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A 67-year-old man was admitted to our hospital with jaundice. A closer examination revealed that he had obstructive jaundice due to bile duct obstruction caused by a multifocal cystic tumor of the pancreas. Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis of the distal bile duct and leakage of contrast medium into the pancreatic cyst. Pancreaticoduodenectomy was performed, and a pinhole fistula was found connecting the cyst and the bile duct. Histological examination led to the diagnosis of serous cystadenoma (SCA). Herein, we report a rare case of SCA with obstructive jaundice and penetration of the bile duct, which was treated by radical resection.

At present, the prevailing concept is that high-grade serous carcinoma (HGSC) arises from the fallopian tubes (FTs). We report an HGSC case occurring in a serous ovarian cyst against the background of a serous tubal intraepithelial carcinoma (STIC)-like lesion. We also provide a literature review that contains references to clinical cases of the occurrence of STIC-like lesions in the ovary and phylogenetic studies that do not always reveal obvious bonds between early dysplastic serous lesions and HGSC. The article discusses cases of association between HGSCs of serous borderline tumors (SBTs) and low-grade serous carcinomas (LGSCs) in the context of their possible histogenetic relationship. We propose a concept in which high-grade serous carcinogenesis, represented by the p53-signature-STIC-HGSC continuity, occurs in the serous epithelium of both the FT and other locations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Introduction: Differentiating pancreatic serous cystadenoma (SCA) from well-differentiated neuroendocrine tumors (WDNETs) based on histomorphology is critical yet challenging, particularly in small biopsy samples. Our study aimed to examine the expression profile of INSM1 in cytologic and surgical resection specimens from pancreatic SCA to evaluate its potential as a discriminative marker against pancreatic WDNET., Methods: We characterized INSM1 immunohistochemistry in 34 patients with pancreatic SCA, comprising 23 surgical resections and 11 cytology specimens. As a control, we used 28 cytology specimens from pancreatic WDNET. Clinical information was retrieved through a review of electronic medical records., Results: All 11 pancreatic SCA cytology specimens and 15 of 23 pancreatic SCA surgical resections exhibited absent INSM1 immunostaining. Each of the remaining eight surgical resection specimens demonstrated 1 % immunoreactivity. In contrast, 27 out of 28 (96 %) pancreatic WDNET cytology specimens were positive for INSM1 immunostaining, with a median immunoreactivity of 90 % and a range of 30-90 %. Overall, INSM1 immunostains perform similarly to chromogranin and synaptophysin in pancreatic SCA., Conclusions: The results indicate that INSM1 immunohistochemistry staining may serve as a useful neuroendocrine marker to differentiate pancreatic SCA from pancreatic WDNET in clinical practice. To our knowledge, this represents the first large-scale study to evaluate INSM1 immunostaining in surgical and cytology specimens from pancreatic SCA., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Pancreatic serous cystic neoplasm (SCN) is a benign cystic neoplasm that is likely to be surgically resected due to preoperative misdiagnosis or tentative diagnosis even using endoscopic ultrasonography (EUS). We aimed to analyze EUS findings of SCN associated with misdiagnosis., Methods: Between January 2012 and September 2023, histologically confirmed pancreatic SCN were included and EUS features were reviewed., Results: Overall, 294 patients with 300 surgically resected SCNs were included. The median age of the patients was 51 years and 75.9% were females. The lesions were predominantly located in the body/neck/tail of the pancreas (63.0%). The overall preoperative diagnostic rate of SCN was 36.3%, with the most common misdiagnosis being intraductal papillary mucinous neoplasm (IPMN) (31.3%), while 16.3% remained undefined. The preoperative diagnostic rate of SCN varied across different endosonographic morphologies, with oligocystic, macrocystic, microcystic, and solid patterns yielding rates of 12.8%, 37.9%, 76.5%, and 19.2%, respectively. Notably, the presence of central scar and vascularity improved the diagnostic accuracy and correctly identified 41.4% and 52.3% of the lesions. While mucus or pancreatic duct (PD) communication significantly increased the likelihood of misdiagnosis, particularly as IPMN. Multivariate analysis revealed a morphological pattern, mucin-producing signs, wall thickening, vascularity, and PD communication were independent factors related to preoperative misdiagnosis, with an overall accuracy of 82.3%., Conclusions: Preoperative diagnosis of SCN remains challenging. The microcystic pattern emerged as a reliable feature, while mucin-producing signs, including mural nodules, mucus, and PD communication, pose diagnostic pitfalls despite the presence of typical central scar or vascularity commonly in SCN., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.

Background: Fine-needle aspiration (FNA) diagnosis of pancreatic serous cystadenoma (SCA) remains challenging. This retrospective study aimed to evaluate the roles of cyst fluid ancillary testing and combined fine-needle biopsy (FNB) in improving the diagnostic yield., Methods: The authors retrospectively reviewed cytology cases that were histologically confirmed SCAs. Clinical features and FNA cyst fluid biochemical and molecular analysis results along FNB findings were reviewed., Results: The study cohort included 31 cases from 13 male and 18 female patients with a mean age of 65. The original cytologic diagnoses were nondiagnostic (n = 6, 19%), negative for malignant cells/cyst contents (n = 7, 23%), atypical cells (n = 3, 10%), nonmucinous cyst (n = 11, 35%), and serous cystadenoma (n = 4, 13%). Cyst fluid carcinoembryonic antigen (CEA) analysis was performed in 17 cases, all of which showed a low CEA level (<192 ng/mL). All 14 cases with molecular testing showed a wild-type KRAS. Inhibin immunohistochemistry was retrospectively performed on the FNA cell blocks, inhibin was positive in six of seven cases tested. In 15 cases with concurrent FNA and FNB biopsies, the diagnosis of SCA was seen in only one FNA case (7%) but 13 FNB cases (87%)., Conclusions: This study suggests that FNA diagnosis of SCA remains challenging even with ancillary testing including cyst fluid CEA level and KRAS mutation analysis. Adjunct inhibin immunostaining may help improve the cytologic diagnosis of selective SCA cases. FNB appears superior to FNA for a definite diagnosis of SCA., (© 2024 American Cancer Society.)

Serous cystadenoma is a rare lesion in the para-testicular tissue, with even rarer reports of this entity occurring in the scrotum post-orchidopexy. We present such an occurrence, adding support for its existence as a distinct entity., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas]., Patients and Methods: Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety., Results: All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1-46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was -4.2 mm per year (range, -7.9 to -0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred., Conclusions: Belzutifan continued to show robust activity and manageable safety in VHL disease-associated pNETs., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: The purpose of the study was to develop and validate a radiomics model by using contrast-enhanced ultrasound (CEUS) data for pre-operative differential diagnosis of pancreatic cystic neoplasms (PCNs), especially pancreatic serous cystadenoma (SCA)., Methods: Patients with pathologically confirmed PCNs who underwent CEUS examination at Chinese PLA hospital from May 2015 to August 2022 were retrospectively collected. Radiomic features were extracted from the regions of interest, which were obtained based on CEUS images. A support vector machine algorithm was used to construct a radiomics model. Moreover, based on the CEUS image features, the CEUS and the combined models were constructed using logistic regression. The performance and clinical utility of the optimal model were evaluated by area under the receiver operating characteristic curve (AUC), sensitivity, specificity and decision curve analysis., Results: A total of 113 patients were randomly split into the training (n = 79) and test cohorts (n = 34). These patients were pathologically diagnosed with SCA, mucinous cystadenoma, intraductal papillary mucinous neoplasm and solid-pseudopapillary tumor. The radiomics model achieved an AUC of 0.875 and 0.862 in the training and test cohorts, respectively. The sensitivity and specificity of the radiomics model were 81.5% and 86.5% in the training cohort and 81.8% and 91.3% in the test cohort, respectively, which were higher than or comparable with that of the CEUS model and the combined model., Conclusion: The radiomics model based on CEUS images had a favorable differential diagnostic performance in distinguishing SCA from other PCNs, which may be beneficial for the exploration of personalized management strategies., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Isolated unilateral ovarian tumour without obvious concomitant tubal pathology is unlikely to cause intrabdominal abscess or septicaemia. Benign serous cystadenoma is a fairly common ovarian tumour but rarely causes fatality. We present a patient in mid-30s with massive ovarian serous cystadenoma presenting with abscess and septicaemia, leading to mortality. To our knowledge, no previous serous cystadenoma causing abscess formation has been reported before., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: A 2.6-cm solid cystic lesion in the pancreatic head was found in a 51-year-old woman on CT. A pancreatic neuroendocrine tumor was suspected, and a 68 Ga-DOTATATE PET/MRI was performed, which showed increased tracer uptake in the lesion. However, postsurgical pathologic examination indicated a pancreatic serous cystadenoma. Here, we reported a case of microcystic pancreatic serous cystadenoma that could be misdiagnosed as a pancreatic neuroendocrine tumor on a 68 Ga-DOTATATE PET/MRI., Competing Interests: Conflicts of interest and sources of funding: This research was supported by the National Natural Science Foundation of China (NSFC: 81971644) and the Shanghai Jiaotong University School of Medicine (KY20192098)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Over the years, the detection rate of pancreatic cystic neoplasms (PCNs) has significantly increased; however, the differential diagnosis and identification of high-risk PCNs remain challenging. We sought to investigate whether chromosomal instability (CIN) features in cell-free DNA in the cystic fluid of PCNs could help to identify high-risk PCNs., Methods: Pancreatic cystic fluid samples from 102 patients with PCNs were intraoperatively collected for detection of CIN using an ultrasensitive chromosomal aneuploidy detector. Clinical and imaging data were retrospectively collected, and statistical analysis was performed to assess the potential role of CIN in clinical practice., Results: CIN was investigated in a total of 100 patients. Sixteen of 26 serous cystic cystadenomas (SCAs) harbored deletions of chr3p and/or chr6p, whereas low rates of CIN were detected in mucinous cystic neoplasms. Most malignant PCNs presented with more than one type of CIN; amplification of chr1q and chr8q found in nine and seven of 11 malignant PCNs (81.8% and 63.6%), respectively, could aid in distinguishing high-risk IPMNs from low-risk ones, with a higher sensitivity than imaging. A combination of the mural nodule imaging feature and amplification of chr1q and chr8q achieved a sensitivity of 70.0% and a specificity of 82.4% in identifying high-risk IPMNs., Conclusions: Our work revealed the distinct CIN signature of different types of PCNs. Deletions of chr3p and chr6p defined a subtype of SCAs. Gains of chr1q and chr8q were associated with insidious malignant PCNs and helped identify high-risk IPMNs., (© 2023. Society of Surgical Oncology.)

Increased use of cross-sectional imaging has resulted in frequent detection of incidental cystic pancreatic lesions. Serous cystadenomas (SCAs) are benign cysts that do not require surgical intervention unless symptomatic. Unfortunately, up to half of SCAs do not have typical imaging findings ("atypical SCAs"), overlap with potentially malignant precursor lesions, and thus pose a diagnostic challenge. We tested whether the analysis of circulating extracellular vesicle (EV) biomarkers using a digital EV screening technology (DEST) could enhance the discrimination of cystic pancreatic lesions and avoid unnecessary surgical intervention in these atypical SCAs. Analysis of 25 different protein biomarkers in plasma EV from 68 patients identified a putative biomarker signature of Das-1, Vimentin, Chromogranin A, and CAIX with high discriminatory power (AUC of 0.99). Analysis of plasma EV for multiplexed markers may thus be helpful in clinical decision-making., (© 2023. The Author(s).)

Oncogenic activation of the mitogen-activated protein kinase (MAPK) pathway due to KRAS or BRAF gain-of-function mutation is frequently found in ovarian serous borderline tumor (SBT) and their extraovarian implants. We investigated mutational status of KRAS and BRAF of the primary ovarian SBTs that had a high stage presentation in correlation with clinical outcome. Among 39 consecutive primary SBTs with either invasive implants (20 cases) or non-invasive implants (19 cases), KRAS and BRAF mutational analysis was informative in 34 cases. Sixteen cases (47%) harbored a KRAS mutation, while 5 cases (15%) had a BRAF V600E mutation. High-stage disease (IIIC) was seen in 31% (5/16) of patients with a KRAS mutation and 39% (7/18) of patients without a KRAS mutation (p = 0.64). KRAS mutations were present in 9/16 (56%) tumors with invasive implants/LGSC versus 7/18 (39%) tumors with non-invasive implants (p = 0.31). BRAF mutation was seen in 5 cases with non-invasive implants. Tumor recurrence was seen in 31% (5/16) of patients with a KRAS mutation, compared to 6% (1/18) of patients without a KRAS mutation (p = 0.04). A KRAS mutation predicted an adverse disease-free survival (31% survival at 160 months) compared to those with wild-type KRAS (94% at 160 months; log-rank test, p = 0.037; HR 4.47). In conclusion, KRAS mutation in primary ovarian SBTs is significantly associated with a worse disease-free survival, independent of the high tumor stage or histological subtypes of extraovarian implant. KRAS mutation testing of primary ovarian SBT may servce as a useful biomarker for tumor recurrence., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Histomorphological differentiation between pancreatic serous cystadenoma (SCA) and clear cell renal cell carcinoma (RCC) can be challenging. We aimed to study Paired box 8 protein (Pax8) expression profile in cytologic and surgical specimens with pancreatic SCA to assess its utility as a differentiating marker from clear cell RCC., Methods: We characterized Pax8 immunohistochemistry in 33 patients with pancreatic SCA (23 surgical resections and 10 cytology specimens). Nine cytology specimens from metastatic clear cell RCC involving pancreas were used as control tissue. Electronic medical records were reviewed to retrieve clinical information., Results: All 10 pancreatic SCA cytology specimens, and 16 of 23 pancreatic SCA surgical resections showed absent Pax8 immunostaining, while the remaining 7 surgical resection specimens showed 1%-2% immunoreactivities. Islet and lymphoid cells adjacent to the pancreatic SCA expressed Pax8. In contrast, the proportion of Pax8 immunoreactivity ranged from 50 to 90% (average of 76%) in nine cases of metastatic clear cell RCC involving pancreas. Using a 5% immunoreactivity cutoff, all cases of pancreatic SCA are interpreted as negative for Pax8 immunostains while all cases of metastatic clear cell RCC involving pancreas are interpreted as positive for Pax8 immunostains., Conclusions: These results suggest that Pax8 immunohistochemistry staining can be a useful adjunct marker to differentiate pancreatic SCA from clear cell RCC in clinical practice. To the best of our knowledge, this is the first large-scale study of Pax8 immunostaining on surgical and cytology specimens with pancreatic SCA., (© 2023. The Author(s).)

Objective: The molecular characteristics of low-grade serous carcinoma (LGSC) in serous effusions have not been studied previously. The present study analysed the molecular profile of LGSC at this anatomical site., Methods: Specimens consisted of a series of 17 serous effusions (15 peritoneal, 2 pleural) from 16 patients, of which 15 were LGSC and 2 serous borderline tumour (SBT) who later progressed to LGSC. For comparative purposes, 9 surgical specimens from 6 patients with LGSC were analysed. Fresh-frozen cell pellets and surgical specimens underwent targeted next-generation sequencing covering 50 unique genes., Results: Mutations were found in tumours from 14 of the 22 patients, of whom 4 had 2 different mutations and 10 had a single mutation. Overall, the most common mutations were in KRAS (n = 3) and BRAF (n = 3), followed by NRAS (n = 2), CDK2NA (n = 2), TP53 (n = 2), ATM (n = 2). Mutations in MET, STK11, ERBB2 and FLT3 were found in one case each. Patient-matched specimens had the same molecular profile. Both effusions with TP53 mutation had concomitant ATM mutation, and both stained immunohistochemically with a wild-type pattern. The absence of mutations was associated with a trend for shorter overall survival in univariate analysis (p = 0.072)., Conclusions: The molecular alterations in LGSCs in serous effusions are consistent with those found in solid tumours, with frequent alterations in the mitogen-activated protein kinase pathway. Mutations in LGSC may be a marker of better outcomes., (© 2023 John Wiley & Sons Ltd.)

Background: Although emerging data evidences that EUS-guided needle-based confocal laser endomicroscopy (nCLE) accurately diagnoses pancreatic cystic lesions (PCLs), there are a lack of interobserver agreement (IOA) studies utilizing reference histopathological diagnosis and for specific PCL subtypes. Hence, we sought to assess the IOA, intra-observer reliability (IOR), and diagnostic performance of EUS-nCLE using a large cohort of patients with histopathological diagnosis amongst a broad panel of international observers., Methods: EUS-nCLE videos (n = 76) of subjects with PCLs [intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystadenoma (SCA), pseudocyst, and cystic-neuroendocrine tumors/solid pseudopapillary neoplasm (cystic-NET/SPN)], simulating clinical prevalence rates were obtained from 3 prospective studies. An international panel of 13 endosonographers with nCLE experience, blinded to all PCL data, evaluated the video library twice with a two-week washout for PCL differentiation (mucinous vs. non-mucinous) and subtype diagnosis., Results: The IOA (κ = 0.82, 95% CI 0.77-0.87) and IOR (κ = 0.82, 95% CI 0.78-0.85) were "almost perfect" to differentiate mucinous vs. non-mucinous PCLs. For PCL subtype, IOA was highest for SCA (almost perfect; κ = 0.85), followed by IPMN (substantial, κ = 0.72), and cystic-NET/SPN (substantial, κ = 0.73). The IOA was moderate for MCN (κ = 0.47), and pseudocyst (κ = 0.57). Compared to histopathology, observers differentiated mucinous vs. non-mucinous PCLs with high accuracy (94.8%, 95% CI 93.3-96.1). For detecting specific PCLs subtypes, EUS-nCLE was highly accurate in diagnosing non-mucinous cysts (SCA: 98%; cystic-NET/SPN: 96%; pseudocyst: 96%) and slightly less accurate for mucinous lesions (IPMN: 86%; MCN: 84%)., Conclusion: Diagnosis of PCLs by EUS-nCLE guided virtual biopsy is very accurate and reliable for the most prevalent pancreatic cysts in clinical practice., Competing Interests: Declaration of competing interest Krishna SG is PI of an investigator-initiated study. The study in part is funded by a grant to The Ohio State University Wexner Medical Center from Mauna Kea Technologies, Paris, France. Pereira SP was supported by the NIHR Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust and UCL., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The development of cross-sectional imaging techniques has enhanced the detection of pancreatic cystic lesions (PCLs). PCLs are found in approximately 2% of the general population, often as incidentally detected lesions on computed tomography or MRI during the evaluation of other medical conditions. Broadly, PCLs are classified as mucinous or nonmucinous. Mucinous PCLs include mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. Nonmucinous PCLs include pseudocysts, serous cystadenomas, solid pseudopapillary neoplasms, and cystic pancreatic neuroendocrine tumors, as well as cystic acinar cell carcinoma, cystic degeneration of pancreatic ductal adenocarcinoma, lymphoepithelial cyst, and others., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Context.—: Because of new and improved imaging techniques, cystic/intraductal pancreatobiliary tract lesions are increasingly being discovered, and brushings or endoscopic ultrasound/computed tomography/magnetic resonance imaging-guided fine-needle aspiration biopsies from these lesions have become an integral part of pathologists' daily practice. Because patient management has become increasingly conservative, accurate preoperative diagnosis is critical. Cytologic distinction of low-risk (pseudocysts, serous cystadenoma, lymphoepithelial cysts, and squamoid cysts of the pancreatic duct) from high-risk pancreatic cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) requires incorporation of clinical, radiologic, and cytologic findings, in conjunction with chemical and molecular analysis of cyst fluid. Cytopathologists must ensure appropriate specimen triage, along with cytologic interpretation, cyst classification, and even grading of some (mucinous) cysts. Epithelial atypia in mucinous cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) has transitioned from a 3-tiered to a 2-tiered classification system, and intraductal oncocytic papillary neoplasms and intraductal tubulopapillary neoplasms have been separately reclassified because of their distinctive clinicopathologic characteristics. Because these lesions may be sampled on brushing or fine-needle aspiration biopsy, knowledge of their cytomorphology is critical., Objective.—: To use an integrated, multidisciplinary approach for the evaluation of cystic/intraductal pancreatobiliary tract lesions (incorporating clinical, radiologic, and cytologic findings with [chemical/molecular] cyst fluid analysis and ancillary stains) for definitive diagnosis and classification., Data Sources.—: Review of current literature on the cytopathology of cystic/intraductal pancreatobiliary tract lesions., Conclusions.—: Our knowledge/understanding of recent updates in cystic/intraductal pancreatobiliary lesions can ensure that cytopathologists appropriately triage specimens, judiciously use and interpret ancillary studies, and incorporate the studies into reporting., Competing Interests: The author has no relevant financial interest in the products or companies described in this article.

Rationale: Gastric-type endocervical adenocarcinoma (GAS) is a rare type of cervical adenocarcinoma that is a mucinous adenocarcinoma with a variety of gastral patterns. To date, there are no systematic clinical diagnosis and treatment guidelines., Patient Concerns: In our case, a 49-year-old woman underwent pelvic magnetic resonance imaging (MRI) due to a pelvic mass, and cervical lesions were unexpectedly found. After receiving relevant surgical treatment, the pathological results showed the particularity of the tumor type-cervical gastric adenocarcinoma with a borderline serous tumor of both appendages and the right ovary., Diagnoses: Postoperative routine pathological examination showed mucoepithelial metaplasia accompanied by a borderline serous tumor., Interventions: After gynecological/urinary ultrasound, blood tests, MRI, cervical biopsy, and uterine curettage, "robot-assisted laparoscopic radical hysterectomy + bilateral salpingectomy-ovariectomy + pelvic lymph node dissection + pelvic adhesiolysis" were performed. After the surgery, the patient was treated with radiotherapy and concurrent chemotherapy., Outcomes: After the operation, radiotherapy, and chemotherapy, the patient had no tumor recurrence and is still in good condition., Lessons: The diagnosis of GAS is relatively difficult, its clinical manifestations lack specificity, and the pathogenesis has nothing to do with human papillomavirus infection. The patient was misdiagnosed with vaginitis at a local hospital. However, we found that MRI and pathological examination were helpful for the diagnosis of the disease. Although there are no relevant guidelines to explain the treatment principles of GAS, we believe that early surgery is conducive to the prognosis of the disease because GAS has a certain tolerance to radiotherapy and chemotherapy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

High-grade serous ovarian cancer (HGSOC) is characterized by TP53 mutation and somatic copy number alterations (SCNAs). Here we show that the oncogenic transcription factor EVI1 (ecotropic viral integration site-1) is amplified and overexpressed up to 30% of 1640 HGSOC cases in The Cancer Genome Atlas (TCGA). Functionally, EVI1 promotes proliferation/invasion in vitro and tumor growth of xenograft model in vivo. Importantly, we discover that EVI1 regulates estrogen signaling by directly activating ESR1 (estrogen receptor 1) transcription determined by the ChIP and luciferase assay. Interestingly, EVI1 and ESR1 share common regulatory targets as indicated by the analysis of ChIP-Seq data. EVI1 and ESR1 collaborate in the regulation of some estrogen receptor-regulated genes. Furthermore, EVI1 drives tumor aggressiveness partially by regulating estrogen signaling. Estrogen enhances the proliferation, invasion and xenograft growth of ovarian cancer cells. Importantly, estrogen can rescue the inhibition of proliferation, invasion and xenograft growth induced by silencing EVI1. These findings suggest that EVI1 functions as a novel regulator of the estrogen signaling network in ovarian cancer., (Copyright © 2021. Published by Elsevier B.V.)

Research Question: What are ovarian stimulation cycle outcomes and acceptance rates of an oocyte accumulation programme in young women with benign ovarian tumour (BOT)?, Design: Retrospective cohort study conducted at the Academic Assisted Reproductive Technology and Fertility Preservation Centre, Lille University Hospital, between January 2016 and December 2019. The number of metaphase II oocytes per cycle and per patient after accumulation were evaluated. Two groups were identified for the analysis: endometrioma ('endometrioma') and dermoid, mucinous or serous cyst ('other cysts')., Results: A total of 113 fertility-preservation cycles were analysed in 70 women aged 27.9 ± 4.8 years. Almost all women had undergone previous ovarian surgery before fertility preservation (89%). Mean anti-Müllerian hormone levels before ovarian stimulation was 12.5 ± 8.7 pmol/l. A total of 6.4 ± 3.4 oocytes were retrieved, and 4.3 ± 3.4 metaphase II (MII) oocytes were vitrified per cycle. All agreed to the oocyte accumulation programme and all underwent at least one cycle. To date, 36 (51%) patients achieved two or three fertility- preservation cycles. After accumulation, 7.0 ± 5.23 MII oocytes were vitrified per patient. No difference was found in ovarian response and oocyte cohort between the 'endometrioma' and 'other cysts' groups. Questionnaires completed after oocyte retrieval revealed abdominal bloating and pelvic pain in most patients, with no difference according to the type of cyst. No serious adverse events occurred., Conclusions: Oocyte accumulation should be systematically offered to young women with BOT irrespective of histological type, as it seems to be well-tolerated. Long-term follow-up is needed to assess the efficiency of oocyte accumulation to optimize the chances of subsequent pregnancies., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Aims: Because serous cystadenoma (SCA) does not usually require excision, it is critical to distinguish it from differential diagnoses which do, especially neuroendocrine tumour (NET). The gold standard for diagnosing SCA is assessment of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNAB) material. Inhibin immunohistochemistry aids this assessment, but such positivity is not absolutely sensitive or specific to SCA. The following is the largest known study of SCA EUS-FNAB specimens and the first to compare four potential SCA immunomarkers between themselves and inhibin, compared against NET., Methods and Results: Immunohistochemistry for calponin, mucin 6 (MUC6), glucose transporter 1 (GLUT1) and vascular endothelial growth factor A (VEGFA) was performed on 30 EUS-FNAB and three resection specimens of SCA and 32 EUS-FNAB specimens of NET. GLUT1 and VEGFA were suboptimal as diagnostic immunomarkers of SCA, being expressed by 10 and 44% of NETs, respectively. Further, their expression by cellular constituents of blood which often contaminate EUS-FNAB specimens hampered identification of neoplastic cells, especially in hypocellular samples. While 19% of NETs showed nuclear MUC6 positivity, cytoplasmic expression of the protein showed 100% specificity and sensitivity as an SCA marker. However, assessing MUC6 in EUS-FNAB specimens must also consider the protein's focal expression in physiological pancreatic, gastric or duodenal tissues, which can contaminate these specimens. Calponin was less sensitive (71% versus 100%) but more specific (100% versus 91%) than inhibin, although easier to assess in EUS-FNAB specimens than MUC6., Conclusions: Of the four potential immunomarkers of SCA suggested by the existing literature, calponin and MUC6 are useful complementary studies to inhibin for application to EUS-FNAB specimens., (© 2021 John Wiley & Sons Ltd.)

Introduction: Determining the risk of malignancy in a pancreatic cyst (PC) is a clinical and diagnostic challenge. Monoclonal antibody (mAb) Das-1 test was shown to have high sensitivity, specificity, and accuracy in detecting high-risk (HR) cysts. Das-1 mAb test detects HR mucinous cysts with high-grade dysplasia (HGD), invasive carcinoma, and/or intestinal-type epithelium. Correlation of mAb Das-1 testing of PC fluids with cytomorphologic findings has not been evaluated., Materials and Methods: We correlated cytology with mAb Das-1 test results and resection histology in 26 PCs. There were 18 intraductal papillary mucinous neoplasms (IPMN), 1 intraductal oncocytic papillary neoplasm (IOPN), 4 mucinous cystic neoplasms (MCN), 2 serous cystadenomas, and 1 cystic pancreatic neuroendocrine tumor (PanNET). HR cysts included cysts with high-grade atypia on cytology or HGD on histology, invasive carcinoma, IOPNs, and cystic PanNETs. Intestinal type IPMNs were also HR cysts on histology., Results: In 17 cases (65.38%), cytology and mAb Das-1 test correlated with histology. There were 2 (7.69%) mAb Das-1 test negative HR PCs diagnosed by cytology. Five (19.23%) mAb Das-1 test positive HR PCs had mucin only or cells with low-grade dysplasia on cytology. Two mAb Das-1 test positive HR PCs had nondiagnostic cytology. HR IOPN and cystic PanNET were not detected by mAb Das-1 test., Conclusion: The mAb Das-1 is a sensitive and specific biomarker for detecting HR mucinous PCs. Adding cytology to mAb Das-1 testing improves the sensitivity for the detection of nonmucinous HR PC. Together, cytology with mAb Das-1 testing is more accurate than either one alone., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate multiparametric analysis in differential diagnosis between pancreatic serous cystic neoplasms (SCNs) and mucinous cystic neoplasms (MCNs) as well as the differentiation of the benign and malignant MCNs with 18 F-FDG (18-fluorodeoxyglucose) PET/CT (positron emission tomography)., Methods: Forty patients with total of 41 lesions (SCNs: 27/41; MCNs: 14/41), who were preoperatively examined with 18 F-FDG PET/CT, were retrospectively analyzed. Multiple quantitative parameters using conventional and texture features were included. The combined model was established with complementary PET/MR parameters. The differential diagnostic efficacy of each independent parameter and the combined model were evaluated with receiver operating characteristic (ROC) analysis. Integrated discriminatory improvement (IDI) and net reclassification improvement (NRI) were used to evaluate improvement of diagnostic efficacy by using combination of multiple parameters., Results: Among all independent parameters, the percentile 5th (0.88 ± 0.38 vs 0.47 ± 0.23, P < 0.001) showed the highest discriminative diagnostic value. The combination of multiple parameters can improve the differential diagnostic efficacy of SCNs and MCNs (sensitivity = 71.4%, specificity = 77.8%, and AUC = 0.788), and the addition of texture parameters to the conventional parameters allowed a significant reclassification with IDI = 0.236 (95% CI: 0.095-0.377) and categorical NRI = 0.434 (95% CI: 0.030-0.838). SURmax (tumor to normal pancreas ratio, T/P) and SURmax (tumor to aorta ratio, T/A) both showed the highest discriminative diagnostic value (sensitivity = 100.0%, specificity = 70.0%, AUC = 0.900, and Youden index = 0.700) in the differential diagnosis of benign and malignant MCNs, with the cutoff values of 0.84 and 0.90, respectively., Conclusion: Combination of multiple parameters using 18 F-FDG PET/CT could further improve differentiation between pancreatic SCNs and MCNs. SURmax (T/P) and SURmax (T/A) could improve differential diagnosis of benign and malignant MCNs., Competing Interests: Yue Wu was employed by Siemens Healthineers Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guanyun Wang et al.)

Recent studies have shown that the expression of ENPP1 is related to differentiation, death, dissemination and chemosensitivity of tumor cells. So far, there is no research in ovarian carcinoma. This study aimed at exploring the role of ENPP1 gene in ovarian carcinoma, the relationship with prognostic indicators and chemotherapy resistance, and investigates the possibility of molecular targeted therapy. The expression of ENPP1 in 41 normal ovarian epithelial tissues, 97 ovarian serous cystadenoma and 103 HGSOC tissues was detected by IHC. In ovarian cancer tissues and ovarian cancer cell lines, mRNA and protein expression of ENPP1 was determined by qRT-PCR and Western blot. The ENPP1 expression was knockdowned by siRNA. Cell proliferation was measured with the BrdU Cell Proliferation ELISA. Cell migration and invasion were detected by Wound-Healing, Transwell migration and Matrigel invasion assay. Caspase 3 activity was determined by the CaspACE. The expression of EMT markers such as E-cadherin, N-cadherin, and Vimentin was measured, and the expression of PCNA and MMP9 was also be detected. The results showed that the expression of ENPP1 was significantly increased in high-grade ovarian serous carcinoma, the number of strong expression was 85.4% (22.3%+63.1%) and only 1.03% (1.03%+0.0%) in serous cystadenoma, but no in normal ovarian epithelium (P< 0.05). And the stronger the expression of ENPP1, the later the FIGO stage and the poorer differentiation of cells (P = 0.001 or <0.001, respectively). However, no correlation was found between the expression of ENPP1 and chemosensitivity. ENPP1 was also highly expressed in ovarian cancer tissues and in epithelial ovarian cancer cell lines (A2780, CaoV3, OVCAR3, SKOV3 and 3ao). After down-regulation of ENPP1 expression by RNA interference, the cell proliferation, migration and invasion of ovarian cancer cell decreased significantly, the expression of apoptosis related gene caspase 3 increased significantly, while the expression of PCNA and MMP9 was significantly down regulated. In addition, EMT biological characteristics of A2780 and SKOV3 cells were also inhibited. In summary, the increased expression of ENPP1 may be related to the occurrence of HGSOC, and indicate that the disease progresses rapidly and the prognosis is poor. ENPP1 may be considered as a potential molecular therapeutic target., Competing Interests: The authors have declared that no competing interests exist.

Abstract: The subtypes of serous ovarian tumors (SOTs), including benign serous cystadenoma, serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSC), and high-grade serous ovarian carcinoma (HGSC), remain poorly understood. Herein, we aimed to characterize the cell adhesion molecule 1 (CADM1)/signal transducer and activator of transcription 3 (STAT3)/human epidermal growth factor receptor 2 (HER2) axis and identify its clinical significance in patients with serous cystadenoma, SBT, LGSC, and HGSC.The immunohistochemical expression of CADM1, HER2, and STAT3 was assessed in 180 SOT specimens, and its association with clinical data was determined.High levels of CADM1 expression were detected in 100% of serous cystadenomas and 83.33% of SBTs, while a loss of CADM1 expression was observed in 44% of LGSCs and 72.5% of HGSCs. Relative to the levels in benign cystadenomas and SBTs, higher levels of HER2 and STAT3 expression were observed in LGSCs and aggressive HGSCs. Furthermore, the expression profile of the CADM1/HER2/STAT3 axis was significantly associated with histologic type, International Federation of Gynecology and Obstetrics stage, and lymph node metastasis in patients with SOT.Our study identified the changes in the CADM1/HER2/STAT3 axis that were closely associated with the clinical behavior of SOTs. These molecular data may provide new insights into SOT carcinogenesis and aid in the diagnosis and treatment of patients with SOT., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ovarian cancer is the fifth leading cause of cancer-related mortality in women. Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme and there is growing evidence to suggest that it plays an important role in cancer progression. This is the first study to examine the expression of NNMT in serous ovarian cystadenomas, serous borderline tumours, low grade serous carcinomas (LGSC) and high grade serous carcinomas (HGSC) and investigate the potential independent association of NNMT expression with survival. Tissue samples were analysed immunohistochemically for NNMT expression. The stromal NNMT score was significantly higher in HGSC compared to serous cystadenomas and serous borderline tumours ( p  < .001, p  < .043, respectively). The mean stromal NNMT score of patients with HGSC was significantly higher than patients with LGSC ( p  = .043). Patients with low expression of NNMT had a significantly higher mean recurrence-free survival than patients with high expression ( p  = .036). NNMT may support tumour progression in ovarian cancer by promoting desmoplastic stromal tumour reaction. NNMT overexpression may be associated with poor prognosis and can be a therapeutic target in ovarian cancer.IMPACT STATEMENT What is already known on this subject? Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that is overexpressed in many malignancies. Its overexpression was shown to lead to histone hypomethylation, which in turn can decrease and increase the expression of tumour suppressor proteins and onco-proteins, respectively. NNMT was also shown to play a role in epithelial-to-mesenchymal transition, which is critical in tumour progression and the stromal tumour reaction. The stromal tumour reaction was recently targeted with promising therapeutic results in ovarian cancer. What do the results of this study add? The expression of NNMT in various ovarian neoplasms including serous cystadenomas, borderline tumours and serous carcinomas has not been studied and independently associated with poor survival, previously. This study suggests that NNMT is progressively overexpressed in the stroma of ovarian neoplasms from benign cysts to HGSCs. NNMT overexpression appears to be independently associated with poor survival in ovarian cancer. What are the implications of these findings for clinical practice and/or further research? The implications of these findings are that NNMT may play an important role in the stromal tumour reaction, and therefore its overexpression may contribute to poor survival. NNMT overexpression may be an important target of ovarian cancer therapy.

Background: Serous cysto-adenoma (SCA) is a rare benign neoplasm of the pancreas. SCA can mimic other pancreatic lesions, such as neuroendocrine tumours. 68Gallium-DOTA-peptide Positron Emission Tomography (PET) is able to image in vivo the over-expression of the somatostatin receptors, playing an important role for the identification of neuroendocrine neoplasms., Case Presentation: We reported a case of 63-year-old man, with a solid lesion of 7 cm of diameter of the body-tail of the pancreas. Two fine-needle-aspirations (FNA) were inconclusive. A 68Ga-DOTA-peptide PET-CT revealed a pathological uptake of the pancreatic lesion. The diagnosis of a pancreatic neuroendocrine neoplasm was established and a laparoscopic distal splenopancreatectomy and cholecystectomy was performed. Final histopathological report revealed the presence of a micro-cystic SCA., Conclusions: The current case firstly reports a pancreatic SCA showing increased radiopharmaceutical uptake at 68Ga-DOTA-peptide PET-CT images. This unexpected finding should be taken into account during the diagnostic algorithm of a pancreatic lesion, in order to minimize the risk of misdiagnosis and overtreatment of SCA.

This case report describes a right-sided borderline ovarian tumour diagnosed unexpectedly following suspected torsion in the third trimester of pregnancy. The patient had had a right mucinous cystadenoma and left serous cystadenoma in her previous pregnancy and underwent bilateral ovarian cystectomy at the time of her first elective caesarean section. The management of borderline ovarian tumours is generally difficult in younger women of reproductive age and is made more complex by pregnancy. The authors share the challenges of managing this condition in pregnancy together with a review of the literature., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features., Experimental Design: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting., Results: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations., Conclusions: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications. See related commentary by McMullen et al., p. 5271 ., (©2020 American Association for Cancer Research.)

Ovarian epithelial type tumor of the testis is a rare entity. Herein, we report borderline serous papillary tumor of the testis in a 37-year-old male, which was clinically suspected to be a testicular malignancy.

Background: Paraovarian/paratubal cysts constitute 5-20% of all adnexal lesions and typically originate from the paramesonephric or Müllerian duct. The primary epithelial tumors arising from paraovarian cysts account for 25% of the cases, but giant cystadenomas of paraovarian origin are extremely uncommon during childhood and adolescence with very few cases reported in the literature., Case: We present the case of a 15-year-old female that presented with a bulky mass in the abdomen and pelvis. An initial clinical and radiological examination indicated an ovarian cyst measuring ∼25 × 20 cm. However, explorative laparotomy revealed a giant paratubal cyst that was successfully treated with complete excision using fertility-sparing surgery. Histopathological examination was consistent with a serous cystadenoma. The postoperative course was uneventful and the girl was discharged on the seventh postoperative day. At the follow-up of 6 months, the patient was doing well., (Copyright © 2020 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis 1 . To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA sequencing to profile ~11,000 cells from 22 ascites specimens from 11 patients with HGSOC. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations. We found that the previously described immunoreactive and mesenchymal subtypes of HGSOC, which have prognostic implications, reflect the abundance of immune infiltrates and fibroblasts rather than distinct subsets of malignant cells 2 . Malignant cell variability was partly explained by heterogeneous copy number alteration patterns or expression of a stemness program. Malignant cells shared expression of inflammatory programs that were largely recapitulated in single-cell RNA sequencing of ~35,000 cells from additionally collected samples, including three ascites, two primary HGSOC tumors and three patient ascites-derived xenograft models. Inhibition of the JAK/STAT pathway, which was expressed in both malignant cells and cancer-associated fibroblasts, had potent anti-tumor activity in primary short-term cultures and patient-derived xenograft models. Our work contributes to resolving the HSGOC landscape 3-5 and provides a resource for the development of novel therapeutic approaches.

Background: Patients with 46, XY disorder of sex development (DSD) are predisposed to the development of gonadal tumors, particularly germ cell tumors and gonadoblastoma. However, to the best of our knowledge, there are no publications in the existing literature that refer to the coexistence of 46, XY DSD and serous tumors in the ovary., Case Presentation: Here, we report the case of a 23-year-old female (social gender) patient with 46, XY DSD presenting with primary amenorrhea. Imageology revealed a huge mass in the left adnexa. Subsequent pathological analysis revealed a serous borderline tumor of the ovary., Conclusion: Gonadal tumors of patients with 46, XY DSD are not necessarily malignant tumors and can coexist with borderline tumors with primitive corded gonads. The coexistence of DSD and serous borderline tumors is rare. Clearly, an early and accurate diagnosis plays an important role in the treatment of these patients. Although there may not be a clear correlation between the two lesions, it is vital that we specifically analyze the mechanisms involved so that we can determine whether patients with DSD are associated with an increase of developing serous borderline tumors of the gonad.

Background: Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and immunohistochemical features with the more common mesonephric adenocarcinoma (MAC), which mostly arises the uterine cervix. Despite the similarities between these tumors, the histogenesis of M-LAC is still disputable., Case Presentation: Sixty-one-year-old woman presented with an advanced tumor of the left ovary with intraabdominal spread and liver metastases. After receiving 5 cycles of neoadjuvant chemotherapy, she underwent a hysterectomy with bilateral salpingo-oophorectomy, and resection of the liver metastasis, omentum, and appendix. Histologically, the ovarian tumor consisted of two components, whose morphology and immunohistochemical results were typical of either a serous borderline tumor (immunohistochemical positivity for PAX8, WT1, ER and PR) or a mesonephric-like carcinoma (immunohistochemical positivity for PAX8, TTF1 and GATA3). Only the component of the mesonephric-like adenocarcinoma metastasized to the omentum and liver. A molecular analysis with a panel of 271 genes (size 1020 kbp) was performed separately on samples from the borderline tumor, primary ovarian mesonephric-like adenocarcinoma, and liver metastasis. The results showed the clonal origin of all samples, which shared the same KRAS (NM&#95;004985.3:c.34G > T, p.(G12C)) and PIK3CA (NM&#95;006218.2:c.1633G > A, p.(E545K)) somatic mutations. Moreover, in the sample from the primary mesonephric-like carcinoma and its liver metastasis a likely pathogenic somatic MYCN mutation (NM&#95;005378.4:c.131C > T, p.(P44L) was found. In all samples, the deletion of exons 9-10 in the CHEK2 gene was present, which is in concordance with the previously performed genetic testing of the blood specimen which revealed the hereditary CHEK2 mutation in this patient., Conclusions: Our result support the theory that at least some mesonephric-like ovarian adenocarcinomas are of Müllerian origin. The serous borderline tumor seems to be a precursor of mesonephric-like adenocarcinoma, which has been proven in our case by both tumors sharing the same mutations, and the presence of cumulative molecular aberrations in the mesonephric-like adenocarcinoma.

Background/objectives: Pancreatic cystic neoplasms (PCNs) are common, among which 13%-23% are serous cystic neoplasms (SCNs). However, diffuse and multifocal variants of SCNs are extremely rare. The differential diagnosis of SCNs from other PCNs is important as the former entities are benign and do not become invasive., Objective: This study analyzes the clinical characteristics of multifocal/diffuse SCN through a systematic review of the literature and a case report., Methods: A comprehensive literature search was executed in the Ovid MEDLINE, Embase, and Google Scholar databases. The search strategy was designed to capture the concept of multifocal/diffuse SCN cases with sufficient clinical information for detailed analysis. Using the final included articles, we analyzed tumor characteristics, diagnostic modalities used, initial management and indications, and patient outcomes., Results: A review of 262 articles yielded 19 publications with 22 cases that had detailed clinical information. We presented an additional case from our institution database. The systematic review of 23 cases revealed that the diffuse variant is more common than the multifocal variant (15 vs 8 cases, respectively). Patients were managed with surgical intervention, conservative treatment, or conservative treatment followed by surgical intervention. Indications for surgery following conservative management mainly included new onset or worsening of symptoms. Only one case reported significant tumor growth after attempting an observational approach. No articles reported recurrence of SCN after pancreatectomy, and no articles reported mortality related to multifocal/diffuse SCNs., Conclusion: Despite their expansive-growing and space-occupying characteristics, multifocal/diffuse SCNs should be treated similarly to their more common unifocal counterpart., Competing Interests: Declaration of competing interest The authors have no conflict of interests., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: Cancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing., Methods: In this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens., Results: Our model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential., Conclusions: Short duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Serous cystadenoma, often known as ovarian serous cystadenoma, is one of the common benign ovarian neoplasms. On the other hand, primary retroperitoneal serous cystadenoma is an extremely rare benign entity whose pathogenesis has not been well understood. Clinical presentation and symptomatology vary greatly and are highly dependent on the size and location of the lesion. Primary retroperitoneal serous cystadenomas are homogeneous, unilocular, thin-walled cystic masses. If they grow large enough, they tend to compress and deform adjacent organs, giving clinicians a misimpression of malignant pattern of behavior. Therefore, it is crucial to differentiate benign primary retroperitoneal serous cystadenomas from other epithelial and nonepithelial cystic lesions or masses involving retroperitoneal regions. Management-wise, complete cyst excision without rupture or spillage of the cyst contents is the recommended therapeutic method for primary retroperitoneal serous cystadenomas. This review will highlight the current knowledge on its pathogenesis and discuss its histopathologic features and differential diagnoses from the pathologist's point of view.

Serous pancreatic cystadenomas are benign tumours and most cases are detected incidentally. Complications are unusual. A patient with a history of a large pancreatic serous cystadenoma (SCA) presented to the emergency department with abdominal pain and haemodynamic shock. After haemodynamic stabilisation, an urgent abdominal CT scan revealed a large hemoperitoneum but the origin of the bleeding was not found. The patient was submitted to an angiography that revealed a bleeding hypervascular pancreatic mass and an embolisation was done successfully. After 3 weeks, the patient underwent a laparotomic left pancreatectomy with en bloc splenectomy. The anatomopathological results were consistent with a microcystic SCA of the pancreas. Despite the high vascularity of pancreatic SCA, haemorrhage is a very rare but life-threatening complication., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Pancreatic serous cystic neoplasms (SCNs), such as serous cystadenoma (SCA), are generally recognized as benign because malignant counterparts of SCNs have been extremely rare. In clinical practice, pancreatic cystic neoplasms diagnosed as SCNs have been managed by conservative observation, as long as the patients remained asymptomatic. We herein report a case of metachronous ductal adenocarcinoma that was discovered during long-term follow-up of SCN and review the related literature. To our knowledge, this was the first reported case of the local presence of ductal adenocarcinoma adjacent to SCA that was preoperatively diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Serous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow-up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine-needle aspiration (EUS-FNA). In this brief report, we describe six EUS-FNA cases from five patients that were reported as "benign, consistent with serous cystadenoma". Samples were hypocellular, composed of loose clusters and single cuboidal, bland-looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α-inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS-FNAs of SCA commonly result in non-diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management., (© 2019 Wiley Periodicals, Inc.)