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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.

IntroductionRecent 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 MethodsThe 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.ResultsThe 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).ConclusionThe 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.

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.

Context.—Appendiceal mucinous neoplasms are considered enigmatic tumors of unpredictable biologic potential. Their importance lies in their potential to spread to the peritoneum and viscera in the form of gelatinous mucin deposits. Extra-appendiceal spread of these tumors is the most common etiology of pseudomyxoma peritonei, which is a descriptive term encompassing a number of neoplastic and nonneoplastic peritoneal disorders. Many studies aimed at evaluating the biologic importance of appendiceal mucinous neoplasms and pseudomyxoma peritonei have employed inconsistent histologic criteria for their diagnosis and descriptive terminology for their classification. As a result, appendiceal mucinous neoplasms and associated peritoneal disease represents one of the most confusing and controversial areas in gastrointestinal pathology. Objectives.—To summarize the literature regarding the biologic potential of appendiceal mucinous neoplasms and pseudomyxoma peritonei and to discuss the similarities and differences between proposed systems for their classification. Data Sources.—Literature review and case-derived material. Conclusions.—Many studies have contributed to an increased understanding of the natural progression of mucinous neoplasms of the appendix and peritoneum, and the adoption of a uniform reporting system, as advocated by the American Joint Committee on Cancer and the World Health Organization, will facilitate clear communication among pathologists and clinical colleagues.

The nomenclature and classification of pseudomyxoma peritonei (PMP) is confusing and controversial. Numerous classification systems have been proposed, none of which are easily reproducible or a useful guide for treatment. Patients with PMP of appendiceal origin were identified from our institution's database. Kaplan-Meier analyses were performed based on a proposed new PMP classification, a three-tiered grading system designated PMP1, PMP2, and PMP3. These results were compared with the established schemes by Ronnett and Bradley et al. There were 211 patients included in the analysis with a mean age of 51 ± 12 years at diagnosis. For PMP1, 86 patients (40.8%) included cases with abundant extracellular mucin and columnar non-stratified epithelium without dysplasia or atypia. For PMP3, 50 patients (23.7%) consisted of PMP with any percentage of signet ring cells (SRCs), For PMP2, 75 patients (35.5%) included all other patients. The mean age (± standard deviation) for PMP 1, 2, and 3 were 51 ± 12, 51 ± 12, and 51 ± 10 years, respectively ( P = 0.90). The three groups had similar sex distribution ( P = 0.24) and resection status ( P = 0.47). Kaplan-Meier analyses showed median survivals of 120, 88, and 40 months and 5-year survival rates of 85.7, 63.05, and 32.2 per cent ( P < 0.0001) for PMP 1, 2, and 3, respectively. Three distinct categories, PMP1, 2, and 3, were identified, which provide better stratification in terms of overall survival and represent differences in tumor biology that may impact treatment recommendations.

Background Unlike novel molecular-targeted therapies for metastatic gastrointestinal stromal tumors (GIST), conventional treatments for peritoneal sarcomatosis (PS) are mostly ineffective. As with carcinomatosis of epithelial origin, a rationale base supports an aggressive locoregional treatment of PS, but the use of CRS and HIPEC in this setting is still controversial. We assessed the outcome of clinically and pathologically homogeneous subsets of patients with PS uniformly treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods A prospective database of 37 patients who underwent CRS and close-abdomen HIPEC with cisplatin and doxorubicin or mitomycin-C was reviewed. PS originated from GIST (pre-imatinib era) in 8 patients, uterine leiomyosarcoma (ULS) in 11, retroperitoneal liposarcoma (RPLP) in 13, and other sarcoma in 5. Results CRS was macroscopically complete in 28 patients (75.7%). Operative mortality was 3.7% and morbidity 21.6%. After median follow-up of 104 (range, 1–131) months, peritoneal disease progression occurred in 16 patients, distant metastases in 5, and both in 13. For all patients, median overall survival was 26.2 months; 7 patients were alive at 46–130 months (ULS, n  = 4; RPLP, n  = 2; GIST, n  = 1). RPLP had the best overall survival (median, 34 months) but 100% peritoneal relapse; GIST had dismal overall, local–regional-free and distant-free survival; ULS had the higher proportion of long survivors and best local–regional-free survival. Conclusions Overall, results of CRS and HIPEC did not compare favorably to those of conventional therapy. In a subgroup analysis, the combined approach did not change GIST and RPLS natural history. The interesting results with ULS may warrant further investigations.

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.

Background Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis. Methods We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum. Results Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1–P2, p  = 0.0024) and absence of hematogenous metastases ( p  < 0.0001) were associated with R0 resection. Conclusions P1–P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.

ABSTRACT 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.

ObjectiveThis 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.MethodsClinical 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.ResultsIn 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.ConclusionsThe 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.