What is the differential diagnosis (ddx) for a patient with testicular swelling and pain, previously treated for epididymitis (inflammation of the epididymis), with an unremarkable scrotal ultrasound (US)?

Differential Diagnosis for Testicular Pain with Failed Epididymitis Treatment and Normal Ultrasound

In a patient with persistent testicular swelling and pain despite epididymitis treatment and an unremarkable scrotal ultrasound, you must urgently reconsider testicular torsion (particularly intermittent or partial torsion), testicular malignancy, segmental testicular infarction, or chronic/complicated epididymitis with venous infarction. 1, 2

Critical Immediate Considerations

Testicular Torsion (Including Intermittent/Partial Torsion)

• False-negative Doppler ultrasound occurs in 30% or more of cases, particularly with partial torsion or spontaneous detorsion, making this diagnosis possible even with "unremarkable" imaging 2
• Partial torsion (<450 degrees) can show preserved arterial flow because venous obstruction occurs first, potentially appearing normal or near-normal on Doppler 2
• Intermittent torsion presents with recurrent episodes of testicular pain that may spontaneously resolve, and the Bell-clapper deformity is found in 82% of these patients 2
• If clinical suspicion remains high despite normal ultrasound, immediate urological consultation and surgical exploration should proceed without delay, as testicular viability is compromised after 6-8 hours 2

Testicular Malignancy

• A painless solid testicular mass is pathognomonic for testicular tumor, but patients more commonly present with testicular discomfort or swelling suggestive of epididymitis or orchitis 1
• Persistent tenderness, swelling, or any palpable abnormality after failed antibiotic treatment warrants further evaluation for malignancy 1
• Germ cell tumors constitute approximately 95% of all testicular tumors and can present with pain in up to 30% of cases 3
• Obtain serum tumor markers (AFP, β-HCG, LDH) immediately, as these are critical for diagnosis and staging 1
• The differential diagnosis for failed epididymitis treatment explicitly includes tumor 1

Secondary Diagnostic Considerations

Complicated Epididymitis with Testicular Infarction

• Global testicular infarction is an exceedingly rare but devastating complication of epididymoorchitis, caused by mixed arterial and venous insufficiency 4
• Severe epididymitis can progress to venous outflow obstruction, causing absent or reversed diastolic flow and potentially complete infarction 2
• Ultrasound may show testicular hypovascularity with hypoechoic changes of the testicular parenchyma, though this can be missed on initial imaging 4

Segmental Testicular Infarction

• Presents as a wedge-shaped avascular area on ultrasound, though it may also appear as round lesions with variable Doppler flow 2
• Can mimic tumor or other pathology and may not be evident on initial "unremarkable" ultrasound 2
• Median age of presentation is 37-38 years 2

Other Considerations

• Tuberculous or fungal epididymitis should be considered when swelling and tenderness persist after completion of standard antimicrobial therapy 1
• Abscess formation can complicate epididymitis and may require drainage 1
• Acute idiopathic scrotal edema is a rare, self-limiting condition with marked scrotal wall thickening, though typically painless or minimally painful 2

Diagnostic Algorithm for This Clinical Scenario

Immediate Actions

• Obtain serum tumor markers (AFP, β-HCG, LDH) immediately to evaluate for testicular malignancy 1
• Perform careful repeat physical examination looking for any palpable testicular mass or asymmetry 1
• Review the original ultrasound images with a radiologist to ensure adequate technique and complete evaluation 2

Repeat Imaging Protocol

• Order repeat Duplex Doppler ultrasound with specific attention to:
  • Power Doppler assessment (more sensitive for low-flow states) 2
  • Spectral Doppler analysis of upper, mid, and lower poles of each testicle 2
  • Grayscale assessment for the "whirlpool sign" of twisted spermatic cord 2
  • Comparison to contralateral testis as internal control 2
  • Assessment for segmental infarction or focal lesions 2

If Repeat Ultrasound Remains Unremarkable

• Consider MRI of the scrotum, which can identify the Bell-clapper deformity with 83% sensitivity and show T2 hyperintense changes consistent with infarction 2, 4
• MRI with contrast can demonstrate lack of testicular enhancement consistent with global infarction 4

Urgent Urological Consultation Indications

• Any clinical suspicion for testicular torsion despite normal imaging 2
• Elevated tumor markers 1
• Palpable testicular mass or persistent abnormality 1
• Failure to improve within 3 days of appropriate antimicrobial therapy 1

Common Pitfalls to Avoid

• Never rely solely on ultrasound to exclude testicular torsion - clinical judgment supersedes imaging, and false-negative rates are substantial 2, 5
• Real-time scrotal sonography can be misleading in subacute testicular torsion, showing inhomogeneous testicle with hypoechoic and hyperechoic areas that mimic tumor or epididymitis 5
• An "unremarkable" ultrasound does not exclude significant pathology - ultrasound sensitivity for torsion ranges from only 69-96.8% 2
• Do not give repeated courses of antibiotics without comprehensive reevaluation - this delays diagnosis of surgical emergencies and malignancy 1
• Significant overlap exists in clinical presentation between different causes of acute scrotal pain, making diagnosis challenging even with imaging 2

Treatment Based on Final Diagnosis

If Torsion Confirmed or Highly Suspected

• Immediate surgical exploration and detorsion within 6-8 hours of symptom onset 2
• Bilateral orchiopexy to prevent contralateral torsion 2

If Malignancy Suspected

• Inguinal orchiectomy is the primary treatment for suspicious testicular mass 1
• Discuss sperm banking before any therapeutic intervention 1

If Complicated Epididymitis

• Consider broader antimicrobial coverage, drainage of abscess if present, and supportive care with bed rest, scrotal elevation, and analgesics 1