What does a bilateral testicular fine‑needle aspiration showing moderately cellular material with Sertoli cells and occasional Leydig cells indicate, and what is the appropriate management?

Bilateral Testicular FNAC Showing Sertoli Cells with Occasional Leydig Cells: Interpretation and Management

This cytology pattern most likely indicates Sertoli cell-only syndrome (SCOS), which represents non-obstructive azoospermia with absent spermatogenesis and carries a poor prognosis for fertility.

Cytologic Interpretation

The finding of predominantly Sertoli cells with only occasional Leydig cells on bilateral testicular fine-needle aspiration is characteristic of Sertoli cell-only syndrome. In normal spermatogenesis, you would expect to see all stages of spermatogenic cells (spermatogonia, spermatocytes, spermatids, and spermatozoa) along with Sertoli cells 1, 2. The absence of germ cells and predominance of Sertoli cells defines SCOS 3, 4.

Key Cytologic Features to Confirm:

• Absence of spermatogenic cells at all stages (no spermatogonia, spermatocytes, spermatids, or spermatozoa)
• Predominance of Sertoli cells with their characteristic oval nuclei and prominent nucleoli
• Occasional Leydig cells (though these are typically uncommon in FNAC unless there is Leydig cell hyperplasia) 2
• Adequate cellularity to ensure the sample is representative 1

Important Caveat About Leydig Cells:

The presence of "occasional" Leydig cells is actually expected. In SCOS, there may appear to be relative Leydig cell hyperplasia histologically, but this is due to loss of virtually all Sertoli cells and germ cells from the tubules, making the interstitial Leydig cells more prominent by comparison rather than true hyperplasia 5. However, Leydig cells are generally uncommon in FNAC specimens unless true hyperplasia exists 2.

Differential Considerations

Before finalizing the diagnosis, consider:

1. Adequacy of sampling: FNAC can miss focal areas of spermatogenesis. Bilateral sampling with multiple aspirations provides better mapping 1. If only scanty material was obtained, the diagnosis may be inaccurate 3.

2. Maturation arrest: Would show spermatogenic cells up to a certain stage (e.g., spermatocytes present but no spermatids/spermatozoa). Your case lacks all germ cells, ruling this out 1, 2.

3. Severe hypospermatogenesis: Would still show some germ cells, just markedly reduced. Complete absence points to SCOS 4, 6.

4. Unilateral vs bilateral disease: In 4-11% of cases, findings differ between testes 1, 6. Ensure both testes were adequately sampled.

Clinical Correlation Required

Hormonal Profile:

• Expect elevated FSH (follicle-stimulating hormone) due to absence of germ cells and reduced inhibin B from Sertoli cells
• Testosterone levels may be normal or low-normal, but elevated LH is common (>80% of cases with primary testicular failure) indicating compensated hypogonadism 5
• Check if patient has Klinefelter syndrome (47,XXY), which commonly presents with SCOS pattern and small testes (<6 mL) 5

Physical Examination:

• Testicular volume: Typically small (<12 mL) in SCOS
• Rule out cryptorchidism history (associated with increased risk of germ cell neoplasia) 7
• Assess for testicular microlithiasis on ultrasound, which may warrant biopsy for intratubular germ cell neoplasia 7

Management Algorithm

1. Confirm Non-Obstructive Azoospermia

• Verify semen analysis shows azoospermia (not severe oligospermia)
• Rule out obstructive causes clinically (normal vas deferens, no history of infections/surgeries)

2. Fertility Counseling

• SCOS has very poor prognosis for sperm retrieval. Success rates with testicular sperm extraction (TESE) are low compared to other patterns 1
• If fertility is desired, consider micro-TESE (microsurgical testicular sperm extraction) as it may identify rare focal areas of spermatogenesis missed by FNAC
• Sperm cryopreservation is not applicable here as no sperm are present 7

3. Screen for Associated Conditions

• Klinefelter syndrome karyotyping (47,XXY) if clinical features suggest it (gynecomastia, tall stature, small firm testes) 5
• If Klinefelter confirmed, screen for:
  • Extragonadal germ cell tumors (especially mediastinal) - low threshold for chest imaging 5
  • Thyroid nodules (higher prevalence) 5
  • Metabolic/cardiovascular risk (increased in KS) 5

4. Rule Out Malignancy Risk

• If patient has risk factors (cryptorchidism history, testicular atrophy, infertility with testicular microlithiasis), consider testicular biopsy to exclude intratubular germ cell neoplasia 7
• Do NOT perform routine biopsy for isolated SCOS without additional risk factors 7

5. Testosterone Replacement

• If biochemical hypogonadism is confirmed (low testosterone with elevated LH), initiate testosterone replacement therapy
• This is particularly important in Klinefelter syndrome patients 5

Common Pitfalls to Avoid

1. Assuming FNAC is 100% accurate: FNAC has 97% correlation with histology, but inadequate sampling can miss focal spermatogenesis 3. If fertility is critical, consider open biopsy or micro-TESE.

2. Missing Klinefelter syndrome: Always check karyotype in young men with small testes and SCOS pattern, as this has major implications for cancer screening and hormonal management 5.

3. Overlooking malignancy risk: In patients with cryptorchidism corrected in adulthood, simultaneous biopsy for intratubular germ cell neoplasia is strongly recommended 7.

4. False reassurance about Leydig cells: The presence of occasional Leydig cells does NOT indicate normal testicular function - it's expected in SCOS due to relative prominence after tubular atrophy 5, 2.