What is the differential diagnosis and next steps for a 31-year-old female presenting with multiple subcutaneous (under the skin) masses, some of which are soft and cyst-like, while others are rubbery and harder, with varying mobility and some attached to muscle?

Differential Diagnosis and Next Steps for Multiple Subcutaneous Masses

Most Likely Diagnosis

The clinical presentation of multiple, non-tender, rubbery subcutaneous masses with varying consistency (soft/cyst-like to firm/rubbery) and mobility in a 31-year-old woman most strongly suggests multiple lipomas or lipomatosis, though the differential must include other benign soft tissue tumors and, less likely, multiple neurofibromas or low-grade soft tissue sarcomas. 1

Differential Diagnosis

Benign Lesions (Most Likely)

• Multiple lipomas: Most common soft tissue tumor; typically soft, mobile, well-circumscribed subcutaneous masses that can vary in consistency 1, 2
• Neurofibromas: Rubbery, mobile masses that can be multiple, especially if associated with neurofibromatosis type 1 (NF1) 3
• Epidermoid/sebaceous cysts: Soft, cyst-like consistency; typically more superficial 1, 3
• Vascular malformations: Can present as soft, compressible masses 1

Concerning Features Requiring Exclusion

• Atypical lipomatous tumors (ALT): Especially for deeper masses or those >5 cm 1, 4
• Low-grade soft tissue sarcomas: Less likely given chronicity and lack of symptoms, but must be excluded 1
• Pleomorphic lipomas: Can have variable consistency and may lack typical fat content 5

Immediate Next Steps

Initial Imaging Protocol

Begin with plain radiographs of the affected areas (forearms and shoulder), followed immediately by ultrasound examination of all palpable masses. 1, 4

Radiographs First

• Radiographs should be the initial imaging study for any suspected soft tissue mass 1
• Can identify intrinsic fat (11% of cases), calcification (27%), or bone involvement (22%) 1
• May reveal unsuspected skeletal abnormalities or foreign bodies 1

Ultrasound as Primary Diagnostic Tool

• Ultrasound is the most useful initial imaging modality for superficial/subcutaneous masses, with sensitivity 94.1% and specificity 99.7% 1, 2, 6
• Characteristic lipoma features on ultrasound include: 2, 4
  • Hyperechoic or isoechoic appearance compared to surrounding fat
  • Well-circumscribed margins
  • Thin, curved echogenic lines within the mass
  • Minimal to no internal vascularity on Doppler
  • No acoustic shadowing

Red Flags Requiring Advanced Imaging or Biopsy

Any of the following features mandate MRI and/or core needle biopsy: 1, 4, 6

• Size >5 cm (the new shoulder mass should be measured) 4, 6
• Deep location (masses fixed to or beneath fascia/muscle) 1, 4
• Rapid growth (the patient notes some masses have "slightly grown") 4, 6
• Pain or tenderness (absent here, which is reassuring) 4
• Atypical ultrasound features (heterogeneous echotexture, increased vascularity, irregular margins) 1, 4
• Location in lower extremity (forearm masses warrant closer attention) 4

The Shoulder Mass Requires Special Attention

The new shoulder mass that is fixed to muscle (stays in place when skin is moved) is concerning and requires MRI evaluation regardless of size. 1, 4

• Deep-seated masses have higher risk of being atypical lipomatous tumors or sarcomas 4, 7
• Fixed masses suggest involvement of deeper structures 7
• MRI can differentiate benign lipomas from atypical lipomatous tumors in up to 69% of cases 4

Recommended Diagnostic Algorithm

Step 1: Clinical Assessment

Document for each mass: 7

• Exact size (measure with calipers)
• Depth (subcutaneous vs. subfascial)
• Mobility relative to skin and underlying structures
• Rate of growth (stable vs. enlarging)
• Duration of presence

Step 2: Imaging Sequence

1. Plain radiographs of forearms and shoulder 1
2. Ultrasound examination of all palpable masses 1, 4, 6
3. MRI without and with contrast for: 1, 4
   • The shoulder mass (deep, fixed to muscle)
   • Any forearm mass >5 cm
   • Any mass with atypical ultrasound features
   • Any rapidly growing mass

Step 3: Biopsy Indications

Percutaneous core needle biopsy (multiple cores) is indicated if: 1, 6

• MRI shows features concerning for sarcoma (heterogeneous signal, enhancement, infiltrative margins)
• Any mass demonstrates growth despite benign imaging features
• Clinical suspicion remains high despite reassuring imaging

Step 4: Referral Criteria

Refer to a sarcoma specialist center BEFORE biopsy if: 1

• Imaging suggests possible soft tissue sarcoma
• Any mass is deep-seated and >5 cm
• Diagnostic uncertainty exists after imaging

Critical Pitfalls to Avoid

• Do not rely on physical examination alone: Only 85% of lipomas are correctly identified by palpation 2, 6
• Do not perform excisional biopsy without imaging: This constitutes "whoops surgery" and may compromise definitive treatment if malignancy is present 7
• Do not assume all masses are benign because they are multiple: Multiple soft tissue sarcomas, though rare, can occur 3
• Do not skip imaging for the "fixed" shoulder mass: Deep location and fixation to muscle are concerning features requiring MRI 4, 7
• Ultrasound is considerably less accurate for deep masses: The shoulder mass requires MRI regardless of ultrasound findings 4

Management Based on Findings

If Imaging Confirms Typical Lipomas

• Small (<5 cm), superficial, asymptomatic lipomas with typical imaging features can be observed 6
• Clinical follow-up at 6-12 months to assess for growth 6

If Concerning Features Present

• Complete surgical excision is standard treatment for symptomatic, rapidly growing, large (>5 cm), or atypical masses 6
• Biopsy tract must be planned for removal during definitive surgery if malignancy is suspected 1