濾泡性淋巴瘤

Buzzwords → Dx

Diagnostic Criteria

• WHO 5e / ICC 2022: FL is a B-cell neoplasm with t(14;18) and follicular growth pattern.
• Grading by centroblast count per HPF: grade 1–2 (≤15/HPF) vs 3a (>15, centrocytes still present) vs 3b (sheets of centroblasts, no centrocytes).
• Grade 3b FL is treated as aggressive lymphoma (DLBCL-like) — distinct entity in WHO 5e.
• Pediatric-type FL is genetically distinct (BCL2-neg, no t(14;18), localized) — often curable with surgery alone.
• Staging: Lugano (Ann Arbor I–IV + B-symptoms).

Workup

• Excisional biopsy with full IHC (CD10, BCL2, BCL6, CD20, Ki-67, CD3) and FISH for BCL2, BCL6, MYC (rule out HGBL transformation in suspicious cases).
• PET-CT for staging (Deauville for response).
• Marrow biopsy if PET equivocal or cytopenias.
• CBC, LDH, β2-microglobulin, HBV/HCV/HIV, echo.
• GELF criteria assessment for treatment indication.

Treatment indications (GELF criteria — ≥1 = high tumor burden)

• Any nodal/extranodal mass >7 cm
• ≥3 nodal sites each >3 cm
• Symptomatic splenomegaly
• Compression syndrome (ureteral, orbital, GI)
• Pleural/peritoneal effusion
• Cytopenia (Hb <10, ANC <1.5, plt <100) due to FL
• Leukemic phase (>5 × 10⁹/L abnormal lymphocytes)
• B-symptoms

Treatment Algorithm

flowchart TD
  A[Confirmed FL grade 1-3a] --> B{Stage}
  B -- Stage I-II<br>limited --> C[Involved-site RT 24 Gy<br>± rituximab]
  B -- Stage III-IV --> D{GELF criteria met?}
  D -- no, asymptomatic --> E[Watch and wait]
  D -- yes / symptomatic --> F[R-Benda or R-CHOP<br>or G-Benda / G-CHOP<br>GALLIUM]
  F --> G[Maintenance rituximab/obinutuzumab × 2 yr]
  G --> H{Relapse / POD24?}
  H -- POD24 --> I[Aggressive 2L: change class<br>R-CHOP if not used; CAR-T early]
  H -- late relapse --> J[Repeat R-chemo<br>or zanubrutinib<br>or tazemetostat if EZH2m]
  I --> K[Consider auto-HCT or<br>CD19 CAR-T axi-cel/tisa-cel<br>or bispecific mosunetuzumab]
  J --> K

Pearls / Pitfalls

• Watch and wait is the right answer for asymptomatic low-burden FL — picking immediate chemo is wrong. No survival benefit to early treatment.
• Grade 3b FL is treated as DLBCL (R-CHOP / Pola-R-CHP), not as indolent FL. Look for sheet-like centroblasts on path.
• POD24 (progression within 24 mo of frontline) is the strongest adverse prognostic marker — these patients should go to clinical trial / CAR-T early.
• Histologic transformation to DLBCL/HGBL: rising LDH + new B-symptoms + dominant FDG-avid mass → re-biopsy. Treat as the aggressive histology (R-CHOP, Pola-R-CHP, or DA-EPOCH-R if double-hit).
• Obinutuzumab + bendamustine caused excess fatal infections in some studies; risk-benefit varies — current evidence supports obi + chemo for high-tumor-burden FL.
• Maintenance rituximab × 2 yr prolongs PFS but not OS (PRIMA trial); newer practice often holds maintenance after frontline R-benda or G-benda due to infection risk.
• EZH2 mutation → tazemetostat for relapsed FL (oral, well-tolerated).
• CAR-T (axi-cel ZUMA-5, tisa-cel ELARA) approved for ≥3rd line FL — durable remissions.
• Bispecifics (mosunetuzumab) approved for R/R FL after ≥2 prior lines; outpatient step-up dosing.
• Pneumocystis prophylaxis during obi + benda + maintenance.
• HBV reactivation with rituximab/obinutuzumab — check HBsAg + anti-HBc; entecavir prophylaxis if positive.

Cross-references

• Cytogenetics Atlas — t(14;18), BCL2, EZH2
• Staging — Lugano, FLIPI, FLIPI-2
• Drug Regimens — R-Benda, R-CHOP, G-CHOP, BR
• DLBCL — transformation target
• CAR-T axi-cel ZUMA-5, tisa-cel ELARA

相關題目

• Q-040 — FL — watch-and-wait indication
• Q-041 — FL — POD24 prognostic significance
• Q-042 — FL — histologic transformation suspicion

Sources