What is the differential diagnosis for an adult male with no prior medical history presenting with scrotal tenderness and enlargement?

Differential Diagnosis for Scrotal Tenderness and Enlargement

The differential diagnosis for an adult male presenting with scrotal tenderness and enlargement includes epididymitis/epididymo-orchitis (most common in adults), testicular torsion (surgical emergency), inguinal hernia, hydrocele, varicocele, segmental testicular infarction, and testicular malignancy. 1

Age-Stratified Primary Considerations

Adults (Most Likely Diagnoses)

• Epididymitis/epididymo-orchitis is overwhelmingly the most common cause of testicular pain in adults, representing approximately 600,000 cases annually in the United States 1
• Characterized by gradual onset of pain, enlarged epididymis with increased blood flow on Doppler ultrasound, and scrotal wall thickening 1
• May have abnormal urinalysis, though normal urinalysis does not exclude epididymitis 1

Critical Emergency: Testicular Torsion

• Testicular torsion is rare in patients over 35 years of age but remains a surgical emergency that must be excluded in any patient with acute scrotal pain 1
• Characterized by abrupt onset of severe scrotal pain, negative Prehn sign (pain not relieved with testicular elevation), and nausea/vomiting 1, 2
• Surgical exploration and detorsion must be performed within 6-8 hours of symptom onset to prevent permanent ischemic damage, with salvage rates exceeding 90% when surgery occurs within 6 hours 1, 3
• Normal urinalysis does not exclude testicular torsion 1

Complete Differential Diagnosis List

Infectious/Inflammatory

• Epididymitis/epididymo-orchitis: Gradual pain onset, increased vascularity on Doppler, warmth and tenderness present, up to 20% concomitant orchitis rate 1, 2
• Caused by Neisseria gonorrhoeae, Chlamydia trachomatis, or enteric bacteria in adults 3

Vascular/Ischemic

• Testicular torsion: Abrupt severe pain, decreased or absent blood flow on Doppler, "whirlpool sign" of twisted spermatic cord with 96% sensitivity 1
• Intermittent testicular torsion: Presents with intermittent pain and swelling during torsion episodes, testis may detorse spontaneously creating intermittent presentation 4
• Segmental testicular infarction: Classic wedge-shaped avascular area on ultrasound, may also present as round lesions with variable Doppler flow, median age 37-38 years 1

Structural/Anatomic

• Inguinal hernia: Intermittent lump that appears and disappears with position changes or Valsalva maneuver, palpated separate from the testicle 4, 5
• Hydrocele: Painless scrotal swelling, absence of warmth, erythema, or tenderness effectively rules out inflammatory causes 2
• Varicocele: Dilated veins in scrotum, more prominent when standing and less noticeable when lying down 4
• Spermatocele: Benign cystic mass, most patients require no treatment 3

Neoplastic

• Testicular malignancy: Causes pain in 15% of cases, typically presents as painless mass, any intratesticular mass on ultrasound requires timely urology referral 1, 5
• Patients with history of inguinal hernia have increased risk (RR 1.37) 4

Rare Conditions

• Acute idiopathic scrotal edema: Rare, self-limiting condition, usually painless or minimally painful with marked scrotal wall thickening, diagnosis of exclusion 1
• Torsion of testicular appendage: Most common in prepubertal boys, "blue dot sign" pathognomonic but only seen in 21% of cases 1
• Fournier gangrene: Life-threatening necrotizing fasciitis requiring emergent surgical debridement 6

Diagnostic Algorithm

Step 1: Immediate Clinical Assessment

• Determine timing and onset of pain: Abrupt onset suggests torsion, gradual onset suggests epididymitis 1
• Assess for surgical emergency signs: Sudden severe pain, nausea/vomiting, high testicular position, abnormal cremasteric reflex all suggest torsion 1, 5
• Perform urinalysis: Always perform, but remember normal urinalysis does not exclude torsion or epididymitis 1

Step 2: Risk Stratification

• High clinical suspicion for torsion (TWIST score 6-7 or clinical judgment): Proceed directly to immediate urological consultation and surgical exploration without delay for imaging 1, 4
• Intermediate suspicion (TWIST score 1-5): Urgent Duplex Doppler ultrasound of scrotum 1
• Low suspicion with gradual onset and inflammatory signs: Ultrasound can be performed but treat empirically for epididymitis while awaiting results 1

Step 3: Imaging Protocol (When Indicated)

Duplex Doppler ultrasound is the first-line imaging modality with sensitivity 69-96.8% and specificity 87-100% for testicular torsion 1

Ultrasound examination must include:

• Grayscale examination to assess testicular homogeneity and identify "whirlpool sign" of twisted spermatic cord (96% sensitivity) 1, 4
• Color Doppler assessment of testicular perfusion with sensitivity 96-100% 1
• Power Doppler particularly useful for prepubertal testes with slow flow 1
• Spectral Doppler analysis of upper, mid, and lower poles of each testicle 1
• Always use contralateral asymptomatic testicle as internal control 1

Step 4: Diagnosis-Specific Ultrasound Findings

Testicular Torsion:

• Decreased or absent blood flow to affected testicle 1
• "Whirlpool sign" of twisted spermatic cord (most specific sign) 1
• Enlarged heterogeneous testis appearing hypoechoic 1
• Ipsilateral hydrocele and scrotal skin thickening 1

Epididymitis/Epididymo-orchitis:

• Enlarged epididymis with increased blood flow on color Doppler (sensitivity near 100%) 1, 2
• Scrotal wall thickening and hydrocele 1
• Inflammatory signs including warmth and tenderness 2

Testicular Malignancy:

• Intratesticular mass on ultrasound mandates immediate urologic referral for radical inguinal orchiectomy 4
• Obtain tumor markers (AFP, β-HCG, LDH) before any intervention 4

Critical Clinical Pitfalls to Avoid

• False-negative Doppler evaluations occur in 30% or more of cases, particularly with partial torsion, spontaneous detorsion, or early presentation within first few hours 1
• Never rely on Prehn sign alone to differentiate epididymitis from torsion, as it has poor sensitivity and specificity 4
• Significant overlap exists in clinical presentation between different causes of acute scrotal pain, making diagnosis challenging 1
• When clinical suspicion for torsion remains high despite normal Doppler, immediate urological consultation and surgical exploration should proceed 1
• Never perform scrotal biopsy or scrotal incision for suspected malignancy—only inguinal orchiectomy is appropriate 4
• Complete torsion >450 degrees results in absent arterial and venous flow, but partial torsion can present with diminished arterial velocity and decreased diastolic flow, making diagnosis more challenging 1
• False-positive Doppler evaluations can occur in infants and young boys who often have normally reduced intratesticular blood flow 1

Management Based on Diagnosis

Testicular Torsion (Confirmed or High Suspicion)

• Immediate urological consultation and urgent surgical exploration within 6-8 hours 1, 3
• Do not delay surgery for imaging if clinical suspicion is high 4
• Bilateral orchiopexy required during surgery to prevent contralateral torsion (Bell clapper deformity found in 82% of intermittent torsion cases) 1

Epididymitis/Epididymo-orchitis

• Antibiotics appropriate for age and risk factors (cover N. gonorrhoeae, C. trachomatis, or enteric bacteria) 3
• Bed rest, scrotal elevation, and analgesics until inflammation subsides 1, 3

Intratesticular Mass

• Immediate urologic referral for radical inguinal orchiectomy 4
• Obtain tumor markers (AFP, β-HCG, LDH) before intervention 4
• Discuss sperm banking before therapeutic intervention in reproductive-age men 4

Inguinal Hernia

• Emergent surgery indicated for strangulated hernia 5
• Non-emergent surgical referral for reducible hernias 5

Benign Masses (Hydrocele, Varicocele, Spermatocele)

• Most require no treatment 3
• Varicoceles associated with documented infertility or scrotal pain should be referred to urology subspecialist for consideration of surgical management 3