High-risk biology in DLBCL NOS: double-expressor (MYC + BCL2 by IHC, no rearrangement), T...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-DLBCL-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-25 \| pending_clinical_signoff
Diseases	`DIS-DLBCL-NOS`
Sources	`SRC-ESMO-DLBCL-2024` `SRC-NCCN-BCELL-2025`

Red Flag Origin

Definition	High-risk biology in DLBCL NOS: double-expressor (MYC + BCL2 by IHC, no rearrangement), TP53 mutation, or non-GCB cell-of-origin in elderly / high-IPI context. Distinct from HGBL "double-hit" which is its own entity (DIS-HGBL-DH) — but double-expressor remains DLBCL NOS and shifts toward intensified backbone.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-DLBCL-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "double_expressor_status",
      "value": true
    },
    {
      "finding": "tp53_mutation",
      "value": true
    },
    {
      "all_of": [
        {
          "finding": "cell_of_origin_hans",
          "value": "non-GCB"
        },
        {
          "finding": "high_ipi",
          "value": true
        }
      ]
    }
  ],
  "type": "biomarker"
}

Notes

Double-expressor (≈30% of DLBCL): inferior PFS/OS on R-CHOP; POLARIX subgroup analysis shows Pola-R-CHP benefit largest in non-GCB + double-expressor. TP53 mutation: PFS halved on R-CHOP; consider Pola-R-CHP and earlier consolidation discussion. Strict double-/ triple-hit (FISH break-apart) is captured by the separate DIS-HGBL-DH entity per WHO 5th classification, not here.

Used By

Algorithms

ALGO-DLBCL-1L - ALGO-DLBCL-1L

Indications

IND-DLBCL-2L-LISOCEL - IND-DLBCL-2L-LISOCEL

Red flag

RF-AAIPI-HIGH - Age-adjusted IPI ≥2 in patient <60 yo — high-risk young-adult DLBCL; supports DA-EPOCH-R...
RF-DLBCL-CD79B-MUT-MCD-CANDIDATE - CD79B mutation (most commonly Y196 hotspot in ITAM domain) in DLBCL, often co-occurring w...