Can Chronic Lymphocytic Leukemia (CLL) have cutaneous manifestations?

Cutaneous Manifestations of Chronic Lymphocytic Leukemia

Yes, CLL can have cutaneous manifestations, occurring in up to 25% of patients, presenting as specific leukemic infiltrations (leukemia cutis) or nonspecific secondary lesions. 1

Types of Cutaneous Involvement

CLL-related skin lesions fall into three distinct categories that require different clinical approaches 2:

1. Specific Lesions (Leukemia Cutis)

• Direct infiltration of skin by malignant B-lymphocytes, manifesting as solitary, grouped, or generalized papules, plaques, nodules, or large tumors 1
• Can present as papules, macules, plaques, nodules, ecchymoses, palpable purpura, ulcerative lesions, erythroderma, or bullous lesions 3
• Head and neck are most commonly involved sites 4
• Papulonodular lesions represent the most common clinical presentation 4
• Histopathologic examination of the skin lesion is essential for definitive diagnosis 5

2. Secondary Cutaneous Lesions Without Leukemic Infiltrate

• Most commonly infectious or hemorrhagic in origin 1
• Include vasculitis, purpura, generalized pruritus, exfoliative erythroderma, and paraneoplastic pemphigus 1
• Exaggerated reactions to insect bites and insect bite-like reactions have been observed 1
• Notably, CLL skin involvement at sites of old herpetic lesions is common 4

3. Secondary Malignancies

• Eightfold higher occurrence of skin cancer in CLL patients 1
• Alkylating agents and purine analogs may be associated with increased incidence of secondary cutaneous malignancies 1

Clinical Significance and Prognosis

Prognostic Implications

• Prognosis in CLL patients with leukemia cutis is rather good, and many authors claim it does not significantly affect survival 1
• Overall survival of patients with specific skin lesions of CLL is significantly better compared with other types of leukemia 5
• However, prognosis is poor when leukemic infiltrations appear after the initial CLL diagnosis or when blastic transformation (Richter's syndrome) occurs 1

Temporal Relationship

• Cutaneous leukemic lesions may be concomitant with or preceding the diagnosis of systemic leukemia 3
• Rarely, aleukemic leukemia cutis presents with skin lesions before evidence can be detected in peripheral blood or bone marrow 5
• All patients ≤60 years had early-stage disease, while all patients with advanced-stage were >60 years 4

Treatment Approach

Early-Stage, Localized Disease

• Patients with early-stage and localized leukemia cutis can benefit from observation alone 4
• The majority of patients (77.8%) responded to treatment when intervention was needed, with 25 achieving complete remission and 10 achieving partial remission 4

Advanced Disease

• Intervention in young patients with advanced disease is warranted 4
• Treatment modalities vary widely due to disease rarity, with the majority treated with chemotherapy 4
• Very low progression rate overall when treated appropriately 4

Critical Diagnostic Considerations

Skin biopsy is essential and may be helpful in detecting leukemia, facilitating the diagnostic work-up 3. The demonstration of leukemia in skin represents dissemination of systemic disease 3. Look specifically for infiltration patterns involving all layers of the skin on histopathology 5.