Search Results (6)

DICER1 syndrome (DICERs) represents a tumor predisposition genetic syndrome, inherited in an autosomal dominant manner. Germline loss-of-function variants of the DICER1 gene lead to impaired processing of microRNA, gene expression, and increased risk of tumorigenesis. Although pleuropulmonary blastoma (PPB) is the hallmark of the syndrome, multiple extrapulmonary malignant and non-malignant conditions have also been described, including multinodular goiter (MNG) and sex-cord stromal tumors. MNG is one of the most common components and is associated with an increased risk of thyroid carcinoma. Sertoli–Leydig cell tumor (SLCT) represents the most prevalent type of sex-cord stromal tumor associated with the syndrome, whereas juvenile granulosa cell tumor (JGCT) is considered to be a very rare phenotype. They both may present with abdominal pain due to mass effect and menstrual irregularities in case of hormone production. Although they exhibit low rates of mortality, recurrence rates highly depend on the grade of malignancy. Herein, we report a novel pathogenic DICER1 variant associated with MNG, bilateral ovarian SLCT, and JGCT in a young Greek patient. Clinicians should be aware of a potential germline DICER1 variant when evaluating MNG in young patients, especially if it coexists with other neoplasms. Full article

Testicular granulosa cell tumors (TGCTs) are rare tumors of sex cord-stromal origin. TGCTs are classified into two main categories, the adult type and the juvenile type. The adult type is extremely rare, with only 93 known cases reported in the literature. Herein, we present a report of a case of a 30-year-old male patient who presented with a testicular mass and underwent radical inguinal orchiectomy; the pathology examination revealed an adult-type granulosa tumor. Additionally, we review the literature to summarize the scientific knowledge of an entity barely described worldwide. Full article

Fas-associated factor 1 (FAF1), a member of the Fas family, is involved in biological processes such as apoptosis, inflammation, cell proliferation and proteostasis. This study aimed to explore the biological role of FAF1 in testicular tissue at different ages (juveniles (1 and 2 years old), adults (3, 4, 6, and 7 years old) and old-aged animals (11 years old)) and ovaries during different reproductive cycle phases (follicular, luteal, and pregnancy phases). FAF1 mRNA, relative protein expression and protein expression localization were determined in testes and ovaries using real-time quantification, WB and immunohistochemistry (IHC), respectively. Real-time quantification of testis tissues showed that the relative expression of FAF1 mRNA in testis tissues at 3, 4 and 7 years of age was significantly higher than of those in other ages, and in ovarian tissues was significantly higher in luteal phase ovaries than those in follicular and pregnancy phase ovaries; follicular phase ovaries were the lowest. WB of testis tissues showed that the relative protein expression of FAF1 protein was significantly higher at 11 and 7 years of age; in ovarian tissue, the relative protein expression of FAF1 protein was significantly higher in follicular phase ovaries than in luteal and pregnancy phase ovaries, and lowest in luteal phase ovaries. The relative protein expression of FAF1 at 3, 4 and 7 years of age was the lowest. IHC showed that FAF1 was mainly expressed in spermatozoa, spermatocytes, spermatogonia and supporting cells; in ovarian tissue, FAF1 was expressed in ovarian germ epithelial cells, granulosa cells, cumulus cells and luteal cells. The IHC results showed that FAF1 mRNA and protein were significantly differentially expressed in testes of different ages and ovarian tissues of different reproductive cycle phases, revealing the significance of FAF1 in the regulation of male and female B. grunniens reproductive physiology. Furthermore, our results provide a basis for the further exploration of FAF1 in the reproductive physiology of B. grunniens. Full article

Juvenile in vitro embryo technology (JIVET) provides exciting opportunities in animal reproduction by reducing the generation intervals. Prepubertal oocytes are also relevant models for studies on oncofertility. However, current JIVET efficiency is still unpredictable, and further improvements are needed in order for it to be used on a large-scale level. This study applied bioengineering approaches to recreate: (1) the three-dimensional (3D) structure of the cumulus–oocyte complex (COC), by constructing—via bioprinting technologies—alginate-based microbeads (COC-microbeads) for 3D in vitro maturation (3D-IVM); (2) dynamic IVM conditions, by culturing the COC in a millifluidic bioreactor; and (3) an artificial follicular wall with basal membrane, by adding granulosa cells (GCs) and type I collagen (CI) during bioprinting. The results show that oocyte nuclear and cytoplasmic maturation, as well as blastocyst quality, were improved after 3D-IVM compared to 2D controls. The dynamic 3D-IVM did not enhance oocyte maturation, but it improved oocyte bioenergetics compared with static 3D-IVM. The computational model showed higher oxygen levels in the bioreactor with respect to the static well. Microbead enrichment with GCs and CI improved oocyte maturation and bioenergetics. In conclusion, this study demonstrated that bioengineering approaches that mimic the physiological follicle structure could be valuable tools to improve IVM and JIVET. Full article

Ovarian gynandroblastoma (GAB) is an extremely rare sex cord-stromal tumor showing morphological evidence of both female (granulosa cell tumor) and male (Sertoli–Leydig cell tumor (SLCT)) components. Almost all GAB cases have been reported in children, adolescents, or women of reproductive age, and most of them typically have adult granulosa cell tumors as the female component. In contrast, GAB with a juvenile granulosa cell tumor (JGCT) component is a very rare condition; to the best of our knowledge, only one case of GAB with JGCT in a postmenopausal woman has been reported. In this report, we present an extremely rare case of ovarian GAB with JGCT in an elderly patient. A 65-year-old woman presented with an abdominal mass. Abdominopelvic magnetic resonance imaging revealed a large multiseptated cystic mass measuring 20 cm. No peritoneal seeding, lymph node enlargement, or hematogenous metastasis was identified. Laboratory test showed a slight elevation of serum CA 125 level (37.1 U/mL). Based on the preoperative clinical impression of ovarian cancer, she underwent a total hysterectomy with bilateral salpingo-oophorectomy. Grossly, the ovarian mass had a smooth and glistening surface without excrescences. The cut sections showed yellow-to-tan solid areas with foci of necrosis, myxoid degeneration, and hemorrhage, as well as multilocular cystic cavities filled with serosanguinous fluid. Histologically, the female component was characterized by JGCT displaying nodular growth patterns with follicle-like structures of various shapes and sizes. Most of the microcysts contained eosinophilic or basophilic secretions. The JGCT cells had indistinct cell borders, an abundant eosinophilic cytoplasm, and round-to-oval hyperchromatic nuclei with many mitotic figures. The SLCT component consisted predominantly of intermediately differentiated Sertoli cells forming lobulated solid nodules. They were arranged in cords, solid tubules, or nests, and possessed oval-to-spindle-shaped darkly stained nuclei and scant cytoplasm. In several foci, well-formed Sertoli cell tubules were loosely aggregated within areas of moderately differentiated SLCT. In summary, we described GAB in a postmenopausal woman with JGCT and SLCT as the female and male components, respectively. This is the second case of GAB with JGCT occurring in an elderly patient. Our findings can help pathologists and clinicians make accurate histological diagnoses of GAB with a JGCT component and plan an adequate treatment strategy for this rare tumor. Full article

Ovarian tumors associated with hormonal changes of the peripheral iso-sexual precocious puberty are of common presentation. We describe here a rare case of juvenile granulosa cell tumor in a female with central precocious puberty (CPP). An 8-year old girl with CPP presented with vaginal bleeding four months after the diagnosis and before starting treatment with gonadotropin-releasing hormone (GnRH)-analogs. Suppression of basal follicle-stimulating hormone (FSH) level, elevation of serum estradiol, progesterone and Cancer Antigen-125 were documented. Abdominal ultrasound examination (US) and magnetic resonance imaging showed a pelvic mass affecting the left ovary. A left salpingo-oophorectomy was performed and the mass was totally resected. Juvenile granulosa cell ovarian tumor was diagnosed. One month post surgery, estradiol and progesterone decreased to values of the first evaluation and FSH increased; Cancer Antigen-125 resulted normal while ultrasound pelvic examination showed absence of pelvic masses. In our patient, the tumor had grown very quickly since hormonal data demonstrated a CPP without any evidence of ovarian mass on US only four months before diagnosis. The overstimulation of the FSH or aberrant activation of FSH receptors may have contributed to the development of the mass. Full article