Differential Diagnosis of a Rapidly Growing Subcutaneous Lump with Normal Overlying Skin
A rapidly growing lump on the back with normal overlying skin and a family history of melanoma most likely represents a subcutaneous soft tissue mass, with lipoma, epidermoid cyst, dermatofibroma, or subcutaneous metastasis being the primary considerations—though the family history warrants urgent evaluation to exclude amelanotic melanoma or nodular melanoma despite the normal skin appearance.
Primary Differential Considerations
Benign Subcutaneous Lesions
Lipoma: The most common benign soft tissue tumor, presenting as a mobile, soft, subcutaneous mass with completely normal overlying skin. These can grow rapidly but are typically painless and well-circumscribed.
Epidermoid (sebaceous) cyst: Presents as a firm, mobile subcutaneous nodule that may have a central punctum (though not always visible). The overlying skin appears normal unless the cyst becomes inflamed or infected.
Dermatofibroma: A firm, fixed nodule that typically dimples when pinched laterally. While usually small, these can occasionally present as larger subcutaneous masses with normal overlying skin.
Malignant Considerations Given Family History
Amelanotic melanoma: Accounts for 2-8% of melanomas and presents without pigmentation, making the overlying skin appear normal 1. This subtype is particularly concerning given the family history and rapid growth pattern.
Nodular melanoma: Comprises approximately 5% of melanomas and grows vertically rather than horizontally, potentially presenting as a subcutaneous lump before significant surface changes occur 1. The rapid growth pattern described is characteristic of this aggressive subtype.
Subcutaneous metastasis: While the patient's family history suggests primary melanoma risk rather than metastatic disease, melanoma can metastasize to subcutaneous tissue with normal overlying skin 2.
Critical Risk Stratification Based on Family History
The family history of melanoma significantly elevates this patient's baseline risk and changes the clinical approach:
Patients with one or more first-degree relatives with melanoma have up to eight times the risk of developing melanoma compared to those without family history 3.
If this patient has three or more family members with melanoma (or a mix of melanoma and pancreatic cancer), genetic counseling for CDKN2A mutation testing should be pursued, as these individuals have up to 91% penetrance for melanoma 3, 4.
The BAP1 tumor syndrome should be considered if there is family history of uveal melanoma, mesothelioma, or renal cell carcinoma alongside cutaneous melanoma 3.
Immediate Diagnostic Algorithm
Step 1: Urgent Dermatology Referral
Any rapidly growing lump in a patient with family history of melanoma requires immediate dermatologic evaluation 3. The UK guidelines specifically recommend referral to a Specialist Skin Cancer Multidisciplinary Team for patients with skin lesions of uncertain malignant potential 3.
Step 2: Biopsy Technique Selection
- Deep scoop shave, saucerization, punch biopsy, or full-thickness excision is required to ensure the entire lesion is captured and accurate Breslow depth can be measured if melanoma is present 5.
- Superficial shave biopsies are inadequate and should be avoided, as they may miss the diagnosis or prevent accurate staging 5.
Step 3: Examination for Additional Features
- Examine the entire skin surface for multiple atypical nevi (>50 nevi), which combined with family history suggests familial atypical multiple mole melanoma syndrome 3, 4.
- Palpate regional lymph nodes draining the area of the lump 3.
- Document any history of changing moles, as a changing mole in an adult is often indicative of melanoma development 3.
Common Pitfalls to Avoid
Do not reassure the patient based solely on normal overlying skin appearance. Amelanotic melanoma and nodular melanoma can present without visible pigmentation or surface changes, and the rapid growth pattern is concerning regardless of skin appearance 1, 6.
Do not delay biopsy for imaging studies. The diagnosis requires histopathologic confirmation, and imaging should only be pursued after tissue diagnosis if staging is needed 3.
Do not perform superficial sampling. If melanoma is present, inadequate biopsy depth will prevent accurate Breslow thickness measurement, which is critical for staging and determining need for sentinel lymph node biopsy 5.
Genetic Counseling Considerations
If the family history includes three or more melanomas or a combination of melanoma and pancreatic cancer across family members, refer for genetic counseling immediately 3. These patients require: