What is the treatment for non-Hodgkin's lymphoma (NHL) that has spread to the skin?

Treatment of Non-Hodgkin Lymphoma with Skin Involvement

For non-Hodgkin lymphoma that has spread to the skin secondarily (not primary cutaneous lymphoma), treat according to the systemic lymphoma subtype with standard systemic chemotherapy regimens, as skin involvement represents stage IV disease requiring aggressive systemic therapy rather than skin-directed treatments.

Critical Distinction: Primary vs. Secondary Cutaneous Involvement

• Primary cutaneous lymphomas present in the skin with no extracutaneous disease at diagnosis and require skin-directed therapies 1
• Secondary skin involvement from systemic NHL (your patient's scenario) represents disseminated disease and mandates systemic chemotherapy based on the underlying lymphoma histology 1
• This distinction is crucial because primary cutaneous lymphomas have different clinical behavior, prognosis, and therapeutic approaches compared to systemic lymphomas secondarily involving skin 1

Treatment Approach for Diffuse Large B-Cell Lymphoma (Most Common NHL Subtype)

For Patients ≤60 Years Old

Low-risk patients (age-adjusted IPI 0-1):

• Six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) given every 14 days with eight doses of rituximab is the current standard for CD20+ DLBCL of all stages 1, 2
• Skin involvement places the patient at stage IV, but treatment follows the same systemic approach 1

High-risk patients (age-adjusted IPI ≥2):

• Six to eight cycles of R-CHOP given every 14-21 days are most frequently applied 1, 2
• These patients should preferably be enrolled in clinical trials as there is no current standard with sufficient efficacy 1
• CNS prophylaxis with intrathecal methotrexate and/or cytarabine should be considered in high-risk patients 1

For Patients >60 Years Old

• Eight cycles of R-CHOP combined with eight doses of rituximab given every 21 days is the current standard 1, 2
• If R-CHOP is given every 14 days, six cycles are sufficient 1

Critical Pre-Treatment Considerations

Tumor Lysis Syndrome Prevention

• Administer prednisone 100 mg orally daily for 5-7 days as "prephase" treatment before starting R-CHOP in patients with high tumor burden 3, 2
• This corticosteroid prephase is mandatory for patients with bulky disease or extensive involvement 3
• Ensure adequate hydration and consider prophylactic allopurinol or rasburicase for highest-risk patients 3

Dose Intensity Maintenance

• Avoid dose reductions due to hematological toxicity as this compromises treatment efficacy 1, 4, 2
• Prophylactic use of hematopoietic growth factors is justified for febrile neutropenia in patients treated with curative intent 1, 4, 2

Staging and Baseline Assessment Required

• Complete blood count, LDH, uric acid, HIV and hepatitis B/C screening 1
• CT scan of chest and abdomen 1
• Bone marrow aspirate and biopsy 1
• PET scanning to delineate disease extent and establish baseline for response evaluation 1
• Cardiac function assessment (left ventricular ejection fraction) before anthracycline-based therapy 1
• Calculate International Prognostic Index (IPI) and age-adjusted IPI for risk stratification 1

Response Evaluation

• Repeat imaging after 3-4 cycles and after completion of treatment 1
• PET scanning is highly recommended for post-treatment assessment to define complete remission 1
• Histological confirmation of PET positivity is strongly recommended if therapeutic consequences are being considered 1

Common Pitfalls to Avoid

• Do not use skin-directed therapies (topical steroids, PUVA, local radiation) as primary treatment for secondary cutaneous involvement from systemic NHL 1
• Do not reduce chemotherapy doses to accommodate hematological toxicity unless absolutely necessary, as this significantly compromises outcomes 1, 3, 4
• Do not skip the corticosteroid prephase in patients with high tumor burden, as tumor lysis syndrome can be fatal 3
• Do not assume primary cutaneous lymphoma without confirming absence of systemic disease, as this fundamentally changes the treatment approach 1

Relapsed/Refractory Disease

• Obtain histological verification, especially for relapses >12 months after initial diagnosis 1
• For suitable patients (age <65-70 years, adequate performance status): salvage regimen with rituximab and chemotherapy (R-DHAP, R-ESHAP, or R-ICE) followed by high-dose chemotherapy with stem-cell support 1, 2
• Patients not suitable for high-dose therapy may receive salvage regimens combined with involved-field radiotherapy 1