Synergy of the microRNA Ratio as a Promising Diagnosis Biomarker for Mucinous Borderline and Malignant Ovarian Tumors.

Epithelial ovarian cancers (EOCs) are a heterogeneous collection of malignancies, each with their own developmental origin, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis and a 5-year survival of 11% for advanced stages (III/IV). At the early stages, these malignant forms are clinically difficult to distinguish from borderline (15%) and benign (80%) forms with a better prognosis due to the large size and heterogeneity of mucinous tumors. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in tumor progression and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, the comparison of miRNA microarray expression profiles between malignant and borderline tumor FFPE samples identified 10 down-regulated and 5 up-regulated malignant miRNAs, which were validated by individual RT-qPCR. To overcome normalization issues and to improve the accuracy of the results, a ratio analysis combining paired up-regulated and down-regulated miRNAs was performed. Although 21/50 miRNA expression ratios were significantly different between malignant and borderline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 pairs of miRNA ratios (double ratio) showed high discriminatory potential, with 100% of accuracy in distinguishing malignant and borderline ovarian tumors, which suggests that miRNAs may hold significant clinical potential as a diagnostic tool. In summary, these ratio miRNA-based signatures may help to improve the precision of histological diagnosis, likely to provide a preoperative diagnosis in order to adapt surgical procedures.

Primary squamous cell carcinoma of the ovary accompanied by transition of a mucinous borderline ovarian tumor.

This report describes a woman with a rare primary squamous cell carcinoma of the ovary accompanied by transition of a mucinous borderline ovarian tumor. A woman in her late 40s was referred for abdominal discomfort, which worsened during defecation. Pelvic magnetic resonance imaging showed a multiloculated cystic lesion in the left adnexa measuring approximately 7.5 × 9.5 × 7.0 cm. An intraoperatively obtained frozen biopsy sample of the mass in the left ovary was positive for malignancy, resulting in a surgical staging operation. The tumor was composed of squamous cell carcinoma and mucinous borderline tumor. There was no evidence of capsular invasion or invasion of other internal organs, including pelvic and para-aortic lymph nodes (0/41). Immunohistochemistry showed that the tumor was diffusely positive for cytokeratin 7, cytokeratin 20, Ki-67, and P40 but negative for P16. After a debulking operation, the patient has been monitored regularly without adjuvant therapy owing to final surgical staging of the tumor as stage IA.

Progression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review.

STUDY OBJECTIVE: To study the progression of benign ovarian lesions to mucinous borderline ovarian tumors (mBOTs); analyze the clinicopathologic features, diagnosis, and management of mBOTs in pediatric and adolescent girls; and provide a review of the literature on mBOTs in this population. DESIGN: Retrospective chart review of female adolescents younger than 18 years diagnosed with mBOTs between July 2017 and February 2021. SETTING: Yale New Haven Hospital, New Haven, Connecticut; and Yale New Haven Health Bridgeport Hospital, Bridgeport, Connecticut. PARTICIPANTS: Three female patients diagnosed with mBOTs between ages 12 and 17 years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinical presentation, preoperative characteristics, surgical technique, histology, tumor stage, treatment, progression, outcome, and rate of recurrence. RESULTS: Three adolescent patients were identified to have mBOTs. All three patients presented with a chief complaint of abdominal pain. One of the 3 patients was premenarchal at presentation. Two of the 3 patients were initially diagnosed with a mucinous cystadenoma and had recurrences of an ovarian cyst in the same ovary within 5 and 17 months, respectively. Pathology of the recurrent cyst was consistent with mBOT. Two of the 3 patients initially underwent cystectomy, and all ultimately had a unilateral salpingo-oophorectomy. Subsequent surveillance over 2 to 4 years found no evidence of disease recurrence. CONCLUSION: mBOTs are rare in the pediatric and adolescent population and could arise from benign ovarian tumors.

Primary female genital system lymphoma complicated by a recurrent mucinous borderline ovarian tumor: a case report and review of the literature.

BACKGROUND: Primary female genital system lymphoma (PFGSL) is an infrequent entity. All genital organs may be affected, and most PFGSLs are localized to the cervix, uterine body, and ovaries. The clinical manifestations are nonspecific, which complicates a timely diagnosis. We report an unexpected case of PFGSL and discuss the disease characteristics by reviewing the literature. CASE PRESENTATION: A 48-year-old G3/P2 woman presented to the Department of Gynecology with a physical examination. Ultrasound examination and CT revealed pelvic masses. The woman underwent surgical treatment because of the pelvic masses and underwent a hysterectomy for a recurrent mucinous borderline ovarian tumor. However, the results of the postoperative pathological examination showed diffuse large B-cell lymphoma of the endometrium. After four courses of chemotherapy, the woman was in good condition. The clinical manifestations were nonspecific, which made a timely diagnosis complex. CONCLUSION: This case highlights the importance of the difficulty in detecting early PFGSL early and how easily nonspecific manifestations can be ignored. It may lead to missing the best time for early treatment.

Effect of tumor size on the accuracy of frozen section in the evaluation of mucinous borderline ovarian tumors.

OBJECTIVE: This study aims to evaluate the accuracy of frozen section (FS) in mucinous borderline ovarian tumors (BOTs) and to examine the factors associated with misdiagnosis. METHODS: In this retrospective study, cases diagnosed as mucinous BOTs by FS or final pathologic (FP) results were studied. The results of FS and FP were compared, and the factors associated with misdiagnosis were analyzed. RESULTS: Seventy-nine cases were examined. The median tumor diameter was 16 (6-50) cm, and 89.9 % of cases had tumors ≥10 cm. The overall agreement ratio between FS and FP was 79.7 %. Over-diagnosis and under-diagnosis rates were 3.8 % and 16.5 %, respectively. The sensitivity and positive predictive values were both 88.7 %. None of the underdiagnosed patients (13 cases) had recurrence during the 100-month median follow-up (9-222). Misdiagnosis was more common in tumors <10 cm (p = 0.025). The under-diagnosis rate for tumors <10 cm was 30.8 %. Tumor size <10 cm was significantly associated with misdiagnosis in univariate and multivariate analyses (Odds ratio {OR} 4.92, 95 % Confidence Interval {CI} (1.08-22.45) p = 0.040; OR 5.17, 95 % CI (1.07-25.05) p = 0.041, respectively). Laterality and preoperative CA 125 levels were not associated with misdiagnosis. CONCLUSION: Tumor size <10 cm is associated with misdiagnosis in mucinous BOTs. Laterality and CA 125 levels do not affect diagnostic accuracy. The evaluation of FS by gynecologic pathologists can help to increase the accuracy of FS.

Factors associated with misdiagnosis of frozen section of mucinous borderline ovarian tumor.

OBJECTIVE: This study was performed to investigate the diagnostic accuracy of frozen section (FS) of mucinous borderline ovarian tumors (mBOTs) and the diagnostic value of various risk factors for misdiagnosis. METHODS: Patients with either an FS or permanent pathologic diagnosis of mBOT were included. Optimum cut-off values for serum tumor markers and maximal tumor diameter were determined, and risk factors for underdiagnosis of mucinous malignant ovarian tumors (mMOTs) were evaluated. The sensitivity, specificity, Youden's index, and diagnostic odds ratio of the risk factors were assessed to determine their diagnostic value for mMOTs. RESULTS: Of 121 included patients, 97 were diagnosed with mBOTs by FS. Relatively abnormal cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) levels; bilateral tumors; and specific pathological features showed significant associations with underdiagnosis of mMOTs in the univariate analysis. The presence of specific pathological features was the only significant risk factor in the multivariate analysis. The CA125, CA19-9, and CEA levels and specific pathological features demonstrated certain diagnostic value in detecting malignant cases among FS-diagnosed mBOTs. CONCLUSIONS: In patients with FS-diagnosed mBOT, significant predictors of malignancy were relatively higher CA125, CA19-9, and CEA levels; bilateral tumors; and tumors with specific pathological features.

Fatal hematogenous relapse of mucinous borderline ovarian tumor of intestinal type.

We describe an unusual case of fatal hematogenous relapse of borderline mucinous ovarian tumour of intestinal type after three years of primary optimal cytoreduction with dissemination to liver, bones and lymphangitic pattern of spread in lungs with resistance to standard chemotherapy.