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1.
Anticancer Res ; 40(5): 2429-2438, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366386

RESUMO

Endometriosis is an estrogen-dependent disease, which affects 10% of women in the reproductive age. Malignant transformation is an uncommon event, which affects approximately 0.7-2.5% of women, and, when it occurs, it involves ovarian and extraovarian sites in 75% and 25% of the cases, respectively. Endometriosis correlates with presentation of clear cell and endometrioid carcinoma of the ovary. Activation of phosphatidylinositol 3-kinase (PIK3) - protein kinase B (AKT) - mammalian target of rapamycin (mTOR) pathway, aberrant chromatin remodeling due to AT-rich interactive domain-containing protein 1A (ARID1A) mutation and inactivation of estrogen receptor-α signaling seem to play a major role in the carcinogenesis. To date, little data are available regarding endometriosis-associated extraovarian malignancies. The aim of the present study was to review the clinical, pathological and prognostic features of endometriosis-related neoplasms arising from extraovarian sites, with particular focus on intestinal malignancies, urinary tract malignancies and tumors arising from surgical scars.


Assuntos
Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/etiologia , Transformação Celular Neoplásica , Endometriose/complicações , Endometriose/patologia , Biópsia , Carcinoma Endometrioide/terapia , Estudos de Casos e Controles , Progressão da Doença , Endometriose/etiologia , Endometriose/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Gradação de Tumores , Estadiamento de Neoplasias , Patologistas
2.
J Cancer Res Clin Oncol ; 146(4): 971-983, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31927619

RESUMO

PURPOSE: Endometrial mesonephric-like adenocarcinoma (ML-AC) represents a recently recognized subtype of endometrial adenocarcinoma (AC) associated with a subtle immunophenotype with a characteristic KRAS-mutation. Detailed clinico-pathologic analyses and prognostic data on ML-AC are limited. METHODS: We report a series of four cases with histopathological, immunohistochemical, and molecular analyses. These cases as well as the data of previously published cases were reviewed for clinico-pathologic variables and clinical follow-up information. RESULTS: Forty cases of ML-AC were identified. ML-AC represents about 1% of all endometrial carcinomas. Similar to other types of endometrial AC, vaginal bleeding was the leading presenting symptom, and the mean age was 60.0 years (range 31-91). More than a half of the patients presented with locally advanced disease (≥ FIGO stage II) at time of diagnosis, developed a recurrence or died of the disease within a mean follow-up period of 24.7 months (range 3-144.5 months). The most common site of distant disease was pulmonary involvement. Microscopically, ML-ACs present with mixed morphology and show a co-expression of so-called mesonephric and Müllerian markers, suggesting a Müllerian origin of the tumors. Immunostaining for PD-L1 was negative in all tested cases, using different antibodies against PD-L1. Retained staining for mismatch repair proteins on immunohistochemistry and a POLE-mutation suggest a copy number low phenotype within the molecular classification of endometrial carcinomas. Almost all cases showed a KRAS-mutation at codon 12 (mostly G12V). CONCLUSION: Uterine ML-AC represents a distinct subtype of invasive endometrial AC, associated with KRAS-mutations and characteristic immunohistochemical findings. Clinically, ML-AC may show an aggressive behavior with a high rate of recurrent disease and a substantial risk for distant metastatic disease, especially to the lungs.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias do Endométrio/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patologia , Diagnóstico Diferencial , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico
3.
Pathologe ; 40(6): 609-618, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31578630

RESUMO

Dedifferentiated endometrial carcinomas (ECs) are composed of undifferentiated EC and a FIGO grade 1 or 2 endometrioid carcinoma. The undifferentiated component represents a malignant epithelial neoplasm with no obvious differentiation and immunohistochemical loss of PAX8, E­cadherin and focal expression of EMA and/or CK18 and the predominant presence of nuclear staining for INI1 (SMARCB1) and BRG1 (SMARCA4). The main differential diagnoses include poorly differentiated endometrioid EC, neuroendocrine carcinoma, lymphoma, plasmocytoma, high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas (UUS), carcinosarcomas, and metastases to the endometrium. The histogenesis is not yet fully understood and molecular data are still limited. Some tumors represent a loss of MHL1 and PMS2 staining due to MLH1-promotor methylation. Rare cases are associated with Lynch syndrome or POLE mutation. The un- or dedifferentiated EC represents a high-grade endometrial carcinoma that requires extended surgery and indicates a poor prognosis. In cases with mismatch repair protein deficiency or POLE mutation, immuno-oncological treatment with checkpoint inhibitors are a therapeutic option.


Assuntos
Carcinoma Endometrioide , Carcinossarcoma , Neoplasias do Endométrio , Biomarcadores Tumorais , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/patologia , Diagnóstico Diferencial , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica
4.
BMJ Case Rep ; 12(5)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31154347

RESUMO

Sister Mary Joseph (SMJ) nodules are rare malignant metastatic umbilical nodules, indicating disseminated disease and associated with a poor prognosis. This is the case of an 80-year-old woman who presented with umbilical discomfort and an ulcerated umbilical nodule. She was noted to have a bulky uterus and vaginal bleeding. CT abdomen-pelvis showed an enlarged uterus and right-sided lymphadenopathy, extending from the groin to the para-aortic area. Upper and lower endoscopies were normal. Biopsy of the umbilical nodule revealed metastatic endometrioid adenocarcinoma grade 1-2 with the endometrium and the ovary suggested as potential primary sites. The patient had cytoreductive surgery including en bloc resection of the umbilical tumour. Final histology confirmed Stage IVb endometrioid adenocarcinoma of the uterus. This unusual case highlights the diagnostic challenges faced with the presentation of an umbilical nodule. Gynaecological malignancy should always be considered within the initial differential diagnosis of an SMJ nodule.


Assuntos
Carcinoma Endometrioide/diagnóstico , Nódulo da Irmã Maria José/diagnóstico , Neoplasias Uterinas/diagnóstico , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/diagnóstico por imagem , Carcinoma Endometrioide/secundário , Carcinoma Endometrioide/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Metástase Neoplásica , Nódulo da Irmã Maria José/diagnóstico por imagem , Nódulo da Irmã Maria José/secundário , Nódulo da Irmã Maria José/cirurgia , Umbigo/patologia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia
5.
J Obstet Gynaecol Res ; 45(8): 1613-1618, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183953

RESUMO

Laparoscopic port site endometriosis is less common in abdominal wall endometriosis, and malignant transformation of abdominal wall endometriosis is rare. We reported a case of mixed endometrioid and clear cell carcinoma arising from port site endometriosis. The patient was a 49-year-old woman with a history of laparoscopic excision of ovarian endometrioma. Physical examination revealed a subcutaneous solid tumor around the laparoscopic surgical scar. Imaging showed a suspicious malignancy. She underwent radical marginal resection of the abdominal wall tumor, flap reconstruction of the abdominal wall, hysterectomy, bilateral salpingo-oophorectomy and omental biopsy. Histological examination revealed mixed endometrioid and clear cell carcinoma. Computed tomography scan showed no evidence of recurrence after six cycles of chemotherapy. This is the first case of malignant transformation from laparoscopic trocar site endometriosis.


Assuntos
Neoplasias Abdominais , Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Transformação Celular Neoplásica , Endometriose , Laparoscopia/efeitos adversos , Doenças Ovarianas , Neoplasias Abdominais/diagnóstico , Neoplasias Abdominais/etiologia , Neoplasias Abdominais/cirurgia , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/etiologia , Adenocarcinoma de Células Claras/cirurgia , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/etiologia , Carcinoma Endometrioide/cirurgia , Endometriose/complicações , Endometriose/diagnóstico , Endometriose/etiologia , Endometriose/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Ovarianas/diagnóstico , Doenças Ovarianas/etiologia , Doenças Ovarianas/cirurgia
6.
J Gynecol Obstet Hum Reprod ; 48(7): 473-477, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31212025

RESUMO

OBJECTIVE: To determine cilinicopathologic characteristics of recurrent endometrioid type endometrial cancer patients and analyze the methods applied in detection of recurrent disease during follow-up period. METHODS: We have retrospectively reviewed the file records of the 226 patients who had endometrioid type carcinoma. Bimanual pelvic examination, speculum examination, carcinogenic antigen-125 (CA125) testing, vaginal cuff cytologic screening, transabdominal ultrasound (TAUS) and transvaginal ultrasound(TVUS) imagings were performed within the context of routine follow-up control examinations in the post-treatment period in every 3 months within the first 2 years and in every 6 months in the following 2 years and with annual control in the consecutive years. RESULTS: Mean follow-up durations was 25.7±18.9 months while recurrence rate was 3.1%. The study patient group underwent totally 1116 times TVUS and 1084 times whole TA-US evaluations, 973 times vaginal cuff cytological screening, 1125 times pelvic and general physical examinations beside 1060 times CA-125 testings were performed in accordance with our routinely performed follow-up protocol. The asymptomatic recurrent cases ; one of those was dignosed with pelvic examination while diagnosis was established using TA-USG evaluation in the other asymptomatic patient. The other 5 cases were symptomatic. Pelvic examination, Computed Tomograhy and Magnetic Resonance Imaging were utilized in diagnosing 1, 3 and 1 of those patients, respectively. CONCLUSION: The presence of symptoms and pelvic examination seem to be the most effective modalities in detecting recurrence in follow-up of endometrial cancer. It would be reasonable to optimize intervals between follow-up visits and to determine the appropriate evaluations by considering risk levels of the patients.


Assuntos
Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Monitorização Fisiológica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Antígeno Ca-125/análise , Antígeno Ca-125/sangue , Carcinoma Endometrioide/patologia , Colo do Útero/patologia , Citodiagnóstico , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Teste de Papanicolaou , Valor Preditivo dos Testes , Estudos Retrospectivos , Ultrassonografia , Esfregaço Vaginal
7.
J Obstet Gynaecol Res ; 45(8): 1479-1487, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31074203

RESUMO

AIM: To examine the hysteroscopic morphological features in each histological grade of endometrial cancer, and to distinguish high- and low-grade cancer and low-grade cancer and atypical endometrial hyperplasia (AEH), using hysteroscopy. METHODS: In total, 135 patients who underwent hysterectomy after hysteroscopy were analyzed. They were divided into four categories: benign lesion; AEH; low-grade cancer, including endometrioid carcinoma grades 1 and 2 (G1/2); and high-grade cancer, including endometrioid carcinoma grade 3 and other high-grade carcinomas (G3/others). Three blinded gynecologic oncologists independently evaluated hysteroscopic video images for abnormal vessels, surface smoothness, papillary structure and polypoid structure. Prevalence rates of each finding were compared between the four categories. The accuracy of blind biopsy in outpatient settings and hysteroscopic endometrial biopsy in the four categories were also investigated. RESULTS: The number of patients with benign lesions, AEH, G1/2 and G3/others was 8, 7, 84 and 36, respectively. Patients with G3/others exhibited more polypoid (86% vs 61%, P = 0.0095) and less papillary (59% vs 80%, P = 0.023) structures than those exhibited by patients with G1/2. AEH and G1/2 were indistinguishable using hysteroscopy. Hysteroscopic biopsy was more accurate than outpatient biopsy in patients with G3/others (84% vs 52%, respectively, P = 0.010). Both biopsies were not sufficiently accurate to diagnose AEH (outpatient; 0%, hysteroscopic; 57%). CONCLUSION: Hysteroscopic papillary and polypoid structures can help distinguish between high- and low-grade cancer. Hysteroscopic differentiation between AEH and low-grade cancer is difficult. These findings are considerable in preoperative assessment to determine adequate surgical strategies.


Assuntos
Carcinoma Endometrioide/diagnóstico , Carcinoma Papilar/diagnóstico , Hiperplasia Endometrial/diagnóstico , Neoplasias do Endométrio/diagnóstico , Histeroscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Endometrioide/patologia , Carcinoma Papilar/patologia , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade
8.
Int J Surg Pathol ; 27(7): 757-759, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31113276

RESUMO

Peritoneal keratin granulomatosis is a rare tumor-like lesion caused by deposition of tumor-produced keratin. It may be associated with endometrial or ovarian endometrioid adenocarcinoma, atypical polypoid adenomyoma of the endometrium, or ruptured mature teratomas of the ovary. We present 2 cases of peritoneal keratin granulomatosis associated with FIGO (International Federation of Gynecology and Obstetrics) stage 1 endometrial adenocarcinoma. This entity can mimic advanced-stage disease clinically and radiologically, as it did in those cases, and constitutes a diagnostic pitfall that pathologists and surgeons must be aware.


Assuntos
Carcinoma Endometrioide/complicações , Neoplasias do Endométrio/complicações , Granuloma/diagnóstico , Doenças Peritoneais/diagnóstico , Idoso , Biópsia , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/cirurgia , Diagnóstico Diferencial , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Endométrio/patologia , Feminino , Granuloma/etiologia , Granuloma/patologia , Humanos , Histerectomia , Queratinas/metabolismo , Doenças Peritoneais/etiologia , Doenças Peritoneais/patologia , Peritônio/patologia , Salpingo-Ooforectomia
9.
Surg Pathol Clin ; 12(2): 529-564, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31097114

RESUMO

This review is an appraisal of the current state of knowledge of 2 enigmatic histotypes of ovarian carcinoma: endometrioid and clear cell carcinoma. Both show an association endometriosis and the hereditary nonpolyposis colorectal cancer (Lynch) syndrome, and both typically present at an early stage. Pathologic and immunohistochemical features that distinguish these tumors from high-grade serous carcinomas, each other, and other potential mimics are discussed, as are staging, grading, and molecular pathogenesis.


Assuntos
Adenocarcinoma de Células Claras/patologia , Carcinoma Endometrioide/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/complicações , Adenocarcinoma de Células Claras/diagnóstico , Carcinoma Endometrioide/complicações , Carcinoma Endometrioide/diagnóstico , Diagnóstico Diferencial , Endometriose/complicações , Feminino , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Prognóstico
10.
Kaohsiung J Med Sci ; 35(5): 303-309, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30887645

RESUMO

Raised triglycerides (TG) and reduced high density lipoprotein cholesterol (HDL-c) are components of metabolic syndrome. Both high TG and metabolic syndrome have been reported to be risk factors of endometrial cancer. Therefore, triglycerides-to-high density lipoprotein cholesterol ratio (TG/HDL-c ratio) may be a useful biological indicator in managing endometrial cancer. We aimed to explore the association between pretreatment TG/HDL-c ratio and endometrial cancer in postmenopausal women, and to evaluate its potential role in the disease. Pretreatment serum lipid profile and TG/HDL-c ratio were retrospectively analyzed for 167 postmenopausal women with endometrial cancer and 464 matched noncancer controls. Compared with controls, pretreatment TG/HDL-c ratio in endometrial cancer patients significantly elevated regardless of whether patients had diabetes or overweight/obesity (P < 0.05). Further analyses showed that pretreatment TG/HDL-c ratio increased significantly with advanced tumor stage. Interestingly, TG/HDL-c ratio of type I endometrial cancer patients was higher than those with type II endometrial cancer. A positive association was found between pretreatment TG/HDL-c ratio and tumor stage (adjusted r = 0.176, P = 0.027) in endometrial cancer group. Receiver operating characteristic curve analysis yielded the cut-off value of 1.52 for TG/HDL-c ratio to discriminate patients with cancer from controls (area under the curve, 0.689; sensitivity, 51.5%; specificity, 84.1%). Multivariate logistic regression model identified TG/HDL-c ratio ≥ 1.52 (odds ratio = 4.123; P < 0.001) as an independent predictor of endometrial cancer. TG/HDL-c ratio was positively associated with endometrial cancer clinical features, such as tumor stage and pathogenetic type. Accordingly, pretreatment TG/HDL-c ratio might be a potential marker for endometrial cancer.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Endometrioide/sangue , HDL-Colesterol/sangue , Diabetes Mellitus/sangue , Neoplasias do Endométrio/sangue , Síndrome Metabólica/sangue , Obesidade/sangue , Triglicerídeos/sangue , Idoso , Área Sob a Curva , Carcinoma Endometrioide/complicações , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/patologia , Estudos de Casos e Controles , Complicações do Diabetes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/patologia , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/patologia , Pós-Menopausa/sangue , Curva ROC , Estudos Retrospectivos , Fatores de Risco
11.
Int J Mol Sci ; 20(6)2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30884769

RESUMO

Anti-Müllerian hormone (AMH) is a commonly known factor secreted by Sertoli cells, responsible for regression of the Müllerian ducts in male fetuses. AMH has also other functions in humans. In vivo and in vitro studies have shown that AMH inhibits cell cycle and induces apoptosis in cancers with AMH receptors. The aim of the study was to assess whether the tissue of pre-cancerous states of endometrium (PCS) and various histopathologic types of endometrial cancer (EC) exhibit the presence of AMH. We aimed to investigate whether the potential presence of the protein concerns menopausal women or those regularly menstruating, and whether is related to cancers with a good or a bad prognosis, as well as what other factors may influence AMH expression. The undertaken analysis was carried out on tissues retrieved from 232 women who underwent surgical treatment for PCS and EC. Tissues were prepared for immunohistochemical assessment with the use of a tissue microarrays method. AMH expression was confirmed in 23 patients with well differentiated endometrioid adenocarcinoma (G1), moderately differentiated endometrioid adenocarcinoma (G2), clear cell carcinoma (CCA) and nonatypical hyperplasia. AMH was not found in EC tissues in regularly menstruating women. An appropriately long mean period of breastfeeding in line with a prolonged period of hormonal activity had a positive effect on AMH expression. Our results may suggest that AMH is a factor which protects the organism against cancer, and should be further investigated as a potential prognosis marker and a therapeutic agent.


Assuntos
Hormônio Antimülleriano/análise , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Adulto , Idoso , Aleitamento Materno , Carcinoma Endometrioide/diagnóstico , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Menopausa , Menstruação , Pessoa de Meia-Idade , Prognóstico
12.
Int J Gynecol Cancer ; 29(5): 886-889, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30826751

RESUMO

OBJECTIVE: We conducted a retrospective study to evaluate the correlation between pre-operative and post-operative histological diagnoses on endometrial cancer, and to describe the treatments and outcomes when post-operative diagnoses are downgraded from pre-operative histology. METHODS: Patients who underwent surgery for endometrial cancer in our facility between 2010 and 2013 were enrolled in the study. The definition of downgrade discordance is in accordance with the following criteria: 1) the pre-operative and post-operative histological diagnoses were both endometrioid and the final pathology was a lower grade than the pre-operative pathology and 2) the pre-operative diagnosis was not endometrioid, whereas the post-operative diagnosis was endometrioid grade 2 or less. RESULTS: A total of 250 patients were enrolled, and the concordance rates were 56% for endometrioid adenocarcinoma grade 1 (EMG1), 67% for EMG2, 67% for EMG3, 82% for carcinosarcoma, 71% for serous carcinoma, and 67% for clear cell carcinoma. Eighteen cases (6.6%) were identified as downgrade discordancy. Of the 18 patients, the triage for adjuvant therapy remained the same for 15 cases (83%), all of whom had no evidence of disease at their last visit. Three cases had discordances with respect to triage for adjuvant therapy; the therapies were triaged based on post-operative diagnosis. Of these patients one had a recurrence. CONCLUSIONS: Good correlation was observed between pre-operative and final histological diagnoses of endometrioid carcinoma (56%-67%) and type 2 carcinoma (67%-82%). Approximately 7% (18/250) of patients had downgrade discordancy; however, triage for adjuvant therapy did not change for approximately 80% (15/18) of the patients with downgrade discordancy. Further studies are needed to evaluate the effectiveness of triages that are based on post-operative diagnoses.


Assuntos
Neoplasias do Endométrio/diagnóstico , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Gradação de Tumores , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Estudos Retrospectivos , Salpingo-Ooforectomia
13.
Virchows Arch ; 474(5): 599-608, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30734108

RESUMO

Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients' survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Neoplasias Ovarianas/patologia , Receptor ErbB-2/metabolismo , Quinase do Linfoma Anaplásico/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/diagnóstico , Proteínas de Ciclo Celular/metabolismo , Reparo de Erro de Pareamento de DNA/genética , Feminino , Humanos , Imuno-Histoquímica/métodos , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Ovarianas/diagnóstico , Prognóstico , Serina Endopeptidases/metabolismo
14.
Arch Pathol Lab Med ; 143(1): 47-64, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785337

RESUMO

CONTEXT.­: Epithelial tumors of the ovary are one of the most frequently encountered gynecologic specimens in the frozen section laboratory. The preoperative diagnostic workup of an ovarian mass is typically limited to imaging studies and serum markers, both of which suffer from low sensitivity and specificity. Therefore, intraoperative frozen section evaluation is crucial for determining the required extent of surgery, that is, cystectomy for benign tumors, oophorectomy or limited surgical staging for borderline tumors in younger patients to preserve fertility, or extensive staging procedure for ovarian carcinomas. Ovarian epithelial tumors may exhibit a wide range of morphologic patterns, which often overlap with each other and can mimic a variety of other ovarian nonepithelial neoplasms as well. A combination of careful gross examination, appropriate sampling and interpretation of morphologic findings, and familiarity with the clinical context is the key to the accurate frozen section diagnosis and successful intraoperative consultation. OBJECTIVE.­: To review the salient frozen section diagnostic features of ovarian epithelial tumors, with special emphasis on useful clinicopathologic and morphologic clues and potential diagnostic pitfalls. DATA SOURCES.­: Review of the literature and personal experience of the author. CONCLUSIONS.­: Frozen section evaluation of ovarian tumors continues to pose a significant diagnostic challenge for practicing pathologists. This review article presents detailed discussions of the most common clinical scenarios and diagnostic problems encountered during intraoperative frozen section evaluation of mucinous, serous, endometrioid, and clear cell ovarian tumors.


Assuntos
Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico , Carcinoma Endometrioide/diagnóstico , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Ovarianas/diagnóstico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/patologia , Carcinoma Endometrioide/patologia , Feminino , Secções Congeladas , Humanos , Período Intraoperatório , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Encaminhamento e Consulta , Sensibilidade e Especificidade
15.
Korean J Radiol ; 20(3): 364-377, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30799567

RESUMO

Adenocarcinoma currently accounts for 10-25% of all uterine cervical carcinomas and has a variety of histopathological subtypes. Among them, mucinous carcinoma gastric type is not associated with high-risk human papillomavirus (HPV) infection and a poor prognosis, while villoglandular carcinoma has an association with high-risk HPV infection and a good prognosis. They show relatively characteristic imaging findings which can be suggested by magnetic resonance imaging (MRI), though the former is sometimes difficult to be distinguished from lobular endocervical glandular hyperplasia. Various kinds of other tumors including squamous cell carcinoma should be also differentiated on MRI, while it is currently difficult to distinguish them on MRI, and HPV screening and pathological confirmation are usually necessary for definite diagnosis and further patient management.


Assuntos
Adenocarcinoma/diagnóstico , Imagem por Ressonância Magnética , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/diagnóstico por imagem , Adenocarcinoma de Células Claras/patologia , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/diagnóstico por imagem , Carcinoma Adenoescamoso/patologia , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/diagnóstico por imagem , Carcinoma Endometrioide/patologia , Diagnóstico Diferencial , Feminino , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia
16.
Taiwan J Obstet Gynecol ; 58(1): 99-104, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30638490

RESUMO

OBJECTIVE: National health insurance coverage for the laparoscopic staging surgery for patients with stage IA endometrial cancer started from April 2014 in Japan. We conducted this retrospective study to evaluate the surgical outcomes of the laparoscopic surgery for patients with low-risk endometrial cancer compared with those of the laparotomy. MATERIALS AND METHODS: A total of 120 patients with presumed low-risk endometrial cancer, who were treated at Tottori University Hospital between 2005 and 2016, were eligible for this study. The laparoscopic staging surgery included only the pelvic lymphadenectomy and not the para-aortic lymphadenectomy. We evaluated the discrepancy between preoperative presumption and postoperative diagnosis of recurrent risk factors. RESULTS: Forty patients underwent the laparoscopic surgery and 80 patients received the laparotomy. The laparoscopic surgery resulted in less intraoperative blood loss and shorter hospital stay. The operative time was significantly longer for the laparoscopic surgery compared with the laparotomy, but this difference was not seen in obese patients with a body mass index ≥30 kg/m2. The type of the surgical procedure did not affect the incidence of perioperative complications. Among 120 patients, 104 (86.6%) were diagnosed as FIGO stage IA, 118 (98.3%) with endometrioid adenocarcinoma grade 1 or 2, and 107 (89.1%) with myometrial invasion depth <50%. CONCLUSION: The laparoscopic staging surgery is a feasible and safe alternative to the laparotomy for patients with presumed low-risk endometrial cancer, especially for obese patients. To perform the laparoscopic surgery for patients with stage IA endometrial cancer under the current national health insurance system, it is important to limit the candidates to low-risk disease based on a precise diagnosis before the surgery.


Assuntos
Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/cirurgia , Histerectomia/métodos , Laparoscopia/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/patologia , Intervalo Livre de Doença , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Japão , Laparotomia/métodos , Tempo de Internação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
17.
Diagn Pathol ; 14(1): 7, 2019 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-30684972

RESUMO

BACKGROUND: Currently, ribosome-binding protein 1 (RRBP1) is considered to be a novel oncogene that is overexpressed in colorectal cancer, lung cancer, mammary cancer, esophageal cancer and other carcinomas. However, the relationship between RRBP1 and endometrioid-type endometrial carcinoma (EC) remains unknown. Our purpose is to explore the function of RRBP1 in endometrioid-type endometrial carcinoma. METHODS: We investigated the expression of RRBP1 protein by immunohistochemistry on paraffin-embedded surgical specimens from one hundred thirty patients with endometrioid-type endometrial carcinoma. We also evaluated the differences in RRBP1 expression between endometrial cancer samples (n = 35) and normal endometrial tissues (n = 19) by western blotting. RESULTS: RRBP1 was more highly expressed in endometrial cancer samples than in normal samples (P < 0.05). High levels of expression of RRBP1 were strongly correlated with pathological features, such as the Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, depth of myometrial invasion and lymph node metastasis (P < 0.05). Furthermore, RRBP1 expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) in patients with EC (both P < 0.05). CONCLUSION: This experiment identifies the utility of RRBP1 in predicting EC prognosis, revealing that it may be a potential target for therapeutics of EC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/diagnóstico , Proteínas de Transporte/metabolismo , Neoplasias do Endométrio/diagnóstico , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patologia , Progressão da Doença , Intervalo Livre de Doença , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Endométrio/metabolismo , Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico
18.
J Obstet Gynaecol ; 39(2): 237-241, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30370797

RESUMO

Recently, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or prognostic nutritional index (PNI) have been investigated as prognostic parameters in various malignancies. Herein, we detail how we have investigated the prognostic significance of NLR, PLR and PNI together with the other clinicopathological factors for International Federation of Gynaecology and Obstetrics stage IVB endometrial carcinoma. Thirty-two patients with clinical stage IVB disease were enrolled. The relationship between clinicopathological factors, NLR, PLR or PNI and overall survival (OS) rates was investigated. The 5-year OS rate was 9.7%, and the median survival time was 9 months. In univariate analysis, PS 0-1, G1-2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. In multivariate analysis, only a histology (G1-2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma. Impact Statement What is already known on this subject? Several parameters representing the systemic inflammatory response (e.g. neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR)) or the nutritional condition (e.g. prognostic nutritional index (PNI)) have been investigated as prognostic parameters in various malignancies, whereas they have not been thoroughly investigated in endometrial carcinoma. What the results of this study add? In univariate analysis of various factors for overall survival, the performance status (PS) 0-1, grade 1-2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. However, in a multivariate analysis, only the histology (grade 1-2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. What the implications are of these findings for clinical practice and/or further research? This retrospective study identified that neither inflammatory parameters nor the nutritional index were revealed to be independent prognostic factors by multivariate analyses. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma to improve the poor prognosis of this disease.


Assuntos
Carcinoma Endometrioide/diagnóstico , Neoplasias do Endométrio/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/imunologia , Carcinoma Endometrioide/mortalidade , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Japão/epidemiologia , Contagem de Linfócitos , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Prognóstico , Estudos Retrospectivos
19.
Int J Gynecol Pathol ; 38 Suppl 1: S25-S39, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30550482

RESUMO

This article provides practical recommendations developed from the International Society of Gynecological Pathologists Endometrial Carcinoma Project to address 4 issues that may arise in the diagnosis of uterine corpus low-grade endometrioid carcinoma: (1) The distinction between atypical hyperplasia and low-grade endometrioid carcinoma. (2) The distinction between low-grade endometrioid carcinoma and serous carcinoma. (3) The distinction between corded and hyalinized or spindle cell variants of low-grade endometrioid carcinoma and carcinosarcoma. (4) The diagnostic criteria for mixed endometrial carcinomas, a rare entity that should be diagnosed only after exclusion of a spectrum of tumors including morphologic variants of endometrioid carcinoma, dedifferentiated endometrial carcinoma, carcinosarcoma, and endometrial carcinomas with ambiguous morphology.


Assuntos
Carcinoma Endometrioide/diagnóstico , Carcinossarcoma/diagnóstico , Neoplasias do Endométrio/diagnóstico , Neoplasias Uterinas/diagnóstico , Carcinoma Endometrioide/patologia , Carcinossarcoma/patologia , Diagnóstico Diferencial , Neoplasias do Endométrio/patologia , Feminino , Ginecologia , Humanos , Patologistas , Guias de Prática Clínica como Assunto , Sociedades Médicas , Neoplasias Uterinas/patologia , Útero/patologia
20.
Int J Gynecol Pathol ; 38 Suppl 1: S40-S63, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30550483

RESUMO

This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors' review of the literature followed by discussions at the Endometrial Cancer Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible, given that the levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamous areas), or when an architecturally FIGO grade 2 endometrioid carcinoma exhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed "dedifferentiated carcinoma") is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Carcinoma Endometrioide/classificação , Carcinoma Endometrioide/diagnóstico , Neoplasias do Endométrio/classificação , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Gradação de Tumores , Guias de Prática Clínica como Assunto , Sociedades Médicas
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