Rare Ovarian Tumor Research Articles

Ovarian steroid cell tumor, not otherwise specified: A rare case of postmenopausal vaginal bleeding.

Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS) are particularly rare ovarian tumors, which are composed of steroid-hormone secreting cells. The majority of patients with this tumor produce excessive quantities of testosterone and virilization is common. The current report presents a rare case of SCT in a 59-year-old female who presented with postmenopausal vaginal bleeding. The patient had experienced irregular vaginal bleeding for two months, 12 years after menopause. Transvaginal ultrasound and magnetic resonance imaging identified a solid adnexal mass and the pathological result of diagnostic curettage showed a proliferative endometrium. The patient’s serum estrogen and testosterone levels were elevated (393.71 nmol/l and 22.28 nmol/l, respectively). The patient underwent an exploratory laparotomy, hysterectomy and bisalpingectomy. The neoplasm was well-circumscribed, solid, homogeneous and yellow in color. Microscopically, the tumor was predominantly composed of granular eosinophilic or vacuolated cytoplasm. Reinke’s crystals, prominent nucleoli and Call-Exner bodies were not observed, and there was no mitotic figure. Immunohistochemistry demonstrated that the tumor cells were strongly positive for inhibin. The present rare case aims to expand the current knowledge of this type of ovarian tumor.

Oncogénétique et tumeurs malignes rares de l’ovaire (TMRO)

This development of the current knowledge allows individualizing some rare malignant ovarian tumors and specifying the indications of oncogenetics consultation for the clinicians. Contrary to the classic ovarian cancers arising at a young age evoking a BRCA mutation, the discovery of a rare ovarian tumor at a young age does not evoke necessarily a genetic origin and mostly without relationship with the BRCA genes.

FDG PET/CT in Serous Psammocarcinoma of the Ovary

Serous psammocarcinoma of the ovary is a rare variant of ovarian serous carcinoma with a favorable prognosis. We present a case of bilateral ovarian serous psammocarcinoma showing extensive calcification in the primary and disseminated lesions with intense FDG uptake on FDG PET/CT. It may be difficult to differentiate the extensively calcified omental and peritoneal metastases from benign calcified lesions on CT images. This case indicates FDG PET/CT may have an advantage over conventional CT in differentiating malignant calcification from benign calcification based on glucose metabolic activity, and may be helpful for diagnosis and staging of this rare ovarian tumor.

English

Sertoli- Leydig cell tumor or Androblastoma or Arrhenoblastoma is a rare virilizing tumor of ovary, mostly with masculinizing features. Many but certainly not all tumors are hormonally active. Although classified under malignant tumors the degree of malignancy is less than that of ovarian carcinoma in general. Unilateral oophorectomy was done and the patient recovered well with diminution of masculinizing features. INTRODUCTION: Sertoli-Leydig cell tumor (SLCT) is a rare ovarian tumor that belongs to the group of sex-cord stromal tumors. These constitute less than 0.5% of ovarian tumors .Most tumors are unilateral, seen during the second and third decades of life and are of less well differentiated variety. Many patients have symptoms of virilization due to the presence of androgen element in tumor. The degree of differentiation is age related. 1 Intermediate differentiated tumors comprises of 54% of tumors (data reference 2).

Ovarian Paraganglioma

A rare case of ovarian paraganglioma was incidentally found as a 1.2-cm intraovarian mass in a 68-year-old hypertensive female operated for an endometrial carcinoma. Histologically, it was arranged in characteristic Zellballen composed of polygonal clear cells with a granular cytoplasm that expressed diffusely CAM5.2 cytokeratin, chromogranin, neuron-specific enolase, synaptophysin, and CD56, while S-100 protein was only present in sustentacular cells. We analyzed differential diagnoses with other rare ovarian tumors such as Sertoli cell tumor, with which it may share an immunophenotype expressing cytokeratins, S-100, and other neural markers, and extra-axial ependymoma, which invariably expresses diffusely GFAP, that may be positive only in the sustentacular cells of paraganglioma. However, on simple hematoxylin-eosin inspection, ovarian paraganglioma displays characteristic Zellballen clusters and cells with a granular cytoplasm but lacks the distinctive Sertoli cell tubules and the characteristic rosettes and fibrillary cytoplasm of ependymoma. Pathologists should be aware of the unusual locations of paraganglioma.

Sclerosing stromal tumor of the ovary: A rare entity with distinctive features

Sclerosing stromal tumor (SST) is an extremely rare ovarian sex cord-stromal tumor with distinctive pathological featuresand benign nature. Awareness of such entity is crucial because of its histopathologic similarity with other neoplastic andnon-neoplastic lesions of the ovary. In this report, a 29-year-old woman was presented with menstrual irregularities andpelvic pain. She underwent unilateral oophorectomy after detecting a right ovarian mass by ultrasonography. The case wasdiagnosed as ovarian sclerosing stromal tumor based on clinicopathologic and immunohistochemical features. Differentialdiagnosis is discussed with review of the literature data.

A Case of Clear Cell carcinoma of the Ovary

Although Clear cell carcinoma of ovary is a rare epithelial ovarian tumor, prevalence in Asian is higher than other ethnicity. Recently, Clear cell carcinoma has increased in its incidence. Clear cell carcinoma of the ovary constitutes 5-6% all ovarian malignancies. Clear cell carcinoma is frequently present at early stage with unilateral large pelvic mass, deep vein thrombosis, hyper kalemia. Atypical endometriosis is a malignant precursor which associated with clear cell carcinoma 35.9%. Microscopic feature are multiple papillae, densely hyaline basement membrane and hyaline bodies. Mitosis are less frequent than in other types of ovarian carcinomas. Clear cell carcinoma of ovary was known poor prognosis compared to other epithelial ovarian carcinoma because of Platinum based chemotherapy resistance. We experienced a case of clear cell adenocarcinoma of the ovary in 40 years old woman. Clinicopathologic findings of one case with a brief review related literatures are presented.

Sclerosing stromal tumour of the ovary: A case report and the review of literature.

Sclerosing stromal tumours are rare benign ovarian neoplasms of the sex cord stromal that occur predominantly in the second and third decades of life. To date, 208 cases have been recorded in the literature. Most patients have menstrual irregularities and pelvic pain. Infertility and virilisation have also been described. In this article, histopathological features and differential diagnosis of the benign sclerosing stromal tumour were described together with the literature data. It is imperative to consider the differential diagnosis of a sclerozing stromal tumour of the ovary in a young woman with an ovarian tumour. A combination of morphological, immunohistochemical, radiological and clinical findings is needed in differentiating the tumour from thecoma, fibroma/fibrosarcoma, lipoid tumours and Krukenberg tumour.

Advanced Ovarian Dysgerminoma Infiltrating Both Ovaries and Uterus in a 7-Year-Old Girl

Introduction. Ovarian dysgerminoma is a rare malignant ovarian germ cell tumor with its peak incidence in young women. Abdominal pain, abdominal distention, and the presence of a palpable mass are common symptoms at presentation. Depending on the FIGO stage at presentation the prognosis of dysgerminomas after surgical treatment, adjuvant chemotherapy, and radiotherapy is promising. Case Presentation. A 7-year-old girl was presented at our clinic with abdominal pain in all abdominal quadrants. Later the pain localized in the region of her right ovary. CT scan revealed a massive formation which was connected to her right ovary. Conclusion. Although malignant ovarian germ cell tumours are rare in children, physicians must always consider the possibility of MOGT-occurrences. The clinical symptoms might not be specific: abdominal pain, abdominal distention, nausea, and vomiting. In order to make a correct diagnosis the patients should undergo a complete clinical examination including radiological scans. Initial management is frequently surgery, followed by adjuvant chemotherapy and radiotherapy. Although disgerminoma is malignant tumor, the prognosis is promising.

Clinical and Pathologic Features of Patients with Rare Ovarian Tumors: Multi-Center Review of 167 Patients by the Anatolian Society of Medical Oncology

Non-epithelial malignant ovarian tumors and clear cell carcinomas, Brenner tumors, transitional cell tumors, and carcinoid tumors of the ovary are rare ovarian tumors (ROTs). In this study, our aim was to determine the clinicopathological features of ROT patients and prognostic factors associated with survival. A total of 167 patients with ROT who underwent initial surgery were retrospectively analyzed. Prognostic factors that may influence the survival of patients were evaluated by univariate and multivariate analyses. Of 167 patients, 75 (44.9%) were diagnosed with germ-cell tumors (GCT) and 68 (40.7%) with sex cord-stromal tumors (SCST); the remaining 24 had other rare ovarian histologies. Significant differences were found between ROT groups with respect to age at diagnosis, tumor localization, initial surgery type, tumor size, tumor grade, and FIGO stage. Three-year progression-free survival (PFS) rates and median PFS intervals for patients with other ROT were worse than those of patients with GCT and SCST (41.8% vs 79.6% vs 77.1% and 30.2 vs 72 vs 150 months, respectively; p=0.01). Moreover, the 3-year overall survival (OS) rates and median OS times for patients with both GCT and SCST were better as compared to patients with other ROT, but these differences were not statistically significant (87.7% vs 88.8% vs 73.9% and 170 vs 122 vs 91 months, respectively; p=0.20). In the univariate analysis, tumor localization (p<0.001), FIGO stage (p<0.001), and tumor grade (p=0.04) were significant prognostic factors for PFS. For OS, the univariate analysis indicated that tumor localization (p=0.01), FIGO stage (p=0.001), and recurrence (p<0.001) were important prognostic indicators. Multivariate analysis showed that FIGO stage for PFS (p=0.001, HR: 0.11) and the presence of recurrence (p=0.02, HR: 0.54) for OS were independent prognostic factors. ROTs should be evaluated separately from epithelial ovarian cancers because of their different biological features and natural history. Due to the rarity of these tumors, determination of relevant prognostic factors as a group may help as a guide for more appropriate adjuvant or recurrent therapies for ROTs.

Impact of a second opinion using expression and molecular analysis of FOXL2 for sex cord-stromal tumors. A study of the GINECO group & the TMRO network

ObjectiveOvarian sex cord-stromal tumors (SCSTs) are rare and their diagnosis is often difficult to establish. Recently, immunostaining and molecular analysis for Forkhead box L2 (FOXL2) have been developed in this pathology. This study aims to assess the benefit of an algorithm incorporating these new tools for a better diagnosis and classification of SCSTs MethodsSeventy-two tumors with a potential diagnosis of SCSTs were addressed by 37 different pathologists to one French rare ovarian tumor expert center, member of the Rare Malignant Ovarian Tumor network (TMRO). Then a “second opinion” (SO) through an algorithm incorporating immunostaining (IHC) and molecular analysis of FOXL2 was performed for all these cases. This algorithm was then validated by all pathologists of the TMRO network. ResultsAfter a second opinion including molecular analysis and immunostaining for FOXL2 the initial diagnosis was changed in 15 of 72 samples (21%). FOXL2 mutation was present in 44 out of 47 adult granulosa cell tumors (94%), in 3 out of 8 Thecomas (37%), in 1 out of 10 Sertoli–Leydig cell tumors (SLSTs) (10%) and in 3 out of 5 undifferentiated-SCSTs (Und-SCSTs) (60%). Immunoexpression of FOXL2 was available in 45 cases of SCSTs: FOXL2 was expressed in 44 of them (98%). ConclusionsA second opinion in an expert center for all cases of SCSTs is fundamental to get an optimal classification of these rare tumors. This second opinion could be performed with an algorithm which integrates FOXL2 mutation and expression status of FOXL2 in order to standardize the practice.

English

INTRODUCTION: Steroid cell tumor of the ovary a very rare androgen secreting tumor accounts for less than 0.1% of ovarian tumors. These tumors may present at any age ranging from 2 to 80 yrs & associated with hormonal activity & virilisation. These tumors are most commonly unilateral, may be both benign or malignant, most of these tumors are usually diagnosed in early stages because of virilisation caused by these tumors. In an extensive literature search (medline & pubmed) from 1979, only around 80 cases of ovarian steroid cell tumors have been reported. As ovarian stromal tumors are infrequent, little attention was given to their response to radiotherapy and chemotherapy. A recent report stated gonadotropin releasing hormone agonist was effective in treating steroid cell tumors. Here we present the case of a rare ovarian steroid cell tumor in a 32 yrs old woman who presented with virilisation. CASE REPORT: A 32 yrs old woman with P2L1D1A1 presented with history of amenorrhea of 7 months duration, hoarseness of voice since 6 yrs, decrease in breast size since 6 yrs, lower abdominal pain which is dull aching type, coarse hair growth over the body since 2 yrs. She attained menarche at the age of 12 yrs. Her previous menstrual cycles were normal. Physical examination revealed male pattern of coarse hair distribution in the beard region, face, chest wall, abdomen, arms and thighs. Both breasts were small in size, no mass palpable per abdominally.

The Pathogenesis of Ovarian Myxoma

Ovarian myxoma is a rare distinctive benign ovarian stromal neoplasm that occurs predominantly in young women and is hormonally inactive. Although typically classified as an ovarian stromal tumor, its exact pathogenesis remains uncertain. We report 4 cases of ovarian myxoma, 3 of which were associated with another type or other types of ovarian stromal tumor and 1 occurred as a pure myxoma. In 2 cases, the myxoma arose from a sclerosing stromal tumor, and the third, most likely arose from a luteinized theca cell tumor (LTCT). Myxoid transformation of the connective tissue of the parent neoplasm appears to be a precursor of ovarian myxoma in some instances. We believe that the occurrence of trisomy 12 or other genetic abnormalities may play a role in this transformation. Whether or not associated with another type of ovarian stromal tumor, ovarian myxoma can be suspected macroscopically by its cystic gelatinous appearance and sharp circumscription. The most important differential diagnosis is a low-grade sarcoma with myxomatous features. We believe that myxomas arising from different anatomic sites likely are genetically, histologically, and biologically distinct. For purposes of classification, they should be considered as separate tumor types.

Diagnostic et prise en charge d’une aménorrhée chez l’adolescente

Amenorrhea in adolescents can be primary, with or without breast development, or secondary. Whether amenorrhea is primary or secondary, height, body mass index, food intake, the level of physical activity per week, the presence of hirsutism or galactorrhea, pelvic pain and past history of intercourse need to be investigated. Initially, blood tests should include hCG, FSH, estradiol, testosterone and prolactin serum levels. This screening will discriminate between hypogonadotropic hypogonadism and amenorrhea from primary ovarian insufficiency (POI). In case of primary amenorrhea, hypogonadism may be due to congenital hypogonadotropic hypogonadism (HH) or more rarely acquired HH. If FSH is elevated, amenorrhea is due to primary ovarian failure, mainly related to Turner syndrome. If pubertal development is normal, a pelvic ultrasound should be performed. It may visualize a hindering of menses output or less frequently an absence of uterus, as in Rokitansky syndrome or androgen insentivity syndrome. The most frequent etiologies of secondary amenorrhea are polycystic ovarian syndrome (PCOS), functional hypothalamic amenorrhea and less frequently POI and hyperprolactinemia. The differential diagnoses of PCOS are late-onset 21-hydroxylase deficiency and very rare ovarian or adrenal tumors. When contraception is not necessary, hormonal replacement therapy, including estrogen and progestins should be administered in order to avoid hypoestrogenism. In case of PCOS, sequential progestins can be prescribed. A contraceptive pill can be considered when contraception is needed and/or when hyperandrogenism needs to be treated.

De novo Ovarian Squamous Cell Carcinoma. A Case Report and Review of Literature

Malignant ovarian tumours comprise of a spectrum of clinicopathologic entities. Many have comparable presenting clinical features, some are associated with unique and intriguing histomorphological features. Not only does a histopathology define a tumour’s ontogeny and biology, they may also predict prognosis and help plan an adjuvant therapy. What follows is a 17th case report of an exceedingly rare primary ovarian tumour (pure, de novo), squamous cell carcinoma (SCC). However, it is known that 2 % of mature teratomas harbour malignant component and up to 80 % will be squamous. Some pure SCCs will arise in association with a foci of endometriosis and very rarely entirely de novo [1–4]. SCC of ovary are aggressive tumours, which may be amenable to multimodality treatment. Due to conflicting evidence from literature, the best therapeutic option cannot be deciphered. Treatment needs to be tailored to patient profile.

Abstract 3480: Impact of a second opinion for sex cord stromal tumors through expression and molecular analysis of FOXL2: a study of the GINECO group and TMRO network.

Abstract Background: Ovarian sex cord-stromal tumors (SCSTs) represent about 7% of ovarian tumors. Since the exact diagnosis of these rare malignancies is difficult to establish and could modify the appropriate therapeutic strategy, the GINECO group (Group of National Investigators for Ovarian Cancer Studies) developed the National Rare Ovarian tumor Observatory in 2002 which proposes a systematic pathological second opinion for all cases of rare ovarian tumor diagnosed in France. We investigated whether a systematic second opinion in one of the expert centers (Lyon, France), using evaluation of FOXL2 mutation and FOXL2 level of expression for all samples of suspected SCSTs cases, could improve diagnosis and classification of sex cord-stromal tumors. Methods: Immunostaining for FOXL2 and new molecular markers is being developed in this pathology. The aim of this study was to evaluate the benefit of a systematic second opinion and the use of a new algorithm that rationalizes the use of these new tools, to allow more accurate diagnosis and classification of SCSTs. Data were collected in a recent database dedicated to rare ovarian cancer “Observatory for rare malignant tumors of the ovary”. Seventy-two patients from the database were included. All tumor samples were referred to referent center for morphological and IHC review. Search for FOXL2C134W mutation and immunostaining of FOXL2 were performed. Results: FOXL2 mutation was present in 44 out of 47 adult granulosa cell tumors (A-GCTs) (94%), in 2 out of 8 thecomas (25%) and in 1 out of 10 sertoli leydig tumors (10%). These results confirm FOXL2 mutation as a specific marker for A-GCTs. Immuno-expression of FOXL2 was present in 44 out of 45 SCSTs (97.8%). After a second opinion, using morphological and classical immunohistochemistry markers only, 15% of the initial diagnoses were modified. With the use of our algorithm, initial diagnosis was changed in 22%. Conclusion: New tools like the search of a FOXL2 mutation are fundamental to obtain an optimal diagnosis and classification of these tumors. The use of an algorithm could be generalized to homogenize practice and rationalize the use of these markers. We hope this algorithm can also adjust and standardize the therapeutic strategy. Citation Format: Thibaut Goulvent, Denis Maillet, Ruth Rimokh, Philippe Cassier, Marie-Cecile Vacher-Lavenu, Pierre Meeus, Patricia Pautier, Pierre Duvillard, Jerome Alexandre, Eric Pujade-Laurraine, Mojgan Devouassoux-Shisheboran, Isabelle Treilleux, Isabelle Ray-coquard. Impact of a second opinion for sex cord stromal tumors through expression and molecular analysis of FOXL2: a study of the GINECO group and TMRO network. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3480. doi:10.1158/1538-7445.AM2013-3480

Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors.

Bilateral Ovarian Sertoli–Leydig Cell Tumors Associated with a Unilateral Dermoid Cyst: An Exceptionally Rare Association

Abstract Background: Sertoli–Leydig cell tumors (SLCT) are rare ovarian tumor that belongs to the group of sex-cord stromal tumors. These constitute less than 0.5% of all ovarian tumors. Most of these (97%) tumors are unilateral, with bilaterality being very rare. Case: Here we report a very unusual case of bilateral SLCT in association with a unilateral dermoid cyst in a 37-year-old female. She presented with a history of abdominal pain, and bilateral abdominal masses. Ultrasound examination revealed bilateral ovarian masses for which a bilateral salphigo-oopherectomy was performed. The histopathological examination revealed a bilateral Sertoli–Leydig cell tumor associated with a unilateral dermoid cyst. Conclusions: This case emphasizes the varied histopathological morphology of an ovarian neoplasm. (J GYNECOL SURG 29:33)

Treatment of high risk Sertoli–Leydig cell tumors of the ovary using a gonadotropin releasing hormone (GnRH) analog

Sertoli–Leydig cell tumors are rare ovarian neoplasms. We report two unusual cases with bilateral SLCTs suggesting evidence of genetic predisposition and at high risk of recurrence. To reduce this risk, we exploited the use of GnRH analog to lower gondadotropin and potentially directly inhibit the tumors through expressed GnRH receptors. We used it as maintenance antitumor therapy for 2 years after completion of chemotherapy, to cover the period of risk for recurrence. Both patients remain in complete remission at >2 years after completing leuprorelin therapy. Of note, both patients carry DICER1 mutations, frequently found in pleuropulmonary blastoma syndrome. Pediatr Blood Cancer 2013; 60: E16–E18. © 2012 Wiley Periodicals, Inc.

Sertoli-Leydig cell tumour: a rare cause of androgenic alopecia in post-menopausal women

Objective: Sertoli-Leydig cell tumour (SLCT) is a rare ovarian tumour often detected in young females between the ages of 20 and 30 years who usually presents with virilising features. We are describing an unusual case of Sertoli-Leydig cell tumour in a 57 year old postmenopausal woman who presented with progressive male pattern hair loss. She had high testosterone levels with poor response to medical therapy and underwent bilateral oophorectomy. Histology showed a Sertoli-Leydig cell tumour in the right ovary with benign characteristics and surgery resulted in an almost complete cure for the patient. Sri Lanka Journal of Diabetes, Endocrinology and Metabolism 2012; 2 : 111-113 DOI: http://dx.doi.org/10.4038/sjdem.v2i2.4782