Medical Disclaimer
genoCDS is a clinical reference tool for qualified healthcare professionals only. Content is derived from published guidelines and regulatory sources and may contain errors or outdated information. It is not a substitute for professional medical judgment, institutional protocols, or individual patient assessment. Always verify recommendations against current primary sources before making clinical decisions. Full disclaimer →
Stage Stage III
Involvement of lymph node regions on both sides of the diaphragm (III), with or without spleen (IIIS) or extralymphatic site (IIIE). Advanced disease.
4 test recommendations across 1 clinical indication
Advanced FL (Stages III–IV). FLIPI score, Ki-67, and TP53 mutation guide treatment urgency. Watchful waiting appropriate for asymptomatic low-bulk disease.
Required — 2 tests
BCL2/BCL6/MYC FISH Panel
Double/Triple-Hit FISH
FISH panel detecting rearrangements of MYC (8q24), BCL2 (18q21), and BCL6 (3q27). MYC + BCL2 rearrangements define double-hit lymphoma (DHL); MYC + BCL2 + BCL6 define triple-hit lymphoma (THL). Both are reclassified as High-Grade B-Cell Lymphoma (HGBL) per WHO 2022 and require intensified induction (DA-EPOCH-R). Required for all newly diagnosed DLBCL.
Ordering Note
Required for all advanced FL. MYC rearrangement mandates urgent re-evaluation for DLBCL transformation. BCL6 rearrangement helps identify Grade 3B.
Specimen
Evidence
Ki-67 Proliferation Index (IHC)
Ki-67
IHC measurement of MKI67 nuclear antigen, reflecting proliferating cell fraction. In MCL: Ki-67 ≥30% = MIPI-b high risk; ≥50% = blastoid/pleomorphic variant. In FL: Ki-67 >20% raises concern for Grade 3B or transformation. In DLBCL: Ki-67 >90% suggests very aggressive biology.
Ordering Note
Required. Ki-67 differentiates Grade 1–2 FL (low, often watch-and-wait) from Grade 3A (treat) and Grade 3B (DLBCL-like treatment). Component of FLIPI-2 and POD24 risk assessment.
Specimen
Evidence
Recommended — 1 test
TP53 Mutation Analysis
TP53
Sequencing of TP53 (17p13.1) for somatic mutations and copy number loss. In MCL: TP53 mutation (~15–20%) is the strongest adverse prognostic factor, predicting chemotherapy resistance and inferior BTK inhibitor outcomes. TP53-mutant MCL requires novel approaches (venetoclax, CAR-T, clinical trial). In FL: TP53 mutation increases transformation risk.
Ordering Note
Recommended for all advanced FL. TP53 mutation identifies high-risk patients with early progression risk (POD24) — may benefit from more aggressive initial therapy or trial enrollment.
Specimen
Evidence
Optional — 1 test
Comprehensive Solid Tumor NGS Panel
Comprehensive NGS
Next-generation sequencing panel covering ≥300 cancer-relevant genes, including all major NSCLC drivers (EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, NTRK, HER2, FGFR), plus tumor mutational burden (TMB) and microsatellite instability (MSI). Examples include FoundationOne CDx, Tempus xT, Caris MI Transcriptome, and equivalent institutional panels. Preferred over single-gene sequential testing for efficiency and cost-effectiveness.
Ordering Note
Optional. EZH2 mutation (~25% of FL) predicts response to tazemetostat (FDA approved R/R FL). Comprehensive NGS identifies CREBBP/EP300, KMT2D mutations relevant for emerging therapies.
Specimen
Evidence
Payer Coverage
Payer Coverage Summary
Coverage status as of last policy review. Prior authorization requirements and coverage criteria may change. Verify directly with each payer before ordering.
| Test | Medicare (CMS) | UnitedHealth | Anthem BCBS | Humana | Cigna | Aetna |
|---|---|---|---|---|---|---|
| Double/Triple-Hit FISH | Covered | Covered | Covered | Covered | Covered | Covered |
| Ki-67 | Covered | Covered | Covered | Unknown | Unknown | Unknown |
| TP53 | Covered | Covered | Covered | Prior Auth | Covered | Covered |
| Comprehensive NGS | Covered | Covered | Covered | Prior Auth | Covered | Covered |
Coverage data last verified via automated policy research. Always confirm current policies with each payer.
Recommendations on this page are derived from publicly available guidelines (NCCN, ASCO, ESMO, FDA, OncoKB) and are paraphrased for reference. They do not constitute medical advice. Evidence levels reflect the grading systems of each respective organization and should be interpreted in clinical context. This reference is updated periodically but may not reflect the most recent guideline revisions.