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 Content is derived from published guidelines and regulatory sources and may contain errors or outdated information.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 II
Involvement of two or more lymph node regions on the same side of the diaphragm (II), or localized extralymphatic involvement + regional nodes on the same side (IIE).
4 test recommendations across 1 clinical indication
Stage II DLBCL. MYC/BCL2/BCL6 FISH and COO required before starting any induction therapy.
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. MYC/BCL2 double-hit FISH at Stage II changes treatment from R-CHOP to DA-EPOCH-R. Critical to complete before any systemic therapy.
Specimen
Evidence
Cell-of-Origin Gene Expression Profiling
COO / GEP
Gene expression profiling to classify DLBCL cell-of-origin (COO) as GCB or ABC/non-GCB. GCB DLBCL has superior outcomes with R-CHOP; ABC/non-GCB benefits from pola-R-CHP (POLARIX) and novel regimens. Lymph2Cx (NanoString) is the validated clinical platform; Hans IHC algorithm is less accurate.
Ordering Note
Required. COO classification essential for treatment planning. Non-GCB DLBCL may benefit from pola-R-CHP over R-CHOP.
Specimen
Evidence
Recommended — 1 test
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
Routinely reported. Ki-67 contributes to IPI-based risk stratification.
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
Consider for comprehensive profiling, particularly for clinical trial eligibility or to identify targetable mutations (EZH2, MYD88) at diagnosis.
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 |
| COO / GEP | Prior Auth | Prior Auth | Prior Auth | Investigational | Prior Auth | Prior Auth |
| Ki-67 | Covered | Covered | Covered | Unknown | Unknown | Unknown |
| 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.