Differential Diagnosis for Mobile Subcutaneous Mass
The differential diagnosis for a mobile subcutaneous mass includes benign lipomas (most common at 96% of superficial masses), atypical lipomatous tumors/well-differentiated liposarcoma, epidermoid cysts, vascular malformations, nerve sheath tumors, dermatofibrosarcoma protuberans (DFSP), pleomorphic dermal sarcomas, and rarely lymphomas or other soft tissue sarcomas. 1
Primary Benign Considerations
Lipomas are the most frequently encountered mobile subcutaneous masses and present as soft, well-defined, mobile masses that indent when depressed with biopsy forceps (pillow sign). 1 These lesions are typically elongated with their greatest diameter parallel to the skin and exhibit well-defined margins in 84% of cases. 2
Epidermoid cysts represent another common benign entity, with ultrasound demonstrating high sensitivity (94.1%) and specificity (99.7%) for superficial soft tissue masses including this diagnosis. 1, 3
Vascular malformations can present as mobile subcutaneous masses and may contain phleboliths visible on radiographs, which are diagnostic when present. 1
Borderline and Locally Aggressive Lesions
Atypical lipomatous tumors (ALT)/well-differentiated liposarcoma must be distinguished from simple lipomas, as ALT has propensity for local recurrence despite being mobile. 1 The key differentiating feature is MDM-2 gene amplification detected by fluorescence in-situ hybridization on core needle biopsy, which definitively separates lipomas from ALT. 1 MRI can differentiate these lesions in up to 69% of cases based on nodularity, septations, stranding, and relative size. 1
Desmoid tumors (aggressive fibromatosis) are characterized by local infiltration rather than distant metastasis and should be considered in the differential. 1
Malignant Considerations
Dermatofibrosarcoma protuberans (DFSP) arises in skin or superficial subcutaneous tissues and requires wide surgical excision. 1 These lesions may initially appear mobile but demonstrate local invasiveness.
Pleomorphic dermal sarcomas can present as large subcutaneous masses and should be diagnosed preoperatively by core/punch biopsy with surgery planned to accommodate possible postoperative radiotherapy. 1
Subcutaneous soft tissue sarcomas can present as mobile masses and are easily recognized, leading to the risk of "whoops surgery" when resected without adequate preoperative imaging and planning. 4 These require careful assessment as they often show invasive patterns along fascia. 4
Diffuse large B-cell lymphoma rarely presents as a clinically subcutaneous mass without visible skin changes or nodal involvement, but can masquerade as a soft tissue mass mimicking sarcoma. 5
Critical Diagnostic Algorithm
Initial imaging must begin with radiographs to identify calcifications (27% yield), bone involvement (22% yield), or intrinsic fat (11% yield), with overall positive findings in 62% of cases. 1, 3, 6 Radiographs can be diagnostic for phleboliths within hemangiomas or osteocartilaginous masses of synovial chondromatosis. 1
Ultrasound is the next appropriate step for small superficial lesions, with sensitivity of 94.1% and specificity of 99.7% for superficial soft tissue masses. 1, 3 Ultrasound can confirm fluid content of suspected ganglion cysts, differentiate solid from cystic lesions, and demonstrate relationship to neurovascular structures. 1, 3
MRI without and with contrast is indicated when ultrasound findings are inconclusive, the mass is deep-seated, or there are atypical features requiring further characterization. 3, 6 MRI provides superior soft tissue characterization and is essential for preoperative planning. 3, 6
Tissue Diagnosis Requirements
Core needle biopsy under image guidance is the standard approach for suspicious masses requiring histopathological diagnosis, with multiple core samples taken to maximize diagnostic yield. 3, 6 This is particularly critical when neoadjuvant therapy is being considered or for suspicion of malignancy other than sarcoma (such as lymphoma or germ cell tumor). 1
Excisional biopsy may be more practical for small subcutaneous lesions less than 5 cm or when imaging characteristics are indeterminate. 3, 6
Critical Pitfalls to Avoid
Physical examination alone correctly identifies only about 85% of soft tissue tumors, making imaging mandatory. 3 The "pillow sign" (soft mass that indents with biopsy forceps) is highly suggestive of lipoma, but atypical features require further evaluation. 1
Never perform biopsy on suspected vascular or cystic lesions until EUS or ultrasound evaluation is completed. 1
Avoid "whoops surgery" by ensuring adequate preoperative imaging and planning before resection of any subcutaneous mass, as inadequate initial surgery requires subsequent radical resection with wider margins and potential soft tissue reconstruction. 4
Any mass with firm consistency, irregular margins, size >5 cm, rapid growth, or deep location requires referral to a specialized sarcoma center with multidisciplinary team evaluation before definitive treatment. 1, 3