Abstract
Primary intratesticular tumors are uncommon in children but incidence and risk of malignancy both sharply increase during adolescence. Ultrasound is the mainstay for imaging the primary lesion and cross-sectional modalities are often required for evaluation of regional or distant disease. However, variations to this approach are dictated by additional clinical and imaging nuances. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary testicular malignancy at diagnosis and during follow-up.
Keywords: ultrasound, MRI, testicular
Introduction
Testicular tumors in prepubertal boys are rare, mostly benign, and are typically teratomas1. The incidence of testicular tumors sharply increases in the second decade of life when malignant tumors predominate1,2. Primary testicular tumors in children may be broadly classified into germ cell tumors (GCT) and sex cord-stromal tumors. In 2016, the World Health Organization (WHO) classification of testicular tumors was modified, further dividing GCT based on presence or absence of germ cell neoplasia in situ (GCNIS)3. Table 1 highlights the different types of testicular tumors along with their differing clinical and imaging features.
Table 1:
Intratesticular tumor imaging and clinical features classified by WHO
Tumor Type | Arise from GCNIS*? |
Imaging features on US | Clinical features |
---|---|---|---|
Seminoma | Yes | Homogenous solid mass | Rare in children |
Embryonal carcinoma | Yes | Poorly circumscribed; heterogenous | May be aggressive |
Choriocarcinoma | Yes | Hypoechoic; poorly defined | Hemorrhagic metastatic potential |
Post-pubertal teratoma | Yes | Heterogenous cyst/solid mass with calcification | Majority are malignant |
Pre-pubertal teratoma | No | Heterogenous cyst/solid mass with calcification | More likely component of mixed GCT. Often benign or indolent. |
Post-pubertal Yolk Sac Tumor | Yes | Heterogenous cyst/solid mass with calcification | Very rare in pure form; elevated α-fetoprotein |
Pre-pubertal Yolk Sac Tumor | No | Solid hypervascular, homogenous mass; diffuse testicular enlargement | More often pure form; elevated α-fetoprotein |
Epidermoid Cyst | No | “Onion ring” appearance; avascular | Non-neoplastic |
Leydig cell tumor | No | Hypoechoic, often small, peripherally situated mass. | Precocious puberty |
Sertoli cell tumor | No | Variable. But often calcified and multiple in children | Associated with Carney and Peutz-Jeghers syndromes |
Gonadoblastoma | No | Findings not well described; rare | Undescended testis or gonadal dysgenesis |
GCNIS – germ cell neoplasia in situ
Testicular cancer is the most common solid tumor diagnosed in males between 15 and 34 years of age4. GCT are the most common tumor type and account for more than 15% of all testicular malignancies diagnosed during adolescence5,6. Patients typically present with a firm, painless mass. Signs of precocious puberty suggest that a sex cord stromal tumor, typically a Leydig cell tumor, is present. Patients with cryptorchidism have a greater risk (3.6 relative risk) of developing a testicular tumor7. Additional risk factors for testicular malignancy include cancer in the contralateral testis and a family history of the disease8.
Staging:
Both the American Joint Committee on Cancer (AJCC) and the Children’s Oncology Group (COG) have published staging systems. In prepubertal children, the COG staging system is most often followed. This staging system includes a mix of surgical and imaging components. Imaging plays an important role in the assessment of local disease, regional nodes (retroperitoneal nodes) and distant metastasis. For post-pubescent boys, there is some controversy regarding the use of the adult-oriented National Comprehensive Cancer Network (NCCN) versus the COG approach as data suggests better outcomes using the former which is itself predicated on use of the AJCC Tumor-Nodes-Metastases (TNM) system1,9. In 1997, the International Germ Cell Cancer Collaborative Group (IGCCCG) published a risk classification scheme which included both adults and children but also included extra-testicular germ cell tumors. The IGCCCG system has been revised and validated based on effective prognostication10-12. Though limited, there is evidence for improved outcomes in adolescents with metastatic GCT when adhering to IGCCCG guidelines as the biology of tumors in this group is more similar to adults13. The IGCCCG Risk Classification scheme is based on the location of disease, the presence and location of metastatic disease, and laboratory values.
Imaging at Diagnosis:
In a boy suspected of having a testicular mass, US is the initial imaging test of choice [GRADE A; SOR 1]. Its reported sensitivity between 92 and 98% allows reliable exclusion of an intratesticular mass when none is present14,15. Additionally, US may reveal another cause for a palpable mass such as hydrocele, epididymal cyst, or an extra-testicular mass. While US can distinguish the above entities from a testicular tumor, it cannot reliably differentiate the histologic types of intratesticular masses16,17. Benign tumors, though, are more common in prepubertal boys and testicular-sparing surgery can be considered in this population. To this end, the radiologist’s impression of spared, viable testicular tissue may be helpful to the surgeon17,18. In post-pubertal boys the pre-test probability of malignancy is considerably higher and testicular-sparing surgery is not commonly performed.
Currently US is the only imaging modality required for evaluation of a primary intratesticular mass [GRADE B, SOR 1.30]. MRI can be employed in cases with inconclusive scrotal US findings or when scrotal US findings are inconsistent with clinical findings19-21. For example, MRI can support the suspicion of an epidermoid cyst after equivocal US findings22. However, to date, data supporting the routine use of MRI for intratesticular tumors remains limited23-25.
In all patients with a malignant intratesticular mass, CT or MRI of the remainder of the abdomen is mandatory to assess retroperitoneal lymphadenopathy and metastatic disease [GRADE A, SOR 1.00]. In a recent systematic analysis of young adult men with testicular tumors, the reported sensitivity and specificity of CT to detect metastatic lymph nodes has ranged between 66.7 – 84% and 66.7 – 95.2% respectively 26-28. There is less data on the performance of MRI. However, studies have shown it to have a sensitivity of 78 – 80% and a specificity of 91 – 96% for the evaluation of retroperitoneal lymph nodes27-29. When describing lymph nodes, it is suggested that the radiologist report two dimensions of any suspicious nodes as the AJCC staging system relies on the long axis, but the COG guidelines are based on short axis [GRADE B, SOR 1.40]6,15,28.
Chest CT should be performed at diagnosis in all adolescent patients with a malignant testicular mass to identify pulmonary metastatic disease [GRADE C, SOR 1.40]. In adults with non-seminomatous GCT, the American Urological Association (AUA) recommends either chest radiograph or CT at diagnosis30. Adolescent event-free survival is less favorable than both prepubescent boys and adult men with non-seminomatous GCT31. Additionally, there is a trend toward higher grade tumors in adolescents. CT offers much higher spatial resolution and is more sensitive for the diagnosis of pulmonary metastases.
Intravenous contrast is required for abdominal CT scans while for MRI, intravenous contrast is preferred [GRADE D, SOR 1.10].
Follow-up Imaging:
In post-pubescent adolescent males with testicular tumors, limited data is available to recommend a detailed imaging surveillance schedule. As such, there is current variability in practice patterns between institutions. Fortunately, varying the interval between scans by several months has not been shown to yield significantly different outcomes32. When considering follow-up imaging, several principles should be kept in mind: 1) Most childhood testicular neoplasms recur within the first two years. In fact, it has been reported that 80% of all relapses of non-seminomatous germ cell tumors occur within one year, 90% by two years and nearly all by three years post-orchiectomy33,34. 2) Recurrence of seminomas can be more delayed compared with non-seminomatous GCT. Therefore, imaging surveillance data derived from adult patients - which is heavily populated by seminomatous tumors - cannot be readily extrapolated to the pediatric population.
Periodic US surveillance of the contralateral testicle is recommended in patients previously treated for a testicular malignancy – especially in the setting of an additional risk factor such as history of cryptorchid testis [GRADE D, SOR 2.0]35,36. In adult series, overall risk of metachronous malignancy in the contralateral testis has been shown to be 12 times higher than the general population37,38. Moreover, the higher risk was skewed toward younger patients37. The recommendation is based on the concept that a small tumor may not be palpable. Incidentally detected testicular lesions have been shown to only rarely harbor malignancy39. However, data on nonpalpable, radiologically detected tumors in the population of patients with a history of testicular malignancy is lacking.
Either CT or MRI of the abdomen should be obtained to surveil for recurrent nodal disease in all adolescent patients with testicular tumors [GRADE B, SOR 1.80] 29,40. Most authors recommend following COG guidelines for follow-up surveillance in pre-pubertal patients and following adult guidelines in post-pubertal patients41,42. There are differing recommendations on the frequency for imaging surveillance. The AUA recommends abdominal CT every 3-6 months in year 1, every 4-12 months in year 2, once in year 3, and once in year 4 or 5 in adult men with Stage I non-seminomatous GCT30. The NCCN recommends surveillance for 3 to 5 years with the frequency of imaging depending on the histology of the tumor, the type of therapy, the stage of the tumor at diagnosis43,44. In both guidelines, imaging is used along with physical exam and laboratory evaluation.
For children with stage I disease, chest radiographs suffice at follow-up45 [GRADE C, SOR 2.40]. This is consistent with adult guidelines which recommend chest radiography for all patients. In the NCCN guidelines, chest CT with IV contrast is recommended for patients with thoracic symptoms or in those with supradiaphragmatic disease at baseline44. Thus, surveillance chest CT is recommended for patients with COG Stage II or higher disease and should be performed in any patient with metastatic disease (stage IV) at initial presentation46 [GRADE C, SOR 1.50].
Routine use of 18F fluorodeoxyglucose (FDG) PET/CT for staging or surveillance of non-seminomatous GCT is not recommended. Instead, its use is reserved to identify occult disease in patients with rising tumor markers and a negative CT or MR, or to evaluate equivocal findings that could affect surgical planning or therapy [GRADE C, SOR 1.78]47. There is an emerging role for fluorodeoxyglucose F 18 (FDG)-PET/CT in problem-solving equivocal findings and also in patients with rising tumor markers in the context of negative CT or MR.47 Although PET offers excellent negative predictive value in the setting of seminomas, The International Global Germ Cell Cancer Group Registry cautions against clinical decisions based on PET positivity alone due to risk of false positives7,48. Currently, there is little evidence to support its routine use in staging or follow-up surveillance in non-seminomatous GCT in the pediatric population however it should be considered in equivocal cases.
Tumor Response Assessment:
All regional lymph nodes ≥ 8 mm in their short axis should be reported [GRADE B, SOR 1.80]. Based on work in adult populations with testicular cancer, it has been suggested that lymph nodes ≥ 8 mm in the short axis be deemed suspicious at diagnosis40,49,50. Because most patients with testicular tumors undergo up-front orchiectomy, tumor response assessment is mainly focused on regional nodes. However, even retroperitoneal nodes less than 1 cm should be reported – especially if ipsilateral to the primary tumor.
During routine post-treatment surveillance imaging, the radiologist should identify complications such as incisional hernia, bowel adhesions, and radiation enteritis. Early evidence of pulmonary fibrosis should be sought in patients receiving bleomycin therapy. Secondary malignancies are the most common cause of death in survivors of testicular cancer, occurring in 1% to 2%. However, to date, there is no data to support long-term screening for secondary malignancy. Other potential late effects from testicular tumor therapy include hypogonadism, infertility, cisplatin-related nephrotoxicity, and atherosclerotic disease. Imaging is currently not used to screen for any of these effects4,51.
Testicular Microlithiasis:
Post-pubertal boys with testicular microlithiasis (TM) should be educated on the importance of regular self-exams in addition to being referred to a urologist for consideration of US screening [GRADE D; SOR 2.20]. The topic of screening for testicular tumors in patients with TM is controversial. Currently, most groups only recommend screening for patients with TM and additional risk factor(s) for testicular malignancy which include cryptorchidism, testicular atrophy and previous testicular cancer52-57. Nevertheless, recent studies in children with TM, including one large multi-institutional retrospective study confirm a statistically significantly strong association between TM and testicular malignancy58,59. It is still possible that the two are not causally related and that TM may be merely a marker of risk in patients with already-known risk factors. However, given the known association and this open question, there is some hesitancy in universally extending the recommendation of no screening to the child and adolescent population60.
If TM is seen in the setting of an additional risk factor, both self-examinations and annual screening US is recommended in post-pubertal boys [GRADE A; SOR 1.40].
The Future of Imaging in testicular tumors:
Although MRI cannot reliably differentiate malignant from benign tumors, any imaging assistance to this end may be helpful in the prepubescent boy in whom testicular-sparing surgery may be feasible. Much work in advancing oncologic MRI is focused on diffusion weighted imaging (DWI). However, in addition to malignant tumors, the testicular parenchyma normally demonstrates restricted diffusion61, an observation which has historically tempered enthusiasm for DWI. Despite this, there is emerging evidence to suggest use of MRI, including DWI with attention to technical details in discriminating benign from malignant lesions62,63. For example, marked restricted diffusion (more than the normal testicular parenchyma) in intratesticular epidermoid cysts has already shown clinical value22.
Additional MRI sequences such as diffusion tensor imaging, magnetization transfer imaging and proton spectroscopy, which can provide further information about the microstructure and microenvironment of the testicular parenchyma, are being explored64. Lastly, radiomics is a promising emerging field that may provide imaging biomarkers for the characterization of testicular masses as well as for the assessment of retroperitoneal metastatic disease65-68,69-73.
Acknowledgments
This manuscript was funded in part by the National Clinical Trials Network Operations Center Grant U10CA180886
Abbreviation
- GCT
Germ Cell Tumor
- WHO
World Health Organization
- GCNIS
Germ Cell Neoplasia In Situ
- AJC
American Joint Committee on Cancer
- COG
Children’s Oncology Group
- NCCN
National Comprehensive Cancer Network
- IGCCCG
International Germ Cell Cancer Collaborative Group
- SOR
Strength Of Recommendation
- AUA
American Urological Association
- TM
Testicular Microlithiasis
- DWI
Diffusion Weighted Imaging
Footnotes
Disclosures: Alexander Towbin has a Grant from the Cystic Fibrosis Foundation, is a Consultant for Applied Radiology and has received Paid travel from KLAS, in addition to Author Royalties from Elsevier
Contributor Information
Gerald G. Behr, Memorial Sloan Kettering Cancer Center/Weill Cornell Medicine, NY
Ajaykumar C. Morani, The University of Texas MD Anderson Cancer Center
Maddy Artunduaga, UT Southwestern Medical Center, Dallas, TX.
Sarah M. Desoky, University of Arizona College of Medicine, AZ
Monica Epelman, Nicklaus Children’s Hospital, Miami, Florida.
Jonathan Friedman, UT Southwestern Medical Center, Dallas, TX.
Shailee V. Lala, New York University Langone Health, NY
Jayne Seekins, Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA.
Alexander J. Towbin, Cincinnati Children’s Hospital, Cincinnati, OH
Susan J. Back, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania
References
- 1.Jarvis H, Cost NG, Saltzman AF. Testicular tumors in the pediatric patient. Semin Pediatr Surg. 2021;30(4):151079. [DOI] [PubMed] [Google Scholar]
- 2.Sanguesa C, Veiga D, Llavador M, Serrano A. Testicular tumours in children: an approach to diagnosis and management with pathologic correlation. Insights Imaging. 2020;11(1):74. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Nguyen HTK, Terao MA, Green DM, Pui CH, Inaba H. Testicular involvement of acute lymphoblastic leukemia in children and adolescents: Diagnosis, biology, and management. Cancer-Am Cancer Soc. 2021;127(17):3067–3081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Baird DC, Meyers GJ, Hu JS. Testicular Cancer: Diagnosis and Treatment. Am Fam Physician. 2018;97(4):261–268. [PubMed] [Google Scholar]
- 5.Horwich A, Shipley J, Huddart R. Testicular germ-cell cancer. Lancet. 2006;367(9512):754–765. [DOI] [PubMed] [Google Scholar]
- 6.Aldrink JH, Glick RD, Baertschiger RM, et al. Update on pediatric testicular germ cell tumors. Journal of pediatric surgery. 2021. [DOI] [PubMed] [Google Scholar]
- 7.Dotzauer R, Thomas C, Jäger W. The use of F-FDG PET/CT in testicular cancer. Translational andrology and urology. 2018;7(5):875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Cheng L, Albers P, Berney DM, et al. Testicular cancer. Nat Rev Dis Primers. 2018;4. [DOI] [PubMed] [Google Scholar]
- 9.Frazier AL, Hale JP, Rodriguez-Galindo C, et al. Revised risk classification for pediatric extracranial germ cell tumors based on 25 years of clinical trial data from the United Kingdom and United States. J Clin Oncol. 2015;33(2):195–201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Mead GM, Stenning SP. The International Germ Cell Consensus Classification: a new prognostic factor-based staging classification for metastatic germ cell tumours. Clin Oncol (R Coll Radiol). 1997;9(4):207–209. [DOI] [PubMed] [Google Scholar]
- 11.Gillessen S, Sauve N, Collette L, et al. Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium. J Clin Oncol. 2021;39(14):1563–1574. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Necchi A, Ross JS, Spiess PE. Improving the Prognostic Ability for Personalized Therapeutic Approaches in Nonseminomatous Germ Cell Tumors. J Clin Oncol. 2019;37(26):2314–2316. [DOI] [PubMed] [Google Scholar]
- 13.Shaikh F, Stark D, Fonseca A, et al. Outcomes of adolescent males with extracranial metastatic germ cell tumors: A report from the Malignant Germ Cell Tumor International Consortium. Cancer. 2021;127(2):193–202. [DOI] [PubMed] [Google Scholar]
- 14.Tallen G, Hernaiz Driever P, Degenhardt P, Henze G, Riebel T. High reliability of scrotal ultrasonography in the management of childhood primary testicular neoplasms. Klin Padiatr. 2011;223(3):131–137. [DOI] [PubMed] [Google Scholar]
- 15.Coursey Moreno C, Small WC, Camacho JC, et al. Testicular tumors: what radiologists need to know—differential diagnosis, staging, and management. Radiographics. 2015;35(2):400–415. [DOI] [PubMed] [Google Scholar]
- 16.Chang MY, Shin HJ, Kim HG, Kim MJ, Lee MJ. Prepubertal Testicular Teratomas and Epidermoid Cysts: Comparison of Clinical and Sonographic Features. J Ultrasound Med. 2015;34(10):1745–1751. [DOI] [PubMed] [Google Scholar]
- 17.Maizlin ZV, Belenky A, Baniel J, Gottlieb P, Sandbank J, Strauss S. Epidermoid cyst and teratoma of the testis: sonographic and histologic similarities. J Ultrasound Med. 2005;24(10):1403–1409; quiz 1410-1401. [DOI] [PubMed] [Google Scholar]
- 18.Patel AS, Coley BD, Jayanthi VR. Ultrasonography underestimates the volume of normal parenchyma in benign testicular masses. J Urol. 2007;178(4 Pt 2):1730–1732. [DOI] [PubMed] [Google Scholar]
- 19.Mohrs OK, Thoms H, Egner T, et al. MRI of Patients With Suspected Scrotal or Testicular Lesions: Diagnostic Value in Daily Practice. American Journal of Roentgenology. 2012;199(3):609–615. [DOI] [PubMed] [Google Scholar]
- 20.Tsili AC, Argyropoulou MI, Astrakas LG, et al. Dynamic contrast-enhanced subtraction MRI for characterizing intratesticular mass lesions. American Journal of Roentgenology. 2013;200(3):578–585. [DOI] [PubMed] [Google Scholar]
- 21.Tsili AC, Bertolotto M, Turgut AT, et al. MRI of the scrotum: Recommendations of the ESUR Scrotal and Penile Imaging Working Group. European radiology. 2018;28(1):31–43. [DOI] [PubMed] [Google Scholar]
- 22.Manfredi R, Mucelli RP. MRI of the Female and Male Pelvis. Springer International Publishing; 2014. [Google Scholar]
- 23.Cassidy FH, Ishioka KM, McMahon CJ, et al. MR imaging of scrotal tumors and pseudotumors. Radiographics. 2010;30(3):665–683. [DOI] [PubMed] [Google Scholar]
- 24.Lee EY, Liszewski MC, Gee MS, Daltro P, Restrepo R. Pediatric Body MRI: A Comprehensive, Multidisciplinary Guide. Springer International Publishing; 2020. [Google Scholar]
- 25.Tsili AC, Bertolotto M, Rocher L, et al. Sonographically indeterminate scrotal masses: how MRI helps in characterization. Diagnostic and Interventional Radiology. 2018;24(4):225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Pierorazio PM, Cheaib JG, Tema G, et al. Performance characteristics of clinical staging modalities for early stage testicular germ cell tumors: a systematic review. The Journal of urology. 2020;203(5):894–901. [DOI] [PubMed] [Google Scholar]
- 27.Ortiz AFH, Beaujon LJF, Villamizar SYG, Lopez FFF. Magnetic resonance versus computed tomography for the detection of retroperitoneal lymph node metastasis due to testicular cancer: A systematic literature review. Eur J Radiol Open. 2021;8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Laukka M, Mannisto S, Beule A, Kouri M, Blomqvist C. Comparison between CT and MRI in detection of metastasis of the retroperitoneum in testicular germ cell tumors: a prospective trial. Acta Oncol. 2020;59(6):660–665. [DOI] [PubMed] [Google Scholar]
- 29.Sohaib SA, Koh DM, Barbachano Y, et al. Prospective assessment of MRI for imaging retroperitoneal metastases from testicular germ cell tumours. Clin Radiol. 2009;64(4):362–367. [DOI] [PubMed] [Google Scholar]
- 30.Stephenson A, Eggener SE, Bass EB, et al. Diagnosis and Treatment of Early Stage Testicular Cancer: AUA Guideline. J Urol. 2019;202(2):272–281. [DOI] [PubMed] [Google Scholar]
- 31.Saltzman AF, Cost NG. Adolescent and Young Adult Testicular Germ Cell Tumors: Special Considerations. Adv Urol. 2018;2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.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):1310–1315. [DOI] [PubMed] [Google Scholar]
- 33.Daugaard G, Gundgaard MG, Mortensen MS, et al. Surveillance for stage I nonseminoma testicular cancer: outcomes and long-term follow-up in a population-based cohort. J Clin Oncol. 2014;32(34):3817–3823. [DOI] [PubMed] [Google Scholar]
- 34.Read G, Stenning SP, Cullen MH, et al. Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party. J Clin Oncol. 1992;10(11):1762–1768. [DOI] [PubMed] [Google Scholar]
- 35.Gaddam SJ, Chesnut GT. Testicle Cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC.; 2022. [Google Scholar]
- 36.gaddam SJ, Chesnut GT. Testicular Cancer. 2022; https://www.ncbi.nlm.nih.gov/books/NBK563159/, 2022. [Google Scholar]
- 37.Fosså SD, Chen J, Schonfeld SJ, et al. Risk of contralateral testicular cancer: A population-based study of 29 515 US men. Journal of the National Cancer Institute. 2005;97(14):1056–1066. [DOI] [PubMed] [Google Scholar]
- 38.Fordham M, Mason M, Blackmore C, Hendry W, Horwich A. Management of the contralateral testis in patients with testicular germ cell cancer. British journal of urology. 1990;65(3):290–293. [DOI] [PubMed] [Google Scholar]
- 39.Scandura G, Verrill C, Protheroe A, et al. Incidentally detected testicular lesions <10 mm in diameter: can orchidectomy be avoided? BJU Int. 2018;121(4):575–582. [DOI] [PubMed] [Google Scholar]
- 40.Sohaib SA, Koh DM, Husband JE. The role of imaging in the diagnosis, staging, and management of testicular cancer. American Journal of Roentgenology. 2008;191(2):387–395. [DOI] [PubMed] [Google Scholar]
- 41.Cost NG, Lubahn JD, Adibi M, et al. A comparison of pediatric, adolescent, and adult testicular germ cell malignancy. Pediatr Blood Cancer. 2014;61(3):446–451. [DOI] [PubMed] [Google Scholar]
- 42.Rescorla FJ, Ross JH, Billmire DF, et al. Surveillance after initial surgery for Stage I pediatric and adolescent boys with malignant testicular germ cell tumors: Report from the Children's Oncology Group. J Pediatr Surg. 2015;50(6):1000–1003. [DOI] [PubMed] [Google Scholar]
- 43.Thomas KL, Jeong D, Montilla-Soler J, Feuerlein S. The role of diagnostic imaging in the primary testicular cancer: initial staging, response assessment and surveillance. Transl Androl Urol. 2020;9(Suppl 1):S3–S13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Gilligan T, Lin DW, Aggarwal R, et al. Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw. 2019;17(12):1529–1554. [DOI] [PubMed] [Google Scholar]
- 45.Harvey ML, Geldart TR, Duell R, Mead GM, Tung K. Routine computerised tomographic scans of the thorax in surveillance of stage I testicular non-seminomatous germ-cell cancer--a necessary risk? Ann Oncol. 2002;13(2):237–242. [DOI] [PubMed] [Google Scholar]
- 46.Fernandez EB, Colon E, Mcleod DG, Moul JW, Sagalowsky AI, Pontes JE. Efficacy of Radiographic Chest Imaging in Patients with Testicular Cancer. Urology. 1994;44(2):243–249. [DOI] [PubMed] [Google Scholar]
- 47.Hung T-J, McLean L, Mitchell C, et al. The role of 18 F-FDG-PET/CT in evaluating retroperitoneal masses-Keeping your eye on the ball! Cancer Imaging. 2019;19(1):1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Cathomas R, Klingbiel D, Bernard B, et al. Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an International Global Germ Cell Cancer Group Registry. J Clin Oncol. 2018:JCO1800210. [DOI] [PubMed] [Google Scholar]
- 49.Hudolin T, Kastelan Z, Knezevic N, Goluza E, Tomas D, Coric M. Correlation Between Retroperitoneal Lymph Node Size and Presence of Metastases in Nonseminomatous Germ Cell Tumors. Int J Surg Pathol. 2012;20(1):15–18. [DOI] [PubMed] [Google Scholar]
- 50.Hale GR, Teplitsky S, Truong H, Gold SA, Bloom JB, Agarwal PK. Lymph node imaging in testicular cancer. Translational Andrology and Urology. 2018;7(5):864–874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Saltzman AF, Cost NG. Adolescent and Young Adult Testicular Germ Cell Tumors: Special Considerations. Adv Urol. 2018;2018:2375176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Elzinga-Tinke JE, Sirre ME, Looijenga LH, van Casteren N, Wildhagen MF, Dohle GR. The predictive value of testicular ultrasound abnormalities for carcinoma in situ of the testis in men at risk for testicular cancer. Int J Androl. 2010;33(4):597–603. [DOI] [PubMed] [Google Scholar]
- 53.Balawender K, Orkise S, Wisz P. Testicular microlithiasis: what urologists should know A review of the current literature. Cent Eur J Urol. 2018;71(3):310–314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Richenberg J, Belfield J, Ramchandani P, et al. Testicular microlithiasis imaging and follow-up: guidelines of the ESUR scrotal imaging subcommittee. European radiology. 2015;25(2):323–330. [DOI] [PubMed] [Google Scholar]
- 55.Stephenson A, Eggener SE, Bass EB, et al. Diagnosis and treatment of early stage testicular cancer: AUA guideline. The Journal of urology. 2019;202(2):272–281. [DOI] [PubMed] [Google Scholar]
- 56.Winter TC, Kim B, Lowrance WT, Middleton WD. Testicular microlithiasis: what should you recommend? American Journal of Roentgenology. 2016;206(6):1164–1169. [DOI] [PubMed] [Google Scholar]
- 57.Yu CJ, Lu JD, Zhao J, et al. Incidence characteristics of testicular microlithiasis and its association with risk of primary testicular tumors in children: a systematic review and meta-analysis. World J Pediatr. 2020;16(6):585–597. [DOI] [PubMed] [Google Scholar]
- 58.Trout AT, Chow J, McNamara ER, et al. Association between testicular microlithiasis and testicular neoplasia: large multicenter study in a pediatric population. Radiology. 2017;285(2):576–583. [DOI] [PubMed] [Google Scholar]
- 59.Cooper ML, Kaefer M, Fan R, Rink RC, Jennings SG, Karmazyn B. Testicular Microlithiasis in Children and Associated Testicular Cancer. Radiology. 2014;270(3):857–863. [DOI] [PubMed] [Google Scholar]
- 60.Canning DA. Re: Association between Testicular Microlithiasis and Testicular Neoplasia: Large Multicenter Study in a Pediatric Population. The Journal of urology. 2018;200(4):687–687. [DOI] [PubMed] [Google Scholar]
- 61.Chavhan GB, Caro-Dominguez P. Diffusion-weighted imaging in pediatric body magnetic resonance imaging. Pediatr Radiol. 2016;46(6):847–857. [DOI] [PubMed] [Google Scholar]
- 62.Fan CY, Min XD, Feng ZY, et al. Discrimination between benign and malignant testicular lesions using volumetric apparent diffusion coefficient histogram analysis. Eur J Radiol. 2020;126. [DOI] [PubMed] [Google Scholar]
- 63.Pressney I, Khoo M, Hargunani R, Saifuddin A. Description of the MRI and ultrasound imaging features of giant epidermal cysts. The British Journal of Radiology. 2020;93(1114):20200413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64.Tsili AC, Sofikitis N, Stiliara E, Argyropoulou MI. MRI of testicular malignancies. Abdominal Radiology. 2019;44(3):1070–1082. [DOI] [PubMed] [Google Scholar]
- 65.Zhang PP, Feng ZY, Cai W, et al. T2-Weighted Image-Based Radiomics Signature for Discriminating Between Seminomas and Nonseminoma. Front Oncol. 2019;9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 66.Lewin J, Dufort P, Halankar J, et al. Applying Radiomics to Predict Pathology of Postchemotherapy Retroperitoneal Nodal Masses in Germ Cell Tumors. Jco Clin Cancer Info. 2018;2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 67.Baessler B, Nestler T, Pinto Dos Santos D, et al. Radiomics allows for detection of benign and malignant histopathology in patients with metastatic testicular germ cell tumors prior to post-chemotherapy retroperitoneal lymph node dissection. Eur Radiol. 2020;30(4):2334–2345. [DOI] [PubMed] [Google Scholar]
- 68.Feliciani G, Mellini L, Carnevale A, et al. The potential role of MR based radiomic biomarkers in the characterization of focal testicular lesions. Sci Rep-Uk. 2021;11(1). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 69.Wakileh GA, Ruf C, Heidenreich A, et al. Contemporary options and future perspectives: three examples highlighting the challenges in testicular cancer imaging. World J Urol. 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70.Feliciani G, Mellini L, Carnevale A, et al. The potential role of MR based radiomic biomarkers in the characterization of focal testicular lesions. Sci Rep. 2021;11(1):3456. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 71.Richie JP. Re: Radiomics Allows for Detection of Benign and Malignant Histopathology in Patients with Metastatic Testicular Germ Cell Tumors prior to Post-Chemotherapy Retroperitoneal Lymph Node Dissection. J Urol. 2020;204(3):621. [DOI] [PubMed] [Google Scholar]
- 72.Zhang P, Feng Z, Cai W, et al. T2-Weighted Image-Based Radiomics Signature for Discriminating Between Seminomas and Nonseminoma. Front Oncol. 2019;9:1330. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 73.Lewin J, Dufort P, Halankar J, et al. Applying Radiomics to Predict Pathology of Postchemotherapy Retroperitoneal Nodal Masses in Germ Cell Tumors. JCO Clin Cancer Inform. 2018;2:1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]