The detailed histopathological characteristics of ovarian fibroma compared with thecoma, granulosa cell tumor, and sclerosing stromal tumor.

BACKGROUND: Ovarian fibromas are benign tumors that can present peculiar morphological features not studied sufficiently. MATERIAL AND METHODS: In this retrospective study, 75 consecutive cases of ovarian fibroma were morphologically compared with 46 thecomas, 16 granulosa cell tumors, and 5 sclerosing stroma tumors for the following factors: the growth pattern as diffuse or nodular, the presence of hyaline plaques, necrosis, keloid-like sclerosis, calcifications, cystic degeneration, fibrous or edematous stroma, prominent vascularity, lutein cells, cellularity, scant or abundant cytoplasm, prominent cell membranes, nuclear grooves, atypia, and mitotic activity. RESULTS: The tumors differed significantly in terms of hyaline plaques presence, nuclear grooves, growth pattern, stroma type, tumor cellularity, cytoplasm, prominence of cell membranes, atypia, mitotic activity, and prominent vascularity. CONCLUSION: Ovarian fibromas can present some maybe unexpected features rather frequently, such as cystic degeneration, hyaline plaques, prominent vascularity, increased cellularity, and some mitotic activity, thus their presence should not always prompt to an alternative diagnosis.

Pathological discrimination between luteinized thecoma associated with sclerosing peritonitis and thecoma.

BACKGROUND: Similarities between luteinized thecoma associated with sclerosing peritonitis (LTSP) and thecoma, cause difficulty in clinical differential diagnoses. To improve the situation, we selected 10 specified molecular pathological markers that are frequently used in clinical pathology of ovarian sex cord-stromal tumors to determine whether they exert a discriminatory effect. METHODS: Applying immunohistochemistry, we analyzed the expression of alpha-1,6-mannosylglycoprotein 6-beta-n-acetylglucosaminyltransferase B (MGAT5B), nuclear receptor coactivator 3 (NCOA3), proliferation marker protein Ki-67 (MKI67), estrogen receptor, progesterone receptor, Vimentin, receptor tyrosine-protein kinase erbB-2, Catenin beta-1 (ß-Catenin), CD99 antigen (CD99) and Wilms tumor protein (WT1) in 102 cases of diseases containing 11 LTSP and 91 thecoma. Whole-exome sequencing and fluorescence in situ hybridization were used to examine the MGAT5B-NCOA3 fusion gene in LTSP. Statistical analysis was performed using t test, one-way analysis of variance test, and post hoc test. RESULTS: Six significant markers were verified for the discrimination between LTSP and thecoma, containing 4 upregulating indicators MGAT5B, NCOA3, MKI67, ß-Catenin, and 2 downregulating markers CD99 and WT1 in luteinized cells. In addition, the MGAT5B-NCOA3 fusion gene was identified in LTSP for the first time with significantly rich expression compared to thecoma. CONCLUSIONS: We verified 6 significant molecular pathological markers containing MGAT5B, NCOA3, MKI67, ß-Catenin, CD99, and WT1 and identified MGAT5B-NCOA3 fusion gene in LTSP; this work will help clinicians to discriminate between medical conditions and treat patients accurately.

Incidental FOXL2 mutated adult granulosa cell tumour of the ovary with thecoma-like foci.

We report on the incidental finding of a FOXL2 mutated adult granulosa cell tumour of the ovary with thecoma-like foci, a rare entity recently described by Jennifer N. Stall and Robert H. Young in a series of sixteen cases in 2019, displaying features differing from conventional adult granulosa cell tumour. Our aim is to specify the morphologic and molecular particularities of this presumably underrecognized finding, with a short presentation of the typical clinical context. Awareness of this rare and challenging neoplasm with indeterminate clinical course is crucial in routine diagnostics.

Giant Ovarian Thecoma Associated with Meigs Syndrome: A Striking Case.

Introduction: Meigs syndrome consists of the presence of a benign ovarian tumor, ascites and pleural effusion, and the latter two subdued after surgical excision of the ovarian tumor. Elevated Ca-125 in this context is confusing and is reported only in a handful of cases. A rare but striking case with the above features is presented herein. Case Presentation: A 46-year-old woman with a giant pelvic/abdominal mass originating from her right adnexa, ascites and pleural effusion, with elevated Ca-125 (938 IU/mL) was treated with the presumptive diagnosis of stage IV ovarian cancer. Imaging modalities showed a 22 cm solid adnexal mass and the patient underwent total abdominal hysterectomy and bilateral salpigooophorectomy, omentectomy and drainage of 4L of ascetic fluid. Surprisingly, final histopathology was negative for malignancy, characterizing the primary tumor as ovarian thecoma. Ascites and pleural effusion resolved by the seventh postoperative day, setting the diagnosis of Meigs syndrome. Discussion: Meigs syndrome accounts for 1% of all ovarian tumors, however it should be considered in the differential diagnosis when clinicians come across the classic triad of the syndrome, even when Ca-125 is elevated. These patients have normal life expectancy with meticulous management, while pathophysiology of this condition remains uncertain in various points.

Ovarian thecoma: A very unusual cause of postmenopausal bleeding.

We describe a 67-year-old woman with postmenopausal bleeding having ceased estrogen plus progestogen therapy nine months before. Transvaginal ultrasonography showed endometrial thickening with normal ovarian appearance. Hormonal studies revealed high estradiol and inhibin B levels but normal androgens and adrenal hormones. Magnetic resonance image demonstrated a 13-mm left ovarian tumour. Hysterectomy and bilateral salpingo-oophorectomy were performed, and the pathological study revealed an 8 mm ovarian thecoma. This case illustrates a very unusual cause of postmenopausal bleeding. We suggest a study protocol and discuss the differential diagnosis of this case.

Luteinized thecoma (thecomatosis) with sclerosing peritonitis: a systematic review of the literature of the last 25 years.

INTRODUCTION: Luteinized thecoma (thecomatosis) with sclerosing peritonitis (LTSP) is a very uncommon syndrome, characterized by the presence of single or bilateral ovarian thecomas and peritoneal fibrotic lesions. The disease occurs in young women and it can lead to peritoneal fibrosis and bowel obstruction. The pathogenesis of this syndrome remains still largely unknown. Surgery represents the cornerstone of treatment, but resection alone does not always allow a complete disease control. Attempts at medical treatments have been reported in recent years, but a real standard therapy has not yet been defined. AREAS COVERED: We performed a systematic review of literature, collecting all the papers that reported cases of LTSP, since its first description in 1994. We found that, in these 25 years, less than 50 cases have been described in literature. EXPERT OPINION: Along with the established role of surgery, adjuvant treatment with hormonal agents, in particular in estrogen receptor expression, seems to be a promising approach. However, more efforts must be carried out to describe treatment and outcome of new cases, improving knowledge about this rare condition.

Triple negative lobular breast carcinoma metastatic to an ovarian fibrothecoma.

A postmenopausal woman with lobular breast carcinoma metastatic to a large ovarian fibrothecoma is presented. The two metastatic tumor nodules were grossly subtle and could have been overlooked in the background of the large ovarian stromal tumor. Thorough sampling of the tumor for histologic examination and supporting immunohistochemical stains were important in establishing the diagnosis. Differential diagnostic considerations are discussed.

Analysis of magnetic resonance imaging features of ovarian thecoma.

To investigate the magnetic resonance imaging (MRI) findings in ovarian thecoma and improve preoperative diagnostic accuracy.Retrospective analysis was performed on 45 patients with surgically and pathologically confirmed ovarian thecoma. Patients were grouped into those with maximum lesion diameter ≥5 cm and <5 cm. Diagnostic scores (up to 6 points) were evaluated on the basis of MRI performance.The ≥5 cm group contained 36 cases (cystic necrosis, 32 cases) with the following findings: T1WI: isointense signal, 22 cases; slightly hypointense signal, 14 cases; T2WI: isointense signal, 6 cases; slightly hypointense signal, 21 cases; slightly hyperintense signal, 9 cases; Diffusion-weighted imaging (DWI): hyperintense signal, 23 cases; mixed hyperintense signal, 13 cases; slight enhancement on dynamic enhanced scans; pelvic fluid accumulation, 31 cases. The diagnostic score evaluations yielded 6 points in 31 cases, 5 points in 1 case, 4 points in 2 cases, and 3 points in 2 cases. The <5 cm group contained 9 cases (cystic necrosis, 3 cases) with the following findings: T1WI: isointense signal, 3 cases; slightly hypointense signal, 6 cases; T2WI: isointense signal, 2 cases; slightly hypointense signal, 4 cases; slightly hyperintense signal, 3 cases; DWI, hyperintense signal; slight enhancement in 8 cases and significant enhancement in 1 case; pelvic fluid accumulation, 4 cases. The diagnostic score evaluations yielded 6 points in 3 cases, 5 points in 1 case, 4 points in 4 cases, and 3 points in 1 case. (iii) Incidence of pelvic fluid accumulation and cystic necrosis differed depending on the size of the lesion (P = .007, .000).Larger lesions show hyperintense or mixed hyperintense signals on DWI along with pelvic fluid and cystic necrosis; whereas, smaller lesions show a hyperintense signal on DWI, cystic necrosis is rare. MRI characteristics along with the patient age and laboratory findings can improve the accuracy of preoperative diagnosis of these lesions.

Adolescent ovarian thecoma presenting as progressive hyperandrogenism: case report and review of the literature.

Hyperandrogenism is frequent and under investigated in adolescent girls. A 15-year-6-month-old French girl presented with oligomenorrhea and slowly progressing virilization 2 years post-menarche. Medical history revealed prenatal pesticide exposure through maternal professional activity and recurrent premature thelarche. Severe hirsutism, mild facial acne and clitoromegaly were noted. Serum androgens (testosterone: 94 ng/dL, 4-androstenedione: 8.23 ng/mL) were high and non-classic 21-hydroxylase deficiency was excluded. Pelvic ultrasonography showed a left ovarian mass, confirmed by computed tomography scan. Tumor markers were negative. Laparoscopic surgery was performed. The pathological diagnosis was benign luteinized thecoma. Postoperatively, the menstrual cycle and serum androgens became normal and hirsutism slowly improved. Hyperandrogenism 2 years after menarche should be systematically investigated, even if slowly progressive, since it may be a symptom of a rare virilizing ovarian tumor, like thecoma.

Diagnostic Performance of MR Imaging-based Features and Texture Analysis in the Differential Diagnosis of Ovarian Thecomas/Fibrothecomas and Uterine Fibroids in the Adnexal Area.

RATIONALE AND OBJECTIVES: To investigate the value of MRI-based features and texture analysis (TA) in the differential diagnosis between ovarian thecomas/fibrothecomas (OTCA/f-TCAs) and uterine fibroids in the adnexal area (UF-iaas). MATERIALS AND METHODS: This retrospective study included 16 OTCA/f-TCA and 37 UF-iaa patients who underwent conventional MRI and DWI between August 2014 and September 2018. Three-dimensional TA was performed with T2-weighted MRI. The clinical, MRI-based and texture features were compared between OTCA/f-TCAs and UF-iaas. Multivariate logistic regression analysis was used for filtering the independent discriminative features and constructing the discriminating model. ROCs were generated to analyse MRI-based features, texture features and their combination for discriminating between the two diseases. RESULTS: Six imaging-based features (ipsilateral ovary detection, arterial period enhancement, lesion components, peripheral cysts, "whorl signs", mean ADCs) and six texture features (Histogram-energy, Histogram-entropy, Histogram-kurtosis, GLCM-energy, GLCM-entropy, and Haralick correlation) were significantly different between OTCA/f-TCAs and UF-iaas (p < 0.05). Multivariate analysis of the MRI-based features revealed that arterial period enhancement (OR = 0.104), peripheral cysts (OR = 16.513), and whorl signs (OR = 0.029) were independent features for discriminating between OTCA/f-TCAs and UF-iaas (p < 0.05). Multivariate analysis of the texture features showed that Histogram-energy and GLCM-energy were independent features for discriminating between OTCA/f-TCAs and UF-iaas (p < 0.05). The area under the curve of imaging-based diagnosis was 0.85, and the combination of imaging-based diagnosis and TA improved the area under the curve to 0.87, with higher accuracy, specificity and sensitivity of 86%, 92%, and 84%, respectively (p < 0.05). CONCLUSIONS: MRI-based features can be useful in differentiating OTCA/f-TCAs from UF-iaas. Furthermore, combining imaging-based diagnosis and TA can improve diagnostic performance.

Practical Review of Ovarian Sex Cord-Stromal Tumors.

Ovarian sex cord-stromal tumors are uncommon tumors and clinically differ from epithelial tumors. They occur across a wide age range and patients often present with hormone-related symptoms. Most are associated with an indolent clinical course. Sex cord-stromal tumors are classified into 3 main categories: pure stromal tumors, pure sex cord tumors, and mixed sex cord-stromal tumors. The rarity, overlapping histomorphology and immunoprofile of various sex cord-stromal tumors often contributes to diagnostic difficulties. This article describes the various types of ovarian sex cord-stromal tumors and includes practical approaches to differential diagnoses and updates in classification.

Bilateral Ovarian Collision Tumours: Serous Carcinomas and Fibrothecomas / Tumores de colisión ováricos bilaterales: carcinomas serosos y fibrotecomas

ABSTRACT A patient had both ovaries affected by clearly demarcated colliding tumour masses of different gross appearance, histological features and immunohistochemical profiles, corresponding to bilateral collision papillary serous high-grade adenocarcinoma and fibrothecoma. Despite the applied chemotherapy, it led to a lethal outcome for the patient nearly a year after the surgery. Bilateral ovarian tumours raise the question of whether they are primary tumours or metastases. Simultaneous bilateral occurrence of surface epithelial tumours with other types of ovarian tumours is rare. Therefore, it poses a great challenge in proper differential diagnostics.

RESUMEN Una paciente tenía ambos ovarios afectados por masas tumorales en colisión, claramente demarcadas. Las mismas mostraban diferente aspecto macroscópico, y diferentes rasgos histológicos y perfiles inmunohistoquímicos, correspondientes a fibrotecomas y adenocarcinomas serosos papilares bilaterales de alto grado en colisión. A pesar de la quimioterapia aplicada, la condición condujo a un resultado fatal para la paciente, casi un año después de realizada la cirugía. Los tumores ováricos bilaterales plantean la cuestión de si se trata de tumores primarios o metástasis. La ocurrencia bilateral simultánea de tumores epiteliales superficiales con otros tipos de tumores ováricos es rara, y por tanto, plantea un gran desafío a la hora de realizar un diagnóstico diferencial adecuado.

Granulosa Cell Tumors of the Ovary With Prominent Thecoma-like Foci: A Report of 16 Cases Emphasizing the Ongoing Utility of the Reticulin Stain in the Modern Era.

Sixteen adult granulosa cell tumors which had conspicuous zones of cells with pale cytoplasm imparting a resemblance to thecoma are reported. The neoplasms occurred in patients from 38 to 86 yr of age, the majority being over 55 yr of age. Ten tumors were incidental findings, the remainder being associated with symptoms or signs related to an adnexal mass. All the tumors were unilateral, typically small, usually under 5 cm, with only 3 being larger. With 1 exception they were uniformly solid and were typically entirely or focally yellow on sectioning. Microscopic examination typically showed a nodular pattern of growth constituted by cells with moderate to abundant pale cytoplasm; the cells resembled those seen in most thecomas. The nodules occasionally became confluent and focally a diffuse pattern was seen. Typical foci of adult granulosa cell neoplasia in the form of foci of conspicuous epithelial differentiation were absent or rare in most cases but were seen in subtle form in 6 cases and overtly in 3. A few tumors had other features seen in some thecomas, hyaline plaques, sclerosis, and calcification. Reticulin stains were examined in 13 cases and showed that the thecoma-like foci exhibited a dearth of reticulum indicating that those areas were predominantly of granulosa cell nature. Most adult granulosa cell tumors have cells with scant cytoplasm; occasional tumors have abundant eosinophilic cytoplasm, so-called luteinized adult granulosa cell tumors. That some granulosa cell tumors have the cytoplasmic features described herein has occasionally been noted but the resemblance to thecoma has not been emphasized to the best of our knowledge and in the past such tumors may have been misdiagnosed as thecoma, the referral diagnosis in 6 of our cases. A reticulin stain is of crucial aid in indicating the epithelial nature of the thecoma-like foci in these cases. Given the small size of the majority of the tumors the distinction between a small adult granulosa cell tumor and thecoma does not have significant prognostic or therapeutic implications in most cases but awareness of this feature of a small subset of adult granulosa cell tumors is warranted. Our findings have import to the diagnosis of thecoma which is uncommon if strict criteria, including exclusion of granulosa tumors of the type described, are used.

FOXL2 Mutation Analysis of Ovarian Sex Cord-Stromal Tumors: Genotype-Phenotype Correlation With Diagnostic Considerations.

Correlation of FOXL2 mutation status with morphologic features and reticulin staining patterns was performed in a comprehensive single-institutional cohort of ovarian sex cord-stromal tumors. Fifty-one cases were included, 35 of which were morphologically diagnosed as adult granulosa cell tumor, 4 as Sertoli-Leydig cell tumor, 11 as fibroma/fibrothecoma and 1 as a thecoma. Of the adult granulosa cell tumors, 31 (88.6%) harbored FOXL2 mutation. Abundant pale cytoplasm was seen in 51.6% (16/31) of FOXL2 mutated tumors, compared with 6.7% (1/15) among FOXL2 wild type tumors (P=0.003). Nearly half of FOXL2 negative tumors showed individual pericellular reticulin staining pattern, while none of the FOXL2 positive cases demonstrated this feature (P=0.0001). Nested reticulin pattern was observed in 67.7% of FOXL2 positive tumors, compared with 20% of FOXL2 negative cases (P=0.004). Indeterminate reticulin staining pattern was seen in nearly one third of cases in both groups. Nested reticulin pattern was 87.5% specific and 67.7% sensitive for FOXL2 mutation, while individual reticulin pattern was 100% specific for absence of FOXL2 mutation. No statistical significance was observed between the 2 groups in tumor size, mitotic activity, nuclear atypia, and nuclear grooves. Follow-up was available for 44 patients ranging from 0.3 to 259 months (mean: 67.5 mo). Two patients developed recurrence, both of them harbored FOXL2 mutation. In conclusion, the pathology diagnosis of sex cord-stromal tumors continues to be difficult, and reticulin staining remains a valuable tool as an initial step in the diagnostic work-up. Individual pericellular reticulin pattern essentially rules out adult granulosa cell tumor, while cases with indeterminate or nested patterns can be subjected to FOXL2 mutation testing to aid the diagnosis.

FOXL2 Mutation Status in Granulosa Theca Cell Tumors of the Ovary.

Ovarian sex-cord stromal tumors that have between 10% and 50% granulosa cells in a prominent fibrothecomatous background have been referred to as granulosa theca cell tumors or mixed granulosa theca cell tumors. The classification and prognosis of these tumors is not clear. Most adult granulosa cell tumors of the ovary harbor a mutation in the FOXL2 gene, whereas fibromas and thecomas lack this mutation. The aim of our study was to assess the FOXL2 mutation status of ovarian granulosa theca cell tumors and to correlate the mutation status with morphologic and clinical characteristics. A FOXL2 mutation was detected in 6 of 12 (50%) granulosa theca cell tumors. Tumors with higher cellularity of granulosa cells were more likely to harbor a FOXL2 mutation as were tumors in which the granulosa cells formed large lobules. No conclusions could be drawn regarding the clinical and prognostic significance of the presence of a mutation given the small number of cases and limited clinical follow-up. Our study shows that half of granulosa theca cell tumors harbor the same FOXL2 mutation that characterizes adult granulosa cell tumors but there is no outcome evidence to guide whether mutation status should alter the classification of the tumor or the management of the patient.

Contribution of ultrasound in the study of ovarian fibrothecomas: a series of 47 cases.

INTRODUCTION: Ovarian fibro-thecoma are rare presenting 1 to 4, 7%of ovarian organictumors. These tumors are of stromal origin and contain varied proportion of fusiform connective tissue cells and theca cells. They mainly affect menopausal or perimenopausal women. This tumor is benign in most cases and may be responsible for hormone secretion. OBJECTIVES: Study the epidemiological and clinical data of patients with ovarian fibro-thecoma, analyze ultrasonographic characteristics of these tumors,and evaluate the sensitivity and specificity of pelvic ultrasound in ovarian fibro-thecoma approach. METHODS: A retrospective study of 47 patients who underwent surgical treatment for ovarian fibro-thecoma was performed. Data were collected in our department of gynecologyand obstetrics A within Charles Nicole hospital in Tunis, over a period of 18 years between January 1994 and December 2012. For each of our observations, we analyzed the clinical and para-clinical data, including U.S. characteristics and available MRI data with confrontation to the final histological results. RESULTS: The average age of patients was 45.2 years. The average gravidity was 4 and the mean parity was 3. . Thirty-eight of our patients were postmenopausal (80.85%). Ovarian tumor was discovered incidentally in 11 cases and on the occasion of functional symptoms in 36 cases including pelvic pain in 18 cases. Physical examination revealed a pelvic mass in 17 patients and pelvic-abdominal in 14 patients. All patients underwent a pelvic ultrasound. . Ultrasound identified 49 tumors (2 cases of bilateral tumors). Average size of tumors was 10, 05 cm (4 to 30 cm). ) . Ovarian tumor was echogenic in 9 cases (18.36%), hypoechoic in 14 cases (28.47%), mixed in 14 cases (28.47%) and anechoic in 12 cases (24.49%). The tumor was found to be solid in 27 cases (55.1%); cystic in 8 cases (16.3%) and solido cystic in 14 cases (28.6%).It was compartmentalized in 10 cases. Extra cystic vegetations were found in 2 patients. The tumor was nonvascularized at color Doppler in 47 cases (95.9%) and slightly vascularized in 2 cases (4.1%). Intra peritoneal effusion was objectified in 15 cases. The diagnosis of ovarian fibro-thecoma was raised based on U.S in 25 cases (51.02%) before surgery .MRI was performed in four cases. All patients underwent surgery. We performed laparotomy in 36 cases and laparoscopy in 11 cases. By laparotomy were performed a total hysterectomy with bilateral oophorectomy in most cases (26 patients). By laparoscopy we did lumpectomy in all cases. . The final pathologic examination revealed 19 fibromas, 14cystadénofibromas and 14 fibrothecomas. CONCLUSION: The paraclinical exploration of ovarian fibro-thecoma isbased, as all ovarian tumors, on ultrasound examination. The most typical features are images of solid tumors with regular contours, echogenic or mixed with the presence of streakedshadows.