Serous Borderline Tumors Research Articles

The value of ultrasonography combined with carbohydrate antigen 125 and 19-9 detection in the diagnosis of borderline ovarian tumors and prediction of recurrence.

This study aimed to investigate the clinical value of ultrasonography combined with tumor markers in the diagnosis and prediction of recurrence of borderline ovarian tumors (BOTs) and analyze the value of the combination of two different auxiliary examinations in the diagnosis and prediction of recurrence of BOTs. Here, 221 patients with BOTs confirmed by postoperative pathology were enrolled. Their clinical data, including the ultrasonography features, tumor markers, and clinicopathological data, were retrospectively analyzed. The statistical data of the 221 cases with BOTs were as follows: 94 (42.5%) with left-sided lesions, 102 (46.2%) with right-sided lesions, and 25 (11.3%) with bilateral lesions. Moreover, 93 cases (42.1%) had a borderline serous tumor, 110 (49.8%) had a borderline mucinous tumor, 12 (5.4%) had a borderline serous mucinous tumor, 2 (0.9%) had a borderline endometrioid tumor, 1 (0.5%) had a borderline Brenner tumor, and 2 (0.9%) had a clear cell BOT. There were 104 cases (47.1%) with a tumor diameter of ≤10 cm and 117 cases (52.9%) with a tumor diameter of >10 cm as suggested by ultrasonography. There were 89 cases (40.3%) with septation, 44 (19.9%) with papilla, and 97 (43.9%) with blood flow as demonstrated by ultrasonography. Carbohydrate antigen 125 (CA 125) was elevated in 132 cases (59.7%), and CA 19-9 was elevated in 52 cases (23.5%). In general, BOTs are difficult to diagnose preoperatively and have a certain recurrence rate. Ultrasonography combined with CA 125 and CA 19-9 is significant for the preoperative diagnosis and selection of surgical modality for BOTs and could be used as a guideline to achieve good preoperative preparation and avoid secondary surgery.

Ovarian endometriosis with borderline serous tumor: A rare occurrence

Ovarian endometriosis with borderline serous tumor: A rare occurrence

Molecular Status of BRAF Mutation in Epithelial Ovarian Cancer: An Analysis of 57 Cases in the Northeast of Iran.

Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer. Previous studies have elucidated different pathways for the progression of this malignancy. The mutation in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, a member of the MAPK/ERK signaling pathway, plays a role in the development of EOC. The current study aimed to determine the frequency of the BRAF V600E mutation in ovarian serous and mucinous tumors, including borderline and carcinoma subtypes. A total of 57 formalin-fixed paraffin-embedded samples, including serous borderline tumors (SBTs), low-grade serous carcinomas (LGSCs), high-grade serous carcinomas (HGSCs), mucinous borderline tumors (MBTs), and mucinous carcinomas, and 57 normal ovarian tissues were collected. The BRAF V600E mutation was analyzed using polymerase chain reaction (PCR) and sequencing. While 40% of the SBT harbor BRAF mutation, we found no BRAF mutation in the invasive serous carcinoma (P=0.017). Also, there was only 1 BRAF mutation in MBT and no mutation in mucinous carcinomas. In addition, we found no mutation in the control group. The BRAF mutation is most frequent in borderline tumors but not in invasive serous carcinomas. It seems that 2 different pathways exist for the development of ovarian epithelial neoplasms: one for borderline tumors and the other for high-grade invasive carcinomas. Our study supports this hypothesis. The BRAF mutation is rare in mucinous neoplasms.

Serous borderline tumor of ovary with BRCA2 germ line pathogenic variants: a case report

Serous borderline tumor of ovary with <i>BRCA2</i> germ line pathogenic variants: a case report

Integrated multi-omic analysis of low-grade ovarian serous carcinoma collected from short and long-term survivors

BackgroundLow-grade serous ovarian cancer (LGSOC) is a rare disease that occurs more frequently in younger women than those with high-grade disease. The current treatment is suboptimal and a better understanding of the molecular pathogenesis of this disease is required. In this study, we compared the proteogenomic analyses of LGSOCs from short- and long-term survivors (defined as < 40 and > 60 months, respectively). Our goal was to identify novel mutations, proteins, and mRNA transcripts that are dysregulated in LGSOC, particularly in short-term survivors.MethodsInitially, targeted sequencing of 409 cancer-related genes was performed on 22 LGSOC and 6 serous borderline ovarian tumor samples. Subsequently, whole-genome sequencing analysis was performed on 14 LGSOC samples (7 long-term survivors and 7 short-term survivors) with matched normal tissue samples. RNA sequencing (RNA-seq), quantitative proteomics, and phosphoproteomic analyses were also performed.ResultsWe identified single-nucleotide variants (SNVs) (range: 5688–14,833 per sample), insertion and deletion variants (indels) (range: 880–1065), and regions with copy number variants (CNVs) (range: 62–335) among the 14 LGSOC samples. Among all SNVs and indels, 2637 mutation sites were found in the exonic regions. The allele frequencies of the detected variants were low (median12%). The identified recurrent nonsynonymous missense mutations included KRAS, NRAS, EIF1AX, UBR5, and DNM3 mutations. Mutations in DNM3 and UBR5 have not previously been reported in LGSOC. For the two samples, somatic DNM3 nonsynonymous missense mutations in the exonic region were validated using Sanger sequencing. The third sample contained two missense mutations in the intronic region of DNM3, leading to a frameshift mutation detected in RNA transcripts in the RNA-seq data. Among the 14 LGSOC samples, 7754 proteins and 9733 phosphosites were detected by global proteomic analysis. Some of these proteins and signaling pathways, such as BST1, TBXAS1, MPEG1, HBA1, and phosphorylated ASAP1, are potential therapeutic targets.ConclusionsThis is the first study to use whole-genome sequencing to detect somatic mutations in LGSOCs with matched normal tissues. We detected and validated novel mutations in DNM3, which were present in 3 of the 14 samples analyzed. Additionally, we identified novel indels, regions with CNVs, dysregulated mRNA, dysregulated proteins, and phosphosites that are more prevalent in short-term survivors. This integrated proteogenomic analysis can guide research into the pathogenesis and treatment of LGSOC.

Immunohistochemical phenotype of fallopian tubes in patients with different grades of serous ovarian carcinoma

During recent years, there is an accumulating evidence that high grade ovarian carcinoma is developed from the fallopian tube epithelial lesions. However, is not yet completely understood and still represents the subject of investigation. We investigated the immunohistochemical phenotype of matched fallopian tubes from the patients with different types and malignancy grades of ovarian carcinoma. Matched fallopian tubes from ovarian cancer patients were available in 260 cases, including mucinous borderline tumor (n=25), mucinous carcinoma (n=15), serous borderline tumor (n=90), low grade serous carcinoma (n=72) and high grade serous carcinoma (n=48). Immunohistochemical investigation included markers of proliferation (Ki67), apoptosis (Bcl2, p53), hormone receptors (ER, PR), epithelial differentiation (CK7), mesenchymal differentiation (vimentin, calretinin) and stem cells (CD44). The results indicate that the presence of fallopian tube carcinoma in situ is significantly correlated with the presence of high grade ovarian serous carcinoma (r=0.44, p&amp;#60;0.001), whilst there was no significant association with low grade and borderline serous tumors or mucinous tumors.

Ciliated Cells in Ovarian Cancer Decrease with Increasing Tumor Grade and Disease Progression.

Ciliated cell markers expressed in epithelial ovarian cancers (EOC) are associated with improved survival. We examined the distribution of cells expressing ciliated cell markers in various EOC histologies and stages. Immunohistochemistry and/or multiplex immunofluorescence were used to determine the expression of FOXJ1 and/or CAPS (ciliated cell markers) in tissue microarrays including 4 normal fallopian tubes, 6 normal endometria, 16 cystadenomas, 25 borderline tumors, 21 low-grade carcinomas, and 118 high-grade carcinomas (HGSOC) (46 serous, 29 endometrioid, 30 clear cell, 13 mucinous). CAPS+ cells were observed in normal fallopian tubes and endometria and in ~85% of serous benign and borderline tumors and low-grade carcinomas but only in <40% of HGSOC. mRNA data from an independent cohort showed higher FOXJ1 and CAPS expression in serous borderline tumors and low-grade carcinomas compared to HGSOC. In HGSOC, ciliated cell-positive markers were observed in 52% primary tumors compared to 26% of patient-matched synchronous metastases, and 24% metachronous metastases (p = 0.009). mRNA data from an independent HGSOC cohort showed lower levels of CAPS in metastases than in primary tumors (p = 0.03). Overall, the study revealed that ciliated cells were less common in mucinous EOC, the percentage of ciliated cell marker-positive cases decreased with increasing grade, and the percentage of ciliated cells decreased in HGSOC metastases compared to patient-matched primary tumors.

Peritoneal Tumors of Mullerian Origin: A Case Report and Review of the Literature

Primary peritoneal tumors share a common anatomical site and therefore their clinical manifestations are very similar. When peritoneal masses are detected, the tentative initial diagnosis is secondary to metastatic disease, which has been determined most frequently in the peritoneal cavity. However, primary peritoneal tumors should always be included in the differential diagnosis. Among the primary malignant peritoneal neoplasms, mesothelial tumors have been identified (malignant mesothelioma, well-differentiated papillary mesothelioma, benign cystic mesothelioma, adenomatoid tumor of the peritoneum), epithelial-type tumors (primary peritoneal serous carcinoma, primary peritoneal serous borderline tumor), tumors of the smooth muscle (disseminated peritoneal leiomyomatosis) and tumors of uncertain or undetermined origin (desmoplastic small round cell tumor, peritoneal solitary fibrous tumor).

ODP537 A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities

Abstract A 1.6cm Androgen Secreting Ovarian Leydig Cell Tumor Evades Detection on Multiple Imaging Modalities Background: Leydig Cell Tumors can present with marked virilization and yet may evade detection with common imaging modalities. This is a case of a patient with hyperandrogenism due to a 1.6cm ovarian Leydig cell tumor that could not be detected on transvaginal ultrasound, contrast enhanced CT or MRI with contrast. Clinical Case: A 61-year woman presented with virilization. She had a history of a right-sided borderline serous ovarian tumor status post right oophorectomy 23 years prior to presentation and a hysterectomy 16 years prior to presentation. She followed up with gynecologic-oncology for several years but eventually stopped as her condition was stable. On re-presenting to establish care with a gynecologist she complained of increased hair growth on her face, abdomen and buttocks as well as hair loss on the front and top of her scalp. On exam, she was noted to have clitoromegaly with no palpable adnexal masses. Labs revealed total testosterone 398ng/dL (8-60ng/dL), free testosterone 9.15ng/dL (0. 06–0.87ng/dL), 17-hydroxyprogesterone 204ng/dL (&amp;lt;51ng/dL) CA-125 of 6.2U/mL (&amp;lt;=38.1U/mL) and DHEAS 23.1mcg/dL (18.9 – 205mcg/dL). Transvaginal ultrasound showed a left ovary of 3cc with no mass or abnormality. She was referred to endocrinology and a CT abdomen and pelvis with contrast was obtained that again showed no adnexal mass but was notable for a 7mm isoattenuating nodule in the left adrenal gland. Additional labs were obtained including 24 hour urinary cortisol and metanephrines, late night salivary cortisol and serum aldosterone and renin activity, all of which were within normal limits. Suspicion remained high for an ovarian source of the hyperandrogenism so a pelvic MRI with and without contrast was performed which showed a normal appearing left ovary measuring 2.3cm×4.2cm×1.8cm. She was referred to gynecologic-oncology and it was decided to proceed with a left oophorectomy. This was performed and the pathology revealed a 1.6cm Leydig cell tumor in the left ovary. Testosterone and 17-hydroxyprogesterone subsequently normalized when checked seven weeks post-op. Conclusion Leydig cell tumors are rare ovarian tumors often presenting with hyperandrogenism in postmenopausal patients and can be difficult to identify on imaging. A review of published case reports revealed 8 cases in which Leydig cell tumors ranging from 1.2cm to 4.6cm could be detected using one of the imaging modalities employed in this case. There were 9 reports of tumors ranging from 0.8cm to 2cm that evaded detection on imaging. When significant hyperandrogenism is present in a postmenopausal patient a strong suspicion for an ovarian source should be maintained even when imaging is apparently normal. Presentation: No date and time listed

Identification of serous ovarian tumors based on polarization imaging and correlation analysis with clinicopathological features

Ovarian cancer is one of the most aggressive and heterogeneous female tumors in the world, and serous ovarian cancer (SOC) is of particular concern for being the leading cause of ovarian cancer death. Due to its clinical and biological complexities, ovarian cancer is still considered one of the most difficult tumors to diagnose and manage. In this study, three datasets were assembled, including 30 cases of serous cystadenoma (SCA), 30 cases of serous borderline tumor (SBT), and 45 cases of serous adenocarcinoma (SAC). Mueller matrix microscopy is used to obtain the polarimetry basis parameters (PBPs) of each case, combined with a machine learning (ML) model to derive the polarimetry feature parameters (PFPs) for distinguishing serous ovarian tumor (SOT). The correlation between the mean values of PBPs and the clinicopathological features of serous ovarian cancer was analyzed. The accuracies of PFPs obtained from three types of SOT for identifying dichotomous groups (SCA versus SAC, SCA versus SBT, and SBT versus SAC) were 0.91, 0.92, and 0.8, respectively. The accuracy of PFP for identifying triadic groups (SCA versus SBT versus SAC) was 0.75. Correlation analysis between PBPs and the clinicopathological features of SOC was performed. There were correlations between some PBPs ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], rqcross, [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]) and clinicopathological features, including the International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grading, preoperative ascites, malignant ascites, and peritoneal implantation. The research showed that PFPs extracted from polarization images have potential applications in quantitatively differentiating the SOTs. These polarimetry basis parameters related to the clinicopathological features of SOC can be used as prognostic factors.

Use and Accuracy of Intraoperative Frozen Section Analysis for Ovarian Masses in Children and Adolescents

Describe the current practice patterns and diagnostic accuracy of frozen section (FS) pathology for children and adolescents with ovarian masses DESIGN: Prospective cohort study from 2018 to 2021 SETTING: Eleven children's hospitals PARTICIPANTS: Females age 6-21 years undergoing surgical management of an ovarian mass INTERVENTIONS: Obtaining intraoperative FS pathology MAIN OUTCOME MEASURE: Diagnostic accuracy of FS pathology RESULTS: Of 691 patients who underwent surgical management of an ovarian mass, FS was performed in 27 (3.9%), of which 9 (33.3%) had a final malignant pathology. Among FS patients, 12 of 27 (44.4%) underwent ovary-sparing surgery, and 15 of 27 (55.5%) underwent oophorectomy with or without other procedures. FS results were disparate from final pathology in 7 of 27 (25.9%) cases. FS had a sensitivity of 44.4% and specificity of 94.4% for identifying malignancy, with a c-statistic of 0.69. Malignant diagnoses missed on FS included serous borderline tumor (n=1), mucinous borderline tumor (n=2), mucinous carcinoma (n=1), and immature teratoma (n=1). FS did not guide intervention in 10 of 27 (37.0%) patients: 9 with benign FS underwent oophorectomy, and 1 with malignant FS did not undergo oophorectomy. Of the 9 patients who underwent oophorectomy with benign FS, 5 (55.6%) had benign and 4 (44.4%) had malignant final pathology. FSs are infrequently utilized for pediatric and adolescent ovarian masses and could be inaccurate for predicting malignancy and guiding operative decision-making. We recommend continued assessment and refinement of guidance before any standardization of use of FS to assist with intraoperative decision-making for surgical resection and staging in children and adolescents with ovarian masses.

Recurrence and 5-year survival rate in patients with borderline ovarian tumors and related factors in Kurdistan.

The aim of this study was to investigate the recurrence rate and five-year survival in patients with borderline ovarian tumors and related factors. This retrospective cohort study was performed on 20 women diagnosed with a borderline ovarian tumor in Kurdistan province, Iran, between 2007 and 2019. Patients' records were reviewed and a researcher-made questionnaire was completed for each patient, which included demographic and clinical variables related to patient survival. The most common type of ovarian borderline tumor was the serous borderline ovarian tumor (75%). In fifty percent of the cases, cystectomy was used as th treatment. Recurrence was observed in three patients (15%), two of which were treated with cystectomy, and the other case was treated by TAH + BSO method (p = 0.64). There was no significant difference in terms of the type of surgery, history of infertility, history of taking contraceptive pills, age, age at diagnosis, and BMI between the two groups with and without recurrence (p > 0.05). The overall survival rate was 100% and none of the patients died at the end of follow-up. There was no relationship between any of the clinical and demographic variables with disease recurrence, and since all patients were alive after the end of the follow-up period. In summary, it was not possible to assess the relationship between patients' survival rate and studied variables.

Cytohistologic immunohistochemical correlation of epithelial tubo-ovarian neoplasms: Can cell blocks substitute for tissue?

Cytologic specimens often represent the initial diagnostic material for tubo-ovarian neoplasms resulting from therapeutic paracentesis for patients presenting with high-volume ascites. However, subtyping and immunohistochemical (IHC) characterization, which have implications in preoperative management and downstream ancillary testing, are not routinely performed in many institutions. This study aims to perform cytohistologic correlation of commonly used IHC stains to establish their reliability in peritoneal fluids/washing specimens. A retrospective search of the laboratory information systems was performed to identify peritoneal fluid/washing specimens involved by borderline or malignant epithelial tubo-ovarian neoplasms and concurrent/subsequent surgical resection specimens. Cell blocks and tissue were stained for PAX8, WT-1, p53, p16, Napsin-A, estrogen receptor, and progesterone receptor, and staining between cytological and surgical specimens was compared. A total of 56 case pairs were included, with the following final diagnoses on histological examination: 37 high-grade serous carcinomas, eight clear cell carcinomas, one endometrioid adenocarcinoma, two low-grade serous carcinomas, and eight serous borderline tumors. There was perfect cytohistologic correlation for PAX8 (Lin's concordance correlation coefficient [LINCCC]=1.00) and WT-1 (LINCCC=1.00), substantial/good correlation for p53 (LINCCC=0.96), p16 (LINCCC=0.93), napsin-A (LINCCC=0.91) and ER (LINCCC=0.77), and moderate correlation for PR (LINCCC=0.54). Immunohistochemical correlation between peritoneal fluid and surgical resection specimens for tubo-ovarian neoplasms is high. Common subtypes of tubo-ovarian carcinomas can be reliably distinguished on fluids using IHC.

Serous Borderline Tumor of the Fallopian Tube: A Case Report and Literature Review

Paratubal cysts account for 5-20% of all adnexal lesions. Malignant modifications seldom arise in the paratubal cysts that are usually known as primary carcinomas of fallopian tube. Paratubal borderline tumors are very infrequent conditions and until now only sixteen cases of primary paratubal borderline tumors have been previously reported in the literature. Herein, we describe a rare paratubal serous borderline tumor occurring in a woman of reproductive age and provide insights into its management. A 32-year-old woman referred to Imam Hussein Hospital, Tehran with chief complaint of amenorrhea for the last year and transvaginal sonography (TVS) report indicating a 68×74 mm persistent right adnexal cyst from 10 months ago. The patient was candidate for laparotomy and due to the report of paratubal serous borderline tumor in frozen section she underwent right total salpingectomy and infracolic omentectomy. No evidence of recurrence or metastasis was observed after 3 years of follow up. Persistent adnexal cysts need to be evaluated precisely even in young women in order to rule out the malignancy of fallopian tubes.

Computational tumor stroma reaction evaluation led to novel prognosis-associated fibrosis and molecular signature discoveries in high-grade serous ovarian carcinoma.

BackgroundAs one of the key criteria to differentiate benign vs. malignant tumors in ovarian and other solid cancers, tumor-stroma reaction (TSR) is long observed by pathologists and has been found correlated with patient prognosis. However, paucity of study aims to overcome subjective bias or automate TSR evaluation for enabling association analysis to a large cohort.Materials and methodsServing as positive and negative sets of TSR studies, H&E slides of primary tumors of high-grade serous ovarian carcinoma (HGSOC) (n = 291) and serous borderline ovarian tumor (SBOT) (n = 15) were digitally scanned. Three pathologist-defined quantification criteria were used to characterize the extents of TSR. Scores for each criterion were annotated (0/1/2 as none-low/intermediate/high) in the training set consisting of 18,265 H&E patches. Serial of deep learning (DL) models were trained to identify tumor vs. stroma regions and predict TSR scores. After cross-validation and independent validations, the trained models were generalized to the entire HGSOC cohort and correlated with clinical characteristics. In a subset of cases tumor transcriptomes were available, gene- and pathway-level association studies were conducted with TSR scores.ResultsThe trained models accurately identified the tumor stroma tissue regions and predicted TSR scores. Within tumor stroma interface region, TSR fibrosis scores were strongly associated with patient prognosis. Cancer signaling aberrations associated 14 KEGG pathways were also found positively correlated with TSR-fibrosis score.ConclusionWith the aid of DL, TSR evaluation could be generalized to large cohort to enable prognostic association analysis and facilitate discovering novel gene and pathways associated with disease progress.

Morphological Types of Epithelial Origin Ovarian Tumours

Aim: To assess the various morphological types of epithelial origin ovarian tumors. Methods: The study involved cases that were presented to the Pathology department between January 2015 to December 2020. Epithelial ovarian tumors that were diagnosed as either benign, borderline, or malignant were analyzed. The inclusion criteria involved pathological specimens of ovarian tumors consisting of cells that are epithelial in origin. Clinical records, ultrasounds, and histopathological investigations of the patients were accessed from the hospital database for analysis. Results: A total of 309 cases were reviewed. Out of these, ovarian epithelial tumors made up at least four-fifths of the total tumors i.e. 258(83.5%). Non-epithelial origin of ovarian tumors only consisted of 51(16.5%) cases. Out of these 153(49.84%) cases were diagnosed as serous, 88(28.48%) as mucinous. A total of 175(61.4%) tumors were benign, 15(5.81%) were borderline, and 68 (26.3%) were malignant. The patients with malignant serous tumors (43.24±13.99 years) were considerably older than individuals with benign (34.54 ± 13.16 years) and borderline (32.71±13.79 years) serous tumors. Conclusion: The present study concludes that epithelial ovarian cancer is the most commonly encountered lesion in our population. Benign and borderline tumors involve slightly younger age groups, mostly below forty years of age. Keywords: Carcinoma, Epithelial-origin tumors, malignancy, ovarian tumors

Effect of Two-Port Laparoscopic Surgery on Pregnancy Outcomes of Patients with Concurrent Adnexal Masses.

Adnexal masses are common in pregnancy, with 2–10% of pregnancies presenting with an ovarian mass and approximately 1–6% of these masses being malignant. For suspected malignancy or masses with symptoms, surgery must be performed as early as possible. We retrospectively investigated the effect of two-port laparoscopic surgery on the outcomes of patients with concurrent adnexal masses between 2012 and 2019 (including large mucinous tumor, large teratoma, serous borderline tumor, and heterotopic pregnancy). Laparoscopic right partial oophorectomy was performed for a 27 cm ovarian mucinous tumor at a gestational age (GA) of 21 weeks, laparoscopic right oophorocystectomy for an 18 cm teratoma at a GA of 10 weeks, and laparoscopic left salpingo-oophorectomy for a 7 cm serous borderline tumor at a GA of 7 weeks after ultrasonographic confirmation of an intrauterine gestational sac with a fetal heartbeat. Laparoscopic excision of a tubal pregnancy was performed in a heterotopic pregnancy at a GA of 12 weeks with massive internal bleeding. Laparoscopic surgery is easier and safe to perform during early pregnancy because a smaller uterus allows for superior visualization. All of these patients had optimal postoperative recovery and normal spontaneous delivery at term. We discussed several aspects of treatment and delivery, namely treatment option (expectant management or surgery), surgery timing (early or advanced pregnancy), surgery type (laparoscopy or laparotomy), and delivery route (normal spontaneous delivery or cesarean section), in patients with concurrent adnexal tumors and their effects on pregnancy outcomes.

The clinical course of women who undergo contemporary management of stage ll-lV low grade serous carcinoma (524)

The clinical course of women who undergo contemporary management of stage ll-lV low grade serous carcinoma (524)

A diagnostic approach to paratesticular lesions with tubulopapillary architecture: a series of 16 serous borderline tumors/low-grade serous carcinoma and 14 well-differentiated papillary mesothelial tumors and mesothelioma

As there is limited literature on paratesticular tumors of müllerian and mesothelial origin, we reviewed archived cases of serous borderline tumors (n=15), low-grade serous carcinoma (n=1), well-differentiated papillary mesothelial tumors (WDPMTs; n=2), and mesothelioma (n=12), for relevant clinicopathologic features. Molecular profiling data from the American Association for Cancer Research (AACR) GENIE registry was accessed for 8 additional patients with testicular mesothelioma. For tumors of mesothelial origin, the median age at surgical excision was 62 years, the median size was 4.5cm, and they consistently exhibited positivity for mesothelial markers (CK5/6, calretinin, WT1, and D2-40). Recurrent alterations of the NF2 gene were identified in 3 of 8patients (38%), and alterations of BAP1 and CDKN2A were relatively infrequent. While one patient with WDPMT had a recurrence, a second patient with WDPMT progressed to a biphasic mesothelioma 2 years after initial resection. For tumors of müllerian origin, the median age at surgical excision was 45 years, the median size was 2.5cm, and these exhibited consistent positivity for ER, WT1, and PAX8. Although no recurrences were documented in patients with serous borderline tumors, a single patient with a low-grade serous carcinoma developed widely metastatic disease and died of disease-related complications. Our study emphasizes the need for close clinical follow-up in patients with WDPMT and highlights the prognostic significance of documenting invasive behavior in tumors of müllerian origin as they can have an aggressive clinical course. Finally, our results suggest that NF2 alterations may play an important role in the pathogenesis of testicular mesothelioma.

Differential epithelial and stromal LGR5 expression in ovarian carcinogenesis

Lgr5 has been identified as a marker of the stem/progenitor cells in the murine ovary and oviduct by lineage tracing. However, little is known regarding LGR5 expression or its functional significance in human ovary tissues. Here, using RNA in situ hybridization and/or immunohistochemistry, we thoroughly investigated LGR5 expression in normal human ovaries, fallopian tubes and various ovarian tumors. We discovered that LGR5 expression is negligible in the human ovary surface epithelium, whereas ovarian stromal cells normally express low levels of LGR5. Remarkably, fallopian tube epithelium, inclusion cysts and serous cystadenomas with a Müllerian phenotype expressed high levels of LGR5, and LGR5 expression was restricted to PAX8+/FOXJ1− secretory cells of the tubal epithelium. Strong stromal LGR5 expression without epithelial LGR5 expression was consistently observed in the path from serous cystadenoma to serous borderline tumor to low grade serous carcinoma (LGSC). Unlike LGSC, high grade serous carcinoma (HGSC), clear cell carcinoma, endometrioid carcinomas displayed various epithelial-stromal LGR5 expression. Notably, high levels of LGR5 expression were observed in serous tubal intraepithelial carcinoma, which slightly declined in invasive HGSC. LGR5 expression was significantly associated with improved progression-free survival in HGSC patients. Moreover, in vitro assays demonstrated that LGR5 expression suppressed tumor proliferation and migratory capabilities. Taken together, these findings indicate a tumor-suppressive role for LGR5 in the progression of HGSC.