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Background: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord–stromal tumour in men, representing 1%–3% of all testicular neoplasms. Among testicular sex cord–stromal tumours, CTNNB1 mutations and nuclear expression of β‐catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of β‐catenin alterations remain incompletely understood in this tumour type. Methods: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using β‐catenin immunohistochemistry and DNA sequencing. Results: Immunohistochemistry revealed focal or multifocal nuclear β‐catenin expression in 47% of the tumours. Diffuse nuclear β‐catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of β‐catenin‐positive and β‐catenin‐negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional β‐catenin‐positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively. Conclusion: These results demonstrate that β‐catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of β‐catenin in this tumour type. [ABSTRACT FROM AUTHOR]

Leydig Cell Tumor (LCT) is very rare in adults. It constitutes only 1% of total testicular tumors. LCTs can produce steroid hormones such as estrogen, progesterone, and testosterone. Sertoli cells are found in seminiferous tubules, they are part of the blood-testis barrier. Sertoli Cells Only Syndrome (SCOS) also known as germ cell aplasia is characterized by azoospermia in which the seminiferous tubules of testicular biopsy are lined only with Sertoli cells. The expected hormone profile in SCOS is increased FSH with normal T and LH. The expected hormone profile in LCT is increased/normal FSH and LH with increased T or E2. A patient presented to our clinic with a well-circumscribed mass in his right testicle and underwent radical orchiectomy. Tumor markers were negative. Azoospermia was detected in the spermiogram. T and E2 were normal, FSH, and LH were high. Right radical orchiectomy was performed. A combination of LCT and SCOS were reported in pathology results. Azoospermia cases secondary to high androgen levels are frequently encountered in LCTs. As in the case we have presented, two different testicular pathologies may present at the same time and create an unexpected hormonal picture. Such situations can cause the laboratory to mask the clinical truth. [ABSTRACT FROM AUTHOR]

Purpose: Serum levels of microRNA-371a-3p (M371) have been shown to be a highly sensitive and specific biomarker for testicular germ cell tumours (TGCT). Little information exists on the expression of this marker in testicular neoplasms deriving from the gonadal stroma or other structures of the gonad. This study presents an expression analysis of the novel TGCT-biomarker M371 in a large cohort of testicular non-germ cell tumours. Methods: The M371 expression was measured by quantitative real time PCR in serum of 99 patients with testicular tumours of non-germ cell origin, thereof 30 patients with malignant testicular lymphomas and 61 patients with gonadal stroma tumours such as Leydig cell tumours, Sertoli cell tumours and 8 cases with miscellaneous benign testicular tumours. Their M371 levels were compared to those of 20 patients with TGCT and to 37 tumour-free male controls. Results: The median expression levels of benign testicular tumours and testicular lymphoma are close to zero, thus, identical with those of controls and significantly lower than those of TGCT. In summary, this study provides further evidence for the notion that M371 is exclusively expressed by germ cell tumours and not by testicular neoplasms of the non-germ cell subtypes. Conclusion: Clinically, the test might be of value in preoperative characterization of benign testicular tumours eligible for conservative surgery. [ABSTRACT FROM AUTHOR]

Aims: To investigate the morphological and molecular characteristics of Leydig cell tumours (LCTs) of the testis for the identification of cases that may metastasise. Methods and results: Six parameters for a predictive model of the metastatic risk were evaluated in 37 benign and 14 malignant LCTs of the testis [LCT Scaled Score (LeSS)]. The tumour size (benign LCTs, mean 13.3 mm; malignant LCTs, mean 44 mm) (P < 0.001) and five other parameters (infiltrative margins, necrosis, vascular invasion, mitotic count, and nuclear atypia) showed significant differences (Wilcoxon's test, P < 0.001). Eight metastatic LCTs and one benign LCT had infiltrative margins. Foci of coagulative necrosis occurred in 10 metastatic LCTs, whereas vascular invasion was identified in nine of 14 metastatic LCTs and none of 37 benign LCTs. Benign LCTs showed <2 mitoses/10 high-power fields (HPFs), whereas a high mitotic count (range, 3-50 mitoses/10 HPFs) was a feature of malignant LCTs. These parameters were selected by use of an inferential analysis based on univariate logistic regression models to develop a score. A LeSS of <4 correctly identified all histologically and clinically benign LCTs. A LeSS of ≥4 correctly identified all malignant LCTs. MDM2 and CDK4 immunostains were applied in all 51 cases: benign LCTs were negative; three of 11 malignant LCTs (27%) showed strong and diffuse immunopositivity and high levels of MDM2 and CDK4 amplification as determined with fluorescence in-situ hybridisation analysis and next-generation sequencing. Conclusion: We provide a new tool, the LeSS, for the prediction of malignant behaviour in LCTs. [ABSTRACT FROM AUTHOR]

Purpose: Leydig-cell tumours (LCT) of the testis are poorly understood clinically. The aim of this report is to analyse the clinical characteristics of LCT in a large patient sample and to compare these findings with corresponding data of germ-cell tumours (GCT). Methods: In a sample of 208 patients treated during 1995–2017 in 33 institutions, the following characteristics were registered: age, presenting symptoms, primary tumour size, testis-sparing surgery (TSS) or orchiectomy, malignancy, laterality, medical history, and outcome. Data analysis included descriptive statistical methods and logistic regression analysis. Results: The ratio LCT:GCT is 1:23 (4.4%). The findings are as follows: median age 41 years, undescended testis 8%, bilateral LCTs 3%, malignant LCT 2.5%, contralateral GCT 2.5%, incidental detection 28%, scrotal symptoms 43%, infertility 18%, elevated estradiol levels 29%. TSS was performed in 56% with no local relapse. Of the patients with malignant LCT, one was cured through surgery. Conclusion: LCT is rare, with a relative frequency (relative to GCT) of 1:23. Malignancy is found in 2.5%. LCT and GCT share a number of clinical features, e.g. bilaterality, history of undescended testis, and presenting age. TSS is safe in benign LCT. Surgery is the treatment of choice in malignant LCT. [ABSTRACT FROM AUTHOR]

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Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro. Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation.

There are various cause of Primary amenorrhea in phenotypically females such as, complete androgen insensitivity syndrome, pure gonadal dysgenesis, 17b-hydroxysteroid dehydrogenase deficiency, or mixed gonadal dysgenesis. Primary amenorrhea in a phenotypically female is commonly encountered in Androgen insensitivity syndrome. In patients of AIS with intra-abdominal testis there is high chances of developing testicular tumour, among them Sertoli cell tumour and seminoma being the most common types. Leydig cell tumour in AIS is very rare and malignant leydig cell tumour is even further rarer. There are few case reported in the literatures of malignant leydig cell tumour with complete androgen insensitivity. Here we are reporting a case of 65 years married elderly patient with malignant leydig cell tumour with CAIS.

Leydig cell tumours of the ovary are rare and represent a diagnostic challenge not only due to their sporadic incidence but also due to the seemingly normal imaging. We present three cases of pre- and postmenopausal women who were presented with severe clinical signs of hyperandogenism where modern imaging modalities (including computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography combined with computed tomography (PET-CT)) failed to identify the tumour. Two patients underwent non-expert ultrasound, CT and MRI examination with uniform conclusion that ovaries are of normal appearance. One of the two patients even had a PET-CT performed, which was inconclusive. Our case reports show the importance of examination by specialists with established skills in gynaecologic ultrasonography in the diagnosis of the Leydig cell tumours. The most useful diagnostic tool seems to be the combination of age (postmenopause), symptoms (onset of hirsutism and virilisation), high total testosterone plasma values and expert sonography. On ultrasound, these tumours are unilateral, usually small, solid intraovarian nodules of a slightly increased echogenicity in contrast to the surrounding ovarian tissue, delineated by abundant perfusion with an enhanced vascularity. The appropriate setting of the sensitive colour Doppler is crucial for the detection of intraovarian Leydig cell tumour. Impact statement What is already known on this subject? A diagnosis of Leydig cell tumours is based on ultrasound performed by a trained examiner or by MRI. CT or PET/CT are not among the primary methods of choice. According to the results of imaging investigations surgical treatment is planned. Because these tumours are usually benign and have a good prognosis the unilateral salpingo-oophorectomy is a standard procedure. What do the results of this study add? Our case series show how difficult it can be to establish the diagnosis of Leydig cell tumours by imaging, including transvaginal ultrasound, the most frequently recommended diagnostic tool. We demonstrate in three cases how easily a small hyperechogenic tumour can be overseen or interchanged for a different gynaecological pathology if transvaginal scan is not performed by an experienced examiner trained in sonographic features of gynaecologic neoplasms. What are the implications of these findings for clinical practice and/or further research? This case series demonstrate how important it is to see the patient in the whole complexity with their medical history, proper clinical symptoms evaluation, laboratory test and not to rely solely just on sophisticated high-end investigations, such as the PET-CT, a CT and an MRI. It also emphasises the importance of specialists with established skills in gynaecologic ultrasonography. Further effort should be made to define the resources for the appropriate training of such sonographers. [ABSTRACT FROM AUTHOR]

Fumarate hydratase, Leydig cell tumour, HLRCC, testis, sex cord-stromal tumour More specifically, there is evidence that at least some FH-deficient LCTs are associated with germline I FH i mutations/HLRCC and FH-deficiency appears to be more common in (albeit likely not exclusive to) neoplasms with aggressive histopathologic features and/or malignant clinical behaviour. Keywords: fumarate hydratase; HLRCC; Leydig cell tumour; sex cord-stromal tumour; testis EN fumarate hydratase HLRCC Leydig cell tumour sex cord-stromal tumour testis 646 647 2 02/09/23 20230301 NES 230301 Leydig cell tumour (LCT) is the most common type of testicular sex cord-stromal tumour (TSCST) and demonstrates a biphasic incidence, with peaks in childhood and early to mid-adulthood, respectively. [Extracted from the article]

Objective: To investigate the pathology of excised testicular lesions <10 mm in size. Patients and Methods: The pathological reports of 2 681 patients with testicular lesions from Barts Health NHS Trust and Oxford University Hospitals NHS Foundation Trust were reviewed as part of a service evaluation audit from January 2003 to May 2016. Cases in which the lesion had a maximum diameter of <10 mm were selected. Clinical features were also accessed, where available, to examine patient demographics, prediagnostic levels of serum markers, ultrasonographic findings and clinical details. Results: A total of 81 patients with a lesion size <10 mm on histology were identified and, of these, 16 (20%) had a lesion diameter <5 mm. Of the 81 patients, 56 (69%) had benign lesions. Of 16 patients with a benign lesion <5 mm in diameter, 15 underwent orchidectomy and just one underwent partial orchidectomy. Preoperative tumour markers were available in 47/81 patients. None of the 16 malignant tumours in these 47 patients were associated with raised tumour markers, while seven of 31 remaining patients with benign lesions had raised α‐fetoprotein and lactate dehydrogenase levels. In total there were 25/81 malignant cases (31%), which were all germ cell tumours (GCTs): 15 seminomas (60%) and 10 non‐seminomatous GCTs (40%). Only one GCT had a diameter of <5 mm, and this was a regressed tumour within an 18‐mm area of granulomatous inflammation. Only one GCT relapsed: a clinical stage I, embryonal carcinoma of 6 mm in maximum diameter. The 56 ‘benign’ cases included 34 sex cord stromal tumours, including 23 Leydig cell tumours (41%), eight Sertoli cell tumours (14%) and three mixed sex cord stromal tumours (5%). None showed any malignant features. The remaining 22/56 lesions (40%) were lesions with no further follow‐up. Benign lesions seemed to be associated with a small diameter, and we found <5 mm to be the best threshold for predicting benign vs malignant lesions (P = 0.002). Conclusion: The majority of testicular lesions <10 mm, identified by radiology, were benign, although approxmiately one‐third were malignant. In the present study, 100% of lesions <5 mm in diameter were benign. Tumour markers appear to be unhelpful in the distinction of these small tumours. We suggest that regular ultrasound surveillance be more widely used for testicular lesions of this size. Testicular tumours now have a very high cure rate and changes in size of lesions may be monitored prospectively with minimal risk of increased morbidity. Patients who undergo an orchidectomy for lesions <5 mm are ‘victims of modern imaging technology’. If surgery is undertaken in lesions 5–10 mm, patients should be counselled that two‐thirds of cases are benign. [ABSTRACT FROM AUTHOR]

Ochratoxin A is best known as a potent renal carcinogen in male rats and mice after necessarily protracted ingestion, although valid extrapolation to any human disease has not been verified. The hypothesis that the toxin is a cause of human testicular cancer was proposed a decade ago and has proliferated since, partly through incomplete study of the scientific literature. Archived tumorous rat testes were available from Fischer F344 rats exposed to continuous dietary exposure for half of or the whole life in London in the 2000s. Renal cancer occurred in some of these cases and testicular tumours were observed frequently, as expected, in both treated and untreated animals. Application of clinical immunohistochemistry has for the first time consistently diagnosed the testicular hypertrophy in toxin-treated rats as Leydig cell tumours. Comparison is made with similar analysis of tumorous testes from control (untreated) rats from U.S. National Toxicology Program studies, both of ochratoxin A (1989) and the more recent one on Ginkgo biloba. All have been found to have identical pathology as being of sex cord-stromal origin. Such are rare in humans, most being of germinal cell origin. The absence of experimental evidence of any specific rat testicular cellular pathology attributable to long-term dietary ochratoxin A exposure discredits any experimental animal evidence of testicular tumorigenicity. Thus, no epidemiological connection between ochratoxin A and the incidence of human testicular cancer can be justified scientifically.

A 13-year old male Poodle dog was presented with a considerable disparity in the size of testes. Palpation demonstrated enlargement of the right testicle; smooth surface without any sign of nodular hyperplasia was detected. Both testes were removed, the enlarged one was sent to a histopathology laboratory. Microscopic examination revealed massive neoplastic proliferation of the testicular germ cell tumour (seminoma) and an accompanying smaller tumour originating from the interstitial Leydig cells (Leydigoma), which was confirmed by immunohistochemistry. Simultaneous occurrence of two different types of tumours in testes is possible, representing a multiple primary malignancy case, which is a rare phenomenon in veterinary practice. [ABSTRACT FROM AUTHOR]

Naloxegol is an opioid antagonist which has been developed for the treatment of patients with opioid induced constipation. In the nonclinical safety program naloxegol was shown to have a very benign toxicity profile. In the rat, but not the mouse, 2-year carcinogenicity study a change in tumour pattern with an increase in testicular Leydig cell tumours (LCT) was observed after dosing at high (supra-pharmacological) concentrations. To establish the basis of the increase in LCT and to assess its potential relevance to humans, studies to exclude and potentially identify mode-of-action (MoA) were performed. A genotoxic mechanism was ruled out following negative results in the Ames, mouse lymphoma, and micronucleus assays. An effect on androgen metabolism was excluded since the treatment of rats with naloxegol for 14 days did not result in any induction of CYP protein levels. It was demonstrated that administration of centrally restricted opioid antagonists naloxegol or methylnaltrexone at high doses induced an increase in LH release with no clear increase in testosterone, in contrast to the centrally acting opioid antagonist naloxone, which showed marked increases in both LH and testosterone. LCT due to increased LH stimulation is common in rats but not documented in humans. Collectively, the lack of genotoxicity signal, the lack of androgen effect, the increase in LH secretion in rats, which is no considered to be relevant for LCT formation in humans, and high margins to clinical exposures, the observed increase in LCT in the rat is not expected to be clinically relevant. [ABSTRACT FROM AUTHOR]

Leydig cell tumours belong to the small group of ovarian steroid tumors, which are hormone producing and derived from specific stromal cells. Morphologically, their endocrine-like structure is characteristic, formed of large, polyhedral cells resembling luteal, adrenocortical and Leydig cells. They contain crystalloids of Reinke in their cytoplasm which have diagnostic significance. Patients with these tumours present with androgenic manifestations. We report the occurrence of Leydig cell tumour in a 35-year-old lady who presented with infertility and hirsutism.

Leydig cell tumour is a benign testicular non-germ cell tumour, and malignant transformation is rare. We report a case of a 35-year-old man who came to our hospital with a painless left testicular mass measuring 1.2 × 1 cm. Histological evaluation of the tumour showed features of a malignant Leydig cell tumour but no infiltration beyond the capsule or metastasis. The small size of the tumour was remarkable.

In order to explore the latest advances in organ-sparing treatment of testicular tumors, a literature search of the Medline/PubMed database was carried out for published data in the English language up to 2007. In the recent past the management of testicular tumors has evolved in favor of a testis-sparing approach in selected cases, both in the adult and pediatric population. The widespread use of high-frequency testicular ultrasound has led to detecting an increasing number of asymptomatic, non-palpable, small-volume masses. A higher proportion of testicular lesions of benign nature than previously reported has now been documented. The high accuracy of frozen section examination and the increasing interest in the potential functional, psychological and cosmetic advantages related to preserved testicular parenchyma are other arguments currently favoring the adoption of an organ-sparing policy for most testicular masses. Greater experience has been gained in also managing conservatively malignant tumors. Patients with germ-cell cancer in solitary testis or bilateral tumors can be submitted to testis-sparing surgery, provided that the maximum size of the lesion is < 2 cm, preoperative testosterone is normal and adjuvant radiotherapy of the residual parenchyma is delivered. Cancer-specific survival is excellent, local recurrence rate very low and androgen supplementation unlikely.

The rupture of an intra-abdominal testicular neoplasm is a rare cause of acute abdomen and massive intra-abdominal haemorrhage. We report the case of a 70-year-old male presenting a massive intra-abdominal bleeding caused by a Leydig cell tumour in an undescended testis. The clinical details and pathology of this rare testicular tumour are discussed.

Leydig cell testicular tumours are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumour causing precocious pseudopuberty. During follow-up, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin releasing hormone analogues. Only 6 other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumour causing precocious pseudo puberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumour presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with gonadotropin releasing hormone analogues appears to be the most effective medical treatment.

Summary A testicular Leydig cell tumour associated with metastatic disease is reported in a dog. An enlarged testis and three cutaneous nodules resected from an 11-year-old golden retriever were submitted for histopathological examination. Both testicular and cutaneous lesions showed identical morphological and cytological changes. Immunohistochemical labelling for expression of inhibin-α and calretinin confirmed the Leydig origin of the cutaneous neoplastic population. Based on the morphological and immunohistochemical findings, a final diagnosis of multiple cutaneous metastasis of a malignant testicular Leydig cell tumour was made. [ABSTRACT FROM AUTHOR]

Leydig cell tumour ( LCT) is an uncommon tumour that typically occurs in the testis. Primary epididymal LCT is extremely rare. To the best of our knowledge, only two cases have been reported in the world literature. Herein, we report a case of primary epididymal LCT in a 41-year-old Chinese male. The patient presented with right epididymal swelling for 3 months without endocrine manifestations, including gynaecomastia and decreased libido. Scrotal ultrasound demonstrated a mass about 1.5 cm in diameter entirely in the cephalic region of right epididymis. No abnormality was found in his bilateral testes. The patient underwent total mass resection without post-operative therapy. Histological examination revealed that the well-circumscribed tumour was separated by conspicuous hyalinised fibrous stroma; the tumour cells were large and polygonal with round nuclei and abundant eosinophilic cytoplasm. Immunophenotypically, the tumour cells expressed four markers of sex cord differentiation (calretinin, melanA, CD99 and inhibin). There was no recurrence at 2-year follow-up. Our observation once again confirms that LCT could primarily occur in the epididymis, and we suppose that it probably originates from the ectopic Leydig cells. As little is known about the pathogenesis and prognosis for such a rare disease, accumulation of more pathological and clinical data can help to better interpret this tumour. [ABSTRACT FROM AUTHOR]

Case Report: A 10-year-old male was referred to our institution due to short stature and bilateral cryptorchidism and reported pubic hair development and acne since the age of 4 years. Laboratory and molecular genetic tests indicated congenital adrenal hyperplasia due to 21-hydroxylase deficiency. After treatment with prednisone, adrenal hormones normalised but testosterone remained elevated. Magnetic resonance imaging of the abdomen due to cryptorchidism revealed uterus and adnexal attachments, a prostate and poorly defined nodules on the iliac chains. Upon exploratory laparotomy, a hysterectomy, bilateral oophorectomy and resection of a peri-adnexal nodular lesion on the patient's right side were performed. Histopathology of the nodule mass was compatible with a Leydig cell tumour with a low proliferation rate according to Ki67. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Wang Z, Yang S, Shi H, Du H, Xue L, Wang L, Dong Y & Han A (2011) Histopathology [ABSTRACT FROM AUTHOR]

The article describes the case of a healthy 15-year old boy who complained of bilateral gynecomastia that was affecting him psychologically. A brief background is provided along with a medical history that revealed multiple micro calcifications associated with hypoechoeic structure in the centre of the right testis. Details of the findings are discussed along with procedures after scrotal ultrasound, such as total orchiectomy and standard synacthen test evidencing Leydig cell tumour with microlithiasis. Information on gynecomastia is also given.

Abstract: Context: According to current guidelines, radical orchidectomy is the standard treatment for testis tumours of malignant and unknown origin. Testis-sparing surgery (TSS) has recently been proposed as an alternative option in selected cases. Objective: Our aim was to analyse the cumulative evidence for TSS in the treatment of adult malignant tumours of different histology, including notes on operative technique, indications, complications, and oncologic and functional outcome. Evidence acquisition: A systematic literature search of the Medline/PubMed database for full-length papers reporting on TSS for adult malignant tumours was performed up to September 2009. Bibliographies of retrieved articles and review articles were also examined. Only those articles with complete data on operative technique, complications, and oncologic or functional outcome were selected. Furthermore, published abstracts at major urologic meetings in the last decade (1999–2009) and guidelines on testis cancer from major oncologic and urologic medical associations were searched and evaluated. Evidence synthesis: No randomised controlled trials have compared TSS and radical orchidectomy; only retrospective outcome studies and case reports on TSS are available. In patients with small malignant germ cell tumours arising in both or in solitary testes, TSS coupled with local adjuvant radiotherapy ensures good oncologic control and is associated with a preserved endocrine function in most cases. In patients with small Leydig cell tumours, TSS can also be performed with elective indications (healthy contralateral testes), provided that pathology fails to reveal aggressive features. Finally, TSS is an option for patients with small ultrasound-detected, nonpalpable tumours even with elective indications because the incidence of benign definitive histology is high at approximately 80%. The overall complication rate is low (<6%). Data on exocrine and endocrine gonadal function, male body image, and health-related quality of life after TSS are still immature. Conclusions: TSS can be safely adopted for the treatment of carefully selected cases of tumours of different histology. Prospective multicentre studies are warranted to further qualify TSS as a treatment option to be recommended as an alternative to radical orchidectomy and to explore the perceived functional advantages of testis preservation. [Copyright &y& Elsevier]

Abstract: Testicular ‘tumour’ of adrenogenital syndrome usually presents as bilateral testicular masses in patients with congenital adrenal hyperplasia. A thorough clinical evaluation is usually sufficient for diagnosis. In most circumstances this condition is well managed by replacement hormone therapy and infrequently requires surgical intervention with consequent histopathology evaluation. Attempt at differentiation from the morphologically similar Leydig cell tumour on biopsy tissue has potential for misdiagnosis; however, this distinction is crucial due to significantly different clinical interventions and the related medico-legal implications of orchidectomy. Through the following case, we illustrate these diagnostic difficulties, provide a summary from review of recent literature to assist in correct interpretation, and also stress the impact of either diagnosis. [Copyright &y& Elsevier]

OBJECTIVE To report our single-centre experience of patients with Leydig cell tumour (LCT) of the testis, which represents the most frequent interstitial neoplasm of the testis, and for which the natural history and therapy are debated. PATIENTS AND METHODS Between 1990 and 2006, 37 patients were treated for LCT of the testis. All patients had testicular markers assessed and 21 (57%) had their hormonal profile assessed (total testosterone, follicle-stimulating hormone, luteinizing hormone and oestradiol). We analysed the symptoms at presentation, laboratory findings, organ-sparing vs. radical surgery and oncological and symptomatic follow-up data. RESULTS Medical referral was for a testicular mass in 32% of patients, gynaecomastia in 8%, testicular pain in 8%, infertility in 11%, and isosexual pseudo-puberty in 5%. The mean (range) diameter of the tumour was 16.5 (6–68) mm. Before surgery testosterone levels exceeded the upper limit in a third of patients, while levels were hypogonadal in 19%. Oestradiol levels were increased in 29% of patients. At surgery, 29 patients (78%) had organ-sparing surgery. The median (range) follow-up was 4.6 (0.6–16.2) years; no patient had disease relapse. Gynaecomastia was present in two of six patients at the follow-up, despite pharmacological treatment. Four patients had a low testosterone level. CONCLUSION Patients diagnosed with LCT have a good prognosis; this study shows the safety of conservative surgery. Surgical removal of the tumour is not always associated with resolution of symptoms and abnormal laboratory values. [ABSTRACT FROM AUTHOR]

In order to explore the latest advances in organ-sparing treatment of testicular tumors, a literature search of the Medline/PubMed database was carried out for published data in the English language up to 2007. In the recent past the management of testicular tumors has evolved in favor of a testis-sparing approach in selected cases, both in the adult and pediatric population. The widespread use of high-frequency testicular ultrasound has led to detecting an increasing number of asymptomatic, non-palpable, small-volume masses. A higher proportion of testicular lesions of benign nature than previously reported has now been documented. The high accuracy of frozen section examination and the increasing interest in the potential functional, psychological and cosmetic advantages related to preserved testicular parenchyma are other arguments currently favoring the adoption of an organ-sparing policy for most testicular masses. Greater experience has been gained in also managing conservatively malignant tumors. Patients with germ-cell cancer in solitary testis or bilateral tumors can be submitted to testis-sparing surgery, provided that the maximum size of the lesion is <2 cm, preoperative testosterone is normal and adjuvant radiotherapy of the residual parenchyma is delivered. Cancer-specific survival is excellent, local recurrence rate very low and androgen supplementation unlikely. [ABSTRACT FROM AUTHOR]

Abstract: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome caused by the inactivation of the responsible gene, MEN1. To date, the lack of MEN1-deficient cell lines derived directly from MEN1 tumours has hampered the detailed study of the MEN1 gene. We have established several stable Men1-deficient Leydig cell tumour (LCT) lines derived from a Leydig cell tumour developed in a male heterozygous Men1 mutant mouse. Our data show that these cell lines maintain the basic characteristics of Leydig cells in terms of both androgen synthesis and gene expression. Interestingly, reconstituted menin expression in one of Men1-deficient LCT cell lines resulted in cell growth inhibition, suggesting that the function of cell growth suppression of the menin pathway, apart from menin itself, is essentially preserved in these cells. Furthermore, we show that menin re-expression in these Men1-deficient cells leads to a block in the transition from G0/G1 to S phase of the cell cycle and an increase in apoptosis, accompanied by a marked increase of p18INK4C and p27Kip1 expression. The current study therefore highlights the importance of menin expression in cell cycle and cell survival control in endocrine cells, and may provide insights into the mechanisms of tumour suppression by menin in related endocrine tumours. [Copyright &y& Elsevier]

Among the various causes of gynaecomastia, testicular malignancies are an uncommon, life-threatening condition, which require prompt treatment. The case of a 26-year-old healthy man is described, who reported a 6-month painful bilateral gynaecomastia associated with secondary hypogonadism. Normal circulating 17β-oestradiol (E2) levels showed an enhanced response to human chorionic gonadotrophin (hCG) testing, which led to a reduced testosterone (T)/E2 ratio. Both clinical and hormonal findings normalized following surgical exeresis of a left testicular mass, which proved to be a Leydig cell tumour (LCT) at histology. This report underlines the importance of ultrasonographic evaluation of the testes, whenever breast enlargement occurs in a healthy man, despite unremarkable findings on testicular examination. In addition, our case demonstrates that normal unstimulated circulating E2 levels do not allow the presence of a stromal testicular tumour to be ruled out and that the response of restored T levels to hCG testing can remain blunted up to 1 year after surgery. Finally, we claim that T/E2 ratio may be a useful tool in evaluating derangement of the endocrine milieu secondary to LCT. [ABSTRACT FROM AUTHOR]

690 patients were treated for testicular tumour in the course of 18 years. The histology of 7 cases showed Leydig cell tumour. In 4 of the 7 cases, a metastatic process leading to death was observed. At the time of diagnosis, 5 patients were found to have low stage, whereas 2 of the patients had advanced lymphatic involvement. The hematogenous and lymphatic metastases proved to be resistant to chemotherapy. Contrary to the major part of the literature, retroperitoneal lymphadenectomy should be performed with this histological type for the exact pathological staging immediately following orchiectomy.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Seven patients (aged 25–38 years) were admitted because of mono- or bilateral gynaecomastia. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, 17-β-estradiol, Δ4-androstenedione, dehydropiandrosterone sulphate (DHEA-S) and 17-OH-progesterone were determined and semen analysis was carried out. FSH and LH levels were also measured after acute LH-RH administration (100 μg intravenously), and testosterone and 17-β-estradiol were also evaluated after acute human chorionic gonadotrophin (hCG) administration (5000 IU intramuscularly). Testicular echography demonstrated the presence of a solid hypoechoic tumour. Therefore all patients were submitted to hemicastration by orchidofuniculotomy and a benign Leydig cell tumour was diagnosed in the removed testes. Hormonal and semen evaluations were repeated 3, 6, 9 and 12 months after surgery. The data before and after surgery were compared with a control group of 10 age-matched males. Before surgery, patients showed low FSH basal plasma levels; high levels of 17-β-estradiol and low testosterone levels similar to those after hCG administration. A dyspermia was observed. Unilateral orchidectomy eliminated the autonomous secretion of oestrogen(s) so an increase of LH, FSH and testosterone levels, together with an improvement of spermatogenesis, were obtained. [ABSTRACT FROM AUTHOR]

Simultaneous occurrence of a well-demarcated interstitial cell tumour and an intratubular seminoma-like tumour, which was beginning to invade peritubular areas, in the contralateral testes of a 3-year-old Dutch-Belted rabbit is described. Morphological hallmarks of carcinoma in situ, which have not been reported previously for the rabbit, were observed in association with the seminoma. These observations indicate that carcinoma in situ, preceding a seminoma-like tumour, occurs in the rabbit and that the rabbit may serve as a practically useful animal model for studying testicular germ cell neoplasia. [ABSTRACT FROM AUTHOR]

Aims Testicular Leydig cell tumours are rare. Although most behave benignly ≈ 10% are malignant. Clinicopathological features have been described which have some value in predicting malignant behaviour, although as with other endocrine tumours uncertainties remain in many individual cases. Our aim was to determine the clinicopathological features of 20 testicular Leydig cell tumours. We wished to investigate whether, in addition to established clinicopathological features, the MIB1 index and/or flow cytometric analysis of nuclear DNA content are of value in predicting malignancy. We also wished to investigate the frequency of p53 protein accumulation in these neoplasms. Methods and results Twenty testicular Leydig cell tumours were studied and the clinical case notes examined. Histological sections were assessed by pathologists involved in the study. Pathological features evaluated included: tumour size, extratesticular extension, nuclear pleomorphism, mitotic activity, necrosis and vascular invasion. Immunohistochemical staining was performed with the anti-p53 monoclonal antibody DO-7 and the cell proliferation marker MIB1. A flow cytometric analysis of nuclear DNA content was also performed. Three tumours behaved in a malignant fashion with the development of metastases. Another had morphological features of malignancy but the patient died a short time after diagnosis from unrelated causes. These four neoplasms were larger than benign tumours, often contained areas of necrosis and sometimes exhibited vascular invasion. They generally exhibited greater nuclear pleomorphism and a higher mitotic rate than benign tumours. Three of the four malignant tumours had a high MIB1 index (20–50%) and the fourth exhibited DNA aneuploidy by flow cytometry. Two malignant tumours showed increased expression of p53 protein, with ≈ 50% of nuclei staining with DO-7. All benign tumours had a low MIB1 index (0–2%) and a diploid DNA profile, except for... [ABSTRACT FROM AUTHOR]

Androgen-producing ovarian tumours can lead to assessment difficulties because of their small size. We present a case of virilising steroid cell ovarian tumour in a 41-year-old woman localised with Fluorine-18-Deoxyglucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT). Although the biochemical evaluation pointed to an ovarian source of androgen, diagnostic attempts to localise the source of hyperandrogenism with transvaginal ultrasound (US), and magnetic resonance imaging (MRI) of pelvis failed. Additional evaluation with 18FDG-PET/CT showed an increased uptake in the right ovary. A laparoscopic right oophorectomy was performed and histopathology examination revealed a 1.2-cm Leydig cell tumour. The patient showed regression of clinical signs. [ABSTRACT FROM AUTHOR]

To describe a microsurgical technique for removing suspected testicular masses with sparing of the testicular parenchyma, and to describe case studies. Six men were referred with testicular lesions (3–6 mm) detected on ultrasonography (US); in one, the lesion was palpable. US showed hypoechoic lesions and in two cases were mixed hypoechoic and anechoic. In these men, the testicular lesion was identified by US before surgery, giving three-dimensional coordinates to facilitate intraoperative recognition. A traditional inguinal incision was used and the funiculus clamped subinguinally without opening the canal. The testicle was isolated after sectioning the gubernaculum testis. In a separate operative field, an equatorial incision of the albuginea was made in a plane orthogonal to the major axis of the testicle, sparing the subtunical vasa. The parenchymal lobuli were dislodged and the seminiferous tubules dissociated, the nodule identified and completely removed, together with ≈ 1 mm of surrounding healthy tissue. This technique can also be used for microsurgical testicular sperm extraction (MicroTESE), to retrieve sperm in infertile men. In two infertile men MicroTESE was also performed. Histology revealed one case each of seminoma, Leydig-cell tumour, Leydig cell hyperplasia, atrophy, normality in the incidental forms, and complicated cysts of the albuginea. In the follow-up for infertility reasons, no scarring was observable on the tunica albuginea in the men who had conservative therapy. One year later the patient with seminoma was free of disease. The increasingly frequent detection of benign testicular lesions, particularly in infertile men, calls for a surgical approach that must be as conservative as possible for the testicular parenchyma. We think that microsurgery should be the first-line technique in small suspected testicular lesions in infertile men. [ABSTRACT FROM AUTHOR]

Although Leydig cell tumour is a rare tumour which constitutes only 1–3% of all testicular tumours, still it is in the focus of interest because of the difficulties in determining its exact nature and subsequently the type of treatment and follow-up. We report a case of Leydig cell tumour with a review of the related literature. [ABSTRACT FROM AUTHOR]

An eight year old male Spitz dog was presented with the history of a palpable lower ventral intra-abdominal mass near the left side of the penis. On clinical examination, the animal had cryptorchid testis and a soft spherical mass of about 5 cm in diameter. The histopathological evaluation of excised mass revealed the features of leydig cell tumour. [ABSTRACT FROM AUTHOR]

Ochratoxin A is best known as a potent renal carcinogen in male rats and mice after necessarily protracted ingestion, although valid extrapolation to any human disease has not been verified. The hypothesis that the toxin is a cause of human testicular cancer was proposed a decade ago and has proliferated since, partly through incomplete study of the scientific literature. Archived tumorous rat testes were available from Fischer F344 rats exposed to continuous dietary exposure for half of or the whole life in London in the 2000s. Renal cancer occurred in some of these cases and testicular tumours were observed frequently, as expected, in both treated and untreated animals. Application of clinical immunohistochemistry has for the first time consistently diagnosed the testicular hypertrophy in toxin-treated rats as Leydig cell tumours. Comparison is made with similar analysis of tumorous testes from control (untreated) rats from U.S. National Toxicology Program studies, both of ochratoxin A (1989) and the more recent one on Ginkgo biloba. All have been found to have identical pathology as being of sex cord-stromal origin. Such are rare in humans, most being of germinal cell origin. The absence of experimental evidence of any specific rat testicular cellular pathology attributable to long-term dietary ochratoxin A exposure discredits any experimental animal evidence of testicular tumorigenicity. Thus, no epidemiological connection between ochratoxin A and the incidence of human testicular cancer can be justified scientifically. [ABSTRACT FROM AUTHOR]