Differential Diagnosis of White Palpable Lesions

Introduction

White papules and nodules result from deposition of keratin, calcium, urate, or other substances within the skin. While many are benign (milia, calcinosis from local causes), some indicate systemic disease (gout, dystrophic calcification in autoimmune disease). Recognition of the morphology, distribution, and clinical context is essential for diagnosis.

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32.1 Keratin Deposits

32.1.1 Milia

• Definition: Small, superficial keratinous cysts.
• Pathogenesis: Keratin-filled cysts originating from the pilosebaceous unit at the level of the sebaceous collar.
• Types:
  • Primary Milia: Occur spontaneously on face, especially in neonates (50% of newborns) and adults (eyelids, cheeks).
  • Secondary Milia: At sites of skin injury: Blistering diseases (Epidermolysis Bullosa, Porphyria cutanea tarda), Burns, Dermabrasion, Topical steroid atrophy.
• Clinical Features:
  • Tiny (1-2mm), white-yellow, dome-shaped papules.
  • Face (especially periorbital), Forehead.
  • Firm, superficial, easily expressed.
• Histology: Small cyst lined by stratified squamous epithelium containing lamellar keratin.
• Treatment: Incision and expression, Electrodesiccation. Neonatal milia: No treatment (self-resolve).

32.1.2 Milia en Plaque

• Definition: Rare variant with milia confined to an erythematous plaque.
• Distribution: Retroauricular, Eyelids.
• Associations: Lupus, Pseudoxanthoma elasticum.

32.1.3 Comedones (Closed = Whiteheads)

• Definition: Non-inflammatory acne lesions due to follicular hyperkeratinization.
• Clinical Features:
  • Small, white papules without central opening.
  • Face, Chest, Back (seborrheic areas).
• Differential from Milia: Comedones are follicular plugs; Milia are cysts.

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32.2 Calcium Deposits (Calcinosis Cutis)

Calcium deposition in the skin occurs through several mechanisms.

32.2.1 Classification

32.2.2 Dystrophic Calcinosis

• Key Feature: Occurs in tissue that is already damaged, but serum calcium and phosphate are NORMAL.
• Associations:
  • Scleroderma (CREST): Calcinosis on fingers, elbows, knees. Part of CREST syndrome.
  • Dermatomyositis: Especially juvenile DM. Can be extensive ("calcinosis universalis").
  • Systemic Lupus: Less common.
  • Panniculitis: Resolved panniculitis may leave calcium deposits.
• Clinical Features:
  • White-yellow, firm to hard papules or nodules.
  • May ulcerate and drain chalky material.

32.2.3 Metastatic Calcinosis

• Key Feature: Elevated serum calcium and/or phosphate causes widespread tissue calcification.
• Common Causes:
  • Chronic Kidney Disease (CKD) / ESRD: Secondary hyperparathyroidism, Hyperphosphatemia.
  • Primary Hyperparathyroidism.
  • Hypervitaminosis D.
  • Milk-Alkali Syndrome.
  • Malignancy (PTHrP-producing tumors, Bone metastases).
• Clinical Features: May affect skin, blood vessels, soft tissues, organs.

32.2.4 Idiopathic Calcinosis

• Subepidermal Calcified Nodule (Winer): Solitary white nodule on face or extremity. Child or young adult. Benign.
• Scrotal Calcinosis: Multiple nodules on scrotum. May be dystrophic (from ruptured cysts).

32.2.5 Tumoral Calcinosis

• Definition: Large periarticular calcified masses.
• Associations: Familial (genetic mutations in phosphate regulation), Secondary to ESRD.
• Location: Hips, Shoulders, Elbows.

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32.3 Urate Deposits (Gout)

32.3.1 Gouty Tophi

• Definition: Deposition of monosodium urate (MSU) crystals in periarticular and subcutaneous tissues.
• Clinical Features:
  • Firm, white-yellow nodules.
  • Location: Ears (helix), Elbows (olecranon), Fingers, Toes, Achilles tendon.
  • May ulcerate and extrude chalky white material.
• Dermoscopy: White, chalky deposits with surrounding erythema ("clouds" or "cotton wool" appearance).
• Diagnosis: Aspiration reveals negatively birefringent needle-shaped crystals under polarized microscopy.
• Associations: Chronic gout, Hyperuricemia.
• Treatment: Urate-lowering therapy (Allopurinol, Febuxostat).

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32.4 Mucinous Deposits

32.4.1 Digital Myxoid Cyst (Covered in Ch. 30)

• Translucent, may appear whitish.
• Dorsum of distal finger.

32.4.2 Focal Mucinosis

• Solitary, skin-colored to whitish papule or nodule.
• Histology: Dermal mucin deposition.

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32.5 Other White Lesions

32.5.1 Osteoma Cutis

• Definition: Bone formation within the dermis.
• Types:
  • Primary: Rare, without pre-existing skin disease. Albright hereditary osteodystrophy.
  • Secondary: Within existing lesions (Acne scars, Pilomatricoma, Nevi, Sites of trauma).
• Clinical Features: Hard, white papules or nodules.
• Diagnosis: X-ray shows bony density in soft tissue. Histology confirms bone.

32.5.2 Granuloma Annulare (Subcutaneous)

• Deep variant that may present as skin-colored to whitish nodules on pretibial area or hands.
• Histology: Palisading granuloma with mucin.

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32.6 Diagnostic Algorithm

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32.7 Summary Comparison Table

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32.8 Clinical Pearls

1. Tiny 1-2mm white papules on face → Milia. Common in neonates (self-resolve) or adults (extraction).
2. White nodules in scleroderma/DM + Normal serum Ca → Dystrophic calcinosis.
3. Widespread calcinosis + CKD → Metastatic calcinosis. Correct Ca/PO4.
4. White nodule on ear/elbow + Hyperuricemia → Gouty tophus. Aspirate for crystals.
5. Hard, radio-dense lesion in scar → Osteoma cutis. Secondary to acne or trauma.
6. Calcinosis may ulcerate and drain chalky material—don't mistake for infection.