Aims: Traditionally, advanced stage ovarian carcinoma is treated by debulking surgery followed by chemotherapy. However, in some circumstances preoperative chemotherapy may be given before optimal surgical debulking. This study aims to describe the morphological features found in ovarian carcinoma after chemotherapy because these have not been detailed previously. Methods: Histological sections were examined from 18 cases of ovarian carcinoma that had been treated by preoperative chemotherapy. The morphology was compared with any pre-chemotherapy biopsies that had been performed. Tumours were classified as showing morphological features suggesting a good response to chemotherapy (n = 14) or as showing little or no response (n = 4). Serum CA125 values before and after chemotherapy were compared. In all cases, the mitotic activity index (MAI), volume percentage of epithelium (VPE), and mean nuclear area (MNA) of tumour cells were calculated. Results: The preoperative biopsies were all typical ovarian serous or endometrioid adenocarcinomas. Morphological features present in the group responding to chemotherapy included the presence of small groups or single tumour cells in a densely fibrotic stroma. Tumour cells were characterised by both nuclear and cytoplasmic alteration, making accurate tumour typing and grading impossible. Nuclear features included the presence of bizarre enlargement with hyperchromatism, irregularity of outline, and chromatin clumping or smudging. Cytoplasmic alterations included intense eosinophilia, vacuolation, or foam cell change. There were pronounced stromal changes of fibrosis, inflammation, collections of foamy histiocytes, cholesterol cleft formation, haemosiderin deposition, fat necrosis, and dystrophic calcification, including the presence of many free psammoma bodies. There was no correlation between morphological response and biochemical response, as determined by serum CA125 values. In all nine cases in which pre-chemotherapy and post-chemotherapy biopsies were available, the MNA increased post-chemotherapy (p = 0.007, paired Wilcoxon test) and in six of nine cases the MAI decreased (p = 0.093). Conclusions: Because preoperative chemotherapy is being used increasingly in the management of ovarian cancer, pathologists should be aware of the resultant morphological effects. Accurate tumour typing and grading is impossible. In some cases, it may be difficult to confirm the presence of residual tumour, making it imperative that pre-chemotherapy tissue biopsies are obtained. Definite confirmation of residual tumour may require the examination of multiple histological sections from areas showing pronounced stromal changes, sometimes with multiple levels and immunohistochemistry. In the absence of definite residual tumour, the report should state that the features are consistent with the prior presence of tumour.

a b s t r a c tObjective. There is a need to develop and validate biomarkers for treatment response and survival in tuboovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into Gynecologic Oncology 154 (2019) 441-448 complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.Methods. We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3-4 NACT cycles and N6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS).Results. 877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5-65) and 28 months (IQR 7-92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45-0·66; P b 0·001) and 0·65 (95% CI 0·50-0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027).Conclusions. CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.• The Chemotherapy response score (CRS) assesses histological effect in ovarian cancer after neoadjuvant chemotherapy (NACT). • The CRS is associated with progression-free and overall survival.• CRS could provide useful information to estimate a patient's probability of early vs. late relapse.• The CRS is an appealing primary endpoint in clinical trials as a surrogate for survival as it can be measured earlier. • We recommend the CRS be incorporated as an endpoint in clinical trials of novel therapeutic agents that have a NACT arm.

Key content Postpartum ovarian vein thrombosis (POVT) is a rare but potentially fatal condition. Symptoms up to 4 weeks postpartum often include vague abdominal pain and pyrexia. A high index of suspicion is required to make the diagnosis. As there is no consensus regarding management, a multidisciplinary approach is advised. Learning objectives Recognise the symptoms and signs of POVT and formulate a differential diagnosis. Recognise the importance of imaging in confirming the diagnosis and involvement of the multidisciplinary team to plan management. Understand that conservative management with low‐molecular‐weight heparin is the first‐line treatment, and understand the situations that may require vena caval filter insertion or surgical intervention. Ethical issues How can we counsel women about risks of conservative and surgical management of this condition when there is no consensus for this management? Should women who have had an ovarian vein thrombosis in a previous pregnancy be counselled toward avoiding future pregnancy?

BACKGROUND. The aim of the study was to assess the feasibility, efficacy, and accuracy of the sentinel lymph node (SLN) procedure in vulvar cancer. METHODS. From April 2004 to September 2006, all patients with vulvar cancer, clinical stages I and II, underwent SLN detection, followed by a complete inguinofemoral lymphadenectomy. Demographic, surgical, and pathologic data on all patients were prospectively entered in a database. RESULTS. Forty‐two patients underwent the SLN procedure. One patient was excluded from further analysis due to metastases to the vulva. The detection rate for at least 1 SLN per patient was 95%, with bilateral SLNs detected in 46% of patients. There was a trend toward improved ability to detect bilateral SLNs and proximity of the cancer to the midline (r = 0.996; P = .057). No contralateral SLNs were identified in patients with lateral vulvar lesions (>1 cm from the midline). For ‘close‐to‐midline’ (≤1 cm from the midline) lesions, SLNs were detected in 93% of ipsilateral groins and bilateral SLNs were found in 46% of patients, whereas lesions abutting the midline had unilateral and bilateral SLN detected in 100% and 93%, respectively. Sixteen of 41 patients (39%) and 18 of 68 groins (26%) revealed metastatic disease in the lymph nodes; all were correctly identified by the SLN procedure. There were no false‐negative SLN results. CONCLUSIONS. SLN dissection is feasible and safe to perform in vulvar cancer. The ability to identify bilateral sentinel inguinal lymph nodes appears to be related to the proximity of the vulvar cancer to the midline. Cancer 2007. © 2007 American Cancer Society.

Background ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications and has completed a Phase 1a clinical trial in ovarian cancer patients and other advanced solid tumours. Methods In vitro, cancer stem cell (CSC) assays in a range of HGSOC cell lines and patient samples, and in vivo tumour initiation, growth delay and limiting dilution assays, were utilised. Mechanisms were determined by using immunohistochemistry, ELISA, qRT-PCR, RNAseq and western blotting. Endogenous FKBPL protein levels were evaluated using tissue microarrays (TMA). Results ALM201 reduced CSCs in cell lines and primary samples by inducing differentiation. ALM201 treatment of highly vascularised Kuramochi xenografts resulted in tumour growth delay by disruption of angiogenesis and a ten-fold decrease in the CSC population. In contrast, ALM201 failed to elicit a strong antitumour response in non-vascularised OVCAR3 xenografts, due to high levels of IL-6 and vasculogenic mimicry. High endogenous tumour expression of FKBPL was associated with an increased progression-free interval, supporting the protective role of FKBPL in HGSOC. Conclusion FKBPL-based therapy can (i) dually target angiogenesis and CSCs, (ii) target the CD44/STAT3 pathway in tumours and (iii) is effective in highly vascularised HGSOC tumours with low levels of IL-6.

Women with germ-line mutations in the mismatch repair genes (responsible for hereditary nonpolyposis colorectal cancer) face an increased risk of colonic and endometrial cancer. However, these germ-line mutations are rare and are responsible for fewer than 1% of endometrial cancers. Therefore, we examined whether or not common variants of the hereditary nonpolyposis colorectal cancer -associated genes might also be associated with an increased risk of endometrial cancer. Three single-nucleotide polymorphisms were selected in the MLH1 and MSH2 mismatch repair genes. All the various 672 women with endometrial cancer and 880 controls were genotyped. Each of these three single-nucleotide polymorphisms was associated with an increased risk of endometrial cancer. Carriers of the MLH1 nt-93 A allele were at a 1.5-fold increased risk of developing endometrial cancer compared with controls [95% confidence interval (95% CI), 1.2-2.0; P = 0.001]. The risk was higher for homozygote carriers [odds ratio (OR), 1.9; 95% CI, 1.2-3.2; P = 0.009]. For carriers of the MSH2 rs2303428 C allele, the OR was 1.4 (95% CI, 1.0-1.9; P = 0.05), and for carriers of the MSH2 rs2059520 G allele, the OR was 1.3 (95% CI, 1.0-1.7; P = 0.03). More than 9% of endometrial cancer cases carried a variant allele in both MLH1 and MSH2. For these women, the risk of endometrial cancer was particularly high (OR, 2.1; 95% CI, 1.2-3.6; P = 0.005). For patients younger than 50 years at diagnosis who carried both variants, the risk was even higher (OR, 3.4; 95% CI, 1.7-6.6; P = 0.0005). In summary, two common variant alleles of the MLH1 and MSH2 genes make a substantial contribution to endometrial cancer incidence in Ontario. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1636 -40)

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An unusual cervical adenocarcinoma is reported in a 50-year-old woman with a history of Peutz Jeghers syndrome. The carcinoma contained two morphologically distinct and spatially separate components, one comprising typical well differentiated adenoma malignum and the other a moderately differentiated neoplasm, in keeping with gastric type adenocarcinoma. Both components were positive for HIK1083 and MUC6 and negative for p16, and did not contain human papillomavirus. It is believed that such a composite tumour has not been described in the literature. It is believed that the component of gastric type adenocarcinoma arose through a process of dedifferentiation within adenoma malignum and we provide circumstantial molecular evidence in support of the interpretation that both components may be clonally related in that they displayed an extra copy of chromosome 7. This raises the possibility of a relationship between these two uncommon types of cervical adenocarcinoma, both of which are thought to exhibit gastric differentiation.