In a 37-year-old male with firm, marble-sized soft-tissue nodules on the plantar aspect of the foot, what is the likely diagnosis and how should it be managed?

Plantar Fibromatosis (Ledderhose Disease)

These are most likely plantar fibromatosis nodules (Ledderhose disease), and the initial management should be active surveillance with conservative measures—surgery should be avoided unless symptoms become severely limiting despite exhaustive non-operative treatment.

Diagnosis

The clinical presentation of firm, marble-sized nodules on the plantar aspect of the foot in a 37-year-old male is characteristic of plantar fibromatosis. This is a benign fibroproliferative disorder affecting the plantar fascia, part of the spectrum of desmoid-type fibromatoses 1, 2, 3.

Key diagnostic steps:

• Ultrasound confirmation: This is the primary imaging modality, showing hypoechoic nodules within the plantar fascia 1, 2
• Core needle biopsy if uncertain: Use 14G or 16G needles for histopathologic confirmation if diagnosis is equivocal 4
• Screen for associated conditions: Check for diabetes mellitus, liver disease, epilepsy, alcohol use, and consider screening for Dupuytren's contracture (hands) or Peyronie's disease (penis) 3, 5
• Consider genetic testing: If CTNNB1 mutation is absent on biopsy, screen for familial adenomatous polyposis (FAP) with colonoscopy, as this is critical not to miss 6

Management Algorithm

First-Line: Active Surveillance (Mandatory Initial Approach)

The most recent 2025 UK guidelines are unequivocal: active surveillance with regular MRI scans and clinical review is the standard first-step management for fibromatosis 6. This applies even to symptomatic cases initially, as many lesions stabilize or regress spontaneously.

• Monitor with clinical examination every 3-6 months
• Serial imaging (ultrasound or MRI) to assess progression
• This approach is based on the unpredictable natural history—some cases remain stable for years 6, 4

Second-Line: Conservative Treatment (If Symptomatic)

If pain or functional limitation develops during surveillance, implement conservative measures before considering any invasive treatment:

• Custom orthotic insoles: Offload pressure from nodules 1, 7
• Physical therapy: Stretching and manual therapy 2, 3, 7
• NSAIDs: For pain control 2, 3
• Ultrasound-guided corticosteroid injection: Can provide symptom relief 1, 8
• Extracorporeal shock wave therapy: Emerging evidence supports this modality 5, 7

Real-world data shows 91% of patients receive conservative treatment, with most requiring multiple interventions (average 2.6 injectable steroid claims, 15.8 PT visits) 8.

Third-Line: Systemic Therapy (If Progressive Despite Conservative Care)

Only if the disease progresses despite surveillance and conservative measures should systemic therapy be considered 6. The 2025 guidelines recommend a stepwise approach starting with least toxic options:

1. Hormonal therapies: Tamoxifen, toremifene (first-line systemic option) 9
2. Low-dose chemotherapy: Methotrexate + vinorelbine or vinblastine 6
3. Tyrosine kinase inhibitors: Sorafenib (phase 3 evidence), pazopanib, imatinib 6
4. Nirogacestat: γ-Secretase inhibitor with phase 3 randomized controlled trial evidence showing benefit in progression-free survival and quality of life 6

Last Resort: Surgery (Rarely Indicated)

Surgery should be avoided in plantar fibromatosis due to extremely high recurrence rates and risk of functional impairment 6. The 2025 guidelines explicitly state that surgery is not optimal treatment for diffuse fibromatosis given high local recurrence and loss of function 6.

Surgery only if:

• Severe functional limitation despite all conservative and systemic options exhausted
• Patient fully counseled on high recurrence risk (often requiring continued conservative treatment post-operatively) 8, 2
• Partial plantar fasciectomy is the procedure of choice if surgery is unavoidable 2

Critical Pitfall to Avoid

The single most important pitfall is rushing to surgery. Real-world data shows that 93% of patients who undergo surgery continue to require conservative treatments afterward, suggesting persistent symptoms or recurrence 8. The plantar location makes this particularly problematic as surgical scarring can cause permanent gait abnormalities and chronic pain.

Prognosis Considerations

• S45F CTNNB1 mutation: If molecular testing shows this specific mutation, expect higher recurrence risk and more aggressive behavior 4
• Age and gender: Young males have higher risk for aggressive disease 6
• Long-term outlook: With conservative management, many patients achieve acceptable symptom control; surgery does not guarantee cure and often leads to complications 8, 2