The association between sonographic features and clinical symptoms of adenomyosis.

PURPOSE: To investigate the association of sonographic features and clinical symptoms of adenomyosis. METHODS: This was a prospective observational study. Only reproductive age women who underwent standardized transvaginal ultrasound examination were included. The diagnosis of adenomyosis was based on sonographic features proposed by Morphological Uterus Sonographic Assessment (MUSA) group. Pictorial blood loss assessment chart (PBAC) and numerical rating scale (NRS) were respectively used for the evaluation of menstrual bleeding and pain. RESULTS: Fifty-three women were recruited. Adenomyosis group consisted of 33 (62.3%) representative cases, whereas control group consisted of 20 (37.7%). Women with adenomyosis experienced significantly heavier menstrual bleeding (p = 0.008) and more painful menstrual periods (p = 0.003). Significant positive correlation between the number of sonographic adenomyosis features and both PBAC (r = 0.613, p < 0.001) and NRS scores (r = 0.402, p = 0.022) was found. PBAC score was significantly higher if either fan-shaped shadowing (r = 0.548, p = 0.001), interrupted junctional zone (JZ) (r = 0.548, p = 0.001) or globular uterus (r = 0.445, p = 0.011) was detected. Interrupted JZ (r = 0.440, p = 0.012) was associated with higher NRS score. Significant positive correlation between PBAC score and adenomyosis spread in uterine layers (r = 0.495, p = 0.004) was established. CONCLUSION: Certain sonographic features of adenomyosis and assessment of its involvement in uterine layers may predict the severity of adenomyosis symptoms.

Visualization Methods for Uterine Sentinel Lymph Nodes in Early-Stage Endometrial Carcinoma: A Comparative Analysis.

BACKGROUND: Sentinel lymph node (SLN) biopsy in early-stage endometrial cancer is recommended over systematic lymphadenectomy due to reduced morbidity and comparable detection rates. The main objective of this study was to compare the overall and bilateral detection rates of SLN in early-stage endometrial cancer using three techniques. METHODS: a prospective cohort study was designed to detect the difference in SLN detection rate in three cohorts: Indocyanine green (ICG), methylene blue (MB), and tracer combination (ICG + MB). Mapping characteristics, detection rate, number of SLNs, and positive SLNs of the three cohorts were compared. RESULTS: A total of 99 patients were enrolled. A total of 109 SLN sites with 164 lymph nodes were detected. No differences were found between the three cohorts in terms of age, BMI, tumor diameter, or other histologic characteristics. The overall SLN detection rate (DR) was 54.3% in the MB group, 72.7% in ICG, and 80.6% in the ICG-MB group. Bilateral DR was 22.9%, 39.4%, and 54.8% in groups, respectively, with the MB method yielding significantly inferior results. CONCLUSIONS: The ICG-MB group demonstrated superior overall and bilateral detection rates, but a significant difference was found only in the MB cohort. Combining tracer agents can enhance the accuracy of SLN identification in initial-stage endometrial cancer without additional risk to the patient.

Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100.

OBJECTIVE: This prespecified exploratory analysis evaluated the association of gene expression signatures, tumor mutational burden (TMB), and multiplex immunohistochemistry (mIHC) tumor microenvironment-associated cell phenotypes with clinical outcomes of pembrolizumab in advanced recurrent ovarian cancer (ROC) from the phase II KEYNOTE-100 study. METHODS: Pembrolizumab-treated patients with evaluable RNA-sequencing (n = 317), whole exome sequencing (n = 293), or select mIHC (n = 125) data were evaluated. The association between outcomes (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) and gene expression signatures (T-cell-inflamed gene expression profile [TcellinfGEP] and 10 non-TcellinfGEP signatures), TMB, and prespecified mIHC cell phenotype densities as continuous variables was evaluated using logistic (ORR) and Cox proportional hazards regression (PFS; OS). One-sided p-values were calculated at prespecified α = 0.05 for TcellinfGEP, TMB, and mIHC cell phenotypes and at α = 0.10 for non-TcellinfGEP signatures; all but TcellinfGEP and TMB were adjusted for multiplicity. RESULTS: No evidence of associations between ORR and key axes of gene expression was observed. Negative associations were observed between outcomes and TcellinfGEP-adjusted glycolysis (PFS, adjusted-p = 0.019; OS, adjusted-p = 0.085) and hypoxia (PFS, adjusted-p = 0.064) signatures. TMB as a continuous variable was not associated with outcomes (p > 0.05). Positive associations were observed between densities of myeloid cell phenotypes CD11c+ and CD11c+/MHCII-/CD163-/CD68- in the tumor compartment and ORR (adjusted-p = 0.025 and 0.013, respectively). CONCLUSIONS: This exploratory analysis in advanced ROC did not find evidence for associations between gene expression signatures and outcomes of pembrolizumab. mIHC analysis suggests CD11c+ and CD11c+/MHCII-/CD163-/CD68- phenotypes representing myeloid cell populations may be associated with improved outcomes with pembrolizumab in advanced ROC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02674061.

Ovarian Leydig Cell Tumor and Ovarian Hyperthecosis in a Postmenopausal Woman: A Case Report and Literature Review.

Ovarian Leydig cell tumor is a rare type of ovarian steroid cell neoplasms, presenting in only 0.1% of all ovarian tumor cases, and is generally androgen-secreting and unilateral. Although they are often malignant non-spreading tumors, which have excellent prognosis, benign ovarian Leydig cell tumors with low-risk malignancy can be also detected. Ovarian hyperthecosis is a rare non-neoplastic disorder, in most cases bilateral. Ovarian tumors and ovarian hyperthecosis are one of the main causes of hyperandrogenism in postmenopausal women, a condition strongly associated with both hormonal and metabolic changes. Here, we report a 65-year-old patient with complaints of excessive body hairiness and alopecia. The laboratory investigation showed increased levels of serum testosterone and dehydroepiandrosterone sulfate (DHEA-S). Imaging, including transvaginal ultrasound and pelvic MRI revealed the presence of two masses in the ovaries. The patient underwent a laparoscopic bilateral salpingo-oophorectomy due to the ovarian tumors unknown etiology, and histopathological examination revealed a unilateral benign left ovarian Leydig cell tumor with bilateral ovarian stromal hyperplasia and ovarian hyperthecosis. Making differential diagnosis between ovarian tumors and ovarian hyperthecosis is difficult. Bilateral salpingo-oophorectomy is the treatment of choice in postmenopausal women with benign Leydig cell ovarian tumor, as well as ovarian hyperthecosis, as it offers both a cure and diagnostic confirmation.

Multiple Rare Primary Malignancies: A Mixed Squamous Neuroendocrine Adenocarcinoma of the Cervix, Metastasized Carcinosarcoma and Extramammary Vulvar Paget's Disease Case Report.

The occurrence of more than one primary malignant tumor in a single patient is rare. Multiple primary malignancies can pose difficulties in differential diagnosis between primary tumors and metastasis. Here, we present a case report with multiple primary malignancies. The patient is a 45-year-old female who was diagnosed with cervical mixed squamous neuroendocrine adenocarcinoma, metastasized carcinosarcoma and extramammary vulvar Paget's disease. The patient was first diagnosed with a microinvasive squamous cervical carcinoma in situ. After a few months, the amputation of a small residual tumor and histological evaluation revealed an IA1-stage poorly differentiated (G3) mixed squamous and neuroendocrine cervical adenocarcinoma. After two years, the disease had progressed and biopsies from altered sites were taken. Histological diagnosis from an ulcerated vulvar region revealed extramammary vulvar Paget's disease. A biopsy from vagina polyp revealed an earlier diagnosed mixed squamous and neuroendocrine cervical adenocarcinoma. However, histological diagnosis from an inguinal lymph node biopsy was unexpected and revealed carcinosarcoma. It indicated either the development of another primary malignancy, or an unusual spread of metastasis. Clinical presentation as well as diagnostic and treatment challenges are discussed in this case report. This case report shows that multiple primary malignancy cases are difficult to manage both for clinicians and the patient because the therapeutic options can become limited. This complex case was managed by a multidisciplinary team.

Quality of Life in Cervical Cancer Survivors Treated with Concurrent Chemoradiotherapy.

Background and Objectives: Cervical cancer is the fourth most common cancer in women globally. As survival rates gradually increase, it becomes necessary to assess the quality of life (QoL) after treatment. It is known that different treatment modalities have different effects on QoL. Therefore, we aimed to evaluate the QoL of cervical cancer survivors (CCSs) treated with concurrent chemoradiotherapy (CCRT). Materials and Methods: A cross-sectional monocentric study, conducted in Vilnius university hospital Santaros klinikos between November 2018 and November 2022, included 20 women, who were interviewed once using the European Organization for Research and Treatment of Cancer (EORTC)-designed Quality-of-Life questionnaire cervical cancer module (QLQ-CX24). The sociodemographic and clinical data as well as the results of the questionnaire are presented in mean, standard deviation and percentages. The QoL scores were compared between different age and stage groups using the Mann-Whitney U test. Results: Twenty participants, aged from 27 to 55 years, with a mean age of 44 years (SD = 7.6) participated in the study. All the participants were CCSs with an International Federation of Gynecology and Obstetrics (FIGO) stage from IB to IIIB and all of them were treated with CCRT. The symptom experience was relatively low and revealed a good result (21.8, SD = 10.2). Mean scores on body image, sexual/vaginal functioning, menopausal symptoms and sexual worry scales indicated moderate functioning and a moderate level of some of the cervical cancer specific symptoms after CCRT. Sexual activity and sexual enjoyment of the CCSs were low (11.7 (SD = 16.3), 14.3 (SD = 17.8), respectively). Conclusions: Cervical cancer survivors report a relatively good quality of life regarding symptom experience; however, women following concurrent chemoradiotherapy tend not to be sexually active and rarely feel sexual enjoyment. In addition, this treatment modality negatively affects a woman's body image and self-perception as a woman.

Laparoscopic Radical Trachelectomy after Neoadjuvant Chemotherapy for Fertility Preservation in Early-Stage Bulky Cervical Cancer: A Case Report and Literature Review.

Management of early-stage cervical cancer (CC) in young women often faces challenges to preserve fertility, as well as to achieve an adequate oncological outcome. Although existing evidence supports a fertility-sparing treatment in the case of tumors <2 cm in diameter, the approach is less clear in bulky early-stage CC. In addition, the outcomes of radical trachelectomy performed by minimally invasive techniques are also highly debatable. Highlighting the high incidences of young women with early-stage CC, the lack of sufficient data raises considerable hindrances towards the proper counseling of this vulnerable patient group. In this report, a case of a young woman with bulky early-stage CC with a strong desire to preserve fertility is presented. A satisfactory oncological outcome was achieved after neoadjuvant chemotherapy followed by laparoscopic radical trachelectomy. Ongoing prospective trials are expected to provide stronger evidence on this topic.

Caesarean Scar Pregnancy: A Case Report.

Caesarean scar pregnancy is a potentially life-threatening gynaecological condition, becoming more common due to steadily increasing rate of caesarean sections worldwide. More than one-third of women presenting with caesarean scar pregnancy are asymptomatic, but over the time if left untreated this condition can lead to the uterine rupture and massive maternal haemorrhage. Therefore it is necessary to diagnose and manage caesarean scar pregnancies properly at the beginning of the first trimester. We present the case of woman with three previous caesarean sections, who was diagnosed with complicated caesarean scar pregnancy and then successfully managed using surgical intervention.

Bowel Rest with Total Parenteral Nutrition as an Alternative to Diverting Ileostomy in High-Risk Colorectal Anastomosis: A Pilot Study.

Anastomotic leakage remains the most feared complication in colorectal surgery. Various intraoperative tests evaluate bowel perfusion and mechanical integrity of the colorectal anastomosis. These tests reduce the risk of postoperative anastomotic leakage; however, the incidence remains high. Diverting loop ileostomy mitigates the damage if anastomotic leakage occurs. Nevertheless, ileostomy has a significant rate of complications, reducing patients' quality of life, and requiring an additional operation. We evaluated six consecutive cases where bowel rest with total parenteral nutrition was used instead of diverting loop ileostomy. All colorectal anastomoses were at high risk of postoperative anastomotic leakage. Total parenteral nutrition was administered for the first seven days postoperatively. There were no serious complications during the recovery period, and no clinical postoperative anastomotic leakage was detected. All patients tolerated total parenteral nutrition. Bowel rest with total parenteral nutrition may be a feasible option in high-risk left-sided colorectal anastomosis and a possible alternative to a preventive loop ileostomy. Further studies are necessary to evaluate it on a larger scale.

Retrospective Comparison of Laparoscopic versus Open Radical Hysterectomy for Early-Stage Cervical Cancer in a Single Tertiary Care Institution from Lithuania between 2009 and 2019.

Background and Objectives: A great debate within the academic arena was evoked by the LACC study, giving rise to doubt regarding the oncological outcomes of the laparoscopic approach for early-stage cervical cancer. This encouraged us to conduct a retrospective analysis of CC treatment surgical approaches applied to the patients at tertiary level Vilnius University Hospital Santaros Clinics, Vilnius, Lithuania, between 2009 and 2019. Materials and Methods: The retrospective study was carried out to evaluate the outcomes after 28 laparoscopic and 62 laparotomic radical hysterectomies for early cervical cancer in a single tertiary care institution performed during the period 2009-2019. For statistical analysis of patients' parameters, SPSS v. 17.0 was applied, together with the Kaplan-Meier method with a long-rank test and the Cox proportional hazard regression model used for bi-variate analysis determining OS outcomes between MIS and open-surgery groups. Results: After computing data with the Cox regression model, there was no significant difference of the 36-months overall survival between laparoscopy and laparotomy groups, as opposed to the LACC study. Conclusions: Our tertiary institution faces a considerable challenge, and we acknowledge the limitations of the study and also feel a responsibility to follow the latest guidelines. Currently, it appears that the most substantial attention should be focused on the cessation of uterine manipulator use as well as laparoscopic technique learning curves.

Cytokeratin Expression Pattern in Human Endometrial Carcinomas and Lymph Nodes Micrometastasis: a Mini-review.

Cytokeratins (CKs) are the largest subgroup of intermediate filament proteins, preferentially expressed in epithelial tissues. CKs play a critical role in determining epithelial structural integrity under stressful conditions in addition to their various fundamental functions in cellular proliferation, apoptosis, migration, adherence and molecular signaling. Immunohistochemical CKs staining could be evaluated with a proper comprehension of their task limitations and their association with the normal morphology to avoid misdiagnosis. Herein, we critically review the CKs expression patterns in ECs in relation to clinicopathological features and patients' outcome. We also briefly discussed the recent advantage of CKs immunohistochemical staining in the detection of EC micrometastasis.

Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis.

PURPOSE: After risk-reducing salpingo-oophorectomy (RRSO), BRCA1/2 pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO. METHODS: Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a BRCA-PV with and without STIC at RRSO until September 2020. Primary outcome was the hazard ratio for the risk of PC between BRCA-PV carriers with and without STIC at RRSO, and the corresponding 5- and 10-year risks. Primary analysis was based on a one-stage Cox proportional-hazards regression with a frailty term for study. RESULTS: From 17 studies, individual patient data were available for 3,121 women, of whom 115 had a STIC at RRSO. The estimated hazard ratio to develop PC during follow-up in women with STIC was 33.9 (95% CI, 15.6 to 73.9), P < .001) compared with women without STIC. For women with STIC, the five- and ten-year risks to develop PC were 10.5% (95% CI, 6.2 to 17.2) and 27.5% (95% CI, 15.6 to 43.9), respectively, whereas the corresponding risks were 0.3% (95% CI, 0.2 to 0.6) and 0.9% (95% CI, 0.6 to 1.4) for women without STIC at RRSO. CONCLUSION: BRCA-PV carriers with STIC at RRSO have a strongly increased risk to develop PC which increases over time, although current data are limited by small numbers of events.

Acute Presentation of Large Size Clear Cell Ovarian Carcinoma as Double Torsed Ovarian Tumor.

We report a 46-year-old patient who presented to the emergency department with complaints of acute abdominal pain, nausea, and vomiting. An abdominal CT scan revealed a large (207 × 155 × 182 mm) thin-walled inhomogeneous tumor connected to the uterus and right ovary. Emergency surgery laparotomy was performed. Inside the abdominal cavity, a 30 × 30 cm heterogenous, dark blue tumor in the right adnexa area, torsed two times, weighing 3700 g was found. Histological examination revealed right ovary clear cell carcinoma. We emphasize the rare nature of the histology and presentation of this case report. Ovarian clear cell carcinomas are relatively rare malignancies, presenting in 5 to 10% of ovarian malignant tumors in the west.

Uterine Arteriovenous Malformation Treated with Selective Embolisation of Uterine Arteries: A Case Report.

Uterine arteriovenous malformation (AVM) is a very rare gynaecological condition, which can potentially lead to life-threatening abnormal uterine bleeding. In most cases uterine AVM is associated with prior pregnancy or pelvic surgery. We present the case of young woman seven weeks after medical termination of pregnancy diagnosed with heavy uterine bleeding due to uterine AVM, which was successfully treated with selective embolisation of uterine arteries.

Failure of multiple surgical procedures and adjuvant chemotherapy in early-stage steroid-cell ovarian tumor treatment: a case report and literature review.

Ovarian steroid-cell tumors (SCTs) are a rare subgroup of sex-cord tumors of the ovary, accounting for less than 0.1% of all ovarian tumors. Not otherwise specified (NOS) tumors are the most common subtype. More than half of patients with SCTs-NOS show hyperandrogenic symptoms. The primary treatment for SCTs is surgery, as most cases are early-staged and benign. Because of the low incidence of metastatic disease, there is insufficient reliable information on the role of adjuvant therapy and the most effective treatment regimen. In this report, a rare case of a recurrent SCT-NOS in a 36-year-old female patient without endocrine symptoms is presented, highlighting the significance of appropriate pathological evaluation and immunohistochemical testing for the accurate diagnosis of this malignancy, particularly in the case of hormonally "silent" tumors. The metastatic tumor described here showed no response to four courses of adjuvant chemotherapy after several debulking surgeries. Based on the clinical findings, the neoplastic etiology should always be considered during the resection of ovarian tumors to prevent possible disease dissemination due to inappropriate surgical techniques.

The incidence of occult ovarian neoplasia and cancer in BRCA1/2 mutation carriers after the bilateral prophylactic salpingo-oophorectomy (PBSO): A single-center prospective study.

BACKGROUND: Due to ineffective ovarian cancer (OC) screening programs, prophylactic bilateral salpingo-oophorectomy (PBSO) is suggested for BRCA1/2 genes mutation carriers. The reported incidence of clinically occult neoplasia and OC detected during PBSO varies widely (2-17 %), reflecting differences in studies design. OBJECTIVE: We aimed to prospectively evaluate the incidence of occult neoplasia in specimens collected during PBSO performed in a single tertiary center and to determine the effectiveness of this procedure in BRCA1/2 mutation carriers. STUDY DESIGN: Between January 2010 and October 2016 a total of 564 new germline BRCA1/2 mutation positive women were identified and 71 carriers underwent laparoscopic PBSO. Patients were prospectively followed-up after the surgery and data on operation, age, complications, histological reports and BRCA1/2 gene mutation types were collected and analyzed. RESULTS: Serous tubal intraepithelial carcinoma (STIC) was diagnosed in 7 (9.85 %) and OC in 4 (5.6 %) women (one advanced (FIGO IIIC) and 3 early (FIGO IA/C) stages); total incidence 15.5 %. Women's mean age at the time of surgery was 46.5 years. The mean age of women diagnosed with STIC and OC was 45.9 years (42-64). The mean follow up time for women being diagnosed with OC/STIC was 3.72 years; no recurrence was observed. The median time to perform laparoscopic PBSO was 43 min. (ranging from 25 to 65 min.), no surgical complications occurred during this operation. Interestingly, we found statistically significant (P = 0.0105) enrichment of STIC lesions in BRCA1 c.4035delA (an established Baltic founder mutation) carriers group. CONCLUSION: The incidence of pathological findings in BRCA1/2 mutation carries after PBSO is sufficiently high and our prospective study data supports PBSO as the most effective measure for reducing the risk of OC in BRCA1/2 mutation carriers. A novel finding of the enrichment of STIC lesions in BRCA1 c.4035delA carriers may show important biological differences in OC tumorigenesis between different BRCA1 mutations, which warrant further investigations.

The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases.

Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2-4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.

Common bile duct villous adenoma: a case report and review of the literature.

BACKGROUND: According to the literature, benign bile duct tumors are exceedingly uncommon. To the best of our knowledge, we report the largest extrahepatic bile duct villous adenoma described in the literature. CASE PRESENTATION: We present a case of a 77-year-old Caucasian woman with obstructive jaundice. Laboratory tests revealed that she had elevated bilirubin and liver enzyme levels. A computed tomographic scan showed a homogeneous 5 × 3-cm mass obstructing the common bile duct. The results of brush cytology were consistent with a bile duct villous papilloma. However, on the basis of the tumor's radiological features, a preliminary diagnosis of extrahepatic bile duct malignant tumor was made. After discussion among the multidisciplinary team, a surgical resection of the bile duct tumor was performed. Histopathological examination confirmed a villous adenoma. The patient's postoperative course was uneventful. CONCLUSIONS: In patients with bulky extrahepatic bile duct tumors, surgical resection alone may be safe and curative.

Successful treatment of advanced stage yolk sac tumour of extragonadal origin: a case report and review of literature.

BACKGROUND: Yolk sac tumour diagnosis should be considered for young age patients admitted to the hospital with non-specific complaints of widespread disease. Correct diagnosis and carefully planned treatment is the key to a successful outcome. METHODS AND MATERIALS: We present a rare case of a widespread yolk sack tumour of a uterine broad ligament. Our team directed a special attention towards the patient's young age, advanced disease, and fertility sparing strategy of treatment. RESULTS AND CONCLUSIONS: Stage IV yolk sac tumours of extragonadal origin are rarely reported in the literature. Hence, diagnosis and treatment often pose a challenge for emergency care unit doctors, gynaecologists, and oncologists. However, it can be a potentially curable disease. Moreover, patients' fertility can also be preserved. We believe that further analysis of similar cases is necessary to study outcomes and evaluate patients' responses to a sequence of medical decisions taken for this specific case.

Prevalence of the BLM nonsense mutation, p.Q548X, in ovarian cancer patients from Central and Eastern Europe.

A nonsense mutation, p.Q548X, in the BLM gene has recently been associated with an increased risk for breast cancer. In the present work, we investigated the prevalence of this Slavic founder mutation in 2,561 ovarian cancer cases from Russia, Belarus, Poland, Lithuania or Germany and compared its frequency with 6,205 ethnically matched healthy female controls. The p.Q548X allele was present in nine ovarian cancer patients of Slavic ancestry (0.5 %; including one case with concurrent BRCA1 mutation). The mutation was not significantly more frequent in cases than in controls (Mantel-Haenszel OR 1.14, 95 % CI 0.49; 2.67). Ovarian tumours in p.Q548X carriers were mainly of the serous subtype, and there was little evidence for an early age at diagnosis or pronounced family history of cancer. These findings indicate that the BLM p.Q548X mutation is not a strong risk factor for ovarian cancer.