Search Results (7)

This study aimed to describe the gross and histological features of multiple endocrine and non-endocrine neoplasia, including multiple PGLs found in two Boxer dogs. Additionally, the identified PGLs were immunohistochemically evaluated, and the subunits 2, 3, and 4 of the SDHD gene were screened for possible mutations. The tumors identified include aortic and carotid body PGLs, thyroid follicular-compact carcinoma, and subcutaneous lipomas. One case also had a Leydig cell tumor and adrenal cortex hyperplasia, while the other had H-type pancreatic carcinoma. Three out of 4 PGLs appeared benign, but one aortic body tumor showed malignant features with neoplastic emboli at its edge. Immunohistochemical analysis confirmed the neuroendocrine origin of all PGLs, with positive staining for Chromogranin A, NSE, and variable positivity for S100. No somatic mutations were found in exons 2, 3, and 4 of the SDHD gene in any of the evaluated PGLs. The absence of mutations in the evaluated SDHD gene subunits suggests the involvement of other genetic factors or pathways in the development of these tumors, warranting further investigation in this field. Full article

Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor (AR) gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient’s gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli–Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient’s karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations—a pathogenic frameshift deletion in the AR gene (c.77delT) and a likely pathogenic missense variant in the RAC1 gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads (n = 225; age: 4–84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases (n = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2–49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS. Full article

We report a case of a 19-year-old male referred to the Endocrine Unit because of gynecomastia. Initial investigation revealed elevated levels of estradiol (E2) along with secondary hypogonadism (hypotestosteronemia and severe oligoasthenoteratozoospermia (OAT)) despite normal testicular volume (12 mL) and secondary sexual characteristics. Surprisingly, an ultrasound examination revealed a small hypoechoic mass (1.1 cm) with intense intralesional vascularization within the right testicle, even though tumor markers were normal. Surgical removal of testicular mass led to the identification of Leydigioma, and the patient showed regression of gynecomastia during the nine-month follow-up. Unexpectedly, hypergonadotropinemia manifested along with normal testosterone (T) levels and significant improvement in OAT. Magnetic resonance imaging (MRI) showed pituitary hyperplasia (PH). Gynecomastia represents an atypical manifestation of Leydig cell tumors and typically resolves after surgical removal. However, unilateral orchiectomy may determine compensatory PH. Currently, it is uncertain whether the shift from hypogonadotropic to permanent hypergonadotropinemia was the only factor responsible for the high sperm count occurring in our patient. Further research is needed to elucidate the underlying mechanisms. Full article

Ovarian Leydig cell tumor is a rare type of ovarian steroid cell neoplasms, presenting in only 0.1% of all ovarian tumor cases, and is generally androgen-secreting and unilateral. Although they are often malignant non-spreading tumors, which have excellent prognosis, benign ovarian Leydig cell tumors with low-risk malignancy can be also detected. Ovarian hyperthecosis is a rare non-neoplastic disorder, in most cases bilateral. Ovarian tumors and ovarian hyperthecosis are one of the main causes of hyperandrogenism in postmenopausal women, a condition strongly associated with both hormonal and metabolic changes. Here, we report a 65-year-old patient with complaints of excessive body hairiness and alopecia. The laboratory investigation showed increased levels of serum testosterone and dehydroepiandrosterone sulfate (DHEA-S). Imaging, including transvaginal ultrasound and pelvic MRI revealed the presence of two masses in the ovaries. The patient underwent a laparoscopic bilateral salpingo-oophorectomy due to the ovarian tumors unknown etiology, and histopathological examination revealed a unilateral benign left ovarian Leydig cell tumor with bilateral ovarian stromal hyperplasia and ovarian hyperthecosis. Making differential diagnosis between ovarian tumors and ovarian hyperthecosis is difficult. Bilateral salpingo-oophorectomy is the treatment of choice in postmenopausal women with benign Leydig cell ovarian tumor, as well as ovarian hyperthecosis, as it offers both a cure and diagnostic confirmation. Full article

Pre-operative testicular tumor characterization is a challenge for radiologists and urologists. New data concerning imaging approaches or immunochemistry markers improve the management of patients presenting with a testicular tumor, sometimes avoiding radical orchiectomy. In the past 20 years, imaging modalities, especially ultrasound (US) and magnetic resonance imaging (MRI), improved, allowing for great progress in lesion characterization. Leydig cell tumors (LCT) are rare testicular tumors developing from the stromal tissue, with relatively scarce literature, as most of the studies focus on the much more frequent germ cell tumors. However, with the increase in testicular sonography numbers, the incidence of LCT appears much higher than expected, with some studies reporting up to 22% of small testicular nodules. Multimodal ultrasound using Doppler, Elastography, or injection of contrast media can provide crucial arguments to differentiate LCT from germ cell tumors. Multiparametric MRI is a second intention exam, but it allows for extraction of quantifiable data to assess the diagnosis of LCT. The aims of this article are to review the latest data regarding LCT imaging features, using multimodal ultrasound and multiparametric MRI, and to focus on the peculiar aspect of the testis of patients with Klinefelter’s syndrome. The possibility of an LCT should be raised in front of a small hypoechoic tumor with a marked corbelling hypervascularization in an otherwise normal testicular pulp. Ultrasonographic modules, such as ultrasensitive Doppler, contrast-enhanced ultrasonography, or elastography, can be used to reinforce the suspicion of LCT. MRI provides objective data regarding vascularization and enhancement kinetics. Full article

Background: Non-obstructive azoospermia (NOA) is a form of male infertility caused by disorders of the testicular parenchyma and impaired spermatogenesis. This study aimed to investigate the nature of Leydig cell changes in patients with NOA, especially whether their actual proliferation occurred. Methods: 48 testicular biopsies from infertile patients with NOA and 24 testicular biopsies originating from azoospermic patients suffering from obstructive azoospermia (OA) were included in the study. Leydig cells and their possible proliferative activity were analysed by immunohistochemistry and morphometry (stereology). Results: Unlike in the OA group, Leydig cells in NOA patients were sometimes organised into larger clusters and displayed an abundant cytoplasm/hypertrophy. Moreover, significant fibrosis of the interstitial compartment was demonstrated in some NOA samples, often accompanied by inflammatory cells. Stereological analysis showed no increase/proliferation of Leydig cells; on the contrary, these cells decreased in number in the NOA group. Conclusions: The decrease in the number of Leydig cells can be explained by previous inflammatory changes within the testicular interstitium and consequent interstitial fibrosis. The interstitial fibrosis might have a deteriorating effect on Leydig cells. Full article

Leydig cells contain significant amounts of constitutively produced steroidogenic acute regulatory protein (STAR; STARD1). Hormone-induced STAR plays an essential role in inducing the transfer of cholesterol into the mitochondria for hormone-dependent steroidogenesis. STAR acts at the outer mitochondrial membrane, where it interacts with a protein complex, which includes the translocator protein (TSPO). Mutations in STAR cause lipoid congenital adrenal hyperplasia (lipoid CAH), a disorder characterized by severe defects in adrenal and gonadal steroid production; in Leydig cells, the defects are seen mainly after the onset of hormone-dependent androgen formation. The function of constitutive STAR in Leydig cells is unknown. We generated STAR knockout (KO) MA-10 mouse tumor Leydig cells and showed that STAR KO cells failed to form progesterone in response to dibutyryl-cAMP and to TSPO drug ligands, but not to 22(R)-hydroxycholesterol, which is a membrane-permeable intermediate of the CYP11A1 reaction. Electron microscopy of STAR KO cells revealed that the number and size of lipid droplets were similar to those in wild-type (WT) MA-10 cells. However, the density of lipid droplets in STAR KO cells was drastically different than that seen in WT cells. We isolated the lipid droplets and analyzed their content by liquid chromatography–mass spectrometry. There was a significant increase in cholesteryl ester and phosphatidylcholine content in STAR KO cell lipid droplets, but the most abundant increase was in the amount of diacylglycerol (DAG); DAG 38:1 was the predominantly affected species. Lastly, we identified genes involved in DAG signaling and lipid metabolism which were differentially expressed between WT MA-10 and STAR KO cells. These results suggest that constitutive STAR in Leydig cells is involved in DAG accumulation in lipid droplets, in addition to cholesterol transport. The former event may affect cell functions mediated by DAG signaling. Full article