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Immunohistochemistry is a valuable adjunct in routine gynaecological pathology. The molecular revolution has redesigned knowledge of gynaecological cancers and refined histological classification. The direct consequence has been the progressive introduction of new immunostainings for diagnostic and classification purposes. Hence, we review the routine diagnostic use of immunohistochemistry in the field of gynaecological neoplasia. We reviewed the immunomarkers useful in gynaecological pathology according to literature revision, our personal experience and research findings. We discuss the application of immunohistochemistry to reach the most accurate diagnosis in morphologically equivocal cases of gynaecological pathology and present the appropriate panel of immunomarkers in the most common scenarios of gynaecological pathology. This short review provides an updated overview of the essential immunohistochemical markers currently used in the diagnostics of gynaecological malignancies along with their molecular rationale., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Non-epithelial ovarian tumours are rare neoplasms that occasionally arise in childhood and adolescence. They can be associated with various cancer susceptibility syndromes. The morphological overlap seen across these tumours and their rarity can make the diagnosis challenging. In the case of an incorrect diagnosis, the underlying genetic susceptibility may be missed. In this review, we outline the genetic background of ovarian non-epithelial tumours arising in children, emphasizing the genes harbouring pathogenic germline variants associated with each tumour type. Specifically, juvenile granulosa cell tumours, Sertoli-Leydig cell tumours, sex cord tumours with annular tubules, Sertoli cell tumours, germ cell tumours and small cell carcinoma of the ovary of hypercalcaemic type are discussed in this review. For each tumour type, we detail the personal and family history features and the presenting characteristics of the ovarian tumour as well as the pathological features and molecular markers that point towards a cancer predisposition syndrome. Throughout, we stress the need for specialised pathological review in difficult cases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Postmenopausal hyperandrogenism is a relatively rare diagnosis resulting from excess androgen production from the adrenals or ovaries. The exclusion of malignant causes is a priority. Laboratory tests and imaging are utilised to help differentiate the source of excess androgens. We report two cases of postmenopausal hyperandrogenism in women aged 75 and 67 years. Both cases presented with clinical features suggestive of hyperandrogenism which had developed gradually over the previous 2 years. Laboratory investigations confirmed a significant elevation in their serum testosterone levels. In both cases, imaging did not reveal any abnormality of the adrenals or ovaries. To help differentiate an adrenal vs ovarian source a single-dose GnRH analogue was given with measurement of testosterone and gonadotrophin levels pre and post. The reduction in gonadotrophins achieved by the GnRH analogue resulted in suppression of testosterone levels which suggested an ovarian source. Both patients proceeded to bilateral oophorectomy. Histology revealed a benign hilus cell tumour in one case and a benign Leydig cell tumour in the other. Learning points: A key part of the work-up of postmenopausal hyperandrogenism is to differentiate between an adrenal or an ovarian source of excess androgens; Imaging may not identify small ovarian tumours or hyperthecosis and may also identify incidental adrenal masses which are non-functioning; Current guidelines suggest ovarian and adrenal venous sampling when imaging is inconclusive but this requires technical expertise and has a high failure rate; GnRH analogue use can successfully confirm ovarian source and should be considered as a diagnostic tool in this setting.

Discusses a case report on growing teratoma syndrome in a female patient with nonseminomatous germ cell tumor (NSGTC) of the ovary. Antineoplastic agents received by the patient for medication; Effect of chemotherapy on serum alfa-fetoprotein; Importance of surgical resection of the enlarging tumor in a case of NSGCT.

We report a patient with Graves' disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves' ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion., Learning Points: It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves' ophthalmopathy.

Microsatellite instability (MSI) testing is tricky in gynaecological cancers (GC). Thus, we aimed to describe the instability patterns to improve MSI test interpretation in sporadic and hereditary GCs. Ninety-five cases, including uterine and ovarian cancers, with known genetic and immunohistochemical (IHC) features, were analysed for MSI by a mononucleotide repeats pentaplex (MRP). We identified 13 ambiguous cases that did not fully meet MSI criteria ('borderline' cases, B-MSI), which were mainly represented by MSH2/MSH6-deficient and Lynch syndrome cases. Also, we evaluated nine additional loci of candidate MSI markers that did not improve the detection of MSI cases, but might be useful for discordant or borderline samples. In conclusion, although MSI and IHC test are highly concordant, a subset of ambiguous MSI cases deserves a careful interpretation in particular when MSH2/MSH6 are involved. RPL22 and SRPR testing may be useful to integrate MRP panel for the analysis of critical cases., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Metastatic ovarian tumours are extremely rare. The commonest primary site is usually stomach and the metastasis from this site is termed as krukenberg tumour. It accounts for 1-2% of malignant ovarian tumours. We present a case of 14 weeks' pregnancy with metastatic bilateral malignant ovarian tumour is presented. Diagnosis was made on ultrasound. Tumour markers were insignificant. Patient underwent staging laparotomy with total abdominal hysterectomy and bilateral salpingo oophorectomy and partial omentectomy. She also had haematemesis. Endoscopy revealed suspicious growth in stomach, but biopsy report excluded it. Case was handed over to the oncologist for further management.

Aims: To evaluate the incidence of PI3KCA, KRAS and BRAF mutations in primary ovarian clear cell carcinoma (OCCC)., Methods: 63 consecutive patients, with a proven diagnosis of OCCC, according to WHO criteria, were included into the study. Pyrosequencing analysis of all three genes hotspot regions were performed on 2.5 µm sections of formalin-fixed paraffin-embedded tissue from primary OCCC., Results: PI3KCA mutations were found in 20/63 (32%) cases; KRAS mutations were found in 8/63 (13%); no BRAF V600 mutations were found. In particular, 12/20 mutations (60%) of PI3KCA were found in the exon 20, whereas the remaining eight cases presented mutations in exon 9 (8/20; 40%). KRAS pyrosequencing analysis revealed higher incidence of codon 12 mutations (7/8; 90%) than codon 13 mutations (1/8; 10%). In five cases (5/66; 8%), synchronous mutations, affecting PI3KCA and KRAS genes, were found. No differences were found in the distribution of hotspot mutations, according to the stage., Conclusions: The high frequency of PI3KCA mutations, the low rate of mutations in KRAS and the absence of mutations in BRAF, indicate a molecular signature of OCCCs different from other ovarian carcinomas. Detection of driver mutations, such as PI3KCA and KRAS, may be the basis for a targeted therapy, although the clinical and therapeutic implications of these findings have to be supported by further studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The aim of this study was to compare the surgical outcomes of robotic single-site (RSS) and laparo-endoscopic single-site (LESS) surgery for adnexal tumours and evaluate the feasibility of RSS surgery., Methods: RSS surgery was performed using the da Vinci Single-Site® surgical platform and LESS surgery using a single multi-channel port system. Surgical outcomes were compared between RSS (n = 20) and LESS (n = 228) after 1:4 propensity score matching., Results: After the propensity score matching, the RSS group showed longer operating times than the LESS (91.1 vs 66.1 min; p = 0.001). While the LESS showed 1.3% of major complication rates, the RSS group had no perioperative complication. For the LESS, 2.5% of patients needed additional port insertion., Conclusions: The RSS surgery for adnexal tumours could be performed safely without complications or additional port insertion. Although it showed a longer operating time, further experience and technical refinements will continue to improve operative results. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Ovarian hyperstimulation syndrome in a spontaneous singleton pregnancy is exceedingly rare. We report a case of ovarian hyperstimulation presenting as bilateral ovarian masses in association with spontaneous pregnancy, occurring in a woman with disturbed liver function. A possible mechanism is discussed. [ABSTRACT FROM AUTHOR]

We report a 7-year-old girl who presented with membranous glomerulonephritis and steroid-resistant nephrotic syndrome in association with a benign ovarian tumour. Surgical excision of the tumor led to complete disappearance of the proteinuria within 2 weeks. Tumour-associated membranous nephropathy in children is rare, as a review of the literature shows. [ABSTRACT FROM AUTHOR]

Aims: BRCA1 mutation carriers are at increased risk of developing high-grade serous ovarian cancer (HGSOC), a malignancy that originates from fallopian tube epithelium. We aimed to identify differentially expressed known and novel miRNAs in BRCA1-associated HGSOC., Methods: Small RNA sequencing was performed on eight normal tubal and five HGSOC samples of BRCA1 carriers. Differential expression of a subset of known and novel miRNAs was validated by qRT-PCR on the samples used for small RNA sequencing and a second sample cohort comprising normal and HGSOC tissue of matched BRCA1 and non-BRCA carriers. Data from The Cancer Genome Atlas were used to determine the clinical relevance of the validated differentially expressed miRNAs., Results: 59 known and 20 novel miRNAs showed a significant >fourfold expression difference between normal tubal tissue and HGSOC. qRT-PCR validation confirmed a significant difference in expression levels for 10 out of 11 known miRNAs. Upregulation of two novel miRNAs could not be confirmed. Interestingly, for seven miRNAs a significant increase in expression was observed when comparing normal tubal tissue of postmenopausal women with premenopausal women. Expression levels of miR-145-5p significantly increased with International Federation of Gynecology and Obstetrics stage, while the expression levels of the other nine validated miRNAs were not associated with clinical characteristics., Conclusions: We report a comprehensive expression signature including both known and novel miRNAs of BRCA1-associated HGSOC. Comparison with previous profiling studies showed a good overlap and a large number of miRNAs not reported to be differentially expressed in HGSOC before underscoring the importance of this study., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: Fibulin-5 is an extracellular matrix (ECM) glycoprotein which has a role in the organisation and stabilisation of ECM structures and regulating cell proliferation and tumourigenesis. Here, the expression of fibulin-5 and its functional effects on the migration and invasion of ovarian cancer cells were assessed., Methods: Expression of fibulin-5 was detected in 44 ovarian tumour tissues by qRT-PCR, Western blotting and immunohistochemistry. We performed cell migration and invasion assays, and cell cycle analysis in fibulin-5 transfected SKOV3 (SKOV3-FBLN5) cells and the parental SKOV3 cells. We further examined the expression of three tissue inhibitors of metalloproteinases (TIMPs) and seven matrix metalloproteinases (MMPs) by RT-PCR., Results: mRNA and protein expression of fibulin-5 were down-regulated (0.05-fold and 0.1-fold) in ovarian carcinomas compared with control tissues (p<0.01 and p=0.022). In wound-healing and invasion assays, significantly fewer SKOV3-FBLN5 cells than SKOV3 control cells migrated and invaded (39.1%, p=0.046 and 70%, p=0.03, respectively), which was reversed by siRNA-treatment. Overexpression of fibulin-5 induced G2/M arrest and increased cyclin B1, CDC2 and CDC25C. Expression of TIMP-2 (0.56-fold), MMP-3 (0.43-fold) and MMP-13 (0.18-fold) was lower and MMP-9 expression (2.20-fold) was higher in SKOV3-FBLN5 cells than in control cells., Conclusions: Fibulin-5 is significantly down-regulated in ovarian carcinoma and acts as a tumour suppressor by inhibiting the migration and invasion of ovarian cancer cells., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: To evaluate the actin-bundling protein fascin-1 (FSCN1) as marker for borderline ovarian tumours (BOTs)., Methods: We analysed a retrospective cohort of 140 BOTs with validated diagnosis by an independent pathologist. Immunohistochemical detection of FSCN1 was quantified as combined immunoreactive score (CIS) blinded to clinical patient data. Analyses were first performed for FSCN1 positive versus negative, and then verified using three categories derived from the observed distribution (negative, weak, strong; CIS 0, 1-2, 3-9)., Results: We detected FSCN1 positivity in 51.4%, and strong expression (CIS 3-9) in 14.3% of the samples. FSCN1 positivity was associated with serous subtype (p<0.001) and micropapillary pattern (p<0.001). Correlation with micropapillary pattern remained significant within the serous BOT (SBOT) subgroup (p=0.022). Strong FSCN1 expression (CIS 3-9) was associated both with the presence of implants (p=0.022), and a higher International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.020)., Conclusions: Our analysis links FSCN1 with SBOT with micropapillary pattern. Strong expression is associated with higher FIGO stage and the presence of implants, both related to elevated risk of recurrence. Hence, FSCN1 is an interesting marker worth further analyses of its prognostic value in BOTs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To assess benefits and the accuracy of the intra-operative frozen section for the operative strategy at suspected ovarian tumours., Type of Study: Retrospective study., Setting: Department of Obstetrics and Gynaecology, Faculty of Medicine and Dentistry, Palacky University in Olomouc., Materials and Methods: Intraoperative frozen section and final histopathology were compared in 53 patients who underwent operative treatment for suspected ovarian neoplazma. The accuracy of the frozen section findings was evaluated according to the histopatological type of tumours and categories - benign, malignant and borderline tumours., Conclusion: In accordance with literature reports a good reliability of the frozen section as for the sensitivity, specificity, positive and negative predictive values were proved. The majority of errors occured in diagnosing mucinous and borderline tumours.

Abstract: Ovarian masses are very frequent and represent one of the most common reasons for gynaecological consultation, even in the paediatric/adolescent population. In recent years, the increased availability of ultrasonography has revealed a great number of ovarian ‘neoplasms’ in different age groups. In more than 90% of cases, these are considered ‘functional’ and resolve spontaneously, and simple ultrasonographic follow-up can demonstrate their disappearance. Rarely, and mainly due to greater size, they can cause complications such as torsion, bleeding and rupture, and require surgical attention. Only a small portion of all ovarian masses are represented by tumours, which can be benign or malignant. The general approach to ovarian tumours must consist of a conservative attitude toward functional and benign neoplasms, and an aggressive and surgically/oncologically correct strategy for malignant tumours. The correct balance between these two positions has to rely on accurate diagnosis and an honest evaluation of the risk represented by a ‘wait and see’ policy. [Copyright &y& Elsevier]

The objective of our study was to evaluate the accuracy of frozen section (FS) in borderline ovarian tumours (BOT) and to define the factors associated with misdiagnosis during FS evaluation. We performed a retrospective review of patients who underwent exploratory laparotomy for an adnexal mass, from January 2007 to July 2012, at a tertiary oncology centre in Turkey. Patients with a diagnosis of BOT either in FS or in permanent pathology were identified. Agreement between FS diagnosis and permanent histology was observed in 37/59 patients (62.7%), which gave a sensitivity and a positive predictive value of 71.2% and 84.1%, respectively. In patients with a diagnosis of BOT by frozen section only (n = 44), the diagnosis was consistent with permanent histopathology in 37/44 patients (84.1%). Frozen section interpreted a malignant tumour as BOT (under-diagnosis) in 6/44 (13.6%) of cases and interpreted a benign lesion as BOT (over-diagnosis) in 1/44 (2.3%) of cases. Slide review of discrepant cases revealed that major pathological causes of under-diagnosis were misinterpretation and sampling errors. Univariate analysis showed that presence of bilateral tumour and positive peritoneal cytology were associated with under-diagnosis. We concluded that, despite significant risk of under-diagnosis, FS analysis is an accurate method for intraoperative diagnosis of BOTs.

Although ovarian tumour in the koi (Cyprinus carpio) does not appear to be an uncommon condition, its occurrence and therapy has rarely been reported. In the present case, the decision for surgery was based on clinical and sonographic findings of an intracoelomic mass. We used tricaine methansulfonate for the anaesthesia. Laparotomy was performed by ventral access and an ovarian tumour of 12-cm diameter was removed. The wound was sutured in two layers using Vicryl®. In addition to the application of an analgesic, an antibiotic and vitamins, the postoperative conditions the patient was kept under were adapted to support wound healing. The fish recovered uneventfully and was clinically healthy during the 16-month observation period. Based on the histological findings, the tumour was diagnosed as a thecoma. Investigations using antibodies against vimentin, cytokeratin, S 100 and glial fibrillary acidic protein (GFAP) failed to provide reliable results.

Background: Brenner tumours (BTs), like other epithelial ovarian tumours, are thought to develop from the ovarian surface epithelium., Aim and Methods: We hypothesised that BTs arise from transitional metaplasia near the tuboperitoneal junction which, when embedded in the ovary as Walthard cell nests, may progress to BTs. The aim of this study was to validate this hypothesis by a morphologic and immunohistochemical (IHC) analysis., Results: The IHC analysis revealed that fallopian tube secretory cells, transitional metaplasia, Walthard cell nests and the epithelial component of BTs shared a similar IHC profile, consistently expressing AKR1C3 (an enzyme involved in androgen biosynthesis) and androgen receptor, but not calretinin. The tumour stromal cells that immediately surrounded the epithelial nests showed strong expression of calretinin, inhibin and steroidogenic factor 1 (markers of steroidogenic cells) in the majority of BTs. Using a highly sensitive immunofluorescent staining method, we detected small groups of cilia in transitional metaplasia and Walthard cell nests, multifocal stretches of cilia and/or ciliated vacuoles in benign BTs and well-developed cilia in atypical proliferative BTs., Conclusions: Our findings suggest a tubal origin of BTs through transitional metaplasia and Walthard cell nests, based on their anatomic proximity, similar IHC profile and the presence of cilia. In addition, we hypothesise a role of androgenic stimulation in the pathogenesis of BT, based on the IHC staining pattern of calretinin, inhibin and steroidogenic factor 1 expressed in the luteinised stromal cells surrounding the epithelial nests of the tumours, and AKR1C3 and androgen receptor expressed in both the epithelial and stromal components., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The article presents the case of a 54-year-old woman with carcinoid syndrome due to a primary ovarian carcinoid tumor. The patient's medical history is described. An exploratory laparatomy was performed on the patient after a diagnosis of carcinoid syndrome secondary to ovarian carcinoid tumor. The patient was treated by resection of the primary tumor.

Introduction: Haemangioma of ovary is a rare tumour., Presentation of Case: We report an ovarian haemangioma which presented as an acute abdomen due to an adnexal mass., Discussion: We report an ovarian haemangioma which presented as an acute abdomen due to an adnexal mass. Haemangiomas have been reported in other organs but ovarian haemangioma is a rare tumor, usually asymptomatic and presenting as an incidental finding. Large lesions tend to present clinically with pain. A few cases have been described in the literature., Conclusion: Considering their rare occurrence such tumors are a diagnostic challenge., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Primary ovarian Burkitt's lymphoma is a rare tumour predominantly affecting children and young adults. We report here on a 17-year-old pregnant woman with a Burkitt's lymphoma of the left ovary. After tumour removal and induced abortion, the patient underwent polychemotherapy. Full remission was achieved 7 months after the initial diagnosis.

We report here the rare case of a 28-year-old woman with a large hydatid cyst in her left lower pelvis with an unusual sonographic presentation mimicking a multicystic ovarian tumor. Laparoscopic evaluation revealed normal uterus and ovaries with a swelling in the left retropritoneal area. We decided to reach this tumour by the vaginal route and multiple scolex, daughter cysts were removed via a left lateral vaginal wall incision. The pericystic cavity was thoroughly washed. The patient was discharged on the first postoperative day. Mebendazole (100 mg twice daily) was administered for 4 months. This parasite should be kept in mind and considered when making the differential diagnosis of pelvic cystic masses, particularly if the patient is from an endemic area.