Apoptosis related gene products in differentiated and tumorigenic rat Leydig cells and following regression induced by the cytotoxin ethane dimethanesulphonate

Androgen secreting Leydig cells in the adult are differentiated with a very low turnover, however, Leydig cell tumours can arise spontaneously or after treatment with toxins. This study in the rat investigated whether changes in components of programmed cell death could be involved. In contrast to their absence in differentiated Leydig cells, antiapoptotic Bcl-2 and proapoptotic Bax were expressed in tumours. Bak and Bcl-xl were found in both tumour and normal Leydig cells. Apoptosis was induced in subcutaneous implants of Leydig cell tumour by ethane dimethanesulphonate (EDS) which is known to kill differentiated Leydig cells. The marked regression of the tumour following EDS treatment was transient and re-growth occurred between 6 and 14 days later. Tumour regression and growth was associated with a similar weight pattern in the seminal vesicles caused by changes in serum testosterone. During tumour regression, clusterin and Bax proteins were elevated but Bak, Bcl-xl and Bcl-2 were unchanged. Fas-R, Fas-L and Bax were upregulated after tumour regression had taken place. These data show that Leydig cell tumours possess many of the apoptosis related gene products and can die by apoptosis, however, regulation is clearly different in differentiated and mitotic Leydig cells.     

Rare testicular tumors. Apropos of 15 cases

In a series of 141 patients treated over the last ten years for testicular tumour, 15 presented lesions considered to be rare: 9 Leydig cell tumours, 3 epidermoid cysts, 1 leiomyoma, 1 primary testicular lymphoma and one testicular localisation of a known leukaemia. The clinical, endocrine and histological features of these different tumours are reviewed on the basis of the present series and a wider discussion of other rare testicular tumours. Leydig cell tumours, epidermoid cysts, mature benign teratomas and testicular lymphomas are the most frequent. Leiomyomas, metastatic tumours and connective tissue tumours are exceptional. Sertoli cell tumours are rare and are similar to Leydig cell tumours in that they raise problems concerning their possible endocrine activity and the evaluation of their malignant potential. The general therapeutic rule of radical orchidectomy for any testicular tumour is still valid.     

Therapy of gonadal stromal cell testicular tumours

At our regional centre, 504 patients with testicular tumour were treated from 1 January 1980 to 31 December 1993. In the course of the treatment, 10 patients (2%) with gonadal stromal cell testicular tumours were found. Histopathological examination identified Sertoli cells in 3 cases, granulosa cells in 1 case, and Leydig cell primary tumours in 6 cases. Leydig cell testicular tumours, the most significant clinically, should not be regarded as benign. In 3 of 6 cases metastatic processes developed. Three patients died in spite of the surgical and chemotherapeutic interventions. Analysis of these cases suggests that, following the semicastration of Leydig cell testicular tumours, a primary retroperitoneal lymph node dissection should be performed, and an exact identification of the pathological stage should be carried out.     

Neuroendocrine characteristics of human Leydig cell tumours

Summary. The neuroendocrine nature of a subset of Leydig cells has already been established. The present investigation deals with neuroendocrine characteristics of Leydig tumour cells. A number of neuroendocrine and neuronal markers were demonstrated in Leydig cell tumours of 7 men aged 25–41 years. The following substances were immunocytochemically tested in Leydig tumour cells: the monoamine-synthesizing enzymes tyrosine hydroxylase and aromatic L-amino acid decarboxylase, the indoleamine serotonin, the calcium-binding protein parvalbumin, the microtubule associated protein-2, neurofilament protein 200, synaptophysin, neuron specific enolase, substance P and neuronal nitric oxide synthase (NOS). Compared to the normal interstitial cells beyond the tumours, all neoplastic cells showed a significantly weaker immunoreactivity for nerve cell markers as well as for testosterone and cyclic guanosine monophosphate (cGMP), which is usually accumulated by nitric oxide (NO). This provides evidence for a certain dedifferentiation of Leydig tumour cells.
However, these results suggest that tumourous development of Leydig cells does not include loss of neuronal phenotype. Moreover, on the assumption that 'neuronal' Leydig cells exist beside 'non-neuronal' ones in normal testicular tissue, we propose the hypothesis that 'neuronal' Leydig cells can transform to tumour cells.     

Gynaecomastia and occult Leydig cell tumour of the testis

Two patients with Leydig cell tumours of the testis are described. Both presented with gynaecomastia, but on initial examination had apparently normal testes. The causative tumour did not become obvious for some months, despite being carefully sought. Review of the literature suggests that gynaecomastia preceding a readily palpable tumour is a recognised problem. The detection and management of Leydig cell tumours of the testis are discussed.     

Leydig cell tumour – A rare testicular tumour

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.     

Cytologic Features of Testicular Tumours in Dog

In this paper, we report on our experience of cytology of fine needle biopsies performed on 92 dogs with testicular tumours during the period from 1998 to 2002. Cytological diagnosis was consistent with seminoma in 20 cases, sertolioma in 16 cases, Leydig cell tumours in 50 cases and mastocytoma in one case. Five cases could not be diagnosed by cytology. Cytological observations were confirmed after surgery by histopathological examination in 87 cases. Cytology provided a sensitivity of 95% for seminoma, 88% for sertolioma and 96% for Leydig cell tumours. The specificity was 100% for all three tumour types. In our experience cytology of fine needle aspirations of testicular tumours is a very reliable technique.     

Testicular lesions other than germ cell tumours: feasibility of testis-sparing surgery

OBJECTIVE

To review all non‐germ‐cell testicular lesions presenting at our institution and to determine the feasibility of testis‐sparing surgery for these patients.

PATIENTS AND METHODS

All surgery for testicular masses between June 1995 and June 2005 were reviewed retrospectively. Patients with atrophy, germ cell tumours, infection or torsion were excluded. The study comprised men who had radical orchidectomy for suspected germ‐cell tumour but had other final pathology, and those where testis‐sparing surgery was attempted for a presumed benign lesion.

RESULTS

Thirteen patients with lesions appropriate for the study were identified; all but one had a palpable lesion. The lesions could be categorized as inflammatory (three hyalinized fibrosis, two sarcoidosis, one chronic inflammation), cystic (one epidermoid cyst, one unilocular cyst), benign neoplasms (two adenomatoid tumours, one Leydig cell tumour, one capillary haemangioma) or malignant neoplasms (one lymphoma). Based on the preoperative impression, testis‐sparing surgery was attempted in eight of the lesions and was successful in six where it was attempted. In the other five, testis‐sparing surgery was not attempted because the preoperative impression was that of a germ cell tumour. Testis‐sparing surgery was successful in only six of the 13 patients with these lesions.

CONCLUSION

Testis‐sparing surgery might be possible if there is significant suspicion of a benign lesion. If frozen‐section analysis is equivocal, a radical orchidectomy is required. Testis‐sparing surgery was feasible in highly selected cases.     

Growth characteristics of human malignant tumours and cell lines in serial passages in nude mice

Two osteosarcoma cell lines, one fibrosarcoma and one undifferentiated mesenchymal tumour obtained at operation, all of human origin, were transplanted in serial passages in athymic nude mice. The growth rate was analysed and the morphologic appearance compared both with the original tumours and after each passage. All tumours retained their morphologic characteristics during the transplantation and passaging in the nude mice with only minor alterations in structure. The growth rates of the tumours showed great variability even in the same passage of each tumour, although the growth rates became somewhat more regular and predictable after some passages.     

Growth Characteristics of Human Malignant Tumours and Cell Lines in Serial Passages in Nude Mice

Two osteosarcoma cell lines, one fibrosarcoma and one undifferentiated mesenchymal tumour obtained at operation, all of human origin, were transplanted in serial passages in athymic nude mice. The growth rate was analysed and the morphologic appearance compared both with the original tumours and after each passage. All tumours retained their morphologic characteristics during the transplantation and passaging in the nude mice with only minor alterations in structure. The growth rates of the tumours showed great variability even in the same passage of each tumour, although the growth rates became somewhat more regular and predictable after some passages.     

Management and outcome of paediatric testicular tumours – A 20 year experience

Objective: To report a 20-year experience highlighting management and outcome(s) of paediatric testicular tumours.Patients and Methods: All males (< 19 years) with an index diagnosis of testicular tumours during the era(s) 1998–2018 in North West England were identified. Data were collected regarding age at diagnosis, disease stage, surgical operations, tumour biology and outcome(s).Results: A total of 34 male patients were identified. Median age at primary diagnosis was 94 months (range: 0–229 months). Eighteen tumours were benign and 16 malignant. Twenty cases (59%) were recorded in pre pubertal children and 14 (41%) in post pubertal males . In the pre pubertal group (0–11 years) - 15 cases of germ cell tumours (unrelated to germ cell neoplasia in situ – non-GCNIS derived) were recorded, including six yolk sac lesions, eight teratomas and one mixed teratoma/yolk sac tumour (pre-pubertal type). Four males with sex cord-stromal tumours included one juvenile granulosa cell tumour, two Sertoli cell tumours and one Leydig cell tumour. One miscellaneous type tumour notably a papillary cyst adenoma was also identified. In the post pubertal male cohort (>12 years) (n = 14) – four non-GCNIS derived tumours were identified (3 epidermoid cysts and one teratoma), eight cases of germ cell tumour derived from germ cell neoplasia in situ (GCNIS derived) included one teratoma, six with mixed germ cell tumours and one embryonal carcinoma. Two males had sex cord stromal tumours: (Leydig cell and granulosa cell biology). Twenty-eight patients underwent high radical inguinal orchidectomy(s) with one male also requiring retroperitoneal surgery to clear distant locoregional disease and a further single case thoracotomy and metastasectomy. Six patients had lesions suitable for ‘testicular sparing’ surgery. Six patients had metastatic disease at presentation (18%). Overall study survival was 97%. A single fatality occurred in an adolescent male with a mixed GCT harbouring liver, lung and para-aortic disease who died 48 months after initiating treatment.Conclusion: We highlight one of the largest study series of paediatric testicular tumours in the UK and Europe. Non-GCNIS derived tumours accounted for the most common tumour biology (56%). Survival for paediatric testicular tumours is reassuringly generally excellent. Delayed presentation however with a malignant testicular tumour may be associated with poor outcome(s).     

Differential expression of microRNAs in luteinising hormone‐treated mouse TM3 Leydig cells

Testosterone is primarily produced by Leydig cells of the mammalian male gonads. The cellular functions of Leydig cells are regulated by the hypothalamus–pituitary–gonad axis, whereas the microRNA (miRNA) changes of LH‐treated Leydig cells are unknown. Mouse TM3 Leydig cells were treated with LH, and deep sequencing showed that 29 miRNAs were significantly different between two groups (fold change of >1.5 or <0.5, p < .05), of which 27 were upregulated and two were downregulated. The differential expression of miR‐29b‐3p, miR‐378b, miR‐193b and miR‐3695 was confirmed by quantitative real‐time polymerase chain reaction. Bioinformatic analysis revealed that miRNAs regulated a large number of genes with different functions. Pathway analysis indicated that miRNAs were involved in the Wingless and INT‐1, adenosine 5′‐monophosphate‐activated protein kinase, NF‐kappa B and Toll‐like receptor signalling pathways. Results showed that miRNAs might be involved in the regulation of LH to Leydig cells.     

Bilateral Leydig cell tumor of the test: a case report

Testicular Leydig cell tumours are uncommon. Bilateral synchronous lesions are exceptional. They cause isosexual pseudo precocious puberty in childhood. The histological diagnosis of malignancy is sometimes difficult to establish and it can be made retrospectively when lymph nodes involvement or visceral metastasis appear in the follow-up. We report a case of a 9 year-old boy presenting bilateral Leydig cell tumour of the testis treated by bilateral radical orchiectomy who developed 2 years after the intervention a pulmonary metastasis.