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PubMed This is a summary of 24 peer-reviewed journal articles Updated
Pathology

Pathology, Biomarkers, and Your Report

At a Glance

A lung cancer pathology report identifies the cancer type and sample details. Biomarker testing checks for gene changes, gene fusions, and the PD-L1 protein; comprehensive results help your oncology team consider targeted treatment or immunotherapy.

Your pathology report is one of the most important documents in your medical journey. It is the “blueprint” of your cancer, detailing its unique genetic makeup and behavioral traits [1]. This information allows your oncology team to select treatments designed specifically for your tumor’s characteristics [2][3].

The Role of the Pathologist

A pathologist is a doctor who specializes in studying tissues and cells to diagnose disease. They examine your biopsy under a microscope to determine if the cancer is Non-Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC) [1][4]. They also use special dyes—a process called immunohistochemistry (IHC)—to identify markers that help distinguish between subtypes like adenocarcinoma and squamous cell carcinoma [5].

Tissue Biopsy vs. Liquid Biopsy

To get this information, doctors collect samples in two primary ways:

  • Tissue Biopsy: A doctor removes a small piece of the tumor. It is essential for determining the cancer’s physical structure (morphology) and is generally preferred for comprehensive biomarker testing when safely available [6][7].
  • Liquid Biopsy (ctDNA): A blood test that looks for circulating tumor DNA (ctDNA) shed by cancer cells into your bloodstream [8]. It is faster and less invasive. An actionable positive plasma result can be incredibly useful to quickly guide treatment [9][10]. However, a negative plasma result does not reliably rule out a mutation; it may simply mean the tumor is not shedding enough DNA into the blood. Therefore, negative liquid biopsies should generally be followed up with tissue testing [11][12].

The Critical Role of Comprehensive NGS

Next-Generation Sequencing (NGS) is a highly advanced test that reads hundreds of genes simultaneously [13]. Current guidelines strongly recommend comprehensive NGS for advanced NSCLC because it identifies actionable mutations that older, single-gene tests might miss [3][14]. A limited panel showing “no alteration detected” is not a substitute for comprehensive NGS.

Key Biomarkers and Targeted Mutations

If your NGS report shows an “actionable” mutation, it means there is a targeted therapy designed specifically for that cancer’s growth signal [15][16]. The panel should cover guideline-recommended DNA and RNA alterations, including but not limited to:

  • EGFR: Common types include “Exon 19 deletion”, “L858R”, and “Exon 20 insertions” [15].
  • ALK, ROS1, RET, and NTRK: These are fusions that often respond very well to specific pills [14][17].
  • KRAS G12C, MET Exon 14 skipping, BRAF V600E, and HER2/ERBB2: Mutations that each have dedicated targeted options [18][16][17].

(Note: Your report may also list a VUS or “Variant of Uncertain Significance.” This means a change was found, but it is not currently known to drive cancer growth or guide treatment. You do not need to actively monitor a VUS.)

PD-L1 and Immunotherapy

While NGS looks for genetic mutations, PD-L1 testing measures a protein on the surface of cancer cells [19]. It is reported as a Tumor Proportion Score (TPS). PD-L1 is an important factor, but it is not a rigid treatment algorithm. It is weighed alongside your histology, symptoms, and overall health [20].

  • TPS <1% (Negative) or 1%–49% (Low): Immunotherapy may still be an option, but it is often combined with chemotherapy to be most effective [20][21].
  • TPS ≥50% (High): This may make single-agent immunotherapy (without chemotherapy) an option for selected patients who do not have an actionable driver mutation, though combinations are still sometimes used depending on disease burden [20][22].

Checklist for Your Reports

Your molecular and pathology results may arrive in multiple separate reports. A complete diagnostic picture typically includes [23][24]:

  • [ ] Histologic Type: Specific diagnosis (e.g., Adenocarcinoma).
  • [ ] Specimen Details: Where the sample was taken and how (biopsy vs. resection).
  • [ ] Tumor Cellularity: The percentage of cancer cells in the sample (needed for accurate NGS).
  • [ ] NGS Results: A comprehensive list of mutations and fusions evaluated.
  • [ ] PD-L1 Status: The specific TPS percentage.
    (Note: Your clinical TNM stage is determined by your doctor using scans and biopsies combined, and will usually not appear on the laboratory pathology report itself.)

Common questions in this guide

What does comprehensive NGS test for in lung cancer?
Comprehensive next-generation sequencing, or NGS, examines many genes at the same time to find mutations and gene fusions that may have targeted treatments. For advanced non-small cell lung cancer, comprehensive testing is generally preferred over testing one gene at a time because limited testing can miss actionable changes.
Does a negative liquid biopsy rule out a lung cancer mutation?
No. A liquid biopsy looks for tumor DNA in a blood sample, but a tumor may release too little DNA for the test to detect a mutation. If the result is negative and tissue can be collected safely, doctors may recommend tissue-based testing.
What does PD-L1 TPS mean on a lung cancer report?
PD-L1 tumor proportion score, or TPS, is the percentage of cancer cells that show the PD-L1 protein. A score below 1%, 1%–49%, or 50% or higher can affect immunotherapy choices, but doctors also consider cancer type, symptoms, overall health, and actionable mutations.
Which lung cancer mutations and gene fusions may guide targeted treatment?
Commonly assessed changes include EGFR, ALK, ROS1, RET, NTRK, KRAS G12C, MET exon 14 skipping, BRAF V600E, and HER2 or ERBB2. When a result is actionable, it may point to a targeted treatment, although the choice depends on the exact result and the rest of the clinical picture.
What is a VUS on a lung cancer molecular report?
A variant of uncertain significance, or VUS, is a genetic change whose effect on cancer is not currently known. It generally does not guide treatment or require separate monitoring unless your clinician gives different advice.
What should be included in a complete lung cancer pathology and molecular report?
A complete diagnostic picture commonly includes the histologic type, specimen details, tumor-cell percentage, comprehensive NGS findings, and the PD-L1 TPS. The clinical TNM stage is usually determined from scans and biopsies together, so it may not appear on the laboratory pathology report.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Was my testing performed using comprehensive NGS, or were genes tested one by one?
  2. 2.What is my specific TPS percentage for PD-L1, and how does that factor into my treatment options?
  3. 3.If my liquid biopsy was negative, do we have enough tissue to confirm the results with a tissue NGS panel?
  4. 4.Are there any gene fusions like ALK, ROS1, or RET that were specifically tested for using RNA-based sequencing?
  5. 5.Is my molecular report complete according to current guidelines, or are we still waiting on any specific results?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

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This page explains lung cancer pathology and biomarker reports for informational purposes only and does not constitute medical advice. Your pathologist and oncology team should interpret your results and discuss treatment options for your situation.

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