Management of the contralateral testis in patients with testicular germ cell cancer

Patients with testicular germ cell tumours (TGCT) are at increased risk of developing a tumour in the contralateral testis. Such a tumour may be preceded by carcinoma in situ (CIS), which is more common in patients with infertility, atrophic testis or a history of cryptorchism. Of 1219 patients with TGCT seen at the Royal Marsden Hospital between 1962 and 1984 in whom the contralateral testis was managed by surveillance, 38 (3.1%) developed a second tumour and 8 died of germ cell tumours. Seventeen of 26 assessable patients (65%) exhibited at least one of the known aetiological risk factors for carcinoma in situ. Diagnosis of carcinoma in situ may lead to more appropriate management of the contralateral testis.     

The effect of patient's delay and doctor's delay in patients with malignant germ cell tumours

In 103 patients with malignant germ cell tumours the initial clinical diagnosis was incorrect in 45 (44%). The correct diagnosis was established within 2 months in only 31% of the patients, and delayed by more than 6 months in 27%.
Stage, distribution and survival were correlated with the histology, but not with the duration of symptoms or the patient's/doctor's delay.
Rapidly growing tumours often belonged to the non-seminornaious group where advanced tumour stages and low survival rates were more common than in the seminoma group.
The overall prognosis of patients with malignant germ cell tumours may be increased by an early diagnosis of testicular tumours in non-symptomatic patients, especially in men with possible risk factors (cryptorchidism, atrophic testis, antecedent contralateral testicular cancer).     

Bilateral testicular cancer: a preventable problem? Experience from a large cancer centre

OBJECTIVE: To report a retrospective review of patients with a testicular germ cell tumour treated in a large cancer centre who developed a second tumour, as 1.8-5% of such patients will subsequently develop a new primary tumour in the contralateral testis. PATIENTS AND METHODS: From a database of 570 men treated for testicular cancer in the West of Scotland between 1989 and 1998, all those who developed bilateral testicular tumours were identified. RESULTS: Nineteen men (3.3%) developed a second primary testicular malignancy; the mean age at diagnosis of the first tumour was 29.5 years, with the mean (range) interval to diagnosis of the second tumour of 76 (11-181) months (except for one man with synchronous tumours). The first tumour was teratoma in 11 and seminoma in seven; one patient had synchronous bilateral teratoma. The second primary was teratoma in 10 and seminoma in eight. Known risk factors for carcinoma in situ were present in nine patients, i.e. a small atrophic contralateral testis in five, a family history of testicular cancer in two, a history of infertility in two and unilateral undescended testis in one. Two patients had had contralateral testicular biopsies at the first diagnosis; both were negative for intratubular germ cell neoplasia (IGCN). Eight patients had chemotherapy to treat the first tumour and 14 for the second. All underwent bilateral orchidectomy. Overall, 18 of 19 men are alive and disease-free, with a median follow-up of 51 months. Pathology for 12 of the second testicular tumours was available for review; there was no IGCN in any of the slides from three patients, it was only present focally around the tumour in seven, and was diffuse in two patients. CONCLUSIONS: Chemotherapy for the first testicular tumour does not eliminate the risk of developing a contralateral tumour. Despite careful follow-up, in most patients the second primary tumour was not diagnosed early enough to avoid chemotherapy. The focal nature of IGCN in the second testis in most patients questions the value of biopsy of the contralateral testis. Improved methods of detecting patients at risk of second testicular tumours are needed.     

Persistent carcinoma in situ of the testis after chemotherapy for advanced testicular germ cell tumours

The chemosensitivity of testicular carcinoma in situ (CIS) was analysed in 25 testes excised 10 weeks to 4.5 years following platinum-based chemotherapy. CIS was present in 8 of the 23 evaluable cases (35%), in 5 of which the lesion coexisted with invasive germ cell tumour. It is concluded that CIS may persist or recur after chemotherapy. This has implications for occult presentation of metastatic germ cell tumours and also for the management of the contralateral testis in patients with testicular germ cell tumours.     

'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.     

Intermediate filament proteins as tissue specific markers in normal and neoplastic testicular tissue

Normal testicular tissue and primary and metastatic testicular germ cell tumours were examined for their intermediate filament protein (IFP) expression. Seminomas were shown to react with antibodies to vimentin, while non-seminomatous germ cell tumours were strongly positive with antibodies to cytokeratin. In the case of teratocarcinoma, several components of the tumour can be distinguished using a combination of monoclonal and polyclonal antisera in the double-label immunofluorescence technique. We conclude that antibodies to cytokeratin and vimentin can be helpful in the diagnosis of testicular germ cell tumours, especially in the differentiation between seminomas and non-seminomatous testis tumours.     

Testicular germ cell cancer despite previous local radiotherapy to the testis

BACKGROUND: Testicular intraepithelial neoplasia (TIN, also carcinoma in situ of the testis) is the uniform precursor of testicular germ cell cancer. Local radiotherapy to the testis with dosages of 18-20 Gy has been found to safely eradicate TIN and germ cells, too. Thus, the general assumption is that the development of invasive germ cell tumours can be prevented by this radiotherapy. PATIENTS AND METHODS: Herein, we report two patients with one-sided testicular tumour and biopsy-proven contralateral TIN. Both of them developed germ cell neoplasms in the remaining testis although local radiotherapy with 20 Gy had been applied to the testis. RESULTS: One patient developed pure seminoma 7 years after completion of radiotherapy, the other developed a combined tumour consisting of embryonal carcinoma and seminoma after 5 years. Treatment consisted of orchiectomy in each of the cases. Histologically, both had TIN in the testicular tissue surrounding the new growths. CONCLUSIONS: Pathogenetically, a small fraction of radioresistent TIN cells overcoming irradiation and progressing to full-blown germ cell cancer in the later course may be the histogenetic clue to explain these unexpected events. Other explanations, though less probable, could be technical radiotherapeutic failure due to targeting problems and a pre-existing radioresistent germ cell tumour in the irradiated testicle.     

Prepubertal testicular tumours and efficacy of testicular preserving surgery

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Testicular tumours in childhood are very rare. Historically, most of these tumours have been considered malignant, but more recent studies indicate that benign lesions, particularly teratoma, are much more frequent than previously thought. Testicular tumours in this age group have traditionally been treated with inguinal radical orchiectomy, but more conservative management has been proposed in view of the higher frequency of benign tumours. In children, most testicular tumours are benign, especially before puberty. A testis‐sparing procedure should be performed in children with a palpable testicular mass and negative tumour markers.

OBJECTIVE

? To report our experience of testicular tumours in children aged ≤13 years, including our experience with testis‐sparing surgery.

PATIENTS AND METHODS

? A retrospective study was performed of 15 patients with testicular tumours aged ≤13 years who presented at our centre between 1984 and 2008. The use of testis‐preserving surgery according to indication was investigated and outcomes were recorded.

RESULTS

? The clinical presentation was increased testicular size with a palpable mass in 80% of the cases. All 15 patients underwent surgery. The tumour was benign in 12 (80%) patients and malignant in three (20%) patients. ? Organ‐preserving surgery was planned and achieved in 11 patients (73%). ? Pathology of the tumourectomy specimens disclosed benign tumours in all cases: four epidermoid cysts, two teratomas, one juvenile granulosa cell tumour, one haemangioma, one lipoma, one fibrous hamartoma and one splenogonadal fusion. ? In four patients who underwent radical orchiectomy, pathology identified one yolk sac tumour (stage I), two mixed germ cell tumours and one gonadoblastoma.

CONCLUSIONS

? In children, most testicular tumours are benign, especially before puberty. A testis‐sparing procedure should be performed in children with a palpable testicular mass and negative tumour markers. ? The lesion, however, should be thoroughly excised to avoid recurrences.     

Testicular and paratesticular tumours in children: 30 years' experience.

BACKGROUND: Testicular or paratesticular tumours in children are rare, making it difficult to achieve the best management for these life-threatening diseases. The aim of this study is to review patients during a 30-year period with these tumours and assess clinical aspects to improve management. METHODS: The records of 68 patients from 1967 to 1996 were reviewed with respect to age at diagnosis, affected sites, presentation, clinical diagnosis, operation, pathology and prognosis. RESULTS: The most common presentation was a painless scrotal mass (84%). The most common testicular tumour was mature teratoma (n = 27) followed by yolk sac tumour (n = 17). Thirteen patients had paratesticular rhabdomyosarcoma. Two teratocarcinomas, three leydig cell tumours, two sertoli cell tumours, one granulosa cell tumour, one fibroma, one gonadoblastoma, and one secondary tumour from acute myeloid leukaemia were found also. Testis-sparing surgery was performed in 21 of 33 patients with benign tumours (27 teratoma, three leydig cell tumours, two sertoli cell tumours, one fibroma), which caused no recurrence. Only two patients with rhabdomyosarcoma and one with mixed germ cell tumour died of their disease. CONCLUSION: Recent combined therapy with surgery and chemotherapy against primary testicular and paratesticular tumours has improved prognosis. Testis-sparing surgery should be considered for benign tumours.     

Bilateral testicular germ cell tumours: a systematic review

What's known on the subject? and What does the study add? Bilateral testicular germ cell tumours (BTGCTs) are rare neoplasms. Most previously published studies consist of case reports or small retrospective case series. Little is known about their epidemiological and clinicopathological characteristics. BTGCT corresponded to 1.82% of testicular tumours. Metachronous disease was about twice as frequent as synchronous disease. The primary tumour histology, chemotherapy use and the interval between metachronous tumours influenced the histology of the second tumour. Overall, synchronous tumours were associated with more advanced disease and presented less favourable survival rates than metachronous tumours. Testicular cancer is the most common tumour in young men. It is known that a second primary contralateral testis tumour may occur in up to 5% of men with a proior tumour. About 35% of these men present with synchronous tumours, and 65% present with metachronous tumours. However there is little data about bilateral testicular germ cell tumours (BTGCT) in the literature and the most published articles are case reports on a small series of men, which makes it difficult to draw conclusions about therapeutic strategies for the treatment of BTGCTs. In fact, current guidelines for the treatment of testicular cancer contain little information related to bilateral disease. Therefore, the aim of our study is to provide a broad overview of BTGCT and to update data focusing on incidence, pathological features, and clinical outcomes of men with BTGCTs. Thus, an extensive review containing 94 studies and more than 50,000 patients was conducted.     

Leydig cell tumor. Two new cases

The Leydig's cell tumours are the most common of all non germ cell tumour of the testis, that clinical findings is different by age of presented. We report two new cases of Leydig cell tumour diagnosed in our centre having different presentation form, in old adults with feminizing features and occult tumour, and as a testicular nodule pain, respectively. The analytical, clinical, diagnostic aspects and therapeutic of the uncommon disease are discussed.     

Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours

Carcinoma-in-situ of the testis (CIS) is the precursor of invasive germ cell tumours. It is believed that CIS cells may originate from early fetal gonocytes. Recently, the proto-oncogene c-kit has been implicated as crucial for the development and migration of primordial germ cells. In this study, CIS and overtly invasive human male germ cell tumours were analysed immunohistochemically for expression of the c-kit proto-oncogene protein product. Testicular tissue samples from 36 patients with various types of testicular germ cell neoplasia and 19 control specimens were stained using an indirect immunoperoxidase method. High expression of c-kit was found in almost all cases of CIS, both when the lesion was the only pathology, and when CIS was adjacent to invasive tumours. The Kit staining was retained in seminomas with variable intensity; the majority of cells in tumour mass exhibited c-kit expression in 61% of the samples while focal expression was observed in 39% of the samples studied. No expression of c-kit was detected in non-seminomas or in normal testicular germ cells. High expression of the proto-oncogene in CIS cells supports the hypothesis of their origin from primordial germ cells. In addition, we propose that the c-kit protein product is a new marker for carcinoma-in-situ of the testis.     

TESTICULAR AND PARATESTICULAR TUMOURS IN CHILDREN: 30 YEARS’ EXPERIENCE

Background : Testicular or paratesticular tumours in children are rare, making it difficult to achieve the best management for these life-threatening diseases. The aim of this study is to review patients during a 30-year period with these tumours and assess clinical aspects to improve management. Methods : The records of 68 patients from 1967 to 1996 were reviewed with respect to age at diagnosis, affected sites, presentation, clinical diagnosis, operation, pathology and prognosis. Results : The most common presentation was a painless scrotal mass (84%). The most common testicular tumour was mature teratoma (n = 27) followed by yolk sac tumour (n = 17). Thirteen patients had paratesticular rhabdomyosarcoma. Two teratocarcinomas, three leydig cell tumours, two sertoli cell tumours, one granulosa cell tumour, one fibroma, one gonadoblastoma, and one secondary tumour from acute myeloid leukaemia were found also. Testis-sparing surgery was performed in 21 of 33 patients with benign tumours (27 teratoma, three leydig cell tumours, two sertoli cell tumours, one fibroma), which caused no recurrence. Only two patients with rhabdomyosarcoma and one with mixed germ cell tumour died of their disease. Conclusion : Recent combined therapy with surgery and chemotherapy against primary testicular and paratesticular tumours has improved prognosis. Testis-sparing surgery should be considered for benign tumours.     

Morphology of testicular germ cell tumours in treated and untreated cryptorchidism

The histology of 75 testicular germ cell tumours in 73 patients with treated or untreated cryptorchidism was investigated in a group of 503 patients with testicular germ cell tumour and evaluated according to the WHO classification. The proportion of pure seminoma was associated with the height of the testis, being 87% in abdominal. 78% in inguinal and 50% in normally positioned testes. In patients operated upon for cryptorchidism, the current site of the testis seemed to be a more important determinant of this proportion than the original site. The proportion of pure seminoma which developed in testes after successful orchiopexy was equal to that in normally-descended testes (50%) and lower (39%) if orchiopexy had been performed before the age of 16 years. Similarly, among non-seminomas, a higher proportion of tumours containing teratoma tissue was found in cryptorchidism was successfully treated in childhood. It was concluded that a successful orchiopexy in childhood decreases especially the risk of seminoma.     

Apoptosis: a key effector mechanism of lymphocyte action in human nonseminomatous testicular carcinoma?

OBJECTIVE: To correlate the number of tumour-infiltrating T lymphocytes (TILs) with the extent of apoptosis in testicular germ cell tumours, as TILs are considered to be a favourable prognostic factor of human testicular tumours, especially of seminomas, but the mechanism by which TIL contribute to an improved outcome is unclear. MATERIALS AND METHODS: Tissue samples from 47 patients with nonseminomatous germ cell tumour (NSGCT) and 15 with seminomatous GCT were investigated immunohistochemically for lymphocyte infiltration and apoptosis. The apoptotic index (AI) was assessed in various categories (DNA condensation and fragmentation) using in-situ end-labelling to identify typical apoptotic DNA strand breaks, and nuclear staining to identify typical apoptotic morphology. RESULTS: In seminomatous GCT there was no correlation between the number of TILs and any AI. In NSGCT there was only a relationship between lymphoid infiltration and those AIs showing morphological criteria of apoptosis in a small subgroup of NSGCT, i.e. metastasized embryonal cell carcinomas. Only 1.2% (AI, chromatin condensation) and 0.8% (AI, fragmentation and condensation) of all tumour cells showed these features of apoptosis. The overall AI in NSGCT was 7.9%. CONCLUSIONS: TILs do not seem to induce apoptosis in testicular tumours. Embryonal cell carcinomas might be susceptible to lymphocyte attack, resulting in apoptosis of the tumour cell. The mechanisms of interaction between lymphocytes and testis tumour cells need further investigation.     

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.     

Bilateral germ cell cancer of the testis: a report of 11 patients with a long-term follow-up

OBJECTIVE: To describe the incidence, clinical characteristics, treatment methods and long-term follow-up of bilateral germ cell tumours of the testis (GCTT) in patients treated at one institution. PATIENTS AND METHODS: Of 552 patients with GCTT, 11 (2%, mean age 26. 9 years) developed bilateral disease; all 11 underwent radical orchidectomy. Additional treatment was planned according to the histological type and clinical stage of the tumour, and previous treatments. Intramuscular testosterone was administered periodically after total castration. The data on survival, sexual status and treatment complications were reviewed. RESULTS: Of the 11 patients, seven developed a second tumour metachronously (median interval 87 months) and four had synchronous bilateral GCTT. Cryptorchidism, infertility or atrophic testis was associated with the development of bilateral GCTT in seven of the 11 patients. All synchronous tumours and most of the sequential tumours had identical histology on both sides. Although all sequential tumours presented at an early clinical stage, three of four synchronous bilateral GCTTs presented at an advanced stage. Five patients received platinum-based chemotherapy; three patients underwent post- chemotherapy resection of the retroperitoneal residual mass. Sexual libido and potency were conserved in all patients. No significant morbidity was recorded as being caused by any of these treatments. At a median follow-up of 11. 6 years, all patients were alive with no evidence of cancer. CONCLUSIONS: All patients with unilateral GCTT have an increased risk of developing a contralateral testicular tumour, even decades after diagnosis. Management should be adapted to each patient. As all patients in this series survived in the long-term, developing a second germ cell cancer does not necessarily predict a poor prognosis.     

Lymphadenectomy for testicular carcinoma

Since 50% of patients with testicular tumour have retroperitoneal metastases at the time of presentation, there has been little argument that the area of primary drainage requires further treatment following orchiectomy. Patients with nonseminomatous germ cell tumours in stages A and B are candidates for retroperitoneal lymphadenectomy because this procedure is of therapeutic value and allows accurate staging of the disease. The development of extremely effective modern, cyclic, multidrug chemotherapy for extensive nonseminomatous testicular tumour has led to a rethinking of the role of lymphadenectomy in treating testicular cancer. Clinical staging is still not 100% accurate even with modern techniques. Lymphadenectomy, therefore, continues to be an important step in managing patients with nonseminomatous germ cell tumours. These facts are endorsed by the authors' review of 72 cases of nonseminomatous germ cell tumours managed at McGill University teaching hospitals over a 10-year period. The authors also discuss the indications for retroperitoneal dissection.     

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.     

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).