RESUMO
BACKGROUND: Early diagnosis of Peritoneal metastasis (PM) is clinically significant regarding optimal treatment selection and avoidance of unnecessary surgical procedures. Cytopathology plays an important role in early screening of PM. We aimed to develop a deep learning (DL) system to achieve intelligent cytopathology interpretation, especially in ascites cytopathology. METHODS: The original ascites cytopathology image dataset consists of 139 patients' original hematoxylin-eosin (HE) and Papanicolaou (PAP) Staining images. DL system was developed using transfer learning (TL) to achieve cell detection and classification. Pre-trained alexnet, vgg16, goolenet, resnet18 and resnet50 models were studied. Cell detection dataset consists of 176 cropped images with 6573 annotated cell bounding boxes. Cell classification data set consists of 487 cropped images with 18,558 and 6089 annotated malignant and benign cells in total, respectively. RESULTS: We established a novel ascites cytopathology image dataset and achieved automatically cell detection and classification. DetectionNet based on Faster R-CNN using pre-trained resnet18 achieved cell detection with 87.22% of cells' Intersection of Union (IoU) bigger than the threshold of 0.5. The mean average precision (mAP) was 0.8316. The ClassificationNet based on resnet50 achieved the greatest performance in cell classification with AUC = 0.8851, Precision = 96.80%, FNR = 4.73%. The DL system integrating the separately trained DetectionNet and Classificationnet showed great performance in the cytopathology image interpretation. CONCLUSIONS: We demonstrate that the integration of DL can improve the efficiency of healthcare. The DL system we developed using TL techniques achieved accurate cytopathology interpretation, and had great potential to be integrated into clinician workflow.
Assuntos
Ascite/diagnóstico , Aprendizado Profundo , Detecção Precoce de Câncer/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Peritoneais/diagnóstico , Área Sob a Curva , Ascite/classificação , Conjuntos de Dados como Assunto , Humanos , Metástase Neoplásica/diagnóstico , Redes Neurais de Computação , Neoplasias Peritoneais/classificação , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Malignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis. METHODS: To search for novel therapeutic targets for PeM, we performed a comprehensive integrative multi-omics analysis of the genome, transcriptome, and proteome of 19 treatment-naïve PeM, and in particular, we examined BAP1 mutation and copy number status and its relationship to immune checkpoint inhibitor activation. RESULTS: We found that PeM could be divided into tumors with an inflammatory tumor microenvironment and those without and that this distinction correlated with haploinsufficiency of BAP1. To further investigate the role of BAP1, we used our recently developed cancer driver gene prioritization algorithm, HIT'nDRIVE, and observed that PeM with BAP1 haploinsufficiency form a distinct molecular subtype characterized by distinct gene expression patterns of chromatin remodeling, DNA repair pathways, and immune checkpoint receptor activation. We demonstrate that this subtype is correlated with an inflammatory tumor microenvironment and thus is a candidate for immune checkpoint blockade therapies. CONCLUSIONS: Our findings reveal BAP1 to be a potential, easily trackable prognostic and predictive biomarker for PeM immunotherapy that refines PeM disease classification. BAP1 stratification may improve drug response rates in ongoing phases I and II clinical trials exploring the use of immune checkpoint blockade therapies in PeM in which BAP1 status is not considered. This integrated molecular characterization provides a comprehensive foundation for improved management of a subset of PeM patients.
Assuntos
Biomarcadores Tumorais/genética , Haploinsuficiência , Mesotelioma/genética , Neoplasias Peritoneais/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Biomarcadores Tumorais/metabolismo , Humanos , Imunoterapia , Mesotelioma/classificação , Mesotelioma/terapia , Mutação , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/terapia , Microambiente Tumoral , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismoRESUMO
INTRODUCTION: The pathological classification of PMP of appendiceal origin has prognostic and treatment implications. Our goals were to ⢠Classify low grade mucinous carcinoma peritonei (LGMCP) into prognostically distinct subgroups based on histological features. ⢠Compare the reproducibility of the WHO and the PSOGI classifications for both PMP and the appendiceal primary tumor. PATIENTS AND METHODS: A retrospective analysis of patients undergoing CRS and HIPEC or debulking surgery was done. All the tumors were re-classified according to the PSOGI classification. LGMCP was further classified into three histological subgroups and the impact on survival was evaluated. RESULTS: From Jun 2011 to June 2016, 101 patients underwent CRS with HIPEC (n = 89) or debulking surgery (n=12). The median PCI was 28 (3-39) and 74.1% patients had CC-0/1 resections. Of the 76.2% patients who had LGMCP, 4 patients (5.1%) were classified as group 1, 54 (70.1%) as group 2 and 19 patients (24.6%) as group 3. At a median follow up of 21 months, the disease free survival was not reached, 30 months and 14 months for groups 1, 2 and 3 respectively (p = 0.09). There was no difference in overall survival. Using the WHO classification, there was a discordance in the grade of the primary tumor and the peritoneal lesions in 19.8% and conflicting terminology was used in 62% of patients. CONCLUSIONS: The subgroups of LGMCP described here are prognostically different though this needs further prospective evaluation in larger series. The PSOGI classification is more uniformly reproducible and should be preferred to the WHO classification.
Assuntos
Adenocarcinoma Mucinoso/terapia , Antineoplásicos/administração & dosagem , Neoplasias do Apêndice/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Adenocarcinoma Mucinoso/classificação , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Feminino , Humanos , Infusões Parenterais , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Prognóstico , Modelos de Riscos Proporcionais , Pseudomixoma Peritoneal/classificação , Pseudomixoma Peritoneal/patologia , Estudos RetrospectivosAssuntos
Neoplasias do Apêndice/classificação , Neoplasias Peritoneais/classificação , Pseudomixoma Peritoneal/classificação , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/patologiaRESUMO
BACKGROUND: In subtypes of non-endometrioid endometrium cancers (non-ECC), it is not clear whether the omentectomy is a part of debulking if visual assessment is normal. Recently, the ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group in their report titled "Endometrial Cancer: diagnosis, treatment and follow-up" recommended that omentectomy be performed in the serous subtype, but not in carcinosarcoma, undifferentiated endometrial carcinoma or clear cell. In this study, the question is whether omentectomy should be a part of a staging procedure in patients with non-ECC. Besides, the sensitivity and specificity of the visual assessment of omentum were analyzed. METHODS: Patients diagnosed with non-ECC in 2 gynecological oncology clinics between 2005 and 2015 were retrospectively reviewed. Occult (absence of visible lesions) and gross (presence of visible lesions) omental metastasis rates of histological subtypes were analyzed. RESULTS: We identified 218 patients with non-ECC. Thirty-four of them (15.1%) had omental metastases and 44.1% of these metastases (n = 15) were occult metastases. The sensitivity of the surgeon's visual assessment of an omentum (positive or negative) was 0.55. The highest rate of omental metastasis was found in carcinosarcoma followed by serous, mixed subtypes, and clear-cell (20.4, 17.3, 16.6, 10.0%, respectively). Adnexal metastasis was the only factor associated with occult omental metastasis (p = 0.003). CONCLUSION: Omental metastases occur too often to omit omentectomy during surgical procedures for non-ECC regardless of histological subtypes, and visual assessment is insufficient in recognizing the often occult metastases. Omentectomy should be a part of the staging surgery in patients with non-ECC.
Assuntos
Neoplasias do Endométrio/prevenção & controle , Omento/cirurgia , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Omento/patologia , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/patologia , Estudos RetrospectivosRESUMO
The roles of histologic characterization and staging are to provide reproducible metrics for cancer classification with which to direct the most appropriate clinical care and to yield the most stable reliable system to allow both prospective and retrospective data analysis. Both the histologic and staging classifications of malignant ovarian/tubal/peritoneal cancers have recently changed. The World Health Organization sponsored a review and reclassification of the pathology of cancers of the ovaries, fallopian tubes, and peritoneum, and published these updates in 2014. In so doing, they codified the two-tiered grading system that has been in use in serous ovarian cancers for nearly a decade. In parallel, FIGO reviewed and updated the surgical staging system, applied to all histotypes of ovarian, tubal, and peritoneal cancers, also published in 2014. In both cases, the changes made are meant to encompass a better understanding of disease, but both have important merits and drawbacks. Changes in staging complicate analysis of retrospective data against current data. Though in some aspects controversial, the changes overall are meant to represent a better biologic understanding of disease that we hope will lead to an improvement in patient care and directed therapy.
Assuntos
Neoplasias das Tubas Uterinas/classificação , Neoplasias Ovarianas/classificação , Neoplasias Peritoneais/classificação , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/terapia , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Estudos RetrospectivosRESUMO
Histologic subtype is recognized as a prognostic factor in malignant pleural mesothelioma. Specifically, epithelial morphology is associated with a better prognosis than other subtypes, and the same association is observed in peritoneal malignant mesothelioma. Recently, prognostic differences based on morphologic subtypes of epithelial peritoneal malignant mesothelioma were reported. Herein, we report the interobserver variability across four pathologists at three institutions. The authors independently reviewed 67 cases of malignant peritoneal epithelioid mesotheliomas and subclassified them according to their epithelial subtype: papillary, tubulopapillary, trabecular, micropapillary, solid and/or pleomorphic. The cases were also evaluated by each author for several other histopathologic parameters including depth of invasion, nuclear grade, lymphocytic host response, mitotic count/index, presence of lymphovascular invasion, and stromal desmoplasia. The interobserver agreement for histopathologic parameters was highest for mitotic rate (κ=0.36) and primary epithelial subtype (κ=0.32). The interobserver variability for solid subtype pattern was moderate (κ=0.49). We found that the interobserver variability for most histopathologic parameters is poor.
Assuntos
Células Epiteliais/patologia , Células Epitelioides/patologia , Mesotelioma/patologia , Neoplasias Peritoneais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Células Epiteliais/química , Células Epitelioides/química , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma/química , Mesotelioma/classificação , Pessoa de Meia-Idade , Índice Mitótico , Gradação de Tumores , Invasividade Neoplásica , Variações Dependentes do Observador , Neoplasias Peritoneais/química , Neoplasias Peritoneais/classificação , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estados Unidos , Adulto JovemRESUMO
Tumor stage, residual postoperative tumor, histological type and grading are considered among the main prognostic parameters in the consensus-based recommendations in the new S3 guidelines for diagnosis, treatment and clinical follow-up of malignant tumours of the ovary. Based on the 2014 update of the WHO Classification of Tumours of the Female Reproductive Organs this article summarizes the most significant changes. For example now the same TNM and FIGO classification applies for tumours of the ovary, peritoneum or fallopian tube. Noninvasive implants of serous borderline tumours are now named implants. In contrast, invasive implants are regarded as low-grade serous carcinoma. By presenting the current background information, we want to provide a basis for discussion, regarding more detailed consensus recommendations for pathologists and clinicians in the future.
Assuntos
Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Neoplasias das Tubas Uterinas/classificação , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/terapia , Feminino , Alemanha , Humanos , Imuno-Histoquímica , Estadiamento de Neoplasias , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Guias de Prática Clínica como Assunto , Organização Mundial da SaúdeRESUMO
INTRODUCTION: Pelvic high-grade serous carcinomas (HGSCs) include carcinoma of ovary, fallopian tube, and peritoneum. Five-year survival, irrespective of the stage, is between 35-40%. Most patients are diagnosed in advanced stages of the disease. The new revised and expanded dualistic model of ovarian carcinogenesis shows that type II tumors are composed for the most part of high-grade serous ovarian carcinoma, carcinosarcoma, undifferentiated carcinoma and can be further subdivided into morphologic and molecular subtypes. Many type II carcinomas develop from STIC predominantly in the distal portion of the fallopian tube and it is very likely the point of the origin of a significant subset of the pelvic high-grade serous carcinomas. OBJECTIVE: To provide an overview of major changes in our understanding of the origin of ovarian cancer, that led to the revision of FIGO (International Federation of Gynecology and Obstetrics) classification and its unification for the ovary, fallopian tube and peritoneum. We summarize the new classification, main changes compared to the former one and their clinical impact. METHODS: For this review, we have used the results of studies and review articles on the subject published in English up to October 2016. They were identified through a search of literature using PubMed, MEDLINE-Ovid, Scopus and Cochrane Library with the keywords ("serous tubal intraepithelial carcinoma" or "high-grade serous ovarian carcinoma" or "FIGO ovarian cancer staging 2014"). We retrieved and assessed potentially relevant studies, and checked the reference lists of all papers of interest to identify additional relevant publications. CONCLUSION: The origin of most cases of pelvic HGSC (carcinoma of ovary, the fallopian tube, and peritoneum) is expected in the fallopian tube epithelium. The main changes in the revised FIGO classification for extrauterine pelvic serous carcinomas were subdivision of stages IC, III and IV and elimination of the stage IIC, based on new knowledge and prognostic data. A prerequisite for the proper treatment of patients is to perform adequate surgical and pathological staging, including determining the grade of carcinoma. These factors, coupled with appropriately performed operation with zero postoperative residuum (R0), are the most important prognostic factors for patients with carcinoma of the ovary, fallopian tube, and peritoneum.
Assuntos
Cistadenocarcinoma Seroso/patologia , Neoplasias das Tubas Uterinas/classificação , Estadiamento de Neoplasias/métodos , Neoplasias Ovarianas/classificação , Neoplasias Peritoneais/classificação , Animais , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologiaRESUMO
BACKGROUND: The impact of histopathologic features on oncologic outcomes for patients with peritoneal metastases from goblet cell carcinoid (GCC) undergoing multimodality therapy, including cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), is unknown. METHODS: This study prospectively analyzed 43 patients with GCC undergoing CRS-HIPEC between 2005 and 2013. Pathology slides were re-reviewed to classify GCC into histologic subtypes according to the Tang classification. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. RESULTS: The 43 patients in this study underwent 50 CRS-HIPEC procedures for peritoneal metastases from GCC, and the majority received neoadjuvant and/or adjuvant systemic chemotherapy. The GCC demonstrated an aggressive phenotype with frequent lymph node and peritoneal metastases without systemic dissemination. The majority of the patients had Tang B GCC. The estimated median overall survival times after surgery for the patients with Tang A, B, and C GCC were respectively 59, 22, and 13 months. In a multivariate Cox-regression analysis, poor survival was associated with patients who had Tang B or C GCC, those undergoing incomplete macroscopic resection, and those with symptoms at the time of CRS-HIPEC. The patients with Tang A GCC demonstrated oncologic outcomes similar to those with intermediate-grade (American Joint Committee on Cancer [AJCC] grade 2) disseminated mucinous appendiceal neoplasms, whereas the patients with Tang B and C GCC demonstrated survival rates similar to or worse than those with high-grade (AJCC grade 3) disseminated mucinous appendiceal neoplasms. CONCLUSIONS: Tang classification is an independent prognostic factor for poor survival after multimodality therapy for GCC. Patients with Tang C GCC demonstrate limited survival and are not ideal candidates for a surgical approach.
Assuntos
Neoplasias do Apêndice/patologia , Tumor Carcinoide/patologia , Tumor Carcinoide/terapia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Antineoplásicos/administração & dosagem , Neoplasias do Apêndice/classificação , Tumor Carcinoide/classificação , Tumor Carcinoide/secundário , Quimioterapia Adjuvante , Terapia Combinada/métodos , Feminino , Células Caliciformes , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/secundário , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: This study aimed to evaluate the prognostic significance of revised International Federation of Gynecology and Obstetrics (FIGO2013) staging classification for cancer of the ovary, fallopian tube, and peritoneum in patients exhibiting high-grade serous histology. METHODS: Clinical records of patients with high-grade serous carcinoma who underwent primary surgery between 2007 and 2012 were reviewed retrospectively. Patients were reclassified according to the FIGO2013 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated for each stage using Kaplan-Meier estimates and compared with the log-rank test. RESULTS: In total, 125 patients were included in the analysis. The distribution of the study cohort according to the revised classification was as follows; stage I, 6 patients; stage II, 9 patients; stage III, 85 patients; and stage IV, 25 patients. Median follow-up time was 36 months (95% confidence interval [CI], 3-110). The median PFS and OS were 14 months (95% CI, 12.4-15.6) and 60 months (95% CI, 47.0-72.9), respectively. Both PFS and OS were significantly different among stages I, II, III, and IV (P < 0.01). Subgroup analyses for stage III disease also revealed significant differences in survival. The median PFS for stages IIIA1, IIIB, and IIIC was 56, 46, and 16 months, respectively (P < 0.01), and the median OS was 104, 95, and 60 months, respectively (P = 0.03). The outcomes of patients with stage IV disease differed slightly but nonsignificantly according to new substages. The median PFS for stages IVA and IVB was 12 and 6 months, respectively (hazard ratio, 1.16; 95% CI, 0.48-2.79; P = 0.72), and the median OS was 41 and 24 months, respectively (hazard ratio, 1.62; 95% CI, 0.58-4.55; P = 0.35). The study sample was insufficient in size for subgroup analyses in stages I and II. CONCLUSIONS: The revised FIGO2013 staging system is highly prognostic for discriminating outcomes of patients with high-grade serous carcinoma across stages I to IV, in subgroups of stage III, but not in subgroups of stage IV.
Assuntos
Neoplasias das Tubas Uterinas/patologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Cistadenocarcinoma Seroso/classificação , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias das Tubas Uterinas/classificação , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/classificação , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/cirurgia , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Molecular pathological research has contributed to improving the knowledge of different subtypes of ovarian cancer. In parallel with the implementation of the new FIGO staging classification, the WHO classification was revised. The latter is mainly based on the histopathological findings and defines the actual type of tumor. It has, therefore, also an important impact on prognosis and therapy of the patient. MATERIALS AND METHODS: The new WHO Classification of Ovarian Cancer published 2014 by Robert Kurman and co-authors is summarized. The major changes compared to the hitherto existing classification are presented. RESULTS: The new classification eliminates the previous focus of mesothelial origin of ovarian cancer. Instead, it features a discussion of tubal carcinogenesis of hereditary and some other high-grade serous carcinomas. The previously assumed pathogenesis pathway may be correct for some, but not for all, serous cancers. The new classification was established to classify ovarian cancer in a more consistent way. The earlier transitional cell type of ovarian cancer has been removed while seromucinous tumors have been added as a new entity. The role of some borderline tumors as one possible step in the progression from benign to invasive lesions is incorporated. The article summarizes the essential updates concerning serous, mucinous, seromucinous, endometrioid, clear-cell, and Brenner tumors. CONCLUSION: The new WHO classification takes into account the recent findings on the origin, pathogenesis, and prognosis of different ovarian cancer subtypes. The tubal origin of hereditary and some non-hereditary high-grade serous cancers is mentioned in contrast to the hitherto theory of mesothelial origin of tumors. Seromucinous tumors represent a new entity.
Assuntos
Adenocarcinoma de Células Claras/classificação , Adenocarcinoma Mucinoso/classificação , Cistadenocarcinoma Seroso/classificação , Neoplasias das Tubas Uterinas/classificação , Estadiamento de Neoplasias/métodos , Neoplasias Ovarianas/classificação , Neoplasias Peritoneais/classificação , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/patologia , Adulto , Animais , Tumor de Brenner/patologia , Carcinogênese , Cistadenocarcinoma Seroso/patologia , Endométrio/patologia , Células Epiteliais/metabolismo , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Lesões Pré-Cancerosas/patologia , Prognóstico , Neoplasias Retroperitoneais/patologia , Sarcoma/patologia , Organização Mundial da SaúdeRESUMO
"Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.
Assuntos
Carcinoma Papilar/classificação , Neoplasias Ovarianas/classificação , Neoplasias Peritoneais/classificação , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Cistadenocarcinoma Seroso/classificação , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Invasividade Neoplásica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto JovemRESUMO
PURPOSE: We evaluated the 7th edition of the American Joint Committee on Cancer (AJCC) staging classification in terms of overall survival (OS) in patients with PMP treated with cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A total of 208 PMP patients treated with CRS/HIPEC were identified from a prospective database. Patients with peritoneal mucinous carcinomatosis (PMCA) were retrospectively staged at time of diagnosis according to AJCC staging classification. Patients with disseminated peritoneal adenomucinosis (DPAM) were evaluated in a separate group. RESULTS: Median follow-up was 5.2 years. Of 208 patients, 124 had PMCA and 84 patients had DPAM. According to the AJCC staging classification 47 lymph node (LN) negative patients with well-differentiated PMCA, were classified as a stage IVA. 77 patients with either moderately or poorly differentiated PMCA irrespective of LN status, or well-differentiated PMCA with positive LN were classified as stage IVB. 84 patients with DPAM, constituted a separate group. OS of stage IVA and IVB patients was 100, 90, 67, and 91, 50, and 27 for 1, 3, and 5 years, respectively (p < 0.001). OS of DPAM patients was 96, 90, and 88 % for 1, 3, and 5 years, respectively (p = 0.025 comparing to IVA). PFS was estimated for IVA and IVB PMCA patients who were considered disease free after CRS/HIPEC and was 78, 52, and 43 % in the IVA patients and 65 %, 15 %, and 0 in the IVB group at 1, 3, and 5 years, respectively (p = 0.004). The adjusted HR for AJCC stages (IVA/IVB) was 3.7 (95 % confidence interval 2.0-6.7) (p < 0.001). CONCLUSIONS: The 7th edition of the AJCC staging classification is a simple, reproducible, and valid classification for staging patients with PMCA undergoing CRS/HIPEC.
Assuntos
Adenocarcinoma Mucinoso/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/patologia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/secundário , Adenocarcinoma Mucinoso/classificação , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/classificação , Neoplasias do Apêndice/terapia , Quimioterapia do Câncer por Perfusão Regional , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Peritoneal surface malignancies (PSMs) are usually staged using Sugarbaker's Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC-s). Although these staging tools are essential for selecting patients and evaluating outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), both scoring models lack some anatomic information, thus making staging laborious and unreliable. Maintaining Sugarbaker's original concepts, we therefore developed a computerized digital tool, including a new anatomic scheme for calculating PCI and CC-s corresponding closely to patients' real anatomy. Our new anatomic model belongs in a web-based application known as the PSM Staging System, which contains essential clinical and pathological data for the various PSMs currently treated. METHODS: The new digital tool for staging PSM runs on a personal computer or tablet and comprises male and female colored anatomic models for the 13 endoabdominal regions, with borders defined according to real anatomic landmarks. A drag-and-drop tool allows users to compute the PCI and CC-s, making it easier to localize and quantify disease at diagnosis and throughout treatment, and residual disease after CRS. CONCLUSIONS: Once tested online by registered users, our computerized application should provide a modern, shareable, comprehensive, user-friendly PSM staging system. Its anatomic features, along with the drag-and-drop tool, promise to make it easier to compare preoperative and postoperative PCIs, thus improving the criteria for selecting patients to undergo CRS plus HIPEC. By specifying the size, site, and number of residual lesions after CRS plus HIPEC, our digital tool should help stratify patients into outcome classes.
Assuntos
Sistemas de Apoio a Decisões Clínicas , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/patologia , Terapia Combinada , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Peritoneais/terapia , PrognósticoRESUMO
Pseudomyxoma peritonei (PMP) is a complex disease with unique biological behavior that usually arises from appendiceal mucinous neoplasia. The classification of PMP and its primary appendiceal neoplasia is contentious, and an international modified Delphi consensus process was instigated to address terminology and definitions. A classification of mucinous appendiceal neoplasia was developed, and it was agreed that "mucinous adenocarcinoma" should be reserved for lesions with infiltrative invasion. The term "low-grade appendiceal mucinous neoplasm" was supported and it was agreed that "cystadenoma" should no longer be recommended. A new term of "high-grade appendiceal mucinous neoplasm" was proposed for lesions without infiltrative invasion but with high-grade cytologic atypia. Serrated polyp with or without dysplasia was preferred for tumors with serrated features confined to the mucosa with an intact muscularis mucosae. Consensus was achieved on the pathologic classification of PMP, defined as the intraperitoneal accumulation of mucus due to mucinous neoplasia characterized by the redistribution phenomenon. Three categories of PMP were agreed-low grade, high grade, and high grade with signet ring cells. Acellular mucin should be classified separately. It was agreed that low-grade and high-grade mucinous carcinoma peritonei should be considered synonymous with disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, respectively. A checklist for the pathologic reporting of PMP and appendiceal mucinous neoplasms was also developed. By adopting the classifications and definitions that were agreed, different centers will be able to use uniform terminology that will allow meaningful comparison of their results.
Assuntos
Neoplasias do Apêndice/patologia , Técnica Delphi , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Peritoneais/patologia , Pseudomixoma Peritoneal/patologia , Terminologia como Assunto , Neoplasias do Apêndice/química , Neoplasias do Apêndice/classificação , Biomarcadores Tumorais/análise , Biópsia , Lista de Checagem , Consenso , Humanos , Metástase Linfática , Mucinas/análise , Muco/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Neoplasias Císticas, Mucinosas e Serosas/química , Neoplasias Císticas, Mucinosas e Serosas/classificação , Neoplasias Peritoneais/química , Neoplasias Peritoneais/classificação , Valor Preditivo dos Testes , Pseudomixoma Peritoneal/classificação , Pseudomixoma Peritoneal/metabolismoAssuntos
Adenocarcinoma Mucinoso/secundário , Neoplasias do Apêndice/patologia , Neoplasias Peritoneais/secundário , Pseudomixoma Peritoneal/patologia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/classificação , Neoplasias do Apêndice/cirurgia , Biomarcadores Tumorais , Terapia Combinada , Diagnóstico Diferencial , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Procedimentos Cirúrgicos em Ginecologia , Hepatectomia/métodos , Humanos , Hipertermia Induzida , Infusões Parenterais , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/etiologia , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/etiologia , Pseudomixoma Peritoneal/cirurgiaAssuntos
Neoplasias das Tubas Uterinas/patologia , Estadiamento de Neoplasias/normas , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Guias de Prática Clínica como Assunto , Neoplasias das Tubas Uterinas/classificação , Feminino , Ginecologia/organização & administração , Ginecologia/normas , Humanos , Agências Internacionais , Estadiamento de Neoplasias/métodos , Obstetrícia/organização & administração , Obstetrícia/normas , Neoplasias Ovarianas/classificação , Neoplasias Peritoneais/classificaçãoRESUMO
INTRODUCTION: Recent molecular research has revolutionized the understanding of ovarian cancer. It is now non-controversial that the term ovarian cancer summarizes a heterogenous group of malignant epithelial tumors. Findings of large clinical trials investigating surgical and systemic therapeutic approaches have defined the most important prognostic parameters. Therefore, the oncology committee of FIGO, headed by the South African gynecologic oncologist Lynette Denny, took the effort to revise the FIGO classification of ovarian cancer that was implemented in 1988. MATERIAL AND METHODS: The recent publication of Jaime Prat describing the new FIGO classification is summarized. The major changes compared to the hitherto existing classification from 1988 are presented. RESULTS: The primary anatomy is now documented (ov for ovarian, ft for fallopian tube, p for peritoneal, X for not assessed). The histological subtype is also documented (HGSC for high-grade serous carcinoma, LGSC for low-grade serous carcinoma, MC for mucinous carcinoma, CCC for clear cell carcinoma, and EC for endometrioid carcinoma). There is no stage I peritoneal cancer. Stage IC is subdivided into intraoperative rupture (IC1), pre-operative rupture (IC2), and malignant ascites or peritoneal washings (IC3). Due to its anatomic position within the pelvis, metastasis to the sigmoid colon is considered stage II. Former stage IIC has been erased. Stage IIIA1 and IIIA2 have been defined for intra-pelvic tumor with metastasis to retro-peritoneal lymph nodes up to 1 cm (IIIA1) or larger than 1 cm (IIIA2). With this, some of the former stage IIIC cases become IIIA and some IIIB, respectively. Involvement of retroperitoneal lymph nodes must be proven cytologically or histologically. Stage IV has been subdivided into IVA (malignant pleural effusions) and IVB (parenchymal metastases and/or extra-abdominal metastases including tumors in inguinal lymph nodes or lymph nodes outside of the abdominal cavity, umbilical tumor deposit, and transmural bowel infiltration (with mucosal involvement). CONCLUSION: The new FIGO classification takes into account the recent findings on the origin, pathogenesis, and prognosis of different ovarian cancer subtypes, summarizes groups of tumors pragmatically, and implies a reproducible and stage-dependent therapeutical approach.
Assuntos
Carcinoma/patologia , Neoplasias das Tubas Uterinas/classificação , Neoplasias das Tubas Uterinas/patologia , Estadiamento de Neoplasias/métodos , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/patologia , Adenocarcinoma de Células Claras/patologia , Adulto , Animais , Cistadenocarcinoma Seroso/patologia , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Linfonodos/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Pélvicas/patologia , Neoplasias Peritoneais/cirurgia , PrognósticoRESUMO
OBJECTIVE: The Japanese classification of peritoneal metastases from colorectal cancer is easy to use for general surgeons in routine clinical practice. However, the objectivity of this classification has not been determined. This study aimed to clarify the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. METHODS: The data of patients with Stage IV colorectal cancer between 1991 and 2007 in 16 hospitals, who were members of the Japanese Society for Cancer of the Colon and Rectum, were investigated. The size, number and extent (nine areas) of peritoneal metastases according to the Japanese classification (P1, P2 and P3) were investigated using Akaike's information criterion. RESULTS: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 had hematogenous metastases. The minimum Akaike's information criterion was obtained with the cutoff value of one area for P1 metastasis and two or more areas for P2 metastasis (P < 0.0001). When P2 metastasis was compared with P3 metastasis, the cutoff value of the number of peritoneal metastases was 10. CONCLUSIONS: The present study proposes a revision that would give objectivity to the present Japanese classification as follows: P1 is defined as peritoneal metastases 20 mm or smaller confined to one area; P2 is defined as 10 or fewer peritoneal metastases disseminated in two or more areas, or peritoneal metastases confined to one area but the size is >20 mm and P3 is defined as >10 peritoneal metastases disseminated in two or more areas.