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.     

Fas和FasL 系统在非梗阻性无精子症睾丸中的表达

目的：为探讨睾丸生精功能障碍与细胞凋亡的关系，研究Fas和FasL系统在非梗阻性无精子症睾丸支持、间质和生精细胞中的表达。方法：对20例非梗阻性无精子症患者行睾丸开放性活检，常规病理检查，按Johnson评分法评价精子发生和发生障碍的程度；采用免疫组化SABC法对睾丸支持、间质和生精细胞进行Fas和FasL表达的检测。结果：睾丸活检生精功能评为8分有14例，3分有2例，6、5、4和2分各有1例。在20例非梗阻性无精子症睾丸的间质、支持和生精细胞均有Fas和FasI。的表达；而支持细胞Fas和FasL的阳性和强阳性表达率明显高于间质和生精细胞。结论：非梗阻性无精子症的睾丸支持、间质及生精细胞Fas和FasL的高表达与精子生成障碍是一致的，非梗阻性无精子症可能与生殖细胞过度凋亡密切相关。     

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).     

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.     

Leydig cell tumor of testis.

In adult patients with Leydig cell tumor of the testis, endocrinologic signs occur in 30 per cent of the cases and often precede the onset of a palpable testicular mass. Gynecomastia is the most common endocrinologic manifestation and probably is due to increased estrogen secretion by the Leydig cells. In the patient with adrenogenital syndrome and testicular enlargement it is difficult to distinguish Leydig cell tumor from adrenal rest hypertrophy. Four patients with Leydig cell tumor and endocrinologic manifestations are discussed; three are adults who presented with gynecomastia and the fourth is a patient with congenital adrenogenital syndrome. In the adult patient inguinal orchiectomy is the treatment of choice, while in the patient with adrenogenital syndrome initial management by high-dose steroid suppression should be attempted prior to testicular exploration.     

Histochemical study on glutathione S-transferase in patients with testicular tumor

Tumor tissue and nontumorous tissue of 31 patients with testicular tumor were examined by the peroxidase antiperoxidase (PAP) procedure using the primary antibody against glutathione S-transferase (GST). Histology of primary tumor was classified as seminoma in 10 cases, non-seminoma in 18 (including 2 cases of yolk sac tumor), and malignant lymphoma in 3. Tumorous tissues except one with yolk sac tumor failed to be stained with GST. The seminiferous tubules of the nontumorous testicular tissue had a positive reaction in the infant cases, but not in the adult cases. The degenerated seminiferous tubules involved in the testicular tumors also had a positive reaction in all the cases. Leydig cells had a positive reaction in all the cases. In particular, diffuse Leydig cell's hyperplasia was observed in a case with high serum beta hCG and urinary hCG levels. These data may be relevant in explaining the inherent hypofertility of these patients.     

Detection of testicular ultrasonographic lesions in severe male infertility

PURPOSE: We retrospectively assessed the number and histology of testicular lesions diagnosed clinically and by ultrasonography in a population of infertile men. MATERIALS AND METHODS: From October 2000 to January 2003, 560 infertile men underwent physical examination, hormonal assessment (follicle-stimulating hormone, luteinizing hormone, testosterone) and scrotal ultrasonography. Eight men were diagnosed with focal testicular ultrasonographic lesions. In 4 cases there was a palpable lesion and in the other 4 cases the lesion was not palpable, diagnosed by ultrasonography (1 was cryptorchid). Only cases of lesions with clear-cut ultrasonographic edges and no history of recent genital infections were considered for explorative surgery through the groin. Microcalcifications were reported if present. The testicle was only preserved when frozen section examination revealed a benign lesion and the margins were negative. RESULTS: Gynecomastia was not present in any patient. No microcalcifications were observed. Follicle-stimulating hormone was high in all patients (range 19.8 to 66.0 mUI/ml, mean 34.4). Luteinizing hormone levels were variable (range 1.32 to 28 mUI/ml, mean 12.3). Testosterone was normal in all cases (range 2.82 to 6.25 ng/ml, mean 4.2). Ultrasonographic features of the lesions were hypoechoic area (6 patients) and mixed hyper-hypoechoic area (2 patients). Histological outcomes of Leydig cell tumor (in 3 patients), focal Leydig cell hyperplasia (1 patient), fibrosis (1 patient), diffuse Leydig cell hyperplasia (1 patient), classic seminoma (1 patient) and embryonal carcinoma (in 1 patient) were observed. CONCLUSIONS: Of 560 infertile patients 8 (1.4%) showed focal testicular lesions, 2 (0.4%) were diagnosed with germ cell tumors and 3 (0.5%) with interstitial cell neoplasms. The malignant tumors were both palpable and in 2 of 3 cases Leydig cell tumors were diagnosed only with ultrasonography.     

Clinical and pathological features associated with the testicular tumor of the adrenogenital syndrome

PURPOSE: Testicular tumor of the adrenogenital syndrome is a rare clinical entity found in young men with endocrine disorders. Histologically it resembles Leydig cell tumor. We 1) reviewed the clinical features of testicular tumor of the adrenogenital syndrome and 2) determined if special histopathological features of the tumor and synaptophysin reactivity could distinguish testicular tumor of the adrenogenital syndrome from Leydig cell tumor. MATERIALS AND METHODS: We reviewed the medical and pathological records for all patients with testicular tumor of the adrenogenital syndrome seen at our institution from 1978 to 2004. These tumors were examined by histological and immunophenotypic methods for comparison to Leydig cell tumor. RESULTS: A total of 14 males with an endocrine disorder had pathological evidence of testicular tumor of the adrenogenital syndrome. These tumors were often bilateral (93% or 13 of 14 cases), associated with pain (92% or 12 of 13) and refractory to medical management with high dose exogenous steroids (93% or 13 of 14). Testicular tumor of the adrenogenital syndrome was managed by tumor enucleation in 7 patients (54%) and by radical orchiectomy in 6 (46%). All patients had resolution of pain at 3-month followup. Upon histological review features found to be more common to testicular tumor of the adrenogenital syndrome compared with Leydig cell tumor were nuclear pleiomorphism, low mitotic activity, extensive fibrosis, lymphoid aggregates, adipose metaplasia and prominent lipochrome pigment. Synaptophysin (ICN, Costa Mesa, California) reactivity was strong in testicular tumor of the adrenogenital syndrome but rarely observed in Leydig cell tumor. CONCLUSIONS: In our series medical treatment failed in patients with testicular tumor of the adrenogenital syndrome and conservative surgical therapy was possible in select individuals. We identified special histopathological and immunophenotypic features, including synaptophysin staining, which distinguish testicular tumor of the adrenogenital syndrome from Leydig cell tumor.     

Is testosterone involved in the initiation of spermatogenesis in humans? A clinicopathological presentation and physiological considerations in four patients with Leydig cell tumours of the testis or secondary Leydig cell hyperplasia

The purpose of this study was to evaluate the role of testosterone on the puberal development of spermatogenesis and to present additional clinicopathological data which bring about new information to this controversial subject. Four pre-pubertal patients are presented, 2 of them bearing Leydig cell tumours of the testis in the form of nodular masses. In both cases seminiferous tubules in the immediate vecinity to the tumours showed complete development of spermatogenesis, while those located away from the tumours were infantile in nature. Gonadotrophic levels were within the normal pre-pubertal range in these 2 cases. In one of the patients, testosterone concentration in the testis showed higher values than normal, and a concentration gradient was detected between the tumoral nodule and non-tumoral parenchyma. The 3rd patient had a pineal choriocarcinoma producing high amounts of hCG and consequently a diffuse hyperplasia of Leydig cells with high levels of plasma testosterone. Seminiferous tubules showed development up to pachytene spermatocytes. The last case was a precocious puberty in a boy with a tumour of the 3rd ventricle area. He had elevated levels of testosterone in the testis and plasma. In the testicular biopsy, stimulation of Leydig cells was detected. The seminiferous tubules showed mature Sertoli cells and pachytene spermatocytes. FSH levels were abnormally low. These 4 cases present in common different situations in which abnormally high amounts of testos-happens in the immature rat, the interaction between testosterone and gonadotrophins is essential for the normal initiation of spermatogenesis in normal puberty. Considerations are discussed on the possible synergistic role of gonadotrophins or other factors in relation with stimulation of seminiferous tubules by testosterone.     

Carcinoid tumours of the testis

OBJECTIVE

To review previous reports of carcinoid (an endocrine tumour mostly of the gastrointestinal tract) tumours of the testis.

METHODS

Carcinoid tumours of the testis are rare and can be divided into primary carcinoid (group 1), testicular metastasis from another location (group 2) and carcinoid within a testicular teratoma (group 3). A case of testicular carcinoid within our clinic prompted us to review previous reports; all the cases found were assessed for patient and tumour characteristics, diagnostic tools used, treatment and prognosis.

RESULTS

In all, 62 cases were assessed and divided into groups 1 (44 patients), 2 (six) and 3 (12), respectively. Seven patients in group 1 developed metastases. A wide variety of diagnostic tools was used to search for other tumour sites. All patients were treated with orchidectomy. Three patients with a primary carcinoid were treated with adjuvant chemotherapy (two) or radiotherapy (one), with unknown results. All but one of the nine patients who died were known to have metastasis, either from a primary testicular carcinoid or testicular metastases from an intestinal carcinoid.

CONCLUSION

When a testicular carcinoid tumour is discovered, other tumour sites should be excluded. The most useful diagnostic tools for this purpose seem to be urinary 5‐hydroxyindoleacetic acid measurement, somatostatin receptor scintigraphy, computed tomography and video‐capsule endoscopy. Localized testicular carcinoid tumours have an excellent prognosis after orchidectomy.     

Enucleation for prepubertal leydig cell tumor

PURPOSE: Leydig cell tumors in children are rare, comprising only 4% to 9% of all primary testis tumors in prepubertal males. Almost all of these boys present with isosexual precocious pseudopuberty associated with increased testosterone, low gonadotropin levels and a testis mass. We present our experience with testis sparing enucleation of Leydig cell tumor in prepubertal boys. MATERIALS AND METHODS: Two patients presented with isosexual precocious puberty at ages 6 and 9 years. Each patient had a well circumscribed, painless testicular mass, increased serum testosterone (101 and 444 ng/dl [normal 0 to 25]), normal gonadotropins and negative alpha-fetoprotein levels. Both patients underwent successful enucleation of the testis mass following proper testis oncological surgical principles. RESULTS: Both patients had normalization of the serum testosterone following enucleation of the Leydig cell tumor. At 9 and 44 months of followup they have maintained normal ipsilateral testicular volume compared to the contralateral gonad, and 1 patient entered puberty spontaneously at 1 year postoperatively. Neither patient suffered any morbidity, and both have presumably benefited from preservation of the involved gonad with preserved testicular volume. CONCLUSIONS: Prepubertal boys with isosexual precocious pseudopuberty, an isolated testis mass, increased testosterone and low or normal gonadotropin levels can reliably be diagnosed with Leydig cell tumors. Based on the ability to establish the diagnosis preoperatively and the universal benign behavior of unilateral, prepubertal Leydig cell tumor, we believe these patients are best treated with testis sparing enucleation of the tumor. In view of the high likelihood that this tumor in prepubertal boys is benign, a transscrotal surgical approach should be considered.     

Regulatory cytokine expression and interstitial fluid formation in the normal and inflamed rat testis are under leydig cell control

Leydig cells have been implicated in several inflammation-related responses of the testis. Specifically, these cells produce the proinflammatory cytokines interleukin-1 (IL-1) and IL-6, stimulate macrophage recruitment, and promote interstitial fluid formation. In addition, the immunoregulatory cytokines macrophage migration inhibitory factor (MIF), transforming growth factor-beta1 (TGFbeta1), and interferon-gamma (IFNgamma) are constitutively expressed by testicular cells, including the Leydig cells. In the present study, the contribution of the Leydig cell to testicular inflammatory responses was examined in adult male rats treated with the Leydig cell-specific toxin, ethane dimethane sulfonate (EDS). Intratesticular testosterone levels were modulated by subcutaneous testosterone implants. After 10 days, animals received an injection of lipopolysaccharide (LPS) to induce an inflammatory response, or saline alone, and were killed 3 hours later. Both depletion of Leydig cells by EDS and LPS treatment caused a decrease in collected testicular interstitial fluid to about 35% of control levels, but the effects were not additive. Maintenance of intratesticular testosterone reversed the interstitial fluid decline following EDS treatment and partially prevented the LPS-induced effect. MIF, TGFbeta1, and IFNgamma were expressed in both the normal and inflamed testis at similar levels. In contrast, EDS treatment caused a significant decline in expression of all 3 cytokines, which was prevented by the testosterone implants. These data indicate that 1) expression of TGFbeta1, MIF, and IFNgamma in the testis is not dependent on the presence of intact Leydig cells but is under direct testosterone control and 2) the decline in testicular interstitial fluid during inflammation involves the Leydig cells, acting via both androgens and nonandrogenic secretions. These data provide further support for a significant role for the Leydig cell in modulating the testicular response to inflammation.     

Rete testis-associated nodular steroid cell nests: description of putative pluripotential testicular hilus steroid cells

A putative hilus interstitial cell has been proposed as the cell of origin for testicular tumors of adrenogenital syndrome, but its normal histology is not documented. We present hitherto undescribed nodular steroid cell nests associated with the rete testis that are distinctive in their morphology and immunohistochemical profile from Leydig cells and do not have the morphology of typical extra-adrenal cortical rests. These nodules measured 1, 1, 1.8, 2, and 2.5 mm in size with a distinct sinusoidal vasculature. Individual cells were rounded to polygonal with evenly distributed moderate-to-abundant eosinophilic cytoplasm. The nuclei were homogenous and round, with fine chromatin and ocasionally with prominent nucleoli. The differential diagnosis included adrenocortical rests, testicular adnexal Leydig cells, carcinoid tumorlets, paraganglionic rests, and adenomatoid mesothelial proliferation. Immunohistochemistry showed positivity for melan A (5/5), inhibin (3/5), and calretinin (2/4), although the immunoreactivity was distinctively different from the concurrent intratesticular Leydig cells and testicular adnexal Leydig cells in all cases. The unique morphology, immunophenotype, and distinctive location of these cells in the testicular mediastinum raises the possibility that these cells represent testicular hilus steroid cells, the putative histogenetic cell implicated for testicular tumors of adrenogenital syndrome. We propose to name these proliferations rete testis-associated nodular steroid cell nests.     

'Burned-out' primary testicular cancer

OBJECTIVE: To report the natural history of 'burned-out' testicular tumour (a testicular tumour that has regressed spontaneously with no treatment and that generally presents at the stage of metastases). PATIENTS AND METHODS: We report five cases of burned-out testicular tumours to illustrate the clinical, radiological and histopathological features, and discuss the hypothesis of natural history of these neoplasms. RESULTS: The findings in the five patients tended to indicate that metastatic progression appears to induce spontaneous regression of the previous tumour site. Patients explored for extragonadal germ cell tumour present with various clinical features depending on the site of the metastases. CONCLUSION: Despite the controversial hypotheses of the origin of these tumours, extragonadal germ cell tumours should be considered to be metastases of a 'burned-out' primary testicular tumour that must be investigated. When a primary testicular tumour is detected, the testis must be removed, and standard chemotherapy yields good long-term results. The hypothesis of an immunological reaction against the tumour inducing the spontaneous necrosis of the primary tumour and possibly the metastases should be considered. Immunological screening should be proposed in patients to investigate this interesting model of spontaneous tumour regression.     

Conservative surgical therapy for leydig cell tumor

PURPOSE: We performed a long-term evaluation of conservative surgical treatment of benign Leydig cell tumor. MATERIALS AND METHODS: A multicenter retrospective clinical study was performed at 6 European centers. Case files of all patients diagnosed with Leydig cell tumor and treated with conservative surgery were examined. Patients underwent physical examination, hormone and tumor marker assays, scrotal and abdominal ultrasound, chest x-ray, and an endocrinological examination. RESULTS: From 1987 to 2006, 22 patients with Leydig cell tumor underwent conservative surgery. Mean patient age was 35 years (range 5 to 61). Mean followup was 47 months (range 1 to 230). No local recurrence or metastasis was observed. Patients presented with a palpable testicular nodule (3 patients, 13.7%) or a nodule diagnosed by ultrasound (15 patients, 68.2%), gynecomastia (2 patients, 9.1%), precocious pseudopuberty (1 patient, 4.5%) or scrotal pain (1 patient, 4.5%). Three patients were monorchid after contralateral orchiectomy for inguinal hernia repair (1 patient, 28 years before surgery) and nonseminomatous germ cell tumor (2 patients, 1 month and 6 years before surgery). Diagnosis after frozen section examination was Leydig cell tumor in 20 of 22 cases (91.0%). Mean histological size of the nodule was 1.11 cm (range 0.5 to 2.5). Preoperative FSH and LH levels were high in 4 patients. Tumor markers were normal before and after surgery. Followup was conducted for all patients every 3 to 6 months with physical examination, tumor markers, scrotal and abdominal ultrasound, chest x-ray. Six patients (27.3%) underwent abdominal computerized tomography. CONCLUSIONS: When diagnosed early Leydig cell tumors present a favorable followup. In select cases with motivated patients, conservative surgery proved to be a feasible and safe choice.