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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 Content is derived from published guidelines and regulatory sources and may contain errors or outdated information.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 MCL (majority of presentations). Full workup: t(11;14) FISH, Ki-67, TP53, MIPI-b score. Ki-67 ≥30% and/or TP53 mutation identifies high-risk disease.
Required — 3 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 MCL diagnosis confirmation. t(11;14) FISH mandatory. Rare blastoid MCL may show MYC rearrangement — identify before treatment.
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 central to MIPI-b score. Ki-67 ≥30% = high-risk MIPI-b → intensified induction (high-dose AraC + ASCT for eligible). Ki-67 ≥50–70% = blastoid/pleomorphic MCL.
Specimen
Evidence
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
Required for all advanced MCL (NCCN Category 2A). TP53 mutation (15–20% of MCL) predicts chemotherapy resistance including BTK inhibitor failure. TP53-mutant MCL is best managed on clinical trial or with novel agents (venetoclax, pirtobrutinib).
Specimen
Evidence
Recommended — 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
Recommended for advanced MCL. Identifies ATM deletion/mutation, CDKN2A loss, NOTCH1/2, and other alterations predicting BTK inhibitor resistance or informing novel combination strategies.
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.