CD79B mutation (most commonly Y196 hotspot in ITAM domain) in DLBCL, often co-occurring w...

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

ID	`RF-DLBCL-CD79B-MUT-MCD-CANDIDATE`
Type	Red flag
Status	reviewed 2026-04-29 \| pending_clinical_signoff
Diseases	`DIS-DLBCL-NOS`
Sources	`SRC-ESMO-DLBCL-2024` `SRC-NCCN-BCELL-2025`

Red Flag Origin

Definition	CD79B mutation (most commonly Y196 hotspot in ITAM domain) in DLBCL, often co-occurring with MYD88 L265P — informational flag for LymphGen MCD subtype (Schmitz NEJM 2018; Wright Cancer Cell 2020). MCD-like DLBCL: ABC subtype + chronic active BCR signaling, frequent extranodal involvement (CNS, testis, breast, skin), inferior outcome on standard R-CHOP. Targeted therapy implications: BTK inhibitor (ibrutinib) hypothesis- generated benefit (PHOENIX subgroup analysis Younes 2019 JCO in age <60 + non-GCB), polatuzumab vedotin (POLARIX subgroup analysis suggests preferential MCD benefit). NOT yet algorithm-shifting in routine NCCN/ESMO 2025 — RF acts as surveillance / MDT-discussion / clinical-trial-eligibility signal pending prospective LymphGen-stratified data. Distinct from RF-DLBCL-HIGH-RISK-BIOLOGY (broader composite).
Clinical direction	investigate
Category	high-risk-biology

Trigger Logic

{
  "all_of": [
    {
      "any_of": [
        {
          "finding": "cd79b_mutation",
          "value": true
        },
        {
          "finding": "cd79b_y196_mutation",
          "value": true
        },
        {
          "finding": "cd79b_itam_mutation",
          "value": true
        }
      ]
    },
    {
      "any_of": [
        {
          "finding": "myd88_l265p_mutation",
          "value": true
        },
        {
          "finding": "lymphgen_subtype",
          "value": "MCD"
        },
        {
          "finding": "abc_subtype",
          "value": true
        },
        {
          "finding": "non_gcb_subtype",
          "value": true
        },
        {
          "finding": "extranodal_involvement",
          "value": true
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notes

Informational RF — surfaces LymphGen MCD subtype for MDT discussion + prospective clinical-trial eligibility (e.g., ESCALADE, ongoing acalabrutinib + R-CHOP trials in non-GCB). Detection: targeted NGS panel (≥20 genes recommended) covering CD79B (exon 5, Y196), MYD88 (L265P), and ABC-subtype defining loci. Clinical correlates: extranodal disease (testicular DLBCL ~75% MCD; primary CNS lymphoma ~70% MCD-like), CNS-IPI score high. CNS-prophylaxis decision is informed by MCD signature + extranodal sites — independent of CD79B per se. Active research: BTKi addition to R-CHOP (PHOENIX, ESCALADE), ibrutinib monotherapy R/R MCD (Wilson Nat Med 2015 ABC subtype ORR 37%). NOT to be used to redirect 1L therapy outside clinical trial — RF is shifts_algorithm: [] by design. STUB — requires clinical co-lead signoff.

Used By

No reverse references found in the YAML corpus.