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  • Review Article
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Diagnosis and management of indeterminate testicular lesions

Nature Reviews Urology volume 21, pages 7–21 (2024)Cite this article

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Abstract

The sophistication and accessibility of modern-day imaging result in frequent detection of small or equivocal lesions of the testes. Traditionally, diagnosis of a testicular lesion with any possibility of malignancy would usually prompt radical orchidectomy. However, awareness is growing that a substantial proportion of these lesions might be benign and that universal application of radical orchidectomy risks frequent overtreatment. Given the potentially profound effects of radical orchidectomy on fertility, endocrine function and psychosexual well-being, particularly in scenarios of an abnormal contralateral testis or bilateral lesions, organ-preserving strategies for equivocal lesions should be considered. Image-based active surveillance can be applied for indeterminate lesions measuring ≤15 mm with a low conversion rate to surgical treatment. However, these outcomes are early and from relatively small, selected cohorts, and concerns prevail regarding the metastatic potential of even small undiagnosed germ cell tumours. No consensus exists on optimal surveillance (short interval (<3 months) ultrasonography is generally adopted); histological sampling is a widespread alternative, involving inguinal delivery of the testis and excisional biopsy of the lesion, with preoperative marking or intraoperative ultrasonographic localization when necessary. Frozen section analysis in this context demonstrates excellent diagnostic accuracy. Histological results support that approximately two-thirds of marker-negative indeterminate solitary testicular lesions measuring ≤25 mm overall are benign. In summary, modern imaging detects many small indeterminate testicular lesions, of which the majority are benign. Awareness is growing of surveillance and organ-sparing diagnostic and treatment strategies with the aim of minimizing rates of overtreatment with radical orchidectomy.

Key points

  • Current data suggest that approximately two-thirds of solitary, clinically indeterminate lesions of the testes measuring ≤25 mm are benign.

  • Urologists are beginning to challenge the traditional approach of recommending radical orchidectomy to men with equivocal lesions.

  • Alternative options to radical orchidectomy include active radiological surveillance (limited outcome data currently available) and excisional biopsy of the lesion to confirm the histopathological diagnosis.

  • Excisional biopsy is performed via inguinal delivery of the testis, with localization assisted by preoperative needle marking or intraoperative ultrasonography, with or without clamping of the spermatic cord.

  • Excisional biopsy is generally complemented by on-table frozen section analysis, which facilitates proceeding to radical orchidectomy in patients who have appropriately consented, if a germ cell tumour is identified.

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Fig. 1: Ultrasonographic images of a 4 mm solid hypoechoic lesion in the lower pole of the left testis.
Fig. 2: Potential approaches to the diagnosis and management of indeterminate lesions of the testes.
Fig. 3: A potential management algorithm for small indeterminate lesions of the testes.

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Authors and Affiliations

  1. Department of Surgery, Royal College of Surgeons, Dublin, Ireland

    Stefanie M. Croghan, Jamil W. Malak & Niall F. Davis

  2. Department of Urology, Blackrock Clinic, Dublin, Ireland

    Stefanie M. Croghan, Jamil W. Malak & Niall F. Davis

  3. Department of Radiology, Beaumont Hospital, Dublin, Ireland

    Pat Rohan & Andrew McGrath

  4. Department of Radiology, Mater Hospital, Dublin, Ireland

    Caoimhe Byrne

  5. Department of Urology & Andrology, Beaumont Hospital, Dublin, Ireland

    Ivor M. Cullen & Niall F. Davis

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Contributions

S.M.C., J.W.M. and P.R. researched data for the article. S.M.C., A.McG., I.M.C. and N.F.D. contributed substantially to discussion of the content. S.M.C. wrote the article. S.M.C., P.R., C.B., A.McG. I.M.C. and N.F.D. reviewed and/or edited the manuscript before submission.

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Correspondence to Stefanie M. Croghan.

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Nature Reviews Urology thanks Dean Huangand the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Review criteria

A search of MEDLINE, Scopus and Cochrane databases was performed for full-text, English-language articles published during the period 1990–2022. The search strategy included search terms: (“Indeterminate” OR “uncertain” OR “equivocal” OR “incidental” OR “small” OR “suspected” OR “suspicious”) AND (“testis” (MeSH term) OR “testicular”) AND (“lesion” OR “mass” OR “neoplasm” OR “abnormality”). Titles and abstracts of potentially eligible publications were screened, and full texts of potentially relevant articles were retrieved. A reference trawl of included articles was also performed. Studies reporting upon the diagnostic evaluation and/or surveillance of indeterminate lesions of the testes were considered eligible for inclusion. Randomized trials and observational studies, including non-comparative case series, were included. Review articles, conference abstracts and case reports were excluded. Lesions radiologically measuring ≤25 mm in maximum dimension and considered indeterminate were included. Lesions were considered indeterminate if reported as such by the study authors for any reason, including small size making characterization difficult or demonstration of radiological features atypical of malignancy. Both lesions existing in isolation and those discovered in the presence of additional equivocal or suspicious abnormalities were included. The size threshold of ≤25 mm was decided upon following a scoping review of the literature, which identified an upper size limit of 21–25 mm in a number of high-quality studies16,17,18,19,20,21,22,23. Studies reporting on lesions existing in the presence of known metastases, with clinical presumption of a diagnosis of germ cell tumour or with a definitive benign nature were excluded. Studies including lesions measuring >25 mm in one plane were excluded, except where it was possible to extrapolate complete data on individual lesions meeting the inclusion criteria. A quality assessment of each included study was conducted by two reviewers, with the Newcastle Ottawa Scale (NOS) for non-randomized studies applied. Relevant variables were retrieved from all studies, using template-based data extraction. Data were compiled with the results synthesized and presented in narrative format in this Review.

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Croghan, S.M., Malak, J.W., Rohan, P. et al. Diagnosis and management of indeterminate testicular lesions. Nat Rev Urol 21, 7–21 (2024). https://doi.org/10.1038/s41585-023-00786-3

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