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. World-wide about 36,000 men are diagnosed with testicular cancer each year.

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Latest Research Publications

Information Patients and the Public (19 links)


Information for Health Professionals / Researchers (10 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Salehi P, Koh CJ, Pitukcheewanont P, et al.
Persistent Müllerian duct syndrome: 8 new cases in Southern California and a review of the literature.
Pediatr Endocrinol Rev. 2012 Dec-2013 Jan; 10(2):227-33 [PubMed]
Persistent Müllerian Duct Syndrome (PMDS) is a 46,XY disorder of sex development (DSD) in which Müllerian structures are found in genotypic males with normally virilized external genitalia and unilateral or bilateral cryptorchidism. It is usually diagnosed incidentally during surgical repair of cryptorchidism or inguinal hernia. The majority of cases are due to a mutation of the anti-Müllerian hormone (AMH) gene or the AMH receptor, type II (AMH-RII) gene. Management of patients with PMDS requires a multidisciplinary approach. Long-term prognosis is good although fertility appears to be decreased and there may be a risk of malignancy due to cryptorchidism and retained Müllerian remnants. We describe 8 new cases of PMDS diagnosed in Southern California in the past 10 years and review the literature.


Lim SD, Kim WS, Kwon GY
ROR2 and Wnt5a expression in stage 1 pure testicular seminomas.
Anal Quant Cytol Histol. 2013; 35(1):41-51 [PubMed]
OBJECTIVE: To elucidate the prognostic utility of several biomarkers including ROR2/Wnt5a in stage 1 pure seminoma, which is a highly curable tumor in need of prognostic markers to avoid unnecessary treatment.
STUDY DESIGN: A total of 47 patients of stage 1 seminoma who underwent radical orchiectomy were included in the study. Tissue microarray-based immunohistochemical analysis of placental alkaline phosphatase, D2-40, c-Kit, Oct-3/4, ROR2, Wnt5a, beta-catenin, CD30, vimentin, pancytokeratin, beta-hCG and p53 was conducted, and relevant clinicopathologic features were assessed.
RESULTS: ROR2 protein revealed strong diffuse membranous immunoreactivity (IR) in 12.8% and partial weak IR in 40.4%, respectively. Cytoplasimc Wnt5a IR was observed in 27.7%. ROR2 IR was correlated with Wnt5a IR (p = 0.029) and Oct3/4 IR (p = 0.035). c-Kit IR was correlated with Wnt5a IR (p = 0.034). No significant differences were found between ROR2/Wnt5a protein expression and the prognostically relevant features such as lymphatic invasion or pathologic T stage. Pathologic T stage was not correlated with rete invasion (p= 0.23). The expression or loss of other aforementioned antibodies was not associated with the prognostic clinicopathologic characteristics.
CONCLUSION: Our results do not support the relevance of ROR2/Wnt5a as biomarkers in stage 1 pure seminomas. The utility of the explored biomarkers as prognostic or differentiation indicators remains to be clarified.


Tsili AC, Argyropoulou MI, Astrakas LG, et al.
Dynamic contrast-enhanced subtraction MRI for characterizing intratesticular mass lesions.
AJR Am J Roentgenol. 2013; 200(3):578-85 [PubMed]
OBJECTIVE: The objective of our study was to analyze the enhancement patterns of various intratesticular mass lesions at dynamic contrast-enhanced subtraction MRI and assess the value of the technique in distinguishing between benign and malignant lesions.
MATERIALS AND METHODS: We retrospectively evaluated the records and images of 44 consecutive men (11 benign and 16 malignant intratesticular lesions) who presented to the department of urology with a variety of clinical symptoms and were referred for imaging. Dynamic contrast-enhanced subtraction MRI was performed using a 3D fast-field echo sequence after the administration of paramagnetic contrast medium. Patients were divided into three groups according to the final diagnosis: benign intratesticular lesions, malignant intratesticular lesions, and normal testes. The patterns of contrast enhancement of both the normal testes and the intratesticular lesions were evaluated. Time-signal intensity plots were created and classified according to shape: Type I presented a linear increase of contrast enhancement throughout the examination, type II showed an initial upstroke followed by either a plateau or a gradual increase in the late contrast-enhanced phase, and type III presented an initial upstroke followed by gradual washout of the contrast medium. The relative percentages of peak height, maximum time, and mean slope were also calculated.
RESULTS: Normal testes enhanced homogeneously with a type I curve. Most benign intratesticular lesions showed inhomogeneous or homogeneous contrast enhancement and a type II curve. Testicular carcinomas showed heterogeneous contrast enhancement with a type III curve. The relative percentages of maximum time to peak proved the most important discriminating factor in differentiating malignant from benign intratesticular masses (p < 0.001).
CONCLUSION: Dynamic contrast-enhanced MRI may be used to distinguish between benign and malignant intratesticular mass lesions.


Albino G, Nenna R, Corvasce A, Marucco EC
Torsion of a neoplastic intrascrotal testis: when the torsion reveals the mass. A case report and review.
Arch Ital Urol Androl. 2012; 84(4):256-9 [PubMed]
Cases of torsion of the spermatic cord are rare in men over 30-years-old. Testicular tumors manifest themselves rarely with symptoms of acute scrotum. We report the case of a 38-years-old patient who presented for a suspected left testis torsion. On examination, the testicle was markedly increased in size and painful. The manual derotation made pain dramatically disappear. He came to our attention after about a month asking for an orchidopexy. During the surgery a biopsy was performed. The diagnosis was a Yolk Sac Tumor. A radical inguinal orchiectomy was performed with left hemiscrotal excision, "in block". He performed four cycles of chemotherapy and with no recurrence after 12 months of follow-up. In literature only seven cases of torsion of an intrascrotal testicle with cancer are reported. Our case is the eighth one.


Choy JT, Wiser HJ, Bell SW, et al.
Predictors of spermatogenesis in orchiectomy specimens.
Urology. 2013; 81(2):288-92 [PubMed]
OBJECTIVE: To evaluate the presence of spermatogenesis in orchiectomy specimens of patients with testicular cancer to determine possible predictors of success with oncologic testicular sperm extraction of the cancerous testis at orchiectomy.
MATERIALS AND METHODS: We retrospectively reviewed the pathology reports and slides from 83 men who underwent radical orchiectomy for testicular cancer at 2 institutions from 1999 to 2010. The presence or absence of spermatogenesis in each specimen was determined. Data on tumor histopathologic type, serum tumor markers, and tumor size were also obtained and analyzed to detect any associations with the presence of spermatogenesis.
RESULTS: The 83 specimens included 41 pure seminomas, 36 nonseminomatous and mixed germ cell tumors, and 6 benign lesions. Overall, spermatogenesis was detected in 48 of 77 (62%) cancerous specimens. Spermatogenesis was present in 22 of 41 (54%) pure seminomas and 26 of 36 (72%) nonseminomatous and mixed germ cell tumors, with no significant difference found between the 2 subtypes (P = .11). No association was found between tumor marker levels and the presence of spermatogenesis. A logistic regression model revealed a statistically significant inverse relationship between tumor size and spermatogenesis presence (P = .004).
CONCLUSION: At orchiectomy, most cancerous testes contained active spermatogenesis and, thus, represent a viable source for sperm cryopreservation with oncologic testicular sperm extraction. A small tumor size proved to be a positive prognostic indicator for the presence of spermatogenesis, although a larger tumor size did not preclude the presence of spermatogenesis.


Niedziela M, Joanna T, Piotr J
Testicular adrenal rest tumors (TARTs) as a male infertility factor. Case report.
Ginekol Pol. 2012; 83(9):700-2 [PubMed]
Since testes and adrenal cortex derive from the same urogenital ridge, adrenal tissue with descending gonads may migrate in early embryonic period. Although most often ectopic tissue undergoes atrophy in some cases, when adrenocorticotrophic (ACTH) overstimulation occurs, the adrenal remnants in the testes may become hypertrophic and form testicular adrenal rest tumors (TARTs). The growth of TARTs in the testes leads to obstruction of the seminiferous tubules which can mechanically impair the function of the gonads and cause irreversible azoospermia. We describe a patient suffering since neonatal period from congenital adrenal hyperplasia (CAH), disorder with defected pathway of cortisol production, which leads to increased ACTH production and to overstimulation of adrenal cortex. He had very poor disease control and therefore in late puberty he was diagnosed with TARTs. At the age of 19.5 he was diagnosed with azoospermia, most likely caused by TARTs. It is the first evidence of TARTs in Polish literature. Although not many cases have been published so far the incidence of TARTs seems to be highly underdiagnosed, so it seems reasonable to consider the disease in differential diagnosis of male infertility.


Sharpe RM, Mitchell RT
The downside of 'inappropriate messaging': new insight into the development of testicular germ cell tumours in young men?
J Pathol. 2013; 229(4):497-501 [PubMed]
How invasive testicular germ cell tumours (TGCTs) develop from precursor carcinoma in situ/intratubular germ cell neoplasia unclassified (CIS/IGCNU) cells, and only after puberty, is unknown. In the current issue of The Journal of Pathology, Jørgensen and colleagues have compared the protein expression profile of CIS before and after puberty and in pre-invasive versus invasive TGCT and show that the mitosis-meiosis controller DMRT1 switches off in CIS cells postpubertally and is associated with invasiveness. They also show that CIS cells express a 'confusing' mix of pro- and anti-meiotic proteins; this may predispose CIS cells to accumulate extra chromosomal material which ultimately leads to tumourigenesis.


Jørgensen A, Nielsen JE, Almstrup K, et al.
Dysregulation of the mitosis-meiosis switch in testicular carcinoma in situ.
J Pathol. 2013; 229(4):588-98 [PubMed]
Testicular germ cell tumours (TGCT) of young adults arise from the intratubular precursor, carcinoma in situ (CIS). CIS cells are thought to be developmentally arrested and transformed fetal germ cells that survive through childhood and gain invasive capacity after puberty. Given that germ cell neoplasms arise frequently in undervirilized and dysgenetic gonads and the striking physiological difference between meiotic entry in ovaries (fetal life) versus testes (at puberty), this study aimed to investigate whether errors in regulation of meiosis may be implicated in the pathogenesis of CIS or its invasive progression to TGCT. The main focus was on a key sex differentiation and meiosis regulator, DMRT1, which has also been linked to TGCT risk in recent genetic association studies. Expression patterns of DMRT1 and other meiosis regulators (SCP3, DMC1, STRA8, CYP26B1, NANOS2, NANOS3) were investigated in pre- and post-pubertal CIS samples and TGCT by quantitative RT-PCR and immunohistochemistry. The results demonstrated that meiosis markers and meiosis inhibitors were simultaneously expressed in CIS cells, in both pre- and post-pubertal testis samples. DMRT1 was present in a restricted subset of CIS cells, which was relatively greater in pre-pubertal (27%) compared to adult (2.6%) samples. In contrast to the majority of CIS cells, DMRT1-positive CIS cells in adult testes were not proliferating. DMRT1 and most of the other meiosis regulators were absent or expressed at low levels in invasive TGCT, except in spermatocytic seminoma (not derived from CIS). In conclusion, this study indicates that meiosis signalling is dysregulated in CIS cells and that a key regulator of the mitosis-meiosis switch, DMRT1, is expressed in 'early-stage' CIS cells but is down-regulated with further invasive transformation. Whether this mixed meiosis signalling in CIS cells is caused by insufficient virilization of the fetal somatic niche or a partial post-pubertal maturation remains uncertain and requires further study.


Gutekunst M, Mueller T, Weilbacher A, et al.
Cisplatin hypersensitivity of testicular germ cell tumors is determined by high constitutive Noxa levels mediated by Oct-4.
Cancer Res. 2013; 73(5):1460-9 [PubMed]
Testicular germ cell tumors (TGCT) are considered a paradigm of chemosensitive tumors. Embryonal carcinoma cells represent the pluripotent entity of TGCTs and are characterized by expression of Oct-4, a key regulator of pluripotency and a determinant of their inherent hypersensitivity to cisplatin. However, the mechanisms underlying this Oct-4-mediated sensitivity are poorly understood. We previously showed that p53 is a major player in cisplatin hypersensitivity and therefore investigated whether Oct-4 may directly affect p53 activity. Despite a significant decrease in sensitivity, depletion of Oct-4 neither did alter cisplatin-induced transactivation of p53 target genes nor its subcellular localization. These data indicate that, rather than directly modulating p53 activity, Oct-4 provides a cellular context that augments the proapoptotic activity of p53. As mitochondrial priming by the Bcl-2 family is a known determinant of chemosensitivity, we compared the constitutive levels of these proteins in Oct-4-positive and -depleted cells. We identified Noxa as the only Bcl-2 family protein to be highly correlated with Oct-4 status and cisplatin sensitivity. Compared with differentiated cells, constitutive Noxa levels were significantly higher in Oct-4-positive cell lines and cancer patient samples. Furthermore, RNA interference-mediated knockdown of Oct-4 resulted in reduced Noxa transcript, in an almost complete loss of constitutive Noxa protein and decreased cisplatin hypersensitivity to a similar extent as did Noxa depletion. In conclusion, our study indicates that Noxa is a central determinant of hypersensitivity to cisplatin. Oct-4-dependent high constitutive levels of this BH3-only protein prime embryonal carcinoma cells to undergo rapid and massive apoptosis in response to p53 activation.


Juniarto AZ, Setyawati BA, Miranti IP, et al.
Gonadal malignancy in 13 consecutive collected patients with disorders of sex development (DSD) from Semarang (Indonesia).
J Clin Pathol. 2013; 66(3):198-204 [PubMed]
AIMS: Caucasian patients with disorders of sex development (DSD) are at a high risk of developing germ cell cancer (GCC). GCC is prominent in young adults in Western countries, while the incidence is significantly lower in Asia. So far, the risk of GCC in Asian DSD patients is unknown.
METHODS AND RESULTS: A detailed study of gonad histology , morphology and immunohistochemistry (OCT3/4, testis-specific protein Y-encoded, VASA, SCF/KITLG, SOX9, FOXL2) of 16 Indonesian DSD patients was undertaken. 13 cases could be analysed, including ovarian tissue (n=3), streak gonad (n=1), undifferentiated gonad (n=1) and testicular tissue (n=8), diagnosed as 46, XX (n=1), 46, XY (n=7) and sex chromosome DSD (n=5). The precursor lesion gonadoblastoma or carcinoma in situ, or GCC was diagnosed in four cases (30.8%; three 46, XY and one sex chromosome DSD ). A hormone producing ovarian Leydig cell tumour was identified in a 46, XX patient, supposed to be a late onset congenital adrenal hyperplasia.
CONCLUSIONS: In spite of the significantly lower risk of GCC in the general Asian population, DSD is a dominant risk factor. The study demonstrates the power of immunohistochemical markers for (early) diagnosis. This knowledge will deepen understanding of the pathobiology of GCC and clinical handling of patients with DSD, globally.


Pandharipande PV, Eisenberg JD, Lee RJ, et al.
Patients with testicular cancer undergoing CT surveillance demonstrate a pitfall of radiation-induced cancer risk estimates: the timing paradox.
Radiology. 2013; 266(3):896-904 [PubMed] Article available free on PMC after 01/03/2014
PURPOSE: To demonstrate a limitation of lifetime radiation-induced cancer risk metrics in the setting of testicular cancer surveillance-in particular, their failure to capture the delayed timing of radiation-induced cancers over the course of a patient's lifetime.
MATERIALS AND METHODS: Institutional review board approval was obtained for the use of computed tomographic (CT) dosimetry data in this study. Informed consent was waived. This study was HIPAA compliant. A Markov model was developed to project outcomes in patients with testicular cancer who were undergoing CT surveillance in the decade after orchiectomy. To quantify effects of early versus delayed risks, life expectancy losses and lifetime mortality risks due to testicular cancer were compared with life expectancy losses and lifetime mortality risks due to radiation-induced cancers from CT. Projections of life expectancy loss, unlike lifetime risk estimates, account for the timing of risks over the course of a lifetime, which enabled evaluation of the described limitation of lifetime risk estimates. Markov chain Monte Carlo methods were used to estimate the uncertainty of the results.
RESULTS: As an example of evidence yielded, 33-year-old men with stage I seminoma who were undergoing CT surveillance were projected to incur a slightly higher lifetime mortality risk from testicular cancer (598 per 100 000; 95% uncertainty interval [UI]: 302, 894) than from radiation-induced cancers (505 per 100 000; 95% UI: 280, 730). However, life expectancy loss attributable to testicular cancer (83 days; 95% UI: 42, 124) was more than three times greater than life expectancy loss attributable to radiation-induced cancers (24 days; 95% UI: 13, 35). Trends were consistent across modeled scenarios.
CONCLUSION: Lifetime radiation risk estimates, when used for decision making, may overemphasize radiation-induced cancer risks relative to short-term health risks.


Giulianelli R, Albanesi L, Attisani F, et al.
A case of angiomyolipoma of the spermatic cord and testicle.
Arch Ital Urol Androl. 2012; 84(3):165-6 [PubMed]
Angiomyolipomas (AML) are mesenchymal tumors of the kidney consisting of varying proportions of vascular, immature smooth muscle and mature fat cells. A rare case of testicular AML is described. A 53 year old male with a history of congenital motor defects, mental retardation, and hypertension, presented to the emergency room with sudden onset, severe left testicular pain. Scrotal sonography demonstrated an hypoechoic mass in the patient's left testicle. The patient was offered and underwent a trans-inguinal exploration of the left testicle which ended in a left inguinal orchiectomy. Pathologic examination of the mass revealed medium to large calibre thick-walled blood vessels with ectatic lumina, surround by sclerotic, fibrous smooth muscle bundles in a fatty milieu. Immunohistochemistry of the lesion demonstrated positive staining for smooth muscle actin (SMA+) and endothelial marker CD34. The lesion did not, however, stain positively for smooth muscle antigen S100 or melanocytic antigen HMB-45.


Sapre N, Pedersen J, Hong MK, et al.
Re-evaluating the biological significance of seminal vesicle invasion (SVI) in locally advanced prostate cancer.
BJU Int. 2012; 110 Suppl 4:58-63 [PubMed]
OBJECTIVE: • To examine the impact of seminal vesicle invasion (SVI) in patients with locally advanced (pT3) prostate cancer on clinical outcome. • To explore the clinical association of SVI with metastatic disease. • To distinguish between the possibilities that either seminal vesicles possess their own biological significance and represent a privileged staging site for systemic tumour cell dissemination, or that their invasion is a surrogate marker for an aggressive large-volume poorly differentiated cancer.
PATIENTS AND METHODS: • Patients with extraprostatic extension (EPE) and/or SVI were identified from a prospectively recorded and maintained prostate cancer database. • Patients were categorised according to the presence of SVI as determined by routine pathological assessment. Tumour volumes were measured routinely by computed planimetry at the time of histological assessment. • The impact of SVI on biochemical recurrence with a definition of a prostate-specific antigen (PSA) level of ≥0.2 ng/mL, as well as a clinically significant recurrence defined as failure with a PSA doubling time of <6 months, was determined by univariable and multivariable Cox regression analysis.
RESULTS: • Of 249 patients with pT3 disease, 46 (18%) had SVI, 40 (87%) by direct extension and six (13%) metastatic. • Tumours with SVI had significantly greater tumour burden as determined by total tumour volume (7.2 vs 3.7 mL, P < 0.001), index tumour volume (6.8 vs. 3.4 mL, P < 0.001) and percentage tumour volume (21.8 vs 12.4 %, P= 0.001). • After controlling for tumour volume and Gleason score, the presence of SVI did not significantly predict for the development of a significant PSA recurrence.
CONCLUSIONS: • Our results suggest that SVI is a surrogate marker of larger and more aggressive tumours with higher Gleason scores rather than a privileged site of tumour cell dissemination.


Lip SZ, Murchison LE, Cullis PS, et al.
A meta-analysis of the risk of boys with isolated cryptorchidism developing testicular cancer in later life.
Arch Dis Child. 2013; 98(1):20-6 [PubMed]
BACKGROUND: Significant variability exists for the relative risk (RR) of testicular malignancy in isolated cryptorchidism.
OBJECTIVE: To perform a meta-analysis to clarify the true magnitude of this risk, allowing clinicians to better counsel patients and their families.
SETTING: Secondary research conducted by undergraduate researchers, clinical academics and a clinical statistician. DESIGN, DATA SOURCES, AND METHODS: A search of the English literature was performed for studies relating to testicular cancer and cryptorchidism, published between 1 January 1980 and 31 December 2010, using Embase and Medline databases. 735 papers were identified and analysed by four authors independently in accordance with our inclusion and exclusion criteria. Studies reporting an association between cryptorchidism and subsequent development of testicular malignancy were included. Genetic syndromes or other conditions which predisposed to the development of cryptorchidism were excluded. Pooled estimates and 95% CIs for the RRs were calculated.
RESULTS: Nine case-control studies and three cohort studies were selected. The case-control studies included 2281 cases and 4811 controls. Cohort studies included 2 177 941 boys, with a total of 345 boys developing testicular cancer (total length of follow-up was 58 270 679 person-years). The pooled RR was 2.90 (95% CI 2.21 to 3.82) with significant heterogeneity (p<0.00001; I(2)=89%).
CONCLUSION: Boys with isolated cryptorchidism are three times more likely to develop testicular cancer. The limitations of this study must be acknowledged, in particular, possible publication bias and the lack of high-quality evidence focusing on the risk of malignancy in boys with isolated cryptorchidism.


Gold E, Marino FE, Harrison C, et al.
Activin-β(c) reduces reproductive tumour progression and abolishes cancer-associated cachexia in inhibin-deficient mice.
J Pathol. 2013; 229(4):599-607 [PubMed]
Activins are involved in the regulation of a diverse range of physiological processes including development, reproduction, and fertility, and have been implicated in the progression of cancers. Bioactivity is regulated by the inhibin α-subunit and by an activin-binding protein, follistatin. The activin-β(C) subunit was not considered functionally significant in this regard due to an absence of phenotype in knockout mice. However, activin-β(C) forms heterodimers with activin-β(A) and activin-C antagonizes activin-A in vitro. Thus, it is proposed that overexpression, rather than loss of activin-β(C) , regulates activin-A bioactivity. In order to prove biological efficacy, inhibin α-subunit knockout mice (α-KO) were crossed with mice overexpressing activin-β(C) (ActC++). Deletion of inhibin leads to Sertoli and granulosa cell tumours, increased activin-A, and cancer-associated cachexia. Therefore, cachexia and reproductive tumour development should be modulated in α-KO/ActC++ mice, where excessive activin-A is the underlying cause. Accordingly, a reduction in activin-A, no significant weight loss, and reduced incidence of reproductive tumours were evident in α-KO/ActC++ mice. Overexpression of activin-β(C) antagonized the activin signalling cascade; thus, the tumourigenic effects of activin-A were abrogated. This study provides proof of the biological relevance of activin-β(C) . Being a regulator of activin-A, it is able to abolish cachexia and modulate reproductive tumour development in α-KO mice.


Maisonneuve P, Marshall BC, Knapp EA, Lowenfels AB
Cancer risk in cystic fibrosis: a 20-year nationwide study from the United States.
J Natl Cancer Inst. 2013; 105(2):122-9 [PubMed]
BACKGROUND: Many patients with cystic fibrosis (CF) now reach adulthood, at which time the risk of cancer is increased. The aim of this study was to determine cancer risks in nontransplanted and transplanted CF patients.
METHODS: From 1990 to 2009, we followed 41,188 patients who received care at one of the 250 CF care center programs in the United States and compared the observed number of cancers in nontransplanted and transplanted patients with that expected in the general US population.
RESULTS: In 344,114 patient-years of observation of nontransplanted patients, the overall cancer risk was similar to the background risk (standardized incidence ratio [SIR] = 1.1, 95% confidence interval [CI] = 1.0 to 1.3). However, we observed an elevated risk of digestive tract cancer (SIR = 3.5, 95% CI = 2.6 to 4.7) involving the esophago-gastric junction, biliary tract, small bowel, and colon. There was also an increased risk of testicular cancer (SIR = 1.7, 95% CI = 1.02 to 2.7) and lymphoid leukemia (SIR = 2.0, 95% CI = 1.2 to 3.1) and a decreased risk of malignant melanoma (SIR = 0.4, 95% CI = 0.2 to 0.9). In 8235 patient-years of observation of transplanted patients, 26 tumors were observed compared with 9.6 expected (SIR = 2.7, 95% CI = 1.8 to 3.9). The increased risk was particularly high for digestive tract cancers (SIR = 17.3, 95% CI = 10.7 to 26.5), with most cases arising in the bowel.
CONCLUSIONS: The overall burden of cancer in CF patients remains low; however they have an increased risk of digestive tract cancer, particularly following transplantation. They also have increased risk of lymphoid leukemia and testicular cancer, and decreased risk of melanoma.


Nitzsche B, Gloesenkamp C, Schrader M, et al.
Anti-tumour activity of two novel compounds in cisplatin-resistant testicular germ cell cancer.
Br J Cancer. 2012; 107(11):1853-63 [PubMed] Article available free on PMC after 20/11/2013
BACKGROUND: Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo.
METHODS AND RESULTS: Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes.
CONCLUSION: The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin.


Brydøy M, Fosså SD, Klepp O, et al.
Sperm counts and endocrinological markers of spermatogenesis in long-term survivors of testicular cancer.
Br J Cancer. 2012; 107(11):1833-9 [PubMed] Article available free on PMC after 20/11/2013
BACKGROUND: The objective of this study was to assess markers of spermatogenesis in long-term survivors of testicular cancer (TC) according to treatment, and to explore correlations between the markers and associations with achieved paternity following TC treatment.
METHODS: In 1191 TC survivors diagnosed between 1980 and 1994, serum-follicle stimulating hormone (s-FSH; n=1191), s-inhibin B (n=441), and sperm counts (millions per ml; n=342) were analysed in a national follow-up study in 1998-2002. Paternity was assessed by a questionnaire.
RESULTS: At median 11 years follow-up, 44% had oligo- (<15 millions per ml; 29%) or azoospermia (15%). Sperm counts and s-inhibin B were significantly lower and s-FSH was higher after chemotherapy, but not after radiotherapy (RT), when compared with surgery only. All measures were significantly more abnormal following high doses of chemotherapy (cisplatin (Cis)>850 mg, absolute cumulative dose) compared with lower doses (Cis ≤ 850 mg). Sperm counts were moderately correlated with s-FSH (-0.500), s-inhibin B (0.455), and s-inhibin B : FSH ratio (-0.524; all P<0.001). All markers differed significantly between those who had achieved post-treatment fatherhood and those with unsuccessful attempts.
CONCLUSION: The RT had no long-term effects on the assessed markers of spermatogenesis, whereas chemotherapy had. At present, the routine evaluation of s-inhibin B adds little in the initial fertility evaluation of TC survivors.


Salehipour M, Kakaei F, Nikeghbalian S, et al.
Mixed germ-cell testicular tumor in a liver transplant recipient.
Saudi J Kidney Dis Transpl. 2012; 23(6):1238-40 [PubMed]
The development of malignancies after solid organ transplants is a well-known complication. Cancer is associated with significant consequences for the organ transplant patient. It is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next few years. We report on a 36-year-old male patient who developed mixed germ-cell testicular tumor seven years after liver transplantation for alcoholic cirrhosis. He was treated with orchiectomy, retroperitoneal lymph node dissection and post-operative chemotherapy.


Méndez-Gallart R, Estevez-Martínez E, Rodríguez-Barca P, et al.
Incomplete unilateral polyorchidism (bilobed testicle) mimicking testicular tumour.
J Pediatr Surg. 2012; 47(11):2140-2 [PubMed]
Incomplete polyorchidism (also called bilobed testicle) is an extremely uncommon congenital anomaly. Only 3 cases of bilobed testicle were previously reported in the available literature. We describe a case of a 4-year-old boy who presented with a 6-month history of an asymptomatic scrotal mass located in the upper pole of the left testicle mimicking testicular tumour. After partial orchiectomy, macroscopic and pathological examination of the lesion confirmed the diagnosis of normal testicular tissue.


Brunocilla E, Pultrone CV, Schiavina R, et al.
Testicular sclerosing Sertoli cell tumor: an additional case and review of the literature.
Anticancer Res. 2012; 32(11):5127-30 [PubMed]
Sertoli cell tumours are very rare testicular tumours accounting for 0.4-1.5% of all testicular neoplasms. In the current report, we present a case of sclerosing Sertoli cell tumour. The histology and clinical features were compared to those of other Sertoli cell tumour subtypes in order to assess if the different subtypes really represent distinct clinical and prognostic entities. The current literature was also reviewed. Only 20 cases of sclerosing Sertoli cell tumours have been encountered. Our case, a 38-year-old man represents the 21st case. Distinction among Sertoli cell tumours is important not only histologically; sclerosing Sertoli cell tumours have a distinct clinical behaviour and prognosis, different from those of classic and large-cell calcifying Sertoli cell tumours. Pathologists and urologists should know and understand all the types of Sertoli cell tumours in order to be able to choose the correct therapeutical approach when they encounter these tumours.


Ibrahim AS, Li C, Al-Jafari MS
Borderline serous papillary tumour of the testis: a case report and review of the literature.
Anticancer Res. 2012; 32(11):5011-3 [PubMed]
Borderline serous tumour of the testis and paratestis is an uncommon entity. We report a case of borderline serous tumour of a 59-year-old male, who presented with a right testicular swelling which was clinically suspicious of carcinoma. Radical orchidectomy was performed and a cystic lesion was identified in the testis. Macroscopically the tumour was composed of a unilocular cyst with excrescences in the inner surface. The histological features were identical to the ovarian counterpart of borderline serous papillary tumour. The excrescences were formed by stratified columnar epithelium, which exhibited mild nuclear pleomorphism and mitotic activity, with a fibrovascular core and scattered psammoma bodies. There was no lymphovascular or stromal invasion. The lesion was surrounded by a dense fibrous wall. On immunohistochemistry, the lining epithelial cells expressed cytokeratin AE1/AE3 but not carcinoembryonic antigen or calretinin. Following the removal of the tumour, the patient was followed up and no recurrence or metastasis has occurred to date. This case highlights the need for clinicians and pathologists to be aware of this rare entity and to develop the best approach for patient management.


Kum JB, Ulbright TM, Williamson SR, et al.
Molecular genetic evidence supporting the origin of somatic-type malignancy and teratoma from the same progenitor cell.
Am J Surg Pathol. 2012; 36(12):1849-56 [PubMed]
Occasionally, testicular teratomas have been observed to occur in association with somatic-type malignancies. The latter may be seen in the primary germ cell tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic relationship between the teratoma and the somatic-type malignancy is uncertain. We examined 27 pairs of teratoma and somatic-type malignancies in metastatic lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded specimens. In addition, we compared the pattern of allelic loss between the teratoma and the somatic-type malignancy using 4 microsatellite DNA markers (D1S508, interferon-α, D13S317, and D18S543). A laser capture microdissection technique was used to procure separate tumor components. The somatic-type malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5), sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma (1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78%) showed a similar pattern of overexpression of 12p and/or i(12p) in both components. Two of the 27 (7%) tumor pairs showed i(12p) only in the teratomatous component, and 4 of the 27 (15%) tumor pairs showed no abnormalities of chromosome 12p by interphase FISH. Eight of the 12 (67%) tumor pairs analyzed had identical patterns of loss of heterozygosity in both the teratoma and the somatic-type malignancy. Four of the 12 (33%) paired cases showed additional allelic loss at the interferon-α locus in the somatic-type malignant component only. Our data show that the somatic-type malignancies that develop in germ cell tumors have the same genetic alterations, detectable by FISH and loss of heterozygosity studies, as in the corresponding teratoma. These findings support that the somatic-type malignancies within metastases and the teratomas are clonally related and likely derived from a common progenitor cell. Interphase FISH can be performed on formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting 12p overexpression and i(12p), thus aiding in establishing the germ cell origin of somatic-type malignancies in this context.


Fu S, Avezbakiyev B, Zhi W, et al.
Germ cell cancer presenting as gastrointestinal bleeding and developing brain metastases: case report and review of the literature.
Future Oncol. 2012; 8(11):1487-93 [PubMed]
This paper describes a rare case of germ cell cancer with duodenum, brain and lung metastases. The patient presented with melena and left testicle enlargement. Orchiectomy revealed mixed germ cell cancer, enteroscopy revealed duodenal choriocarcinoma, and chest x-ray and computed tomography (CT) showed bilateral lung metastases. The patient received and tolerated cisplatinum-based chemotherapy, and responded well. However, he developed seizures 3 months later. MRI showed brain metastases and he was treated with whole-brain radiation. One month later, he developed progressive dyspnea. Chest CT showed worsening lung metastases. He received second-line chemotherapy, but died due to multiorgan failure. Germ cell cancer with nonpulmonary metastases has poor prognosis and the management of these patients requires a multimodal approach. Head CT should be considered as routine screening for all germ cell cancer patients on initial diagnosis and brain MRI should be considered for high-risk patients (with an embryo- or choriocarcinoma histology, dramatically elevated β-human chorionic gonadotropin and lung involvement).


Nitta S, Kawai K, Onozawa M, et al.
Intratubular trophoblasts in the contralateral testis caused elevation of serum human chorionic gonadotropin following complete remission of stage II testicular tumor: a case report.
Jpn J Clin Oncol. 2013; 43(1):83-6 [PubMed]
We report the case of a 22-year-old male who had a history of metastatic right testicular tumor successfully treated with chemotherapy and surgery. Twenty-one months after the initial treatment, the serum human chorionic gonadotropin started to increase gradually, but whole body imaging including the left testis revealed no abnormal finding except testicular microlithiasis. A biopsy of the left testis revealed intratubular germ cell neoplasia, unclassified type. After the human chorionic gonadotropin level reached 6.6 mIU/ml, he underwent left high orchiectomy. Histology demonstrated a small malignant germ cell tumor as well as intratubular germ cell neoplasia, unclassified type, both of which were negative for human chorionic gonadotropin staining. Besides these lesions, there were tiny foci of human chorionic gonadotropin-immunoreactive intratubular trophoblasts. Serum human chorionic gonadotropin normalized immediately after the orchiectomy, and he had no sign of recurrence at 6 months. The present case will provide new insight into the diagnosis of testicular tumor recurrence with isolated elevation of a serum tumor marker.


Hedgire SS, Pargaonkar VK, Elmi A, et al.
Pelvic nodal imaging.
Radiol Clin North Am. 2012; 50(6):1111-25 [PubMed]
Detection of nodal metastases in men with pelvic urogenital malignancies is important for accurate staging and has therapeutic and prognostic implications. Knowledge of clinical anatomy of these nodes and the lymphatic pathways is critical for assigning the correct N or M staging and to assess the treatment response. Both computed tomography and magnetic resonance imaging use size and morphologic criteria for nodal characterization. The limitations of these criteria have formed basis newer functional imaging tools. This article focuses on the clinical anatomy, pathways of lymphatic spread of malignancies, current criteria, and newer advances in imaging of male pelvic nodes.


Micali S, Maggisano V, Cesinaro A, et al.
Sodium/iodide symporter is expressed in the majority of seminomas and embryonal testicular carcinomas.
J Endocrinol. 2013; 216(2):125-33 [PubMed]
Testicular cancer is the most frequent cancer in young men. The large majority of patients have a good prognosis, but in a small group of tumors, the current treatments are not effective. Radioiodine is routinely used in the treatment of thyroid cancer and is currently investigated as a potential therapeutic tool even for extra-thyroid tumors able to concentrate this radioisotope. Expression of Na(+)/I(-) symporter (NIS (SLC5A5)), the glycoprotein responsible for iodide transport, has been demonstrated in normal testicular tissue. In this study, we analyzed NIS expression in a large series of testicular carcinomas. Our retrospective series included 107 patients operated for testicular tumors: 98 typical seminomas, six embryonal carcinomas, one mixed embryonal choriocarcinoma, and two Leydig cells tumors. Expression and regulation of NIS mRNA and protein levels were also investigated in human embryonal testicular carcinoma cells (NTERA) by real-time RT-PCR and western blotting respectively. Immunohistochemical analysis showed the presence of NIS in the large majority of seminomas (90/98) and embryonal carcinomas (5/7) of the testis but not in Leydig cell carcinomas. Expression of NIS protein was significantly associated with lymphovascular invasion. In NTERA cells treated with the histone deacetylase inhibitors SAHA and valproic acid, a significant increase in NIS mRNA (about 60- and 30-fold vs control, P<0.001 and P<0.01 respectively) and protein levels, resulting in enhanced ability to uptake radioiodine, was observed. Finally, NIS expression in testicular tumors with the more aggressive behavior is of interest for the potential use of targeting NIS to deliver radioiodine in malignant cells.


Stoehr B, Schachtner L, Pichler R, et al.
Influence of achieved paternity on quality of life in testicular cancer survivors.
BJU Int. 2013; 111(4 Pt B):E207-12 [PubMed]
OBJECTIVE: To investigate the influence of achieved/non-achieved paternity on quality of life (QoL) in testicular cancer (TC) survivors.
PATIENTS AND METHODS: We invited TC survivors treated at our department between 1989 and 2006 to complete a QoL assessment, including the European Organisation for the Research and Treatment of Cancer QoL questionnaire, EORTC QLQ-C30 (version 3.0©)/+ TC26, and follow-up questions. A total of 311 TC survivors answered the questionnaire, of whom 207 patients who did not desire paternity were excluded. The remaining 104 patients who stated a desire for paternity after TC treatment were further divided in group A (TC survivors who achieved paternity; n = 51) and group B (TC survivors who did not achieve paternity; n = 53). The data obtained were statistically analysed.
RESULTS: Significant differences between groups regarding QoL were detected for social functioning (P = 0.002), emotional functioning (P = 0.001), general QoL (P = 0.018), fatigue (P = 0.025), pain (P = 0.01), sleeping problems (P = 0.024), treatment satisfaction (P = 0.039), financial aspects (P = 0.006), sexual problems (P = 0.017), body image problems (P < 0.001), dyspnoea (P = 0.005) and cognitive functioning (P = 0.019). For all scales except 'sexual enjoyment', patients in group A were found to have a better long-term QoL than those in group B.
CONCLUSIONS: Whilst acknowledging the shortcomings in retrospective analyses, we believe our data clearly underline the important impact on QoL for TC survivors of achieved paternity. Counselling patients early at diagnosis as well as using cryopreservation of semen in all potential patients before treatment (only excluding patients definitely claiming they do not wish to achieve paternity) should therefore be regarded as the standard of care.


Jeurkar N, Mamtani R, Vaughn DJ
Granulomatosis and testicular germ cell tumors.
Urology. 2012; 80(6):1303-6 [PubMed]
OBJECTIVE: To determine the cumulative incidence of granulomatous disease among patients with testicular germ cell tumor (GCT) at the University of Pennsylvania and to describe these patients' characteristics and disease outcomes.
MATERIALS AND METHODS: A computerized search of a large electronic medical database at the University of Pennsylvania was conducted to identify all patients from 1997 to 2012 with a diagnosis of granulomatous disease and GCT.
RESULTS: A total of 14 patients were identified. The median age at the diagnosis of GCT was 32.5 years, and the median age at the diagnosis of granulomatous disease was 31 years. Most patients were diagnosed with granulomatous disease either concomitantly or after their diagnosis of GCT. The estimated cumulative incidence of granulomatous disease in patients with GCT at the University of Pennsylvania from 1997 to 2012 was 168.7/100,000.
CONCLUSION: These data suggest a strong association between granulomatous disease and GCTs. The observed incidence of granulomatous disease among patients with GCT represents a 10-fold increase compared with the general population. Additional investigation is needed to elucidate the true nature of this association.


Blomberg Jensen M, Jørgensen A, Nielsen JE, et al.
Vitamin D metabolism and effects on pluripotency genes and cell differentiation in testicular germ cell tumors in vitro and in vivo.
Neoplasia. 2012; 14(10):952-63 [PubMed] Article available free on PMC after 20/11/2013
Testicular germ cell tumors (TGCTs) are classified as either seminomas or nonseminomas. Both tumors originate from carcinoma in situ (CIS) cells, which are derived from transformed fetal gonocytes. CIS, seminoma, and the undifferentiated embryonal carcinoma (EC) retain an embryonic phenotype and express pluripotency factors (NANOG/OCT4). Vitamin D (VD) is metabolized in the testes, and here, we examined VD metabolism in TGCT differentiation and pluripotency regulation. We established that the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human fetal germ cells, CIS, and invasive TGCTs. VD metabolism diminished markedly during the malignant transformation from CIS to EC but was reestablished in differentiated components of nonseminomas, distinguished by coexpression of mesodermal markers and loss of OCT4. Subsequent in vitro studies confirmed that 1,25(OH)(2)D(3) (active VD) downregulated NANOG and OCT4 through genomic VDR activation in EC-derived NTera2 cells and, to a lesser extent, in seminoma-derived TCam-2 cells, and up-regulated brachyury, SNAI1, osteocalcin, osteopontin, and fibroblast growth factor 23. To test for a possible therapeutic effect in vivo, NTera2 cells were xenografted into nude mice and treated with 1,25(OH)(2)D(3), which induced down-regulation of pluripotency factors but caused no significant reduction of tumor growth. During NTera2 tumor formation, down-regulation of VDR was observed, resulting in limited responsiveness to cholecalciferol and 1,25(OH)(2)D(3) treatment in vivo. These novel findings show that VD metabolism is involved in the mesodermal transition during differentiation of cancer cells with embryonic stem cell characteristics, which points to a function for VD during early embryonic development and possibly in the pathogenesis of TGCTs.


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