Testicular Cancer
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Testicular cancer is most common cancer in men between 15 to 35 years old. There are two broad types: seminoma and nonseminoma histologies. The nonseminoma group of cancers includes embryonal carcinoma, teratoma, yolk sac carcinoma and choriocarcinoma. The two testicles (or testis) produce sperm and male hormones. Men who have an undescended testicle (a testicle that didn't move down into the scrotum) are at higher risk of developing testicular cancer.

In 2010, 2,286 men in the UK were diagnosed with testicular cancer (Source: Cancer Research UK).

This page shows only UK resources. For a more extensive list of resources from around the world see CancerIndex: Testicular Cancer

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications

Information Patients and the Public (11 links)


Information for Health Professionals / Researchers (4 links)

Latest Research Publications

Showing publications with corresponding authors from the UK (Source: PubMed).

Nsengimana J, Barrett JH
Analysis of genetic interactions involving maternal and offspring genotypes at different Loci: power simulation and application to testicular cancer.
Genet Epidemiol. 2012; 36(6):612-21 [PubMed] Free Access to Full Article
The analyses of genetic interaction between maternal and offspring genotypes are usually conducted considering a single locus. Here, we propose testing maternal × offspring (M×O) and maternal × maternal (M×M) genotype interactions involving two unlinked loci. We reformulate the log-linear approach of analyzing cases and their parents (family trios) to accommodate two loci, fit fuller models to avoid confounding in a first analysis step and propose that the model be reduced to the most prominent effects in a second step. We conduct extensive simulations to assess the validity and power of this approach under various model assumptions. We show that the approach is valid and has good power to detect M×O and M×M interactions. For example, the power to detect a dominant interaction relative risk of 1.5 (both M×O and M×M) is 70% with 300 trios and approaches 100% with 1,000 trios. Unlike the main effects, M×O and M×M interactions are conditionally independent of mating types, and consequently, their power is not affected by missing paternal genotypes. When applied to single-locus M×O interaction, our method is as powerful as other existing methods. Applying the method to testicular cancer, we found a nominally significant M×M interaction between single nucleotide polymorphisms from C-Kit Ligand (KITLG) and Sex Hormone Binding Globulin (SHBG) using 210 families (relative risk 2.2, P = 0.03). This finding supports a role of maternal hormones in offspring testicular cancer and warrants confirmation in a larger dataset.
Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, University of Leeds, Leeds
Research funded by:


Arora RS, Alston RD, Eden TO, et al.
Comparative incidence patterns and trends of gonadal and extragonadal germ cell tumors in England, 1979 to 2003.
Cancer. 2012; 118(17):4290-7 [PubMed]
BACKGROUND: It is believed that gonadal and extragonadal germ cell tumors (GCTs) arise from primordial germ cells and may have similar etiopathogenesis. Unlike testicular GCTs, there has been limited comprehensive population-based analysis of ovarian and extragonadal GCTs.
METHODS: All malignant GCTs and all central nervous system (CNS) GCTs with benign and uncertain behavior that were registered in England in the age group 0 to 84 years from 1979 to 2003 were included in the current study. Incidence rates were calculated and adjusted to the world standard population.
RESULTS: There were 33,364 GCTs (92.5% testes, 3.9% ovary, 3.2% extragonadal) in individuals aged 0 to 84 years. The CNS was the most common extragonadal site. An initial peak in incidence at ages 0 to 4 years of nongerminomas was observed at all sites except ovary. Second incidence peaks between ages 10 to 39 years that were more marked among males also were observed at all sites. The ages at these incidence peaks varied by site and were 10 to 14 years (CNS), 15 to 19 years (ovary), 25 to 29 years (other extragonadal sites), and 30 to 34 years (testes). A statistically significant increase in incidence over time was observed in germinomas (testes, CNS) and nongerminomas (testes, ovary).
CONCLUSIONS: The age-incidence patterns observed suggested a common initiation of GCTs in embryonic/fetal life with variable rates of tumor progression as a result of subsequent events that may be site specific. The authors concluded that future genetic studies should consider GCTs from all sites to enable a better understanding of their etiology.
Pediatric Oncology Department, Alder Hey Hospital, Liverpool
Research funded by:


Oliver RT, Mead GM, Rustin GJ, et al.
Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214).
J Clin Oncol. 2011; 29(8):957-62 [PubMed]
PURPOSE: Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported.
PATIENTS AND METHODS: Random assignment was between RT and one infusion of carboplatin dosed at 7 × (glomerular filtration rate + 25) on the basis of EDTA (n = 357) and 90% of this dose if determined on the basis of creatinine clearance (n = 202). The trial was powered to exclude a doubling in RFRs assuming a 96-97% 2-year RFR after radiotherapy (hazard ratio [HR], approximately 2.0).
RESULTS: Overall, 1,447 patients were randomly assigned in a 3-to-5 ratio (carboplatin, n = 573; RT, n = 904). RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT (RT-C 90% CI, 0.7% to 3.5%; HR, 1.25; 90% CI, 0.83 to 1.89). One death as a result of seminoma (in RT arm) occurred. Patients receiving at least 99% of the 7 × AUC dose had a 5-year RFR of 96.1% (95% CI, 93.4% to 97.7%) compared with 92.6% (95% CI, 88.0% to 95.5%) in those who received lower doses (HR, 0.51; 95% CI, 0.24 to 1.07; P = .08). There was a clear reduction in the rate of contralateral GCTs (carboplatin, n = 2; RT, n = 15; HR, 0.22; 95% CI, 0.05 to 0.95; P = .03), and elevated pretreatment follicle-stimulating hormone (FSH) levels (> 12 IU/L) was a strong predictor (HR, 8.57; 95% CI, 1.82 to 40.38).
CONCLUSION: These updated results confirm the noninferiority of single dose carboplatin (at 7 × AUC dose) versus RT in terms of RFR and establish a statistically significant reduction in the medium term of risk of second GCT produced by this treatment.
St Bartholomews and the London Hospital, London
Research funded by:


Lakhoo K
Neonatal teratomas.
Early Hum Dev. 2010; 86(10):643-7 [PubMed]
Teratomas are composed of multiple tissues foreign to the organ or site in which they arise. Their origin is postulated by 3 theories one of which is the origin from totipotent primodial germ cells. Anatomically, teratomas are divided into gonadal or extragonadal lesions and histologically they are classified as mature or immature tumors. Teratomas are mainy isolated lesions and may occur anywhere in the body. In the neonatal age group most of these tumors are benign and occur mainly in the sacrococcygeal area followed by the anterior mediastinum. Diagnosis is usually established prenatally and may require intervention in compromised fetuses. Postnatal imaging with ultrasound, CT scan or MRI provides useful information for surgical intervention. Complete surgical excision is the treatment of choice for neonatal teratomas. Alpha feto protein is the tumor marker of choice and is particularly useful for assessing the presence of residual or recurrent disease.
Children's Hospital Oxford, John Radcliffe Hospital, University of Oxford, Headley Way, Headington, Oxford OX3 9DU


Alam SS, Cantwell MM, Cardwell CR, et al.
Maternal body mass index and risk of testicular cancer in male offspring: a systematic review and meta-analysis.
Cancer Epidemiol. 2010; 34(5):509-15 [PubMed] Free Access to Full Article
OBJECTIVES: To date a number of studies have examined the association between maternal weight and testicular cancer risk although results have been largely inconsistent. This systematic review and meta-analysis investigated the nature of this association.
METHODS: Search strategies were conducted in Ovid Medline (1950-2009), Embase (1980-2009), Web of Science (1970-2009), and CINAHL (1937-2009) using keywords for maternal weight (BMI) and testicular cancer.
RESULTS: The literature search produced 1689 hits from which 63 papers were extracted. Only 7 studies met the pre-defined criteria. Random effects meta-analyses were conducted. The combined unadjusted OR (95% CI) of testicular cancer in the highest reported category of maternal BMI compared with the moderate maternal BMI was 0.82 (0.65-1.02). The Cochran's Q P value was 0.82 and the corresponding I(2) was 0%, both indicating very little variability among studies. The combined unadjusted OR (95% CI) for testicular cancer risk in the lowest reported category of maternal BMI compared to a moderate maternal BMI category was 0.88 (0.65-1.20). The Cochran's Q P value was 0.05 and the corresponding I(2) was 54%, indicating evidence of statistical heterogeneity. The combined unadjusted OR (95% CI) of testicular cancer risk per unit increase in maternal BMI was 1.01 (0.97-1.06). The Cochran's Q test had a P value of 0.05 and the corresponding I(2) was 55% indicating evidence of statistical heterogeneity.
CONCLUSION: This meta-analysis, which included a small number of studies, showed that a higher maternal weight does not increase the risk of testicular cancer in male offspring. Though an inverse association between high maternal BMI and testicular cancer risk was detected, it was not statistically significant. Further primary studies with adjustment for appropriate confounders are required.
Cancer Epidemiology & Health Services Research Group, Centre for Public Health, Queen's University Belfast, Northern Ireland
Research funded by:
  • PHS HHS


Venkitaraman R, George M, Weerasooriya S, Selva-Nayagam S
Late solitary testicular metastasis from rectal cancer.
J Cancer Res Ther. 2010 Jan-Mar; 6(1):89-91 [PubMed]
Isolated testicular metastasis from rectal cancer is rare. We describe the case of a patient who presented with a locally advanced rectal malignancy and underwent multimodality treatment with low anterior resection, postoperative radiotherapy and adjuvant chemotherapy. He developed a painless testicular nodule while on follow-up, five years after the diagnosis of primary rectal cancer. Histopathology and immunohistochemistry of orchidectomy specimen were compatible with a metastatic adenocarcinoma of rectal origin. We hypothesize that this phenomenon of isolated relapse in a sanctuary site could be due to the altered biology and pattern of metastasis as a result of effective adjuvant systemic chemotherapy. Treatment of late isolated relapse in the testis needs to be ascertained.
Ipswich Hospital NHS


Glendenning JL, Barbachano Y, Norman AR, et al.
Long-term neurologic and peripheral vascular toxicity after chemotherapy treatment of testicular cancer.
Cancer. 2010; 116(10):2322-31 [PubMed]
BACKGROUND: Testicular cancer is curable in the majority of men, and persisting treatment toxicity is a concern. The authors report a cross-sectional study of the long-term effects of chemotherapy (C) on neurologic function and development of Raynaud phenomenon.
METHODS: Seven hundred thirty-nine patients who were treated between 1982 and 1992 gave consent to enter the study. Patients were classified according to the receipt of C (n = 384) or no C (n = 355). Patients completed a general health questionnaire and a quality-of-life form (the European Organization for Research and Treatment of Cancer Quality-of-Life C30 questionnaire with testicular module). Symptom scores of 3 or 4 were considered clinically significant. Patients were assessed in the clinic, and clinical history was used to diagnose Raynaud phenomenon (RP) and tinnitus. Examinations included peripheral nerve function testing for light touch and vibration sense. Five hundred seventy-seven patients underwent audiometry.
RESULTS: On physician assessment, peripheral neuropathy and RP were more common after C (21.7% vs 9.1% [P<.001] and 20.3% vs 1.7% [P<.001], respectively). Similar results were obtained for symptom scores (12.5% vs 5.5% [P = .002] and 9.7% vs 3.7% [P<.001], respectively). On multivariate analysis, for peripheral neuropathy, the significant predictors were cisplatin dose, carboplatin dose, and age. For RP, the significant predictor was bleomycin. Significant differences in hearing thresholds were noted at 8000 hertz only and, on multivariate analysis, were related to age, cisplatin dose, and vincristine dose. Auditory symptom scores did not differ between groups.
CONCLUSIONS: With long-term follow-up, peripheral neuropathy and RP remained detectable in approximately 20% of patients and caused significant symptoms in 10% of patients. Detectable effects on high frequency remained but caused little symptomatic problem. These effects persisted and were related to the cumulative chemotherapy dose.
Urology Unit, The Royal Marsden National Health Service Foundation Trust, Sutton, Surrey
Research funded by:


Evans RE, Simon AE, Wardle J
Public perceptions of the harms and benefits of testicular cancer education: a qualitative study.
Cancer Epidemiol. 2010; 34(2):212-9 [PubMed]
BACKGROUND: The value of testicular cancer (TC) education, and in particular advice on testicular self-examination (TSE), has been widely debated by health professionals. One concern centres on its potential to cause unnecessary anxiety among the target population. Views outside the health professional community about TC education's potential benefits and harms have not previously been described. The objective of this study was to investigate the range of views expressed by specific groups thought to have an interest in provision of TC education.
METHODS: One-to-one, in-depth interviews with 37 men and women were completed. Participants included TC patients, men with no prior diagnosis of TC, and parents and teachers of adolescent boys. Verbatim transcripts were analysed using the Framework approach to produce a thematic description of views expressed.
RESULTS: Participants were unanimously in favour of TC education. Key perceived benefits included earlier cancer detection through increasing knowledge of symptoms leading to better treatment outcomes, and motivating help-seeking by reducing emotional barriers such as fear of cancer or embarrassment. Anxiety was acknowledged as a possible harm but was not expected to be widespread or serious.
CONCLUSION: TC education is viewed favourably by members of the public likely to be interested in its provision. Education's potential to cause anxiety was not considered a disincentive to promoting disease awareness.
Department of Epidemiology and Public Health, University College London, Gower Street, London WC1E 6BT
Research funded by:


Cohen MC, Shawis R, Evans C
Paratesticular müllerian-type papillary serous tumor in a child.
Pediatr Dev Pathol. 2009 Jul-Aug; 12(4):297-300 [PubMed]
We describe a case of a 15-year-old male presenting with an unusual right-sided paratesticular mass in whom the diagnosis of an ovarian-like paratesticular müllerian-type papillary serous tumor was made. The tumor, also referred to as serous papillary cystadenoma by some authors, depicted papillae with fibro-vascular cores lined by a bland pseudostratified ciliated epithelium. The immunohistochemistry showed the tumor to have diffuse reactivity against BerEp4, epithelial membrane antigen, and progesterone receptor; focal reactivity against cytokeratins AE1/AE3, cytokeratin 7 (CK7), Ca125, estrogen, and carcinoembryonic antigen; and negative reactivity for calretinin, Wilms tumor 1 (WT1), and CK20. Surgical management involved resection of the tumor followed by regular follow-up. Paratesticular müllerian-type papillary serous tumor is an infrequent lesion that has seldom been described in the pediatric-age patient. To our knowledge, whereas only 2 cases of serous papillary borderline malignancy have been previously described in this age group, this is the 1st time a serous papillary tumor is reported in a child. The pediatric surgeon, the clinicians, and the pathologist should be aware of this entity, as a conservative management would be preferable.
Department of Histopathology, Sheffield Children's NHS Foundation Trust, Western Bank, Sheffield, S10 2TH


Moynihan C, Norman AR, Barbachano Y, et al.
Prospective study of factors predicting adherence to medical advice in men with testicular cancer.
J Clin Oncol. 2009; 27(13):2144-50 [PubMed] Free Access to Full Article
PURPOSE: To identify predictive factors of adherence to medical advice, specifically the likelihood of attendance to a recommended follow-up regimen in patients with newly diagnosed testicular cancer. PATIENTS AND METHODS; This was a prospective study measuring initially not only aspects of the doctor-patient interview, but also a range of demographic, psychological, social, and medical factors, and then recording attendance behavior on follow-up. All 209 new patients with testicular cancer referred between June 1992 and May 1995 were approached, and 184 men consented and completed questionnaires. The nonadherence end point (nonattender) was two failures to attend an outpatient appointment at least 1 month apart, despite a written reminder.
RESULTS: Thirty-two participants (17%) were classified as nonattenders. No significant differences were found between attenders and nonattenders in the majority of psychosocial and medical variables that might have predicted nonadherence to medical advice. There was a highly significant association between nonattendance and a patient's perception of an unsatisfactory affective relationship with his clinician (P = .005; hazard ratio, 3.1; 95% CI, 1.4 to 6.6).
CONCLUSION: Patients who perceived an unsatisfactory affective relationship with their clinician that included an inability to trust the clinician and a perception that they were not being treated as "a person" were subsequently more likely to disregard medical advice regarding follow-up. Attention to the ways young men may wish to communicate with their clinicians is important, bearing in mind that they may not necessarily adhere to stereotypical images of masculine self-dependence.
Academic Radiotherapy Unit, The Institute of Cancer Research and Department of Clinical Research Development, Royal Marsden National Health Service Foundation Trust, Sutton, Surrey
Research funded by:


Featherstone JM, Fernando HS, Theaker JM, et al.
Sex cord stromal testicular tumors: a clinical series--uniformly stage I disease.
J Urol. 2009; 181(5):2090-6; discussion 2096 [PubMed]
PURPOSE: Sex cord stromal testicular tumors are rare. Historically 10% of lesions are said to be malignant but to our knowledge there are no clinical or histological features that can accurately predict potential malignant behavior. Because of this, groups at some centers have advocated prophylactic retroperitoneal lymph node dissection in patients with clinical stage I disease. We reviewed our experience with these tumors to determine whether this policy is justified.
MATERIALS AND METHODS: We retrospectively reviewed the records of all 38 men older than 18 years with sex cord stromal testicular tumors who were referred to the Wessex regional cancer center for treatment or pathological review during the 25-year period of 1982 to 2006. We then compared our series with a malignant sex cord stromal testicular tumor database generated from the world literature.
RESULTS: All Wessex patients were treated with excision of the primary tumor alone and metastatic disease developed in none. All remained disease-free with an overall median survival of 6.8 years (range 1.4 to 25). Features in the literature favoring malignant behavior, ie metastatic disease, included larger tumors (mean 6.43 vs 1.71 cm), a high mitotic rate, tumor necrosis, angiolymphatic invasion, infiltrative margins and extratesticular extension (each p <0.0001). The malignant group had an overall median survival of 2.3 years (range 0.02 to 17.3).
CONCLUSIONS: No patient had disease progression in our study, which is to our knowledge the largest reported United Kingdom series of sex cord stromal testicular tumors. Our data suggest that malignancy is uncommon and prophylactic retroperitoneal lymph node dissection is unjustified for clinical stage I disease.
Department of Urology, University Hospital of Wales, Heath Park


Dick J, Begent RH, Meyer T
Sarcoidosis and testicular cancer: A case series and literature review.
Urol Oncol. 2010 Jul-Aug; 28(4):350-4 [PubMed]
The coincidence of testicular carcinoma and sarcoidosis can result in diagnostic errors and inappropriate treatment unless patients are appropriately investigated. We report 3 such cases; 1 in which sarcoidosis preceded the diagnosis, 1 of coincident diagnoses, and 1 in which the sarcoidosis was diagnosed after testicular carcinoma. We review the investigations that can be used to resolve diagnostic uncertainty and the evidence for an association between the 2 diseases.
Department of Oncology, Royal Free Campus, UCL Medical School, London


Rustin GJ, Mead GM, Stenning SP, et al.
Randomized trial of two or five computed tomography scans in the surveillance of patients with stage I nonseminomatous germ cell tumors of the testis: Medical Research Council Trial TE08, ISRCTN56475197--the National Cancer Research Institute Testis Cancer Clinical Studies Group.
J Clin Oncol. 2007; 25(11):1310-5 [PubMed]
PURPOSE: Surveillance is a standard management approach for stage I nonseminomatous germ cell tumors (NSGCT). A randomized trial of two versus five computed tomography (CT) scans was performed to determine whether the number of scans influenced the proportion of patients relapsing with intermediate- or poor-prognosis disease at relapse.
METHODS: Patients with clinical stage I NSGCT opting for surveillance were randomly assigned to chest and abdominal CT scans at either 3 and 12 or 3, 6, 9, 12, and 24 months, with all other investigations identical in the two arms. Three of five patients were allocated to the two-scan schedule. Four hundred patients were required.
RESULTS: Two hundred forty-seven patients were allocated to a two-scan and 167 to five-scan policy. With a median follow-up of 40 months, 37 relapses (15%) have occurred in the two-scan arm and 33 (20%) in the five-scan arm. No patients had poor prognosis at relapse, but two (0.8%) of those relapsing in the two-scan arm had intermediate prognosis compared with 1 (0.6%) in the five-scan arm, a difference of 0.2% (90% CI, -1.2% to 1.6%). No deaths have been reported.
CONCLUSION: This study can rule out with 95% probability an increase in the proportion of patients relapsing with intermediate- or poor-prognosis disease of more than 1.6% if they have two rather than five CT scans as part of their surveillance protocol. CT scans at 3 and 12 months after orchidectomy should be considered a reasonable option in low-risk patients.
Mount Vernon Cancer Centre, Northwood, Middlesex HA62RN


Xu Q, Pearce MS, Parker L
Incidence and survival for testicular germ cell tumor in young males: a report from the Northern Region Young Person's Malignant Disease Registry, United Kingdom.
Urol Oncol. 2007 Jan-Feb; 25(1):32-7 [PubMed]
The incidence of testicular cancer has increased markedly in most developed countries, although the reasons for this are unclear. In this study, 253 patients with testicular cancer diagnosed younger than 25 years from 1968-1999 were identified from the Northern Region Young Persons' Malignant Disease Registry. The age-standardized incidence rate increased from 0.93 in 1968-1978 to 1.60 per 100,000 in 1990-1999. The increase in incidence was confined to those patients >15 years old, with the rate in younger children remaining very low. The 5-year survival increased significantly from 46% (95% confidence interval [CI] 33% to 58%) to 92% (95% CI 85% to 96%) during 1968-1999 and was significantly higher for seminoma than nonseminoma, 91% (95% CI 78% to 96%) and 77% (95% CI 70% to 82%), respectively. Although increased surveillance and public health campaigns designed to raise awareness of the disease and the advantages of self-examination should continue, further research is required into the etiology of this relatively common cancer among young males.
Paediatric and Lifecourse Epidemiology Research Group, Child Health (School of Clinical Medical Sciences), University of Newcastle upon Tyne, Newcastle upon Tyne


Qazi HA, Manikandan R, Foster CS, Fordham MV
Testicular metastasis from gastric carcinoma.
Urology. 2006; 68(4):890.e7-8 [PubMed]
Secondary neoplasms of the testis have been reported with an incidence of 0.02% to 2.5% on autopsy. Other than leukemias and lymphomas, the most common sites from which metastases occur are the lung and prostate gland. We report the case of a 58-year-old patient, recently diagnosed with gastric carcinoma, who presented with swelling and discomfort of the left testis. An ultrasound scan of the scrotum suggested a malignant mass. Orchiectomy was performed, and the subsequent pathologic examination revealed the mass to be a gastric carcinoma metastasis that appeared to mimic a testicular primary clinically.
Department of Urology, Royal Liverpool University Hospital, Liverpool


Waterston A, Seywright M, White J
A salutary tale of mistaken identity in testicular cancer.
Urol Oncol. 2006 Sep-Oct; 24(5):407-9 [PubMed]
This case report illustrates the importance of not relying on imaging alone. A 26-year-old patient underwent an orchidectomy for mature teratoma; however, as he had abdominal lymphadenopathy, he was treated with 2 cycles of chemotherapy followed by retroperitoneal lymph node dissection. The abdominal histology revealed mature teratoma and he remained on intense surveillance. Three years later, computerized tomography (CT) indicated he had lung lesions and left hilar lymphadenopathy and, despite normal tumor markers, he was thought to have relapsed. He was treated with 2 cycles of second-line chemotherapy but there was no change in the lung lesions. He underwent a CT-guided biopsy which diagnosed sarcoidosis. He was kept under observation by the respiratory physicians and remains well. Sarcoidosis is commonly associated with lymphoma among other malignancies. In the Mayo series, they concluded there was a strong association between sarcoidosis and teratoma but cautioned against a causal relationship as both diseases are rare and found in the same age group. This case report reminds us to always consider the differential diagnoses, particularly if the imaging does not fit the rest of the clinical picture, and when in doubt obtain histology prior to treatment.
Department of Medical Oncology, Beatson Oncology Centre, Glasgow G11 6NT


Carvajal-Carmona LG, Alam NA, Pollard PJ, et al.
Adult leydig cell tumors of the testis caused by germline fumarate hydratase mutations.
J Clin Endocrinol Metab. 2006; 91(8):3071-5 [PubMed]
CONTEXT: Leydig cell tumors (LCTs) are the most common non-germ-cell neoplasms of the testis. LCTs are often hormonally active and can result in precocious virilization or in adult feminization. We identified an LCT in an affected individual from a kindred with hereditary leiomyomatosis and renal cell cancer (HLRCC) and a germline fumarate hydratase (FH) mutation (N64T).
OBJECTIVE: Our objective was to investigate the role of FH mutations in predisposition to LCTs.
DESIGN: We tested for pathogenic effects of the N64T mutation and screened an additional 29 unselected adult LCTs for FH alterations. We also tested these LCTs for mutations in two genes, the LH/choriogonadotropin receptor (LHCGR) and the guanine nucleotide-binding protein alpha (GNAS) that had been implicated in LCT tumorigenesis.
RESULTS: No mutations were found in GNAS, and one tumor had a LHCGR somatic substitution. In addition to the HLRCC case with the N64T germline FH mutation, we identified one other LCT with a previously unreported FH mutation (M411I). Both LCTs from these patients showed loss of the wild-type FH allele. Immunohistochemical and in situ hybridization analyses demonstrated activation of the hypoxia/angiogenesis pathway not only in the tumors belonging to the FH mutation carriers but also in several other mutation-negative LCTs.
CONCLUSIONS: Our study shows that some LCTs are caused by FH mutations and represents one of the first reports of germline mutations in any type of adult testicular tumor.
Laboratory of Molecular and Population Genetics, London Research Institute, Cancer Research UK, London WC2A 3PX


Manikandan R, Nathaniel C, Reeve N, Brough RJ
Bilateral testicular metastases from prostatic carcinoma.
Int J Urol. 2006; 13(4):476-7 [PubMed]
Testicular metastasis from carcinoma of the prostate is rare. We report a case of carcinoma of the prostate with bilateral testicular metastases 7 years after the initial diagnosis. The exact prognosis is not known but it usually indicates advanced disease. Although testicular metastasis is uncommon, it should be considered when a patient presents with a lump in the testis, particularly in a patient known to have another primary malignancy.
Department of Urology, Stepping Hill Hospital, Stockport


Miller FN, Rosairo S, Clarke JL, et al.
Testicular calcification and microlithiasis: association with primary intra-testicular malignancy in 3,477 patients.
Eur Radiol. 2007; 17(2):363-9 [PubMed]
The prevalence of all forms of scrotal and testicular calcification and their association with testicular tumour in a symptomatic paediatric and adult population was investigated. A retrospective study of all testicular ultrasound examinations performed at a single centre over a 5-year period was undertaken. All studies were performed by experienced operators, recorded in a standard method, using high-frequency linear array transducers (> or =10 MHz). All available images (95.2%) were reviewed by experienced operators, recording the location and type of scrotal and testicular calcification according to a pre-determined schedule. A total of 3,854 studies were reviewed on 3,477 patients (age range: 1 month to 91 years). In the adult group, 3,279 examinations were analysed. Prevalence of testicular microlithiasis (TM) was 2.0%, and the prevalence of other non-microlithiasis testicular calcification (non-TM calcification) was 1.7%. Testicular tumour was associated with TM (odds ratio 9.5, P<0.001) and non-TM calcification (odds ratio 11.4, P<0.001) but not with other types of scrotal calcification. A total of 198 paediatric examinations were analysed. Prevalence of TM was 2.0% and the prevalence of non-TM calcification was 0.5%. One tumour (lymphoma) was identified, with no associated calcification. This study confirms the reported association between TM and testicular tumour and finds a previously unreported association between non-TM calcification and testicular tumour.
Department of Radiology, King's College Hospital, Denmark Hill, London, SE5 9RS


McNally RJ, Pearce MS, Parker L
Space-time clustering analyses of testicular cancer amongst 15-24-year-olds in Northern England.
Eur J Epidemiol. 2006; 21(2):139-44 [PubMed]
There has been speculation that environmental exposures may be involved in the aetiology of testicular cancer in adolescent boys and young men. Indirect evidence for this hypothesis would be provided by the finding of space-time clustering. To examine this we have looked for evidence of space-time clustering using data from a population-based cancer registry from Northern England. All cases of testicular cancer diagnosed in males aged 15-24 years during the period 1968-2002 were included in the study. Tests for space-time interactions between cases were applied with fixed thresholds of close in space and close in time. Addresses at birth and diagnosis were used in the analyses. To adjust for the effect of varying population density tests were repeated replacing fixed geographical distances with nearest neighbour thresholds. A total of 257 cases of testicular cancer were identified for analysis. Overall there was no evidence for space-time clustering. However, there was statistically significant space-time clustering for 15-19-year-old based on time of birth and place of diagnosis (p<0.001). The very limited finding of space-time clustering may provide tentative evidence for an environmental, or infectious component to aetiology. However, it may well be a chance finding. A larger study based on national data is required.
School of Clinical Medical Sciences (Child Health), University of Newcastle Upon Tyne, Newcastle upon Tyne


Khan SA, John G, Howell SD
Primary carcinoid tumour of the testis.
J Pak Med Assoc. 2005; 55(12):561-3 [PubMed]
A left radical orchidectomy was performed on a 32-year-old man presenting with a testicular mass. Histology revealed a tumour comprising of cells with monotonous nuclei and granular cytoplasm arranged in an insular pattern. Immunohistochemical expression for NSE, synaptophysin and chromogranin A were positive. No teratomatous elements were seen. Postoperatively, a staging CT and an octreotide scan were normal. Urinary 5-HIAA levels were not elevated. Based on these investigations the tumour was diagnosed as a pure primary carcinoid tumour of the testis. The patient has been followed up for 3 years with no evidence of recurrence.
Department of Urology, Royal Sussex County Hospital, Brighton


Lu YJ, Yang J, Noel E, et al.
Association between large-scale genomic homozygosity without chromosomal loss and nonseminomatous germ cell tumor development.
Cancer Res. 2005; 65(20):9137-41 [PubMed]
The genotype of a tumor determines its biology and clinical behavior. The genetic alterations associated with the unique embryonal morphology of nonseminomatous subtypes of testicular germ cell tumors remain to be established. Using single nucleotide polymorphism microarray analysis, we found in all of the 15 nonseminomas analyzed, large-scale chromosomal homozygosities, most of which were not associated with relative chromosome loss. This unusual genotype, distinguishing nonseminoma from seminomas and other human tumors, may be associated with the special embryonal development morphologic transition of this malignancy. Based on these genetic data, we hypothesized a new potential origin of nonseminomas through sperm fusion. Nonrandom involvement of certain chromosomes also suggests that genes on these chromosome regions may play an important role in nonseminoma development.
Department of Medical Oncology, Barts and London School of Medicine and Dentistry, Queen Mary, University of London, London


Bignell G, Smith R, Hunter C, et al.
Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults.
Genes Chromosomes Cancer. 2006; 45(1):42-6 [PubMed]
The protein kinase gene family is the most frequently mutated in human cancer. Previous work has documented activating mutations in the KIT receptor tyrosine kinase in testicular germ-cell tumors (TGCT). To investigate further the potential role of mutated protein kinases in the development of TGCT and to characterize the prevalence and patterns of point mutations in these tumors, we have sequenced the coding exons and splice junctions of the annotated protein kinase family of 518 genes in a series of seven seminomas and six nonseminomas. Our results show a remarkably low mutation frequency, with only a single somatic point mutation, a K277E mutation in the STK10 gene, being identified in a total of more than 15 megabases of sequence analyzed. Sequencing of STK10 in an additional 40 TGCTs revealed no further mutations. Comparative genomic hybridization and LOH analysis using SNP arrays demonstrated that the 13 TGCTs mutationally screened through the 518 protein kinase genes were uniformly aneuploid with consistent chromosomal gains on 12p, 8q, 7, and X and losses on 13q, 18q, 11q, and 4q. Our results do not provide evidence for a mutated protein kinase implicated in the development of TGCT other than KIT. Moreover, they demonstrate that the general prevalence of point mutations in TGCT is low, in contrast to the high frequency of copy number changes.
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA
Research funded by:


McIntyre A, Summersgill B, Grygalewicz B, et al.
Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults.
Cancer Res. 2005; 65(18):8085-9 [PubMed]
We have previously identified amplification at 4q12 in testicular germ cell tumors of adolescents and adults centered around the KIT gene encoding a tyrosine kinase transmembrane receptor. Analysis of primary testicular germ cell tumors totaling 190 cases revealed 21% of the seminoma subtype with an increased copy number of KIT whereas this change was rarely found in the nonseminomas. In most cases, gain of KIT did not include the immediately flanking noncoding DNA or the flanking genes KDR and PDGFRA. Increased copy number of KIT was not found in the putative precursor lesion, carcinoma in situ (CIS), adjacent to tumor with this change. KIT overexpression was found independent of gain and KIT immunostaining was stronger in selected cases with gain of KIT compared to those without. Taken together with activating mutations of KIT in exon 17 identified in 13% of seminomas, this suggests that the KIT gene product plays a role in the progression of CIS towards seminoma, the further understanding of which may lead to novel less toxic therapeutic approaches.
Molecular Cytogenetics, Section of Molecular Carcinogenesis, The Institute of Cancer Research, Sutton, Surrey


Wilson C, Yang J, Strefford JC, et al.
Overexpression of genes on 16q associated with cisplatin resistance of testicular germ cell tumor cell lines.
Genes Chromosomes Cancer. 2005; 43(2):211-6 [PubMed]
Testicular germ-cell tumors (TGCTs) show exquisite sensitivity to cisplatin-based chemotherapy, and therefore this is considered a good model system for studying the mechanism of chemotherapy resistance. Although the genetic alterations related to TGCT have been well studied, little is known about the genetic basis of chemotherapy resistance, which occurs in a small proportion of TGCTs. In this study, we investigated genomic and expression differences between three cisplatin-sensitive and their paired cisplatin-resistant lines using combined whole-genome screen approaches. Comparative genomic hybridization (CGH) analysis on chromosomes revealed genetic differences between the resistant and parent cell lines in each pair, but did not show any consistent chromosome changes in all three lines. Microarray CGH analysis generated some additional information of DNA copy number gains and losses including some important oncogenes, tumor-suppressor genes, and drug-resistance-related genes. However, no consistent genomic region changes were found in the three cell lines. Interestingly, when comparative expressed sequence hybridization, a technique for gene expression profiling along chromosomes, was applied, we discovered a consistently overexpressed chromosomal region in all three resistant lines compared with their parent lines. The minimum overlapping chromosomal region is at 16q22-23. Further definition of genes in this chromosomal region will aid our understanding of the mechanism of cisplatin resistance and may offer novel therapeutic targets.
Department of Medical Oncology, Barts and London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London


Jones WG, Fossa SD, Mead GM, et al.
Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I Testicular Seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328).
J Clin Oncol. 2005; 23(6):1200-8 [PubMed]
PURPOSE: To assess the possibility of reducing radiotherapy doses without compromising efficacy in the management of patients with stage I seminoma.
PATIENTS AND METHODS: Patients were randomly assigned 20 Gy/10 fractions over 2 weeks or 30 Gy/15 fractions during 3 weeks after orchidectomy. They completed a symptom diary card during treatment and quality-of-life forms pre- and post-treatment. The trial was powered to exclude absolute differences in 2-year relapse rates of 3% to 4% (alpha = .05 [one sided]; 90% power).
RESULTS: From 1995 to 1998, 625 patients were randomly assigned to treatment. Four weeks after starting radiotherapy, significantly more patients receiving 30 Gy reported moderate or severe lethargy (20% v 5%) and an inability to carry out their normal work (46% v 28%). However, by 12 weeks, levels in both groups were similar. With a median follow-up of 61 months, 10 and 11 relapses, respectively, have been reported in the 30- and 20-Gy groups (hazard ratio, 1.11; 90% CI, 0.54 to 2.28). The absolute difference in 2-year relapse rates is 0.7%; the lower 90% confidence limit is 2.9%. Only one patient has died from seminoma (allocated to the 20-Gy treatment group).
CONCLUSION: Treatment with 20 Gy in 10 fractions is unlikely to produce relapse rates more than 3% higher than for standard 30 Gy radiation therapy, and data on an additional 469 patients randomly assigned in a subsequent trial support and strengthen these results. Reductions in morbidity enable patients to return to work more rapidly. Prolonged follow-up is required before any inference can be made about any impact of allocated treatment on new primary cancer diagnoses.
Cookridge Hospital, Leeds


Papatsoris AG, Triantafyllidis A, Gekas A, et al.
Leydig cell tumor of the testis. New cases and review of the current literature.
Tumori. 2004 Jul-Aug; 90(4):422-3 [PubMed]
Leydig cell tumors are the most frequent non-germ cell tumors of the testis, accounting for 1-3% of all testicular tumors. They present most commonly as a testicular mass or with endocrine symptoms. We report three new cases of Leydig cell tumors that presented in different forms. The relevant literature is reviewed and the management of these tumors is discussed.
Department of Urology, Ealing Hospital, Middlesex


Constantinou J, Nitkunan T, Al-Izzi M, McNicholas TA
Testicular granulocytic sarcoma, a source of diagnostic confusion.
Urology. 2004; 64(4):807-9 [PubMed]
We report a case of granulocytic sarcoma of the testis without hematologic manifestations. The patient was disease free 7 years after the initial presentation. The initial pathology interpretation favored a diagnosis of high-grade non-Hodgkin's lymphoma but additional histologic staining confirmed the diagnosis of granulocytic sarcoma. Only 2 cases of testicular granulocytic sarcoma without an associated hematologic disorder have been described. To our knowledge, this is the third reported case. The diagnosis of this rare tumor is difficult and should be in the differential diagnosis when non-Hodgkin's lymphoma is considered.
Department of Urological Surgery, Lister Hospital, Stevenage, Herts


Lavis R, Igbokwe U, Freeman S, Smith M
Intratesticular angioleiomyoma.
Arch Pathol Lab Med. 2004; 128(10):1165-6 [PubMed]
Angioleiomyomas are common benign smooth muscle tumors that occur in the subcutis of the extremities and to a lesser extent, of the head and trunk. Rarely, these tumors have been reported in other deeper tissues, but never within the testis. We present what we believe to be the first report of intratesticular angioleiomyoma, occurring in a 58-year-old man with a painless testicular swelling. Orchidectomy was the treatment of choice in this patient, as there was no reliable imaging technique to clinically distinguish this benign lesion from the more common malignant intratesticular tumors.
Department of Radiology, Derriford Hospital, Plymouth, Devon


Heman-Ackah C, Fox AT, El-Jabbour J
Epididymal metastasis from carcinoma of the prostate.
ScientificWorldJournal. 2004; 4 Suppl 1:150-1 [PubMed]
Epididymal Metastasis from a primary carcinoma of the prostate gland is a rare but recognised phenomena. We describe a case of such metastasis which, unlike previous reports, presents as a painful epididymal mass. Therefore it is important for urologists to consider epididymal metastasis as part of the differential diagnosis in a patient with known carcinoma of the prostate and a tender epididymal mass.
Barnet General Hospital, Wellhouse Lane, Barnet, Herts EN5 3DJ


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