When is a testicular biopsy recommended for a male patient of reproductive age with a history of infertility or suspected testicular cancer?

Testicular Biopsy Indications in Reproductive-Age Males

Testicular biopsy is strongly recommended for contralateral testis evaluation in men with testicular cancer who have high-risk features (testicular volume <12 ml and age <40 years), as this population carries a ≥34% risk of testicular intraepithelial neoplasia (TIN), which progresses to invasive cancer in 70% of cases within 7 years if untreated. 1

Primary Indication: Detection of TIN in Testicular Cancer Patients

High-Risk Patients Requiring Contralateral Biopsy

The biopsy should be offered and strongly discussed with patients who meet these criteria:

• Testicular volume <12 ml AND age <40 years: This combination confers a ≥34% risk of contralateral TIN 1
• History of cryptorchidism with testicular atrophy: Substantially elevates cancer risk independent of current presentation 1, 2
• Extragonadal germ cell tumors BEFORE chemotherapy: Approximately 33% harbor TIN in one or both testes 1

Timing and Technical Requirements

Perform the contralateral biopsy at the time of orchiectomy to avoid a second surgical procedure 1, 2. This is the most practical and cost-effective approach.

Critical technical point: The tissue must be preserved in Stieve's or Bouin's solution—NOT formalin—as formalin fixation prevents accurate TIN detection 1, 2. This is a common pitfall that renders the biopsy useless for TIN diagnosis.

Use open incisional biopsy rather than needle techniques (14-gauge Tru-Cut or fine-needle aspiration), as open biopsy allows proper tissue handling and has 99% sensitivity for TIN detection 1, 2.

Post-Chemotherapy Considerations

Wait at least 2 years after chemotherapy completion before performing testicular biopsy, as chemotherapy eradicates TIN in two-thirds of patients 1, 2. Earlier biopsy (at 6 months as suggested in older guidelines) is no longer recommended based on more recent evidence showing delayed TIN clearance 1.

For extragonadal germ cell tumors, the risk of TIN drops from 33% pre-chemotherapy to approximately 10% post-chemotherapy 1, making routine bilateral biopsy unnecessary after treatment.

Secondary Indication: Infertility Evaluation

When Biopsy is NOT Indicated for Infertility

Diagnostic testicular biopsy for unexplained infertility is no longer recommended in the modern era 3. The indications have been dramatically narrowed with the advent of intracytoplasmic sperm injection (ICSI).

The only remaining diagnostic indication is confirmation of obstructive azoospermia in men with normal testicular size and normal reproductive hormones 3. Even this is often unnecessary if clinical context clearly indicates obstruction.

When Biopsy IS Indicated for Infertility: Therapeutic Sperm Retrieval

Testicular biopsy is now primarily therapeutic rather than diagnostic in infertility management 3, 4:

• Non-obstructive azoospermia: Open testicular biopsy or microsurgical testicular sperm extraction (micro-TESE) for sperm retrieval to be used with ICSI 3, 4
• Obstructive azoospermia: Testicular sperm extraction when reconstruction is not feasible or has failed 4

Open testicular biopsy is more reliable than percutaneous needle techniques for obtaining adequate testicular tissue, particularly in non-obstructive azoospermia where sperm may be focally distributed 4.

Critical Caveat: Incidental Cancer Detection in Infertility Workup

Men with infertility have an elevated risk of testicular cancer, and this risk is further amplified by specific features 3, 5:

• History of cryptorchidism: Dramatically increases both infertility and cancer risk 3
• Testicular atrophy (volume <12 ml): Associated with both impaired spermatogenesis and increased TIN risk 1, 2, 6
• Ultrasonographic abnormalities: Testicular microlithiasis, inhomogeneous parenchyma, or focal lesions increase CIS risk 3

If testicular biopsy is performed for infertility in a man with these risk factors, immunohistochemistry for TIN detection is mandatory 3. Standard hematoxylin and eosin staining alone is insufficient.

Contraindications and Pitfalls

Absolute Contraindications

Never perform scrotal violation (including trucut biopsy) for suspected testicular malignancy as the primary diagnostic approach 7. Radical inguinal orchiectomy with early spermatic cord control at the internal inguinal ring is mandatory to prevent tumor spread 2, 7.

Trucut biopsy may only be considered in highly selected cases:

• Retroperitoneal/mediastinal primary tumors requiring tissue diagnosis before treatment 7
• Small indeterminate lesions in a solitary testis with negative tumor markers 7

Safety Profile and Complications

Contralateral testicular biopsy carries a low complication rate when performed correctly 8:

• Overall complication rate: 2.78% (95% CI: 2.05-3.60%) 8
• Major complications requiring repeat surgery: 0.64% 8
• Testicular loss: extremely rare (1 in 1,874 patients in a large prospective study) 8

Imaging studies show transient abnormalities in 33-45% of patients one week post-biopsy (focal hematoma, edema, or vascular injury), but 96% resolve completely by serial follow-up 8. These are clinically insignificant if vascular anatomy is respected during surgery.

Patient Counseling Algorithm

For Testicular Cancer Patients

Discuss the following with high-risk patients (volume <12 ml, age <40 years, or cryptorchidism history):

1. Risk quantification: 34% chance of harboring TIN in the contralateral testis; 70% of untreated TIN progresses to invasive cancer within 7 years 1
2. Treatment implications: If TIN is detected, definitive treatment (radiotherapy 20 Gy) destroys fertility but prevents cancer 1
3. Surveillance alternative: Acceptable option with regular ultrasound monitoring if fertility preservation is paramount, accepting delayed cancer detection risk 1, 2
4. Fertility status: Baseline fertility is often already compromised in this population independent of biopsy 2

Offer sperm banking before any testicular intervention, ideally before orchiectomy 7.

For Infertility Patients

Testicular biopsy for diagnostic purposes is obsolete except to confirm obstructive azoospermia 3.

For therapeutic sperm retrieval in azoospermia:

• Open biopsy or micro-TESE is the standard approach 3, 4
• If risk factors for TIN are present (cryptorchidism, atrophy, ultrasonographic abnormalities), ensure immunohistochemistry is performed on the specimen 3

Summary Algorithm

Step 1: Identify the clinical scenario

• Testicular cancer patient → Assess for high-risk TIN features
• Infertility patient → Determine if therapeutic sperm retrieval is needed

Step 2: For testicular cancer patients, stratify TIN risk

• High risk (biopsy strongly recommended): Volume <12 ml AND age <40 years, OR cryptorchidism history, OR extragonadal GCT pre-chemotherapy 1
• Lower risk: May offer biopsy but not mandatory; surveillance is acceptable 1

Step 3: Timing considerations

• Perform at time of orchiectomy if indicated 1, 2
• Wait ≥2 years post-chemotherapy if considering post-treatment biopsy 1, 2

Step 4: Technical execution

• Open incisional biopsy via inguinal approach with early cord control 2, 7
• Preserve in Stieve's or Bouin's solution (never formalin) 1, 2
• Ensure immunohistochemistry capability if infertility patient with cancer risk factors 3