I have five small palpable nodules extending from the posterior knee toward the hip; what are the possible causes and recommended evaluation and treatment?

Evaluation and Management of Multiple Subcutaneous Nodules Along the Posterior Thigh

These nodules most likely represent benign lipomas or subcutaneous cysts, but you must urgently rule out soft tissue sarcoma or metastatic disease through imaging before assuming a benign diagnosis.

Immediate Risk Stratification

Any mass that is deep to the fascia, ≥5 cm in diameter, grows rapidly, or presents suddenly without explanation requires expedited imaging and possible referral to orthopedic oncology. 1

High-Risk Features Requiring Urgent Workup:

• Deep location (subfascial or intramuscular) 1
• Size ≥5 cm in any dimension 1
• Rapid growth over weeks to months 1
• Fixed to underlying structures 1
• Associated pain, neurologic symptoms, or functional limitation 2
• History of prior malignancy (concern for metastases) 3

Lower-Risk Features Suggesting Benign Etiology:

• Superficial subcutaneous location 4
• Soft, mobile, painless masses 2
• Slow growth over years 2
• Multiple similar lesions (suggests lipomatosis or multiple lipomas) 5

Diagnostic Algorithm

Step 1: Initial Imaging with Ultrasound

Begin with high-frequency ultrasound (≥10 MHz) to assess size, depth, solid versus cystic nature, and vascularity. 6, 1

• Ultrasound can differentiate superficial lipomas (which appear identical to subcutaneous fat) from deeper masses requiring advanced imaging 1, 5
• Document whether masses are superficial (above fascia) or deep (below fascia or intramuscular) 1
• Assess for increased vascularity using power Doppler, which may suggest malignancy 7

Critical Pitfall: Ultrasound cannot definitively rule out malignancy in solid masses; negative findings do not exclude sarcoma if clinical suspicion remains high. 6, 7

Step 2: MRI with Contrast for Concerning Features

If ultrasound reveals deep location, size ≥5 cm, solid heterogeneous appearance, or significant vascularity, obtain MRI with contrast immediately. 1

• MRI provides spatial orientation and delineates soft tissue masses from surrounding muscles and neurovascular structures 1
• Lipomas appear identical to subcutaneous fat on all MRI sequences and may contain thin septa 5
• Any nonadipose components (areas that don't suppress on fat-suppressed sequences) raise concern for liposarcoma or other malignancy 5

Expedite MRI and referral to orthopedic oncology for high-risk masses due to the high mortality rate of soft tissue sarcomas. 1

Step 3: Tissue Diagnosis When Indicated

Incisional biopsy (not excisional) is required for any mass suspicious for sarcoma before definitive treatment. 1

• Excisional biopsy of a sarcoma can contaminate tissue planes and worsen prognosis 1
• Coordinate biopsy with the surgical oncologist who will perform definitive resection 1

Differential Diagnosis by Location and Characteristics

Most Likely: Subcutaneous Lipomas

• Account for nearly 50% of all soft tissue tumors 5
• Typically painless, slow-growing, mobile masses 2, 4
• Multiple lipomas can occur (lipomatosis) 5
• Imaging shows fat-density lesions identical to subcutaneous fat 5

Alternative Benign Diagnoses:

• Epidermal inclusion cysts: superficial, may have central punctum 4, 1
• Angiolipomas: contain vascular elements, may be tender 5
• Lipomatosis of nerve: diffuse fat overgrowth along nerve distribution, may cause compression symptoms 5, 8

Concerning Diagnoses Requiring Exclusion:

• Soft tissue sarcoma: deep location, rapid growth, size >5 cm, heterogeneous on imaging 1
• Metastatic disease: multiple nodules in patient with cancer history 3
• Rheumatoid nodules: if patient has inflammatory arthritis, though typically over pressure points 3

Treatment Based on Diagnosis

For Confirmed Benign Lipomas:

• Observation is appropriate for asymptomatic lesions 4
• Excision indicated if: painful, cosmetically concerning, functional impairment, or diagnostic uncertainty 4, 1
• Simple excision in office or minor OR for superficial lesions 4
• Larger or deeper lipomas may require more extensive preoperative planning 4

For Suspected Sarcoma:

• Immediate referral to orthopedic oncology 1
• Do not attempt excision in primary care setting 1
• Coordinate incisional biopsy and definitive wide excision with oncology team 1

Common Pitfalls to Avoid

• Never assume benign etiology based on clinical examination alone—imaging is diagnostic in up to 71% of lipomas but required to exclude sarcoma 5, 7
• Do not perform excisional biopsy of masses suspicious for sarcoma—this contaminates tissue planes and worsens outcomes 1
• Do not delay imaging for masses with high-risk features—soft tissue sarcomas have high mortality and require expedited evaluation 1
• Recognize that multiple nodules do not guarantee benign disease—metastases can present as multiple soft tissue masses 3