What are the primary differential diagnoses for a suspected sebaceous cyst?

Differential Diagnoses for Sebaceous Cyst

The primary differential diagnoses for a suspected sebaceous cyst include epidermoid cyst (the most common and often misnamed as "sebaceous"), dermoid cyst, pilar/trichilemmal cyst, lipoma, abscess, inflamed epidermoid cyst, and in cases of chronic unresponsive lesions—particularly with atypical features—sebaceous carcinoma or squamous cell carcinoma. 1, 2

Key Clinical Differentiators

Epidermoid Cyst (True "Sebaceous Cyst")

• Most common benign cutaneous cyst, presenting as a mobile, flesh-colored nodule with a characteristic central punctum (dark opening on the surface) 1, 3
• Contains cheesy keratinous material and normal skin flora even when uninflamed 1, 2
• Typically found on face, neck, trunk, and scalp (hair-bearing areas) 3
• When inflamed, presents as painful, tender swelling that mimics an abscess, but patient reports longstanding painless nodule that recently became symptomatic 2
• A distinct capsule or wall structure can be palpated beneath the skin 2

Dermoid Cyst

• Congenital choristoma containing more complex structures like hair, teeth, and cartilage due to developmental origin 1
• Ultrasound shows hyperechoic components with acoustic shadowing, hyperechoic lines and dots, and sometimes fluid-fluid levels 1
• Typically presents earlier in life than epidermoid cysts 1

Pilar/Trichilemmal Cyst

• Predominantly occurs on the scalp (90% of cases) 3
• Lacks the central punctum seen in epidermoid cysts 3
• Contains more homogeneous keratin without the layered appearance of epidermoid cysts 3

Lipoma

• Soft, rubbery, mobile subcutaneous mass without a punctum 3
• More compressible than cysts and lacks the firm capsule 3
• Does not contain keratinous material 3

Abscess vs. Inflamed Epidermoid Cyst

This distinction is critical for management:

• Abscess: Develops over days without pre-existing mass, purely liquid pus collection without encapsulation, uniformly fluctuant throughout 2
• Inflamed Epidermoid Cyst: Longstanding nodule that recently became inflamed, contains thick white-yellow keratinous debris mixed with pus (not pure liquid pus), palpable cyst wall structure 2
• Pathophysiology difference: Inflammation in epidermoid cysts results from rupture of the cyst wall and extrusion of contents into dermis—not true bacterial infection 1, 2

Red Flags Requiring Biopsy

Consider malignancy when:

• Chronic lesion unresponsive to standard therapy, especially with marked asymmetry 4
• Unifocal recurrent lesion that does not respond to therapy 4
• Loss of normal tissue architecture or focal hair loss (ciliary madarosis in eyelid lesions) 4
• Rapid growth or ulceration 4
• Indurated, irregular borders or fixation to underlying structures 4

Sebaceous Carcinoma

• Must be excluded in chronic unresponsive eyelid lesions with conjunctival cicatricial changes 4
• Requires discussion with pathologist before biopsy regarding need for frozen sections and mapping for pagetoid spread 4
• Fresh tissue may be needed to detect lipids using special dyes like oil red-O 4

Squamous Cell Carcinoma

• Can arise in chronic cysts, particularly those related to chronic wounds, scars, or burns 4
• Presents as indurated nodular keratinizing or crusted tumor that may ulcerate 4
• Malignant transformation in epidermoid cysts is exceedingly rare (0.3% incidence) but documented 5, 6

Diagnostic Approach

Physical examination should specifically assess:

• Presence or absence of central punctum (favors epidermoid cyst) 1, 3
• Mobility and consistency (firm capsule vs. soft lipoma vs. fluctuant abscess) 2, 3
• Duration of lesion (longstanding vs. acute onset) 2
• Recent change in character (suggests rupture or inflammation) 2
• Location (scalp favors pilar cyst; eyelid raises concern for sebaceous carcinoma) 4, 3

Histopathologic evaluation is indicated when:

• Clinical uncertainty exists based on history or physical characteristics 5
• Any features suggesting malignancy are present 4, 5
• Lesion is atypical in location, size (>5 cm), or behavior 5, 6
• Note: Routine pathologic evaluation of all clinically typical sebaceous cysts is unnecessary when no clinical suspicion exists 5

Common Pitfalls

• Misdiagnosing inflamed epidermoid cyst as simple abscess: This leads to inappropriate antibiotic use without addressing the cyst wall, resulting in recurrence 2
• Prescribing antibiotics for inflamed cysts without adequate drainage: Antibiotics alone are insufficient; incision and drainage with complete cyst wall removal is essential 2
• Missing sebaceous carcinoma in chronic eyelid lesions: Always consider biopsy for unresponsive eyelid lesions, especially unilateral cases 4
• Inadequate excision: Failure to remove entire cyst wall leads to recurrence rates up to 40% 3