossly visible lesion. Final margins were satisfactory on all 15 grossly normal specimens. Of the 24 VRT with nonspecific lesions, 2 cases for which no frozen section was performed had unsatisfactory final margins (<5 mm). Of the 14 VRT with grossly visible lesions, 3 cases were inadequately evaluated by frozen section due to sampling errors, which led to unsatisfactory final margin assessment. These results confirm that a frozen section can be omitted on normal looking VRT specimens, but contrary to results published earlier, we recommend that a frozen section be performed on all VRT with nonspecific lesions. As for VRT with a grossly visible lesion, frozen section evaluation is still warranted, and we recommend increasing the sampling to improve the adequacy of frozen sections.


Assuntos
Secções Congeladas/métodos , Procedimentos Cirúrgicos em Ginecologia/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Feminino , Humanos , Vagina/patologia , Vagina/cirurgia
14.
Pathol Res Pract ; 205(9): 657-61, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19577382

RESUMO

Large cell neuroendocrine carcinoma of the ovary is a rare recently established entity. Few cases have been reported in the literature, and they are usually associated with another type of surface epithelial tumor. The association of a large cell neuroendocrine carcinoma with a surface epithelial tumor and a teratoma is even rarer, with only two cases previously described. We report the cases of two patients in their fifties who presented with a growing abdominal mass and died of metastatic disease within less than a year. Histological assessment revealed large cell neuroendocrine carcinoma admixed with mucinous adenocarcinoma and teratoma. Different hypotheses regarding the origin of large cell neuroendocrine carcinoma of the ovary are discussed. The immunohistochemical pattern of staining for cytokeratin 7 and cytokeratin 20 suggests that the composite epithelial tumors originated from the pre-existing teratoma.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Neuroendócrino/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/terapia , Terapia Combinada , Evolução Fatal , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/metabolismo , Neoplasias Primárias Múltiplas/terapia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/terapia , Teratoma/metabolismo , Teratoma/terapia
15.
Diagn Cytopathol ; 37(9): 641-6, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19306425

RESUMO

Radical trachelectomy is a fertility preserving alternative for early cervical cancer patients. This audit assesses the role of isthmic-vaginal smear in postoperative follow-up. A total of 94 patients were identified generating 913 smears. The final surgical margin was at the lower uterine segment in 37 cases (39.4%) and significantly correlated with the presence of lower uterine segment endometrial cells (LUSEC) in smears (P = 0.035). The most common abnormal diagnoses in the presence of LUSEC were ASC-US and AGUS seen in 14.2% and 11.9% of positive smears, respectively. The most common follow-up pattern was initial positive smears, which converted to negative (45.7% of patients), showing that reactive changes are another potential overcall pitfall. The only 2 central recurrences were successfully diagnosed by smears. This study summarizes our experience, emphasizing the role of isthmic-vaginal smears for early detection of central recurrence and highlighting the role of LUSEC and reactive changes as potential overcall pitfalls.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Vagina/cirurgia , Esfregaço Vaginal/métodos , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
16.
Pathol Res Pract ; 205(2): 131-5, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18842349

RESUMO

Primary vulvar adenocarcinomas are rare tumors, and their histogenesis is not fully understood. They are classified into extramammary Paget's disease, sweat gland carcinomas, and "breast-like" adenocarcinomas of the vulva. The latter resemble adenocarcinomas arising in the breast morphologically and immunophenotypically. Rare cases of adenocarcinoma with apocrine features have been reported, and whether these neoplasms originate from the "native apocrine" sweat glands or from "anogenital mammary-like" glands are still debatable. The presence of normal mammary-like glands in the vicinity of the tumor, the transitional malignant morphological features from normal mammary-like glands and the tumor, the breast-like histological features of the tumor, and the expression of estrogen and progesterone receptors generally suggest an origin from anogenital mammary-like glands. Absence of these features points toward native apocrine sweat glands as the source of these neoplasms. In this report, we present a patient who was initially diagnosed with Paget's disease of the right vulva, which was treated by hemi-vulvectomy, and who later presented with primary vulvar apocrine adenocarcinoma with metastasis to the inguinal lymph nodes and intranodal mucinous/colloidal differentiation: a feature, to the best of our knowledge, not reported before. We also reviewed the histogenesis of the vulvar adenocarcinomas, with emphasis on the morphological features that separate the tumors arising from the anogenital mammary-like glands in the vulva from those arising from the native vulvar sweat glands.


Assuntos
Adenocarcinoma/patologia , Glândulas Apócrinas/patologia , Metástase Linfática/patologia , Neoplasias Vulvares/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Idoso de 80 Anos ou mais , Glândulas Apócrinas/metabolismo , Artrite Reumatoide/complicações , Diferenciação Celular , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Hipertensão/complicações , Osteoporose/complicações , Doença de Paget Extramamária/complicações , Neoplasias Vulvares/metabolismo , Neoplasias Vulvares/cirurgia
17.
Int J Gynecol Pathol ; 26(3): 271-7, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17581411

RESUMO

Three cases of histologically proven endometrial carcinoma (EmCa) demonstrated no residual carcinoma or biopsy site on the subsequent hysterectomy specimen. The shared identity of both endometrial biopsy and hysterectomy specimen was proven, and specimen misidentification was excluded in all 3 cases through successful DNA profiling. Just as vanishing cancer in prostatic carcinoma has recently been defined and accepted, it is suggested that vanishing EmCa can also be defined using specific pathological and clinical criteria. DNA profiling may serve to confirm the diagnosis. Vanishing EmCa is only a small subset within hysterectomy specimens that show no EmCa after a histological diagnosis of EmCa. The concept of vanishing EmCa may be useful in both clinical and medicolegal practice.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Adenocarcinoma/genética , Idoso , Impressões Digitais de DNA , DNA de Neoplasias/química , DNA de Neoplasias/genética , Neoplasias do Endométrio/genética , Feminino , Humanos , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
18.
J Proteome Res ; 6(7): 2648-55, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17552551

RESUMO

Verification of candidate protein biomarkers is a necessary step in moving from the initial discovery to application. Here, we report results of a verification exercise involving six candidate endometrial cancer biomarkers previously discovered using mass-tagging and multidimensional liquid chromatography/tandem mass spectrometry (DeSouza L., et al. J. Proteome Res. 2005, 4, 377-386) on a cohort of 148 patient samples by means of immunohistochemistry on a tissue microarray format. A panel of the three best-performing biomarkers, chaperonin 10, pyruvate kinase M2, and alpha-1-antitrypsin, achieved a sensitivity of 0.85, specificity of 0.93, predictive value of 0.90, and positive predictive value of 0.88 in discriminating malignant from benign endometrium. The ruggedness of this panel of biomarkers was verified in a 2/3-training-set-1/3-test-set cross-validation analysis by randomly splitting the cohort in 10 ways. The roles of chaperonin 10 and pyruvate kinase M2 in tumorigenesis confirm them as credible cancer biomarkers.


Assuntos
Biomarcadores Tumorais/análise , Biomarcadores Tumorais/normas , Neoplasias do Endométrio/química , Imuno-Histoquímica/métodos , Análise Serial de Tecidos/métodos , Cromatografia Líquida , Neoplasias do Endométrio/patologia , Endométrio/química , Endométrio/patologia , Feminino , Humanos , Espectrometria de Massas , Proteômica/métodos
19.
Mol Cell Proteomics ; 6(7): 1170-82, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17374602

RESUMO

The utility of differentially expressed proteins discovered and identified in an earlier study (DeSouza, L., Diehl, G., Rodrigues, M. J., Guo, J., Romaschin, A. D., Colgan, T. J., and Siu, K. W. M. (2005) Search for cancer markers from endometrial tissues using differentially labeled tags iTRAQ and cleavable ICAT with multidimensional liquid chromatography and tandem mass spectrometry. J. Proteome Res. 4, 377-386) to discriminate malignant and benign endometrial tissue samples was verified in a 40-sample iTRAQ (isobaric tags for relative and absolute quantitation) labeling study involving normal proliferative and secretory samples and Types I and II endometrial cancer samples. None of these proteins had the sensitivity and specificity to be used individually to discriminate between normal and cancer samples. However, a panel of pyruvate kinase, chaperonin 10, and alpha1-antitrypsin achieved the best results with a sensitivity, specificity, predictive value, and positive predictive value of 0.95 each in a logistic regression analysis. In addition, three new potential markers were discovered, whereas two other proteins showed promising trends but were not detected in sufficient numbers of samples to permit statistical validation. Differential expressions of some of these candidate biomarkers were independently verified using immunohistochemistry.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/metabolismo , Proteoma/metabolismo , Cromatografia Líquida/métodos , Feminino , Humanos , Espectrometria de Massas em Tandem/métodos
20.
J Low Genit Tract Dis ; 10(3): 156-60, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16829755

RESUMO

Adenocarcinomas of the lower genital tract are rare diseases, and most of them arise from the Bartholin glands. Villoglandular adenocarcinoma of intestinal type is a very uncommon neoplasm of unknown origin with only few cases described on the vulva and in the vagina. It is characterized by villoglandular architecture, mucinous-type epithelium with intestinal differentiation (goblet cells), and direct apposition of the tumor with the surface epithelium. We report a case that developed on the hymen of a 64-year-old woman and discuss its possible origin as arising de novo from the squamous epithelium.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma in Situ/diagnóstico , Hímen/patologia , Neoplasias Vulvares/diagnóstico , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Carcinoma in Situ/complicações , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Diagnóstico Diferencial , Epitélio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Descarga Vaginal/etiologia , Neoplasias Vulvares/complicações , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgia
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