Testicular Neoplasia Research Articles

Is testis-sparing surgery safe in small testicular masses? Results of a multicentre study.

Our goal was to evaluate benign and malignant lesions and testicular intraepithelial neoplasia (TIN) in the neighbouring normal-appearing testis tissue in men who underwent radical orchiectomy for testicular mass with a pathologic tumour size of ≤3cm. In this retrospective, multicentre study, data of 252 patients from 11 different institutions were included. Patients were divided into three groups based on tumour size: Group 1 (0-1 cm; n=35), Group 2 (1.1-2cm; n=99), and Group 3 (2.1-3 cm; n=118). Benign lesions and TIN were sought in the neighbouring testicular tissue and compared between groups. Mean patient age was 32.3 years. Benign lesions were reported in 54.3%, 33.3%, and 14.4% of Groups 1, 2, and 3, respectively (p<0.05 between groups). TIN was detected in 20%, 42.4%, and 41.5% of Groups 1, 2, and 3, respectively (p<0.05 for Group 1 vs. Groups 2 and 3; p>0.05 for Groups 2 vs. 3). Multifocality was detected in 8.6%, 4%, and 0% of Groups 1, 2, and 3, respectively (p<0.05 for both Group 1 vs. Group 3 and for Group 2 vs. Group 3; p>0.05 for Group 1 vs. Group 2). A tumour cutoff size of 1.5 cm was found to be significant for detecting benign tumour. TIN and multifocality rates were similar in patients with a tumour size of ≤1.5 vs. >1.5 cm (p>0.05). Benign lesions and TIN in the neighbouring testis were significantly decreased and multifocality was increased in patients with a tumour mass size of ≤1 cm. Testis-sparing surgery should be performed with caution and a safety rim of normal tissue should also be excised.

Prevalence of small testicular hyperechogenic foci in subgroups of 382 non-vasectomized, azoospermic men: a retrospective cohort study.

SummaryTesticular hyperechogenic foci (THF) are associated with Klinefelter's syndrome, cryptorchidism, infertility, and testicular germ cell neoplasia. The aims of the study were to evaluate THF in relation to etiology of azoospermia and to Sertoli cell dysfunction. The structures inside the scrotum of consecutive non‐vasectomized, azoospermic were examined by ultrasonography, and hormone (FSH, LH, testosterone, and prolactin), and genetic analyses (karyotype, Y microdeletions, and CFTR mutations) were performed. At testicular ultrasonography, patients were graduated into: pronounced THF (>7 THF per transducer field), distributed universally (uTHF) or collected in plaques (pTHF), borderline THF (bTHF; 3–7 THF per transducer field), or no THF (<3 THF per transducer field). Diagnostic testicular biopsy was taken open or with TruCut needle (14G). THF status was sufficiently described in 382 of 449 potential participants, and testicular histology was available in 300 cases. Presence of ultrasonographically detectable THF was compared to presence of testicular microlithiasis (TM) detected histologically. Sertoli cell dysfunction was investigated in a subgroup using a three‐stage immunoperoxidase technique for detection of cytokeratin‐18 (CK‐18). The prevalence of THF was 13.4%. uTHF was found in 11 men (2.9%), the pattern was bilateral in four while other four had bTHF in the other testis. pTHF was detected in eight cases (2.1%), and except for one case with Klinefelter's syndrome, pTHF was in all cases occurring unilaterally. bTHF was detected in 32 cases (8.4%), bilaterally in 17 (53%). Pronounced THF was significantly associated with testicular malignancy. CK‐18 was detected in more azoospermic men with sperm production in ≤50% seminiferous tubules than in azoospermic men with spermatogenesis in ≥90% of seminiferous tubules and normal controls (p < 0.05). Unfortunately, TM detected histologically was not detected in any patient expressing THF, and neither THF nor TM was detected in any of the patients examined for CK‐18. Sertoli cell dysfunction was not associated with testicular microlithiasis or hyperechogenic foci.

Postchemotherapy changes in testicular germ cell tumours: biology and morphology.

Advances in modern chemotherapy and targeted treatments have resulted in lengthened survival in a variety of tumour types in the last decade. Increasingly in the 21st century, postchemotherapy resections are considered as a possible mode of treatment. Due to their exquisite chemosensitivity, resection of postchemotherapy masses has long been part of the armamentarium of treatment in testicular germ cell neoplasia, which has resulted in a variety of new morphological variants being described after treatment. Here we discuss the possible reasons for germ cell tumour chemosensitivity and hypotheses on the biological pathways leading to resistance to treatment, as well as an outline of the diverse morphology of those tumours which prove recalcitrant to standard treatment methods. The large range of morphologies and their diagnostic challenges may throw light upon the future problems to be encountered in non-germ cell solid tumour pathology, as the resection of postchemotherapy masses becomes increasingly important in patient management.

Clinical, genetic, biochemical, and testicular biopsy findings among 1,213 men evaluated for infertility

To study the pathologic findings among men evaluated for infertility. A retrospective, single-center, cross-sectional study. University hospital-based research center. We included data from 1,213 medical records from infertile men referred for diagnostic work-up from 2005 to2009. None. Health history, clinical findings, chromosome/genetic aberrations, semen quality, reproductive hormones. In total, 64.4% of the infertile men had one or more reproductive disorders or factors influencing fertility, leaving 35.6% diagnosed as idiopathic infertile. In 244 patients (20%), including seven cases of testicular cancer and/or germ cell neoplasia in situ, a pathologic finding was first detected during diagnostic work-up. Two hundred four patients (16.8%) had a history of cryptorchidism and 154 (12.7%) of varicocele (grade 2 and 3). Thirty-three patients had chromosomal abnormalities, including 16 with sex chromosome abnormalities (11 with 47,XXY). Y-chromosome microdeletions were detected in 65 patients (5.4%). One hundred thirty-three had azoospermia, of which 58 had testicular biopsy findings (Sertoli cell-only syndrome: n = 23; spermatogenic arrest: n = 7; impaired spermatogenesis and atrophy: n = 28). Additionally, in idiopathic infertile men and infertile men with additional symptoms of testicular dysgenesis syndrome, 22.5% presented with a degree of Leydig cell insufficiency, with the highest frequency (33.1%) among patients with sperm concentration <5 million/mL. We report pathologic findings that could explain the male-factor infertility in two-thirds of infertile men referred to our center. Thus, male infertility may be a sign of an underlying disease that warrants attention.

Feminisatie en ernstige pancytopenie veroorzaakt door testiculaire neoplasie in een cryptorche hond

In deze casuïstiek wordt een paraneoplastisch syndroom beschreven veroorzaakt door een testistumor bij een tien jaar oude, cryptorche hond. Feminisatie en pancytopenie werden gezien als gevolg van de productie van oestrogenen door het testiculaire neoplastisch proces. De diagnose van testistumor en geassocieerde beenmergsuppressie werd gesteld door middel van echografie en bloedonderzoek, waarbij de oestrogeenbloedspiegel sterk gestegen was. Urineonderzoek toonde een urineweginfectie aan. De hond werd gecastreerd, kreeg een bloedtransfusie en werd behandeld met antibiotica. Na een initiële verbetering stierf de hond onverwacht, ongeveer drie weken na het stellen van de diagnose. In deze casus wordt benadrukt dat tekenen van feminisatie tijdig opgemerkt dienen te worden bij intacte, mannelijke honden en dit om erge, mogelijk irreversibele, hematologische gevolgen door beenmergsuppressie te vermijden. Electieve castratie van beide testes is sterk aangeraden bij dieren met cryptorchidie omdat neoplastische transformatie van de niet-afgedaalde testis kan optreden, mogelijk met een fatale uitkomst.

Molecular mechanisms of cryptorchidism development: update of the database, disease comorbidity, and initiative for standardization of reporting in scientific literature.

Cryptorchidism is a frequent urogenital abnormality that may be present at birth (congenital form) or develop later in life (acquired form). It represents 2-4% full-term male births. It has a potential effect on health; defects in testes descent usually cause impaired spermatogenesis resulting in reduced fertility and increased rates of testicular neoplasia, and testicular torsion. In our previous study, we developed a cryptorchidism gene database which consists of 217 genomic variations associated with development of cryptorchidism in seven mammalian species. The number of studies and study approaches in this field are increasing; therefore, update of the database was needed. The search of multi-omics data was performed and the updated database includes 280 genomic variations associated with cryptorchidism in seven species. The catalog has been complemented with additional data including: number of participants (patients/controls), race/ethnicity, clinical data (age period at diagnosis), congenital/acquired cryptorchidism, unilateral (left/right)/bilateral cryptorchidism, disease comorbidity, and disease ontology. Collected data revealed that cryptorchidism has been reported to be co-present with 150 comorbid conditions, including several syndromes, reproductive, cardiovascular, ophthalmologic, dermatologic, mental, and bone disorders, deafness, and cancer. However, updating the database is time-consuming because of the heterogeneity of results and methodology in scientific literature. The field lacks a standardized format for reporting associations between genotype and phenotype which would enable faster development of the database, data integration, sharing, and facilitate biomarker development. Therefore, in this study, we updated a database of cryptorchidism genes and suggested a first step toward standardization of the format for reporting results of original as well as review studies which we suggest implementing into the scientific literature that reports genotype-cryptorchidism associations.

Germ cell neoplasia in situ (GCNIS): evolution of the current nomenclature for testicular pre-invasive germ cell malignancy.

The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce the reasoning for uniting behind a new name, endorsed unanimously at the World Health Organization (WHO) consensus classification 2016: germ cell neoplasia in situ (GCNIS).

Is contrast-enhanced MRI efficient in testicular infarction mimicking testicular tumor on scrotal ultrasound?

A 4-year-old boy was admitted to emergency department of our institution with left testicular swelling and pain started 48 h ago. Physical examination revealed left sided erythema and tenderness in scrotum which was refractory to testicular elevation. The parents did not describe undescended testis, trauma or recent mumps history that may explain acute swelling of left scrotum. Immediately after the physical examination, a scrotal Doppler ultrasonography was performed using a high frequency linear transducer. Ultrasonographic evaluation showed heterogeneously enlarged left testis and edema in the left scrotum. Blood supply was decreased in left testis in comparison to the right, however, arterial waveforms were still preserved in the left epididymis. In addition to Doppler and gray scale ultrasonography features, a smooth contoured demarcation line in the left testis was also observed which simulated mass lesion in the left testis. Based on the ultrasonography findings a concurrent testicular neoplasia could not be ruled out completely and the patient was referred to contrast-enhanced magnetic resonance imaging (MRI) promptly after ultrasound examination. MRI revealed left testicular enlargement, scrotal edema, and heterogeneous hypointense areas in T2-weighted images, but there was no solid or cystic mass lesion within the left testis. The affected testis was observed to be prominently hypointense on T1-weighted images compared to right. At post-contrast and subtraction MRI sequences avid contrast enhancement was detected in left paratesticular tissue however, left testis was completely avascular at post-contrast MRI sequences (Fig. 1). Based on the MRI findings, the diagnosis of testicular torsion was made confidently. Emergency surgical exploration confirmed intravaginal testicular torsion but, unfortunately detorsion operation could not have been performed and left sided orchiectomy was required because left testis was observed to be totally necrotic during surgical intervention (Fig. 2). Fig. 1 Post-contrast subtraction axial MRI image reveals left testicular enlargement and left paratesticular enhancement. Note that the affected left testis is hypointense and no contrast enhancement is observed diagnostic for testicular torsion (arrows). However, ... Fig. 2 Photographic view of the left testis during operation shows left testicular necrosis. Intravaginal torsion accounts for most cases of testicular torsion. Most cases are spontaneous but, rarely intravaginal testicular torsion may result from testicular trauma.1 Since irreversible damage may occur within 4–6 h of symptom onset, early diagnosis and urgent surgical intervention are critical.2 In the early stage of torsion, the echogenicity and size of the affected testis may be normal. Later findings include testicular enlargement and increased parenchymal echogenicity. If left untreated, the torsion will eventually progress into infarction which is seen as decreased or absent blood flow in color Doppler ultrasonography.1 The latter is sometimes diagnostic challenge in ultrasonography since, demarcation line of the infarcted testis tissue may simulate tumor particularly in late testicular torsion.3 In the current case, as reported in the literature,4 a testicular tumor was accurately ruled out via emergency contrast-enhanced MRI. In conclusion, late testicular torsion may mimic testicular mass lesion in ultrasonography which may cause a diagnostic challenge in Emergency Medicine. Contrast-enhanced MRI is helpful in the diagnosis as well as in the differential diagnosis in such complex cases.

The role of apparent diffusion coefficient values in detecting testicular intraepithelial neoplasia: Preliminary results

IntroductionThe aim of this study is to improve detection of testicular intraepithelial neoplasia (TIN) by measurement of apparent diffusion coefficient (ADC) values. Materials and methodsFifty-six MRI examinations of the scrotum, including 26 histologically proven testicular germ cell neoplasms were retrospectively evaluated. DWI was performed using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b-values of 0 and 900smm−2. ADC measurements were classified into three groups according to their location: group 1 (n=19), non-tumoral part, adjacent to testicular carcinoma, where the possible location of TIN was; group 2 (n=26), testicular carcinoma; and group 3 (n=60), normal testicular parenchyma. Analysis of variance (ANOVA) followed by post hoc analysis (Dunnett T3) was used for statistical purposes. ResultsThe mean±s.d. of ADC values (×10−3mm2/s) of different groups were: group 1, 1.08±0.20; group 2, 0.72±0.27; and group 3, 1.11±0.14. ANOVA revealed differences of mean ADC between groups (F=38.859, P<0.001). Post hoc analysis showed differences between groups 2 and 3 (P<0.001), groups 2 and 1 (P<0.001), but not between groups 3 and 1 (P=0.87). ConclusionsBased on our preliminary results, ADC values do not provide a reliable differentiation between TIN and testicular carcinoma or normal testicular parenchyma.

Embryonal Carcinoma in Cryptorchid Abdominal Testis of an Infant.

Cryptorchidism is a known predisposing factor for the development of testicular tumors in adults. Age of patient at the time of treatment of undescended testes has some bearing on the risk of neoplasia. Testicular neoplasia at the time of primary surgery for cryptorchidism has been reported rarely in prepubertal period. We report a case where embryonal carcinoma was detected in a cryptorchid testis of an infant.

Expression of Phosphodiesterase 4B cAMP-Specific Gene in Subjects With Cryptorchidism and Down's Syndrome.

Cryptorchidism represents a risk factor for infertility and germ cell testicular neoplasia. An increased rate of cryptorchidism has been reported in subjects with Down's syndrome. Cyclic nucleotide phosphodiesterases (PDEs) are important messengers that regulate and mediate a number of cellular responses to extracellular signals, such as neurotransmitters and hormones. PDE4B, cAMP-specific (PDE4B) gene which maps to chromosome 1p31.3 appears to be involved in schizophrenia, chronic psychiatric illness, learning, memory, and mood disturbances. Expression of PDE4 enzymes have been studied in testes of cryptorchid rats. Expression of PDE4B protein examination showed marked degenerative changes in the epithelial lining of the seminiferous tubules. These findings led us to evaluate PDE4 mRNA expression in leukocytes of peripheral blood of five men with DS and cryptorchidism and eleven subjects with DS without cryptorchidism compared with healthy men (controls) by quantitative Real Time PCR (qRT-PCR). This study showed that the PDE4B gene was downexpressed in men with DS and cryptorchidism compared to normal controls and DS without cryptorchidism. A lower expression of the PDE4B gene may be involved in the neurological abnormalities in subjects with Down's syndrome. Moreover, PDE4B gene may be involved in the testicular abnormalities of men with DS and cryptorchidism.

Testis sparing surgery in the treatment of bilateral testicular germ cell tumors and solitary testicle tumors: A single institution experience.

To assess the oncologic and functional outcomes of testicular sparing surgery (TSS) based on a single institution experience. Forty-one patients with bilateral and 3 patients with solitary testicle tumors were referred to our institution. The inclusion criteria for TSS were normal serum testosterone levels, and tumor size (<2 cm). Sperm analysis and hormone status evaluation were performed preoperatively and postoperatively. None of the patients underwent local radiation therapy following TSS for reasons of fertility preservation. A total of 26 TSS were performed in 24 patients. The median follow-up period was 51.0 months. Seven patients developed local recurrence, of which 5 had TIN and were subjected to radical orchiectomy, whereas re-do TSS was done in remaining 2 patients. The overall survival of the study group was 100%, and the presence of testicular intraepithelial neoplasia (TIN) was associated with worse recurrence-free survival (P=0.031, log-rank). Testosterone values were normal in all of the patients, while 4 patients achieved conception. TSS is acceptable from an oncological point of view, and it enables continuation of a patient's life without lifelong hormonal substitution. Additionally, local irradiation therapy could be delayed in patients with TIN who wish to father children, but with high local recurrence rate.

Anti-Müllerian hormone: a potential biomarker for differential diagnosis of cryptorchidism in dogs

Cryptorchidism, in which the testes fail to descend into the scrotum by six months of age, is a developmental disorder in male dogs (Johnston and others 2001). Cryptorchidism predisposes the...

Contralateral biopsies in patients with testicular germ cell tumours: patterns of care in Germany and recent data regarding prevalence and treatment of testicular intra-epithelial neoplasia.

The precursor of testicular germ cell tumours (GCTs), called testicular intra-epithelial neoplasia (TIN/CIS), is safely diagnosed immunohistologically. Testicular biopsy provides a valuable tool for early detection of GCTs in risk groups. Although this knowledge is undisputed, testicular biopsies are utilized poorly. The patterns of care regarding the use of biopsies remain unknown. Uncertainty exists about the prevalence and specific treatment of TIN/CIS. We asked clinical urologists in Germany whether or not they employed contralateral biopsies in GCT patients. We evaluated the prevalence of contralateral TIN/CIS in a retrospective analysis of 780 consecutive GCT patients. All had contralateral double biopsies. Discordance of TIN/CIS findings among biopsy pairs as well as age, histology of the primary tumour and clinical stage was noted. Evaluation of data comprised descriptive statistical methods. To evaluate treatment options for TIN/CIS, we performed a literature search. 52.1% of German urologists always perform the biopsy, 17% do it mostly, 27.3% in select cases, 3.5% never. Curiously, there was a geographic north-south gradient regarding biopsy use. Contralateral TIN/CIS was found in 5%. The median ages of patients with TIN/CIS and those without were 31.8 and 34.9years respectively (p=0.02). The discordance rate among biopsy pairs was of 33%. Two-site biopsies provide a 17% gain in diagnostic sensitivity. Local radiotherapy with 20Gy is the safest treatment of TIN/CIS failing in 2%. Chemotherapy has significantly lower efficacy. Contralateral testicular biopsies in GCT patients are well accepted among German urologists. The prevalence of contralateral TIN/CIS found in this series is in accordance with previous reports. Double biopsies should be the diagnostic standard because of their diagnostic superiority. Local radiotherapy with 20Gy is the safest way of eradicating TIN/CIS. Failures occur in only 2%, usually many years after irradiation. Cisplatin-based chemotherapy is dose dependent and less effective.

Organ-sparing therapy for testicular cancer

The therapy of malignant testicular neoplasms has always been characterized by a high degree of radicality. Thanks to a number of medical achievements the cure rate of testicular cancer has notably increased through the last decades. In the meanwhile the main focus is on reducing therapy load, scrutinizing radical orchiectomy as the only adequate therapy for the primary tumour. This article discusses the question, if and under which conditions an organ-sparing approach can be used appropriately in clinical practice. A selective literature search was performed in PubMed. A set of data suggest that endocrine and exocrine function of the testis can be preserved using an organ-sparing approach and many patients could benefit regarding their quality of life, e.g., preserving the ability to father a child at least temporarily and avoiding the need for hormone substitution. Different from kidney tumors, precancerous lesions (testicular intraepithelia neoplasia, TIN) can almost inevitably be found in the surrounding tissue of testicular tumors. This has to be considered when making a decision in favor of an organ-sparing approach, because radiation therapy on the affected testis has to be performed after tumor resection. Despite the absence of prospective data, organ-sparing surgical tumor resection can be recommended in carefully selected patients. After careful selection of patients, particularly young men can profit from an organ-sparing therapy regimen. Therefore, organ preservation should always be considered in the surgical treatment of testicular masses.

Tumor testicular bilateral, tipo linfoma no Hodgkin de células T/NK extranasal

Lymphoma is a malignant neoplasia characterized by the proliferation of cells native to the lymphatic system. It makes up 1 % to 9 % of testicular neoplasia. Bilateral testicular tumor presentation was first described by Aberhouse in 1955. Extranodal nasal-type natural killer (NK) lymphoma is the most frequent variant of non-Hodgkin's tumors and presents with extensive vascular destruction and necrosis; the most common extranodal site is the upper respiratory system. It is characterized by poor outcome and systemic dissemination and does not respond well to current treatments.A 45-year-old man presented with bilateral increased testicular volume of 6-month progression, having received multiple treatments. Testicular ultrasound and abdominal computed tomography scan revealed increased testicular volume, retroperitoneal metastasis, and metastasis to the subcutaneous cell tissue. Tumor markers were negative. Right radical orchiectomy and biopsy of the left testis were performed. The definitive histopathologic diagnosis was extranasal- type NK/T-cell non-Hodgkin's lymphoma. The patient was referred to the Hematology Service and chemotherapy and hormone replacement treatment were begun.This tumor represents 1 % of all non-Hodgkin's lymphomas and 5 % of testicular masses. Mean presentation age is 50 years and there is a higher incidence in Asia and South America. Twenty percent of the cases affect areas outside of the nasal cavity. There is no staging classification for this disease. Five-year survival is 60 % and 17 % for disseminated disease. None of the current treatments (orchiectomy, chemotherapy and/or chemo-radiotherapy) are considered the criterion standard.

Evaluation of frozen section results in patients who have suspected testicular masses: a preliminary report.

To report our experience with patients who have suspected testicular masses (STM) managed by ex vivo technique of testicular sparing surgery (TSS) after radical orchiectomy. Between 2007-2011 years, 10 patients with STM were evaluated by history, physical examination, testicular ultrasound and serum tumor markers. STM were defined as; no paratesticular lesions, size of the lesion smaller than 20 mm, and no known presence of elevated tumor markers or metastatic disease. The principles of TSS followed by radical orchiectomy were applied to the removed surgical specimen. Excised mass, multiple biopsies of the adjacent parenchyma and the remaining testis were sent for frozen-section analysis (FSA). Histopathologic sections were re-reviewed for definitive pathologic diagnosis. The mean patient age, mean size and mean length of history of STM were 37 years (25-64), 17.5 mm (10-20) and 6 months (2-12). All STM were palpable and painless. Tumor markers were negative in all patients. Six tumors were benign (2 adenomatoid tumor, 1 epididymitis nodosa, 1 leydig cell tumor, 1 sertoli cell tumor, 1 fibrous pseudotumor) and 4 tumors were malignant (3 seminoma, 1 embryonal carcinoma) on definitive pathologic diagnosis. Excluding one benign lesion, FSA correctly determined 9 lesions and all malignant lesions. Three patients had testicular intraepithelial neoplasia (ones seminoma, ones embryonal carcinoma, ones adenomatoid tumor). Our preliminary report reveals that STM tend to be benign rather than malignant in nature. Also, a careful patient selection and an accurate FSA are crucial points for TSS and it has the potential to become the primary option in selected patients who have testicular lesions instead of the traditional method.

IMAGING DIAGNOSIS – SEMINOMA CAUSING LIVER COMPRESSION IN A SPUR‐THIGHED TORTOISE (TESTUDO GRAECA)

A 13-year-old male spur-thighed tortoise (Testudo graeca) was presented with anorexia, apathy, and prolapse of penile tissue. Ultrasonography revealed a large heterogeneous mass in the coelomic cavity, and fine-needle aspiration demonstrated sperm. Magnetic resonance imaging showed a sharply defined mass originating from the left testis. Appearance and signal intensities were similar to those reported in testicular neoplasms in humans, in particular sharing similarities with seminomas. Necropsy results and histopathological findings were consistent with a seminoma. To the authors' knowledge this is the first report of the diagnosis of testicular neoplasia in a reptile using imaging techniques.

An overview on new anticancer molecular targets in human testicular germ cell tumors

Testicular germ cell tumors (TGCTs) are the most frequent solid malignant tumors in men 20–40 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs can be subdivided into seminoma and non-seminoma germ cell tumors (NSGCTs), including embryonal cell carcinoma, choriocarcinoma, yolk sac tumor, and teratoma. Seminomas and NSGCTs do not only present distinctive clinical features, but they also show significant differences as far as therapy and prognosis are concerned. The different therapeutic outcome might be explained by inherent properties of the cells from which testicular neoplasia originates. The unique treatment sensitivity of TGCTs is unexplained so far, but it is likely to be related to intrinsic molecular characteristics of the primordial germ cells/gonocytes, from which these tumors originate. Many discovered biomarkers including OCT3/4, SOX2, SOX17, HMGA1, Nek2, GPR30, Aurora-B, estrogen receptor β, and others have given further advantages to discriminate between histological subgroups and could represent useful novel molecular targets for antineoplastic strategies.

Sequential bilateral testicular tumours presenting with intervals of 20 years and more

BackgroundAbout 3 – 5% of all patients with testicular germ cell tumour (GCT) develop a contralateral cancer, the majority of which arise within 10–15 years. Little is known about the risk of second GCTs after more than two decades. Here we present 3 cases with very late presenting contralateral GCT and provide a summary of similar cases reported previously.Case presentations(1) This white Caucasian man underwent right-sided orchiectomy for a nonseminomatous GCT at the age of 22 years. Additional treatment consisted of retroperitoneal lymph node dissection (RPLND) and chemotherapy with 4 cycles of vinblastin / bleomycin. 36 years later, contralateral seminoma clinical stage 1 developed. Cure was achieved by orchiectomy. Histologically, testicular intraepithelial neoplasia (TIN; intratubular germ cell neoplasia) was detected in the tumour-surrounding tissue.(2) This white Caucasian male had right-sided orchiectomy for nonseminomatous GCT at the age of 29 years. Pathological stage 1 was confirmed by RPLND. 25 years later, he received left sided orchiectomy for seminoma stage 1. Histologically, TIN was found in the tissue adjacent to seminoma. Two brothers had testicular GCT, too, one with bilateral GCT. (3) This 21 year old white Caucasian man underwent left-sided orchiectomy for nonseminomatous GCT. Pathological stage 1 was confirmed by RPLND. 21 years later, he received organ-preserving excision of a right-sided seminoma, followed by BEP chemotherapy for stage 3 disease. Histologically, TIN was found in the surrounding testicular tissue.22 cases of bilateral GCT with intervals of 20 or more years have previously been reported, thereof three with intervals of more than 30 years, the longest interval being 40 years.ConclusionApart from increased risks of cardiovascular diseases and non-testicular malignancies, patients with GCT face the specific probability of a second GCT in the long run. This risk persists life-long and is not eliminated by chemotherapy. Contralateral testicular biopsy can identify patients at risk by revealing precursor cells of GCT though false-negative biopsies may occur sporadically. However, in view of the multi-facetted late hazards of GCT patients, this minor surgical procedure might somewhat simplify the long-time care of these patients.