Juvenile granulosa cell tumor associated with Ollier disease.

Prior case reports have described synchronous ovarian juvenile granulosa cell tumor (JGCT) and enchondromatosis in patients with Ollier disease and Maffucci syndrome. We present a case of a juvenile granulosa cell tumor with an IDH1 somatic mutation identified in the ovarian tissue in a 15-year-old female who presented with abnormal vaginal bleeding, several months of irregular menses, and a large multicystic adnexal mass. Multiple mixed lytic and sclerotic lesions were identified in the bones of the pelvis on imaging studies obtained during the work-up of her abdominal mass. Like previous reports in patients with undiagnosed enchondromatosis, these lesions were presumed to represent skeletal metastases; however, biopsy tissue revealed a hyaline cartilage neoplasm. Subspecialty review of the imaging findings revealed imaging features classic for Ollier disease involving the flat bones of the pelvis. It is important for radiologists to be familiar with the association between enchondromatosis and JGCT. When a female patient with enchondromatosis presents with a large, unilateral, mixed solid-cystic ovarian mass, the diagnosis of JGCT can be suggested. Alternatively, when a patient is diagnosed with JGCT, any skeletal lesions should be scrutinized for imaging features that suggest a hyaline cartilage neoplasm to avoid the misdiagnosis of skeletal metastases in a patient with previously undiagnosed Ollier disease or Maffucci syndrome. To our knowledge, this is the second reported confirmed case of an IDH1 somatic mutation identified in the ovarian tissue of a JGCT in a patient with Ollier disease.

Hyperestrogenemia resulting from a granulosa cell tumor and causing pulmonary thromboembolism: a case report.

Estrogen modulates platelet activation and aggregation, and it increases the levels of the von Willebrand factor, factors II, VII, VIII, and X, and of fibrinogen, all of which increase the risk for thromboembolism. We report the case of a 59-year-old woman, postmenopausal for 4 years, not using hormone replacement therapy, who was admitted into the emergency room with shortness of breath and increased abdominal volume. After physical examination and imaging and biochemical tests, she was diagnosed with pulmonary thromboembolism and a large left adnexal tumor. The patient was promptly received full anticoagulation therapy for the pulmonary thromboembolism. High levels of estradiol (810.4 pg/mL), anti-Mullerian hormone (16.39 ng/mL), inhibin (11250 pg/mL), and suppressed FSH (<0.16 IU/L) led to a suspicion of granulosa-cell tumor. After clinical stabilization, she underwent to an exploratory laparotomy with total hysterectomy and bilateral adnexectomy to treat the pelvic tumor. Pathologic report confirmed a granulosa-cell tumor.

Androgen-secreting adult granulosa cell tumor in a woman with polycystic ovary syndrome: a case report.

Aim: To present the clinicopathologic findings of the second case of androgen-secreting adult granulosa cell tumor (AGCT) in a woman with polycystic ovary syndrome (PCOS) and discuss in the light of the literature. Methods: Description of a case and discussion of the literature. Results: A patient with oligomenorrhea, amenorrhea and hirsutism who was diagnosed as PCOS and treated by oral contraceptive for three years, then left ovarian solid and liquid mass was found and pathologically confirmed to be androgen-secreting AGCT after left oophorectomy. She got regular menstrual cycle and gave birth naturally, but clinical features of PCOS reappeared after breastfeeding. Conclusion: Androgen-secreting AGCT and PCOS have similar clinical features of hyperandrogenism, it is difficult to diagnose androgen-secreting AGCT when both diseases occur in the same patient. If the size of cystic mass in androgen-secreting AGCT is too small to differentiate from PCOM on imaging, pathological examination after surgery may be the only way to find the disease.

Multiple Luteinized Follicle Cysts of the Ovary in a Patient With a Pituitary Adenoma: Report of a Case and Review of the Literature.

The case of a 36-yr-old woman with a pituitary adenoma who was found to have bilateral ovarian masses is reported. The right ovary was removed, measured 15 cm in maximum dimension, and contained multiple cysts which on microscopic examination had the typical morphology of follicle cysts. The left ovary was grossly similar intraoperatively. Subsequent excision of the pituitary adenoma was followed ∼3 mo later by a return to normal size of the left ovary. The case represents an example of multiple luteinized follicle cysts, analogous to the phenomenon seen occasionally in pregnancy, but with a different clinical background. Periodic documentation of this phenomenon is present in the literature, predominantly the clinical literature with limited pathologic documentation of the nature of the process in many reports. As pertains to the evaluation of follicle cysts encountered during pregnancy the differential diagnosis is with a cystic granulosa cell tumor of either adult or juvenile types, more likely the latter. The cyst lining is identical to that of standard follicle cysts and contrasts with the immature mitotically active nuclei seen in a juvenile granulosa cell tumor. That neoplasm also usually shows follicular differentiation typically absent in follicle cysts. Pathologists should be aware of the rare occurrence of luteinized follicle cysts in patients with a pituitary adenoma to enable correct intraoperative and standard pathologic evaluation.

[Granulosa cell ovarian tumor: precocious puberty in infant less than 1 year of age. Case report]. / Tumor de las células de granulosa: pubertad precoz en lactante menor de 1 año. Caso clínico.

INTRODUCTION: Juvenile granulosa cell tumors (JGCT) are very rare, especially in infants under the age of one. The most frequent presentation is with signs of precocious puberty. OBJECTIVE: Present an in fant with peripheral precocious puberty, diagnosis of JGCT and follow up. CLINICAL CASE: 10-month-old female infant with thelarche, pubic hair and palpable abdominal mass accompanied with eleva ted levels of estradiol, very low gonadotrophins and images that show a very large ovarian mass. A sapingooforectomy was carried out with full regression of symptoms and signs and improvement of laboratory exams. The biopsy showed TCGJ so inhibin B (InB) was taken as tumoral marker after surgery. This hormone was high initially, but rapidly declined. Follow-up was based on InB, antimu-llerian Hormone (AMH) and estradiol as described in this type of tumors. CONCLUSIONS: Juvenil gra nulosa cell tumors are very infrequent in pediatric age, but should be suspected in girl with peripheral precocious puberty. The majority of cases improve with surgery, but strict surveillance of tumoral markers is needed. The most specific markers are inhibin B and anti mullerian hormone (AMH), followed by estradiol levels.

[Peripheral precocious puberty]. / Periferní predcasná puberta (pseudopubertas praecox).

OBJECTIVE: To summarize literature data on peripheral precocious puberty. DESIGN: A literature review. SETTING: Stredomoravská nemocnicní a.s., hospital Sternberk, Department of Obstetrics and Gynaecology, University Hospital, Medical Faculty, Palacky University, Olomouc. METHODS AND RESULTS: We searched in PubMed using the key words stated below according to date and published since 1980.Peripheral precocious puberty occurs in girls with the frequency 1:400-1000. It develops mainly because of peripheral estrogen secretion, the main cause of which are autonomous ovarian cysts. Other causes include McCune Albright syndrome, juvenile granulosa cell tumor and primary hypothyroidism. Typically, peripheral precocious puberty presents with early breast enlargement followed by development of other secondary sex characteristics. Initial treatment is usually conservative with the exception of juvenile granulosa cell tumor where surgery is warranted. Peripheral precocious puberty anti-estrogen therapy seems promising but neither data on its influence on fertility nor data comparing it to surgical treatment are available. Due to the risk of progression into central precocious puberty or McCune Albright syndrome, long-term follow-up is necessary. CONCLUSION: Peripheral precocious puberty should be managed in pediatric gynecology outpatient office and often subsides spontaneously. However, it can also be a sign of malignancy. In most cases, conservative therapy is preferred with medical treatment and surgery warranted in complicated cases. However, optimal treatment has not been established yet.

Granulosa cell tumor presenting with ovarian torsion and de novo borderline mucinous ovarian tumor in the contralateral ovary.

The authors report a case of 25-year-old women with a rare acute presentation of granulosa cell tumor (GCT) as an ovarian torsion. Right salpingoo-ooferectomy was performed. The pathological diagnosis was GCT One month after the surgery there was a three-cm ovarian cyst in the contralateral ovary and the tumor size increased to six cm in diameter in the following month. Serum inhibin-B levels progressively increased. Cystectomy was performed to contralateral ovary as frozen-section examination indicated mucinous tumor. Final histopathological examination revealed borderline mucinous tumor. Regarding her request, the patient was reoperated again and unilateral oophorectomy and hysterectomy were performed. Clinicians must be aware of the possibility of an underlying malignancy associated with adnexal torsion even in young patients. Frozen section will be helpful in order to avoid incomplete surgeries. Cyst rapidly growing in the ovary in young women should raise the suspicion of a de novo malignancy.

[Haemoabdomen and haemothorax in a cow with metastatic granulosa cell tumor]. / Hämoabdomen und Hämothorax bei einem Rind mit metastasierendem Granulosazelltumor.

This case report describes the clinical, ultrasonographic, pathological and histological findings in a two-year-old Swiss Braunvieh cow with granulosa cell tumor and metastases in the abdomen and thorax. The cow was ill and had tachycardia, coughing, increased breath sounds, positive reticular foreign body tests and a tense abdominal wall. Ultrasonography revealed a massive accumulation of hypoechoic fluid in the thorax and abdomen, and abdomino- and thoracocentesis yielded red fluid indicative of abdominal and thoracic haemorrhage. Because of a poor prognosis, the cow was euthanized and examined postmortem. Multiple nodular lesions were seen in the omentum, liver, spleen and lungs. The left ovary was grossly enlarged and nodular in appearance. Histological examination of the lesions revealed granulosa cell tumour of the left ovary and metastases in the omentum, liver, spleen and lungs.

Recurrence of adult granulosa cell tumor of the ovary: experience at a tertiary care center.

Adult granulosa cell tumor (AGCT) is the most common ovarian sex cord stromal tumor with a favorable prognosis. However, a subset of patients develop recurrence. We retrieved and reviewed 156 cases of AGCT reported between 1992 and 2012. The ages ranged from 20 to 84 years (mean, 48 years). The size of the tumor ranged from 0.8 to 25 cm (mean, 10 cm). Histologically, all tumors were composed of round or polygonal cells with indented or grooved nuclei, eosinophilic cytoplasm, and well defined cell borders. A diffuse pattern was seen in the majority followed by microfollicular, trabecular and macrofollicular. The mitotic figures ranged from 2 to a maximum of 21/10 HPFs. Focal necrosis were seen in 17 cases. Associated simple hyperplasia of endometrium was seen in 9 cases, complex hyperplasia in 2, and endometrioid adenocarcinoma of the endometrium in 3 cases. Recurrence was seen in 8 cases with a follow-up of 2 to 19 years (mean, 6 years). The recurrent tumors were mostly >5 cm and sites included the same adnexal site and contralateral ovary, omentum, mesentery of small bowel, abdominal wall, uterine and fallopian tube serosa, lymph nodes, pelvis, and appendix. Histologically, recurrent tumors exhibited a diffuse histologic pattern and a mitotic count of 6.8 as compared to 3.3 in primary tumors. In conclusion, a tumor size of >5 cm and a diffuse histologic pattern were associated with increased recurrence risk. The recurrent tumors hadz increased mitotic figures compared with primary tumors. Appendix, a very rare site of recurrence was seen in one of our cases.

Granulosa cell tumor and concurrent endometrial cancer with (18)F-FDG uptake.

The findings and the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the diagnosis of ovarian granulosa cell tumor (OG) are described. We present the pre-operative findings of (18)F-FDG PET/CT scan of a case of OG concurrent with endometrium cancer and endometrial hyperplasia, which revealed a 48mm mass demonstrating mild increased metabolic activity on the right ovary. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Frozen and paraffin-enbeded sections showed an encapsulated OG. There were few mitoses. There was concurrent atypical endometrial hyperplasia. In conclusion, we reported a case of an encapsulated OG, which showed mild uptake of the (18)F-FDG with concurrent endometrial cancer. There has been only one report of (18)F-FDG findings in primary ovarian granulosa cell tumor, similar to ours.

Ovarian granulosa cell tumor and increased risk of breast cancer.

Granulosa cell tumor of the ovary (GCT) is a rare neoplasm. The tumor often secretes estrogens and then presents at an earlier stage due to hormone-related symptoms. GCT women are at increased risk of endometrial carcinoma, but there is only limited information about GCTs and potential association to other hormone-related neoplasms such as breast cancer. We conducted a retrospective follow-up study on 163 women with GCT. Medical records and histological sections were reviewed and a search in the pathology registry performed. Eight [95% confidence interval (CI); 3.4-15.8] GCT women were diagnosed with a breast neoplasm; one with Paget's disease of the nipple and seven with breast carcinoma. Based on calculations using incidence rates on breast cancer among Danish women, we would have expected 2.5 cases of breast cancer. The odds ratio was 3.3 (95% CI, 1.6-6.6), suggesting an increased risk of breast cancer in GCT women.

Increasing hirsutism due to a granulosa-cell tumor in a woman with polycystic ovary syndrome: case report and review of the literature.

BACKGROUND: Granulosa-cell tumors (GCT), rare malignancies that arise from sex-cord stromal cells, account for less than 5% of ovarian tumors. These tumors present with an endocrine syndrome and mass signs. Surgery is the primary treatment approach. The risk of recurrence is more frequent in the juvenile-onset form. CASE REPORT: We report the case of an obese 18-year-old Caucasian women with hirsutism and oligomenorrhea. Abdominal palpation revealed a voluminous firm mass. Hormonal evaluation documented severe hyperandrogenism. The ovary-specific tumor marker CA125 was elevated, whereas human-chorionic-gonadotropin was in the normal range. Abdominal imaging examination revealed a 19 cm mass in the left ovary. Twenty-four hours after removal of the mass, menstrual flow reappeared and androgens progressively normalized. Microscopically, the predominant pattern was one of uniform, bland, epithelioid to spindle-shaped cells. After three months, a significant weight loss was recorded, hirsutism had decreased slightly and oligomenorrhea reappeared. Δ4-Androstenedione levels remained elevated (4200 ng/L), whereas CA125 had normalized. In light of the pre-existing polycystic-ovary-syndrome (PCOS), the patient started estrogen-progestin treatment. CONCLUSION: We report an interesting case of a woman with severe hirsutism due to GCT, and a history of oligomenorrhea caused by PCOS. After surgery, a dramatic clinical improvement was observed, whereas PCOS signs persisted.

Hemoperitoneum and acute abdomen caused by the rupture of ovarian granulosa cell tumor: a case report.

Granulosa cell tumors (GCT) constitute 70% of all ovarian sex-cord stromal tumors, which account for less than five percent of all ovarian carcinoma. The authors herein report a rare case of a ruptured GCT of the ovary in a 43-year-old female who was admitted to the emergency department with signs of acute abdomen.

An unusual coincidence of giant cervical leiomyoma and incidental ovarian granulosa cell tumor: A case report.

RATIONALE: Leiomyomas are the most common benign tumors of smooth muscle origin in women. They are most frequently found in the submucosal tissue of the uterine corpus; however, they also occur in other areas of the uterus, including the cervix. Their size usually varies between 0.5 to 1.0 cm; however, they can reach great dimensions. A strong correlation between the onset and growth of leiomyomas and estrogen levels was observed. Granulosa cell tumor (GCT) is an infrequent sex cord-stromal ovarian neoplasm. Despite their malignancy, GCTs have a good long-term prognosis. In this study, we present a unique case of coincidence of 2 tumors: leiomyoma of rare location (cervix uteri) and extraordinary size (9, 04 cm diameter) with an adult granulosa cell tumor. PATIENT CONCERNS: A 67-year-old Caucasian woman was transported from an emergency ward to a gynecological surgery department due to a massive vaginal hemorrhage. DIAGNOSES: Preliminary examination showed a presence of an enormous uteri cervix tumor. INTERVENTIONS: Initially, the patient underwent physical and ultrasound examinations. To prevent further bleeding, an urgent surgery (hysterectomy) with bilateral salpingo-oophorectomy was performed. OUTCOME: Postoperative histopathological examination revealed a cervical leiomyoma and the incidental occurrence of an adult GCT in the right ovary. LESSONS: This case shares an interesting coincidence between a rare variant of leiomyoma and GCT. The study suggests that the potential reason for this can be estrogen secreted by the GCT, which causes the enormous size of the patient's cervical leiomyoma and the severe vaginal bleeding. Therefore, we advise it is important in abnormal cases to search for other hidden explanations, as in cases of GCT.

A 12-Year-Old Girl with Juvenile Granulosa Cell Tumor of the Ovary, Presenting with Adolescent Hyperprolactinemia, Galactorrhea, and Amenorrhea.

BACKGROUND Juvenile-type granulosa cell tumors (JGCTs) are a rare subtype of sex cord stromal tumor with a characteristic histology that is commonly found in the first 3 decades of life. It most commonly presents with symptoms of hyperestrogenism, which may present as precocious pseudopuberty or as menstruation-related symptoms, allowing for early detection of the tumor. CASE REPORT We present the case of a 12-year-old girl who presented to her primary care provider (PCP) with secondary amenorrhea with intermittent abdominal pain, who underwent an ultrasound for further evaluation, which revealed a large incidental pelvic mass. She was admitted to the Emergency Department (ED) and had findings of galactorrhea and hyperprolactinemia on examination. Imaging studies demonstrated a large ovarian mass measuring 15.0×9.0×18.8 cm that was resected, and subsequent pathology results showed JGCT stage 1A. CONCLUSIONS Prognosis of granulosa cell tumors (GCT) largely depends on its initial size, stage at diagnosis, residual tumors after surgery, and the subtype of GCT. If the patient is of reproductive age, fertility-sparing surgical options must be considered and patients must be regularly monitored for recurrence. JGCTs can present with minimal to no symptoms of precocious puberty in young girls but may present with amenorrhea, which may be considered normal for their developmental age. Although JGCTs are rare, they are important to include in differential diagnoses of younger female patients with abdominal pain, especially if accompanied by hormonal irregularities.

Sclerosing peritonitis associated with a luteinized adult granulosa cell tumor.

Sclerosing peritonitis is an uncommon condition that has been reported in patients with luteinized ovarian thecomas, although some pathologists have suggested that the underlying ovarian pathology is not always neoplastic. We now report sclerosing peritonitis in a patient with an uncommon, luteinized variant of an adult granulosa cell tumor. To the best of our knowledge, this association has not been described previously. We suggest that sclerosing peritonitis may result from the release of substances by luteinized ovarian stromal cells, in the context of hyperplasia or neoplasia, which stimulate the proliferation of submesothelial fibroblasts.

Primary amenorrhea due to juvenile granulosa-cell tumor of the ovary: a case report.

In general, primary amenorrhea is caused by gonadal dysgenesis, anomalies of internal or external genitalia with or without chromosomal anomalies, and sometimes by hormonal abnormalities that affect the hypothalamus, pituitary, ovaries, adrenals or thyroid, or by chronic or metabolic diseases. We report a rare case of a juvenile granulosa-cell tumor of the ovary that caused primary amenorrhea in a 16-year-old girl. Her hormonal profiles before the operation were characterized by an extremely low level of follicle-stimulating hormone (FSH), a relatively low level of estradiol and a high level of inhibin B. The patient had menarche after the removal of the tumor. Her elevated serum FSH after the operation was the result of a decreased serum level of inhibin that had been produced by the tumor. The present case highlights that a granulosa-cell tumor, known as an inhibin-secreting tumor, should be considered when treating primary amenorrheic girls.

Postmenopausal bleeding should be referred urgently.

Postmenopausal bleeding is an episode of bleeding 12 months or more after the last menstrual period. It occurs in up to 10% of women aged over 55 years. All women with postmenopausal bleeding should be referred urgently. Endometrial cancer is present in around 10% of patients; most bleeding has a benign cause. The peak incidence for endometrial carcinoma is between 65 and 75 years of age. Causes of postmenopausal bleeding include: endometrial carcinoma; cervical carcinoma; vaginal atrophy; endometrial hyperplasia +/- polyp; cervical polyps; hormone-producing ovarian tumours; haematuria and rectal bleeding. The aim of assessment and investigation of postmenopausal bleeding is to identify a cause and exclude cancer. Assessment should start by taking a detailed history, with identification of risk factors for endometrial cancer, as well as a medication history covering use of HRT, tamoxifen and anticoagulants. Abdominal and pelvic examinations should be carried out to look for masses. Speculum examination should be performed to see if a source of bleeding can be identified, assess atrophic changes in the vagina and look for evidence of cervical malignancy or polyps. Ultrasound scan and endometrial biopsy are complementary. Ultrasound scan can define endometrial thickness and identify structural abnormalities of the uterus, endometrium and ovaries. Endometrial biopsy provides a histological diagnosis. The measurement of endometrial thickness aims to identify which women with postmenopausal bleeding are at significant risk of endometrial cancer. If the examination is normal, the bleeding has stopped and the endometrial thickness is < 5 mm on transvaginal ultrasound scan, no further action need be taken.

Ovarian cell tumor in a child with neurofibromatosis type 1.

Juvenile granulosa cell ovarian tumor is a rare cause ofpseudo-precociouspuberty. We report a case of a 6-year-old female with neurofibromatosis type 1 (NF1), associated with pseudo-precocious puberty (PPP). A thorough workup revealed a large multi-cystic right ovarian mass, which turned out to be a juvenile granulosa cell tumor (JGCT). This report documented a rare case of PPP caused by JGCT in a child with NF1. Verbal consent was taken from the family.

Résumé La tumeur ovarienne juvénile à cellules de la granulosa est une cause rare de puberté pseudo-précoce. Nous rapportons le cas d'une fillette de 6 ans atteinte de neurofibromatose de type 1 (NF1), associée à une puberté pseudo-précoce (PPP). Un bilan approfondi a révélé une grande masse ovarienne droite multikystique, qui s'est avérée être une tumeur juvénile des cellules de la granulosa (JGCT). Ce rapport a documenté un cas rare de PPP causé par JGCT chez un enfant atteint de NF1. Le consentement verbal a été recueilli auprès de la famille.. Mots-clés: Cellule de la granulosa, juvénile, neurofibromatose, tumeur ovarienne, puberté précoce.