What are the recommended treatment options for primary cutaneous B‑cell lymphoma (PC‑BCL) based on disease extent, lesion size, location, and patient health?

Treatment of Primary Cutaneous B-Cell Lymphoma

For indolent primary cutaneous B-cell lymphomas (PCMZL and PCFCL), radiation therapy at 24-30 Gy is first-line treatment for localized disease, while the aggressive PCLBCL-LT requires systemic R-CHOP combined with radiotherapy (36-40 Gy) for localized disease. 1

Disease Classification and Prognosis

Primary cutaneous B-cell lymphomas comprise three main subtypes with dramatically different prognoses:

• Primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) are indolent with 5-year disease-specific survival exceeding 95% 2, 3
• Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) is aggressive with 5-year survival approximately 50-58% 1, 4
• PCLBCL-LT has the phenotype and gene expression profile of ABC-type DLBCL and should be treated accordingly 1

Treatment Algorithm for Indolent PCBCL (PCMZL and PCFCL)

Solitary or Localized Lesions (Few Lesions in Single Anatomic Site)

Radiation therapy is the preferred first-line treatment:

• Recommended dose: 24-30 Gy for curative intent 1
• Margin of at least 1-1.5 cm of clinically uninvolved skin 1
• Complete response rates exceed 95% 1
• Relapse rates approximately 40-50%, but relapses are typically cutaneous and do not worsen prognosis 1

Surgical excision is acceptable for small, well-demarcated solitary lesions 1

Multifocal Disease (Multiple Scattered Lesions)

For palliative treatment of multifocal disease:

• Low-dose radiotherapy (4 Gy) is often sufficient for symptomatic lesions 1

For extensive cutaneous disease requiring systemic therapy:

• Single-agent rituximab (375 mg/m² weekly for 4-8 weeks) is first-line systemic treatment 1, 2, 3
  • Complete response rate: 75% in PCFCL 1
  • Well-tolerated with minimal toxicity 1
  • Relapses occur but remain confined to skin 1

Alternative systemic options for extensive disease:

• Chlorambucil for multifocal PCMZL: 64% complete response rate 1
• Consider in patients who cannot receive rituximab 1

Watchful Waiting

Active monitoring without immediate treatment is appropriate for:

• Asymptomatic patients with indolent disease 1
• Few scattered lesions in patients preferring observation 1
• Follow-up every 6-12 months for stable disease 1

When to Avoid Chemotherapy

Multi-agent chemotherapy (CHOP, R-CHOP) should be reserved ONLY for:

• Patients developing extracutaneous disease 1
• Patients with progressive disease not responding to rituximab 1
• High tumor burden failing single-agent therapy 1

Critical caveat: CHOP-based regimens show 85% complete response but 48-57% relapse rates in indolent PCBCL, with no survival benefit over less toxic approaches 1. Overly aggressive treatment does not improve survival or prevent relapse 4.

Treatment Algorithm for Aggressive PCLBCL-LT

Localized Disease

Combined modality therapy is standard:

• R-CHOP chemotherapy (3-6 cycles) PLUS radiotherapy (36-40 Gy) if patient can tolerate multi-agent chemotherapy 1
• If systemic treatment cannot be given, radiotherapy alone at 40 Gy is recommended 1
• This aggressive lymphoma requires treatment comparable to systemic DLBCL 1, 2, 3

Disseminated or Recurrent Disease

Treat according to systemic DLBCL guidelines:

• Multi-agent chemotherapy regimens appropriate for ABC-type DLBCL 1
• Consider clinical trials for novel agents targeting MYD88/CD79B mutations 1

Special Considerations

Borrelia burgdorferi Testing (European Endemic Areas)

In European patients with PCMZL:

• Test for Borrelia burgdorferi by serology and PCR on skin biopsy 1, 5
• If positive, treat with doxycycline 100 mg twice daily for 3 weeks 1, 5
• Can lead to complete resolution without other therapy 5
• Not relevant in Asian or United States cases 1

Follow-Up Strategy

Surveillance intervals based on disease type and status:

• Indolent PCBCL with stable disease or complete remission: Every 6-12 months 1
• Active or progressive disease: Every 4-6 weeks 1
• Focus on history and physical examination; routine imaging not required since recurrences are visible 1

Common Pitfalls to Avoid

Do not use multi-agent chemotherapy as first-line for indolent PCBCL confined to skin—it causes unnecessary toxicity without survival benefit 1, 4

Do not confuse primary cutaneous B-cell lymphoma with systemic lymphoma secondarily involving skin—adequate staging is essential to exclude extracutaneous disease at presentation 1, 4, 2

Do not administer rituximab without confirming CD20 expression histologically 1, 5

Do not treat PCLBCL-LT with skin-directed therapy alone—this aggressive subtype requires systemic chemotherapy like nodal DLBCL 1, 2