# Detection of germ cell neoplasia in situ and testicular cancer risk in men with testicular microlithiasis: Real world results through 10 years

## TL;DR

This study finds that testicular microlithiasis alone doesn't increase cancer risk, but when combined with small testicle size, it may indicate hidden cancer.

## Contribution

The study provides real-world evidence on the cancer risk associated with testicular microlithiasis and clarifies biopsy guidelines.

## Key findings

- Germ cell neoplasia in situ was found in 7.3% of biopsied men with testicular microlithiasis and risk factors.
- Testicular cancer developed in 0.9% of men over a median follow-up of 4.7 years.
- Microlithiasis alone does not increase cancer risk in otherwise normal testicles.

## Abstract

Guidelines recommend biopsies for men <50 years with testicular microlithiasis and cancer risk factors to rule out germ cell neoplasia in situ. Limited data support this practice.

To clarify the significance of testicular microlithiasis by examining pathological findings in men with testicular microlithiasis.

We reviewed charts of men diagnosed with testicular microlithiasis at a tertiary referral center from 2013 to 2023. Patient characteristics, clinical findings, and cancer risk factors including testicular hypotrophy (volume ≤12 mL), infertility, and cryptorchidism were recorded. Men with unknown fertility were offered semen analyses. Histological findings from testicular biopsies and subsequent cancers were noted. Primary endpoints were rates of germ cell neoplasia in situ and testicular cancer diagnoses.

We included 334 men (median age 33 years, range 16–73 years): 27 had testicular hypotrophy, 18 infertility, 25 cryptorchidism, and 56 multiple risk factors. The remaining 208 men had no apparent risk factors. Of these 36 were had reduced semen quality. Overall, 137 of 334 men (41%) underwent biopsies, with germ cell neoplasia in situ in 10 cases (7.3%, 95% confidence interval 3.6%–13%). Four had multiple risk factors (hypotrophy and infertility in two; hypotrophy, infertility, and cryptorchidism in two), three had hypotrophy alone, one had infertility, and two had reduced semen quality. Germ cell neoplasia in situ was unilateral in all cases and only found in testicles with testicular microlithiasis. Unilateral orchiectomy was performed in all germ cell neoplasia in situ cases, with hypotrophy found in all but one. Over a median follow‐up of 4.7 years (range 1.16–11.49 years), testicular cancer developed in three men (0.9%, 95% confidence interval 0.19%–2.6%).

Germ cell neoplasia in situ was only detected in cases with both testicular microlithiasis and testicular hypotrophy, and the rate of subsequent cancer development was low. This suggests that testicular microlithiasis alone does not increase cancer risk in otherwise morphologically normal testicles.

Biopsies should only be considered in men with incidental testicular microlithiasis if the testicular size is reduced.