Primary cutaneous anaplastic large-cell lymphoma

Clinical features

• Solitary (~80%) or grouped large red-violaceous nodules or tumours; frequently ulcerated.
• Trunk, head/neck or extremity; median age 60; M:F ~2:1.
• Spontaneous regression in ~25% — overlap with lymphomatoid papulosis spectrum.
• Cutaneous relapses common (~40%); extracutaneous spread uncommon (10–15%).
• Differential: lymphomatoid papulosis (smaller, recurrent, self-healing crops); systemic ALCL with skin involvement (staging required); transformed mycosis fungoides; CD30+ pseudolymphoma.

Histology

• Diffuse dermal infiltrate of large, pleomorphic CD30+ T cells with abundant cytoplasm and prominent nucleoli; often "hallmark cells" with horseshoe / kidney-shaped nuclei.
• Epidermotropism limited or absent (distinguishes from transformed MF).
• CD30 positive in >75% of tumour cells (by definition).
• CD3+, CD4+, CD45+, CD2 / CD5 / CD7 frequently lost (an aberrant T-cell phenotype).
• ALK-negative by IHC (key distinction from systemic ALK+ ALCL).
• EMA usually negative; cytotoxic markers (TIA-1, granzyme B, perforin) often positive.
• Clonal T-cell receptor rearrangement.
• DUSP22-IRF4 rearrangement (chromosome 6p25) in ~25% — emerging prognostic marker.

Staging

• CT chest/abdomen/pelvis ± PET-CT to exclude systemic ALCL or other extracutaneous lymphoma.
• Bone marrow biopsy in selected cases (multifocal disease, B symptoms).
• Full blood count, LDH, U&E, hepatitis B/C, HIV serology.
• EORTC TNM staging system for cutaneous lymphoma.
• Discuss in MDT with cutaneous lymphoma service (in the UK: Guy's, St George's, Manchester).

Management

• Solitary or grouped lesions:
  • Surgical excision OR low-dose involved-field radiotherapy (typically 24–30 Gy) — both highly effective; first-line.
  • Observation if spontaneous regression has occurred or is in progress.
• Multifocal cutaneous disease:
  • Low-dose oral methotrexate (10–25 mg weekly) — well tolerated, effective.
  • Bexarotene, interferon-α — alternatives.
  • Pralatrexate — antifolate, alternative for refractory disease.
• Refractory or extracutaneous disease:
  • Brentuximab vedotin — anti-CD30 antibody-drug conjugate (NICE TA577); high response rates in pcALCL.
  • CHOP-based chemotherapy reserved for patients with extracutaneous progression — not first-line for skin-limited disease.
• Long-term cutaneous lymphoma surveillance (annual).

Prognosis

Excellent for skin-limited disease — 5-year disease-specific survival 90–95%. Cutaneous relapse (~40%) is common but rarely life-threatening. Extracutaneous spread (~15%) carries a worse prognosis. The key adverse factor is extensive multifocal disease at presentation; DUSP22-IRF4 rearrangement may indicate slightly worse outcomes in some series.