USMLE Prep - Medical Reference Library

Colorectal Cancer - Mismatch Repair and MSI Testing

System: Pathology • Reviewed: Aug 31, 2025 • Step 1Step 2Step 3

Synopsis:

Test all colorectal carcinomas for mismatch repair deficiency by immunohistochemistry or MSI to identify Lynch syndrome and guide immunotherapy decisions.

Key Points

  • Stabilize ABCs; begin targeted evaluation without delaying life-saving therapy.
  • Use system-specific risk tools to guide testing and disposition.
  • Order high-yield tests first; escalate imaging when indicated.
  • Start evidence-based initial therapy and reassess frequently.

Algorithm

  1. Primary survey and vitals; IV access and monitors.
  2. Focused history/physical; identify red flags and likely etiologies.
  3. Order system-appropriate labs and imaging (see Investigations).
  4. Initiate guideline-based empiric therapy (see Pharmacology).
  5. Reassess response; arrange consultation and definitive management.

Clinical Synopsis & Reasoning

For Colorectal Cancer Mismatch Repair Testing Msi, frame the differential by acuity and pathophysiology, then align diagnostics to the leading hypotheses. Prioritize stabilization while obtaining high‑yield studies such as CBC (Baseline hematology), BMP (Electrolytes/renal). Incorporate bedside imaging and targeted labs to define severity and identify complications; synthesize results with clinical trajectory to refine the working diagnosis and disposition needs.


Treatment Strategy & Disposition

Initiate disease‑directed therapy alongside supportive care, titrating to objective response. Pharmacologic options commonly include Analgesia/Antipyretics. Use validated frameworks (e.g., Common Patterns) to guide escalation and site of care. Address precipitating factors, de‑escalate empiric therapies with data, and arrange follow‑up for monitoring and risk‑factor modification; admit patients with instability, high risk of deterioration, or needs for close monitoring.


Epidemiology / Risk Factors

  • Risk factors vary by condition and patient profile

Investigations

TestRole / RationaleTypical FindingsNotes
CBCBaseline hematologyAbnormal counts
BMPElectrolytes/renalDerangements

Common Patterns

IHC lossNext step
MLH1 PMS2Test for BRAF or MLH1 methylation
MSH2 MSH6Genetic counseling for Lynch
Isolated MSH6 or PMS2Consider germline testing

Pharmacology

MedicationMechanismOnsetRole in TherapyLimitations
DexamethasoneGlucocorticoidHoursPeritumoral edema, antiemetic adjunctHyperglycemia
Ondansetron5-HT3 antagonismMinutesAntiemesisQT
Zoledronic acid/Denosumab (if bony metastases)Osteoclast inhibitionDaysPrevent SREsHypocalcemia; ONJ

Prognosis / Complications

  • Prognosis depends on severity, comorbidities, and timeliness of care

Patient Education / Counseling

  • Explain red flags and when to seek emergent care.
  • Reinforce medication adherence and follow-up plan.

Notes

Use validated assays and controls. Include statement about possible implications for other cancers in families.


References

  1. CAP and ASCO recommendations on mismatch repair testing — Link
  2. NCCN colorectal cancer genetic assessment — Link