What is the recommended treatment approach for a patient with B‑cell lymphoma presenting in the neck?

Treatment for B-Cell Lymphoma of the Neck

The treatment approach depends critically on whether this is a primary cutaneous B-cell lymphoma versus nodal/systemic disease, with staging workup being the immediate priority to determine the appropriate therapeutic strategy.

Immediate Staging Requirements

Before initiating any treatment, comprehensive staging must establish the extent of disease 1:

• CT scan of neck, chest, abdomen, and pelvis is mandatory to assess nodal and extranodal involvement 1
• PET/CT scan should be performed for accurate baseline staging, particularly if limited-stage disease is suspected at initial CT, as this will guide treatment intensity and is essential for response assessment 1
• Bone marrow biopsy (monolateral posterior iliac spine, ≥20 mm length with immunohistochemistry) is required for advanced-stage disease (Stage III-IV), presence of B symptoms, or blood count abnormalities 1
• Complete blood count, LDH, beta-2 microglobulin, albumin, ESR for prognostic stratification 1
• Hepatitis B, C, and HIV serology as these infections fundamentally alter treatment decisions 1

Treatment Based on Disease Classification

If Primary Cutaneous B-Cell Lymphoma (Skin-Limited Disease in Neck)

Local radiotherapy is the preferred first-line treatment for localized cutaneous B-cell lymphomas, achieving 99% complete remission rates 1:

• Radiotherapy alone for solitary or localized lesions (complete remission rate 99%, relapse rate 46-47%) 1
• Surgical excision is an alternative for small, accessible lesions (complete remission rate 98-99%, relapse rate 40-43%) 1
• Systemic rituximab (375 mg/m² IV) for multifocal disease or when local therapy is not feasible (complete remission rate 67-89%) 1
• Antibiotics should be considered in European endemic areas if Borrelia burgdorferi serology is positive, particularly for marginal zone lymphoma 1

If Nodal/Systemic B-Cell Lymphoma (Most Likely Scenario)

For Limited-Stage Disease (Stage I-II, no bulk <10 cm)

Combined modality therapy with abbreviated immunochemotherapy followed by involved-site radiotherapy is the standard approach 2:

• 3 cycles of R-CHOP (rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m², prednisone 100 mg days 1-5) every 21 days 3, 4, 2
• Followed by involved-site radiotherapy (24-30 Gy) to the neck region 2
• PET-adapted approach: If PET-negative after 3 cycles, radiotherapy may be omitted in selected patients to minimize long-term toxicity 2

For Advanced-Stage Disease (Stage III-IV or Bulky Disease)

Full-course R-CHOP immunochemotherapy for 6-8 cycles is the standard treatment 1, 3, 5:

• 6-8 cycles of R-CHOP administered every 21 days 3, 5
• Rituximab 375 mg/m² on Day 1 of each cycle 3
• Mid-treatment PET assessment after 2-4 cycles using Deauville 5-point scale (scores 1-3 considered negative) to guide treatment modifications 1
• No adjuvant radiotherapy for patients achieving complete remission without initial bulky disease, as this increases toxicity without survival benefit 1

Critical Treatment Initiation Criteria

Treatment should be started when any of the following features are present 1:

• Systemic B symptoms (fever, night sweats, weight loss)
• High tumor burden (>3 nodes >3 cm or single node >7 cm)
• Rapidly progressive disease
• Symptomatic or life-threatening organ involvement
• Cytopenia due to marrow involvement
• Elevated LDH levels

Watchful waiting is appropriate only for asymptomatic, low-burden disease without these features 1.

Response Assessment Strategy

• PET/CT after 2-4 cycles for early response evaluation 1
• End-of-treatment PET/CT to document complete remission 1
• Restaging bone marrow biopsy is NOT required if end-of-treatment PET is negative, even with baseline marrow involvement (100% negative predictive value) 6

Common Pitfalls to Avoid

• Never use radiotherapy alone for nodal disease, even if limited-stage—combined modality therapy has superior outcomes 2
• Do not delay staging workup to start empiric treatment; proper staging fundamentally determines treatment intensity 1
• Do not assume cutaneous presentation means primary cutaneous lymphoma—systemic disease with skin involvement requires full systemic therapy 1
• Do not omit fertility counseling in patients of reproductive age before initiating chemotherapy, as permanent infertility is common 7, 8, 9