What is the management approach for a patient diagnosed with primary splenic non-Hodgkin lymphoma (NHL)?

Management of Primary Splenic Non-Hodgkin Lymphoma

Splenectomy combined with systemic chemotherapy is the optimal treatment approach for primary splenic non-Hodgkin lymphoma, as this combination achieves superior complete remission rates (31.6-40%), longer remission duration (74.5 months median), and significantly better 5-year overall survival (64.7-67.2%) compared to chemotherapy alone. 1

Initial Diagnostic Requirements

Tissue diagnosis is mandatory before initiating any lymphoma-directed therapy. 2 For primary splenic lymphoma, this typically requires:

• Splenectomy serves dual purposes: diagnostic confirmation and therapeutic intervention 3, 1
• Core needle biopsy may be inadequate given the need to assess splenic architecture and rule out other pathologies 4
• Fine-needle aspiration is insufficient for definitive diagnosis 4

Critical pitfall: Refusing diagnostic splenectomy delays definitive diagnosis and optimal treatment, as demonstrated in a case where spontaneous splenic rupture occurred after empiric chemotherapy 3

Complete Staging Workup

Before finalizing treatment, complete staging must include:

• PET/CT scan (skull base to mid-thigh) for accurate disease extent assessment 4, 5
• Contrast-enhanced CT of neck, chest, abdomen, and pelvis if not part of integrated PET scan 4
• Laboratory evaluation: CBC with differential, LDH, albumin, liver and renal function, ESR 4
• Bone marrow biopsy to confirm truly primary splenic disease versus systemic involvement 6
• Hepatitis B screening (HBsAg and anti-HBc) is mandatory before rituximab-based therapy 4, 5

Treatment Algorithm by Disease Stage

Stage I-II Disease (Spleen Only or Spleen + Splenic Hilum)

Primary treatment approach:

1. Splenectomy as initial intervention 1, 6, 7

   • Provides definitive tissue diagnosis
   • Achieves immediate tumor debulking
   • Corrects cytopenias in most cases
   • Prevents continuous dissemination from primary site 1
   • Eliminates possibility of local splenic relapse 1

2. Followed by systemic chemotherapy regardless of histologic grade 1

   • For low-grade histology: Single-agent or combination chemotherapy after splenectomy achieves 40% complete remission rate 1
   • For intermediate/high-grade histology: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) for 6-8 cycles 5, 8
   • Dose intensity must be maintained; dose reductions compromise efficacy 5

Rationale for combined approach: Splenectomy alone results in 85.7% partial remission but 0% complete remission, while splenectomy plus chemotherapy achieves 31.6-40% complete remission with median remission duration of 74.5 months 1

Stage IV Disease (Disseminated)

For CD20-positive disease:

• R-CHOP remains standard: 6-8 cycles administered every 21 days 5, 8
• Splenectomy role is limited but may be considered for:
  • Symptomatic splenomegaly causing cytopenias 1
  • Diagnostic uncertainty after initial biopsy attempts 3
  • Persistent isolated splenic disease after systemic therapy 1

Essential Supportive Care Measures

Mandatory interventions during treatment:

• Hepatitis B prophylaxis: Entecavir for HBsAg-positive patients receiving rituximab 5
• PJP prophylaxis: Consider for bendamustine/rituximab combinations 5
• Tumor lysis syndrome prophylaxis: In patients with bulky disease 4
• Tumor flare management: Steroids (prednisone 25-50 mg for 5-10 days) for painful lymph node enlargement with lenalidomide-containing regimens 4

Response Evaluation Strategy

Interim assessment:

• After 2-4 cycles of chemotherapy to exclude disease progression 5
• PET-CT is preferred for response assessment in FDG-avid lymphomas 5
• Achieving negative PET should be the goal 5

End-of-treatment assessment:

• PET/CT scan essential for evaluating residual masses 4
• Integrated PET plus diagnostic CT recommended 4

Histologic Grade Considerations

Important nuance: Unlike nodal NHL, histologic subtype does not reliably predict prognosis in primary splenic lymphoma 7. Both low-grade and intermediate/high-grade histologies show favorable outcomes when treated with splenectomy plus chemotherapy 1, 7

Relapsed/Refractory Disease

For disease progression after initial therapy:

• High-dose chemotherapy followed by autologous stem cell transplantation is the treatment of choice 5
• Achieving negative PET status before transplant is the goal of salvage therapy 5

Follow-Up Schedule

Surveillance protocol:

• Every 3 months for first 6 months: History, physical examination, laboratory analysis 5
• Thyroid function monitoring if neck was irradiated 5
• Long-term surveillance for secondary malignancies given favorable prognosis 1, 7

Prognosis

Expected outcomes with optimal treatment:

• 5-year overall survival: 64.7-67.2% with splenectomy plus chemotherapy 1
• Median survival: 7.48 years in truly primary splenic disease 7
• Median remission duration: 74.5 months for complete responders 1

Critical distinction: These favorable outcomes apply only to truly primary splenic lymphoma (stage I-II) without nodal or hepatic involvement 6, 7. Stage IV disease follows standard NHL prognosis based on International Prognostic Index 5