Cancer Staging & Pathology

CANCER STAGE & TUMOR GRADE

Cancer staging and tumor grading are used to classify the extent and characteristics of your cancer and to determine your diagnosis, inform treatment selection, and estimate likely treatment outcomes.  

CANCER STAGING

Your early diagnosis may only include a cancer type or a clinical stage (0-4/0-IV) until more details are gathered by a pathologist from a biopsy or surgical tissue sample. The pathologist will examine the cancer cells under a microscope and run lab tests on the sample to uncover additional information about your cancer. 

Once a surgical pathological assessment is complete, your oncologist will be able to use that information to determine a more specific stage using the pathological TNM staging system. A TNM stage takes a look at the primary tumor (T), surrounding lymph nodes (N), and any metastasis (M). a clinical stage is usually described using roman numerals and letters and a pathological stage is usually described with the T, N, and M letters with numbers. 

What is used to determine your cancer stage? 

• Physical Exam
• Imaging
• Tumor Location
• Biopsy/Surgery Tissue Specimen
• Invasion & Metastasis
• Tumor Grade
• Size of Primary Tumor
• Lab Tests
• Lymph Node Involvement
• Cancer Cell Type

Clinical Stage General Descriptions

Stage 0

• Abnormal cells are present but there is no spread or invasion, locally or otherwise. Also called carcinoma in situ (CIS), meaning “cancer in place.” Considered pre-cancerous.  

Stage I

• Considered “early” cancer that is small and localized (hasn’t spread from original location). Usually, Stage 1 is a less advanced cancer with a better prognosis than stages 2-4, but it can advance and spread if left untreated.  

Stage II

• Cancer has grown larger and/or into surrounding tissues, but it has not spread to distant sites in the body. This stage can be further subdivided into 2a, 2b, and 2c.  

Stage III

• Cancer is larger and has grown into, or invaded, nearby tissues and organs, including lymph nodes. This stage can be further subdivided into 3a, 3b, and 3c.  

Stage IV

• Cancer has metastasized, or spread, to distant tissues and/or organs within the body. This stage is considered advanced and can be further subdivided into 4a and 4b.  

If you see a “c” in front of your stage, that indicates it is a clinical stage based on imaging, biopsies, blood tests, physical exams, etc. If you see a “p” in front of your stage, that indicates it is a pathological (or surgical) stage based on surgical findings and tissue analysis completed after surgery in addition to the factors mentioned in clinical staging. Pathological staging is a more rigorous evaluation of your cancer than clinical staging. You won’t have a pathological stage until after surgery, if that is part of your treatment plan.  

Notations you may see in front of your stage:

c= clinical stage

p= pathological stage

y= restaged after treatment

r= restaged after recurrence or relapse

TUMOR GRADING & CELLULAR DIFFERENTIATION

Histologic tumor grading is a process in which a pathologist assesses cells under a microscope, determining how normal or abnormal the cells look and function in comparison to healthy cells of the same tissue. Normal-looking cells are considered well-differentiated, less aggressive, and slower to grow and spread. The most abnormal-looking cells are considered poorly or undifferentiated, more aggressive, and faster to grow and spread. 

Well-Differentiated

• cancer cells look and function very similarly to healthy cells of the same tissue. They tend to grow more slowly and be less invasive and aggressive than less differentiated cells. 

Moderately Differentiated

• cancer cells are looking more abnormal, less mature, less differentiated than well-differentiated cancer cells 

Poorly Differentiated and Undifferentiated

• cancer cells look and function very differently than healthy cells of the same tissue. They may be shaped oddly, disorganized, immature, less cohesive, more aggressive, quick to reproduce and grow, better able to hide from the immune system, more resistant to anti-cancer treatments, more angiogenic, and more invasive. 

De-differentiated 

• cancer cells are regressive, increasingly losing any differentiated/specialized features and growing in reverse to a less differentiated and more embryonic state. This state can encourage tissue regeneration & cancer proliferation and enable the cell to redifferentiate into multiple cell types that weren’t previously in reach. 

Tumors are graded Gx, G1, G2, G3, or G4 based on cellular differentiation. A grade of G1 indicates cells that are well-differentiated and pretty normal looking whereas G4 indicates undifferentiated, very abnormal looking cells. 

Gx: Undetermined Grade

G1: Low Grade

G2: Intermediate Grade

G3: High Grade

G4: High Grade

Tumor grading is a component of cancer staging based on the microscopic assessment of cancer cells. Cancer grade, along with blood work, imaging, scope procedures, biopsies, physical exams, and other pathology findings are used to determine your cancer stage. Hereditary mutations, genomic characteristics of the tumor, biomarkers/tumor markers, patient age, and other factors can also help determine staging and guide cancer treatment. 

See the graphics below for more details on cancer staging & tumor grading. 

A pathologist studies diseases at a microscopic level, examining tissues and fluids from the body to aid in the determination of a diagnosis, disease characteristics like aggressiveness or progression, what caused the disease, prognosis, and treatment selection. Any time you have tissue removed from your body (via biopsy or surgery), the specimen will be sent to a pathologist for analysis and a report will follow. 

Your pathology reports can provide information on cell malignancy, cancer stage and tumor grade, cancer cell type and tissue of origin, tumor size, cancer invasion & metastasis, cancer cells in lymph nodes, lymph vessels, or blood vessels, how quickly cancer cells are dividing and multiplying (mitotic rate), biomarkers, and if there are clean margins (no cancer cells identified) on the edges of the specimen. If the margins are not clear, it may indicate that cancer cells remain in the body. 

What can pathology tell us? 

• if tissue is cancerous (malignant) or non-cancerous (benign)
• what type of cells makeup your cancer and where in the body those cells originated
• if/where tumor cells have spread and to what extent
• if the cancer is aggressive and fast growing
• the grade of the tumor cells (how cancer cells compare to normal, mature cells of the same tissue)
• if specific proteins or genes are overexpressed or show a loss of expression
• if you're eligible for immunotherapy based on immunohistochemical (IHC) studies (microsatellite instability (MSI) and loss of expression of DNA mismatch repair (MMR) genes, for example)
• if you're eligible for certain therapies based on molecular pathology tests for targetable variants (mutations) in KRAS, BRAF, BRCA1, BRCA2, ALK, NTRK, and other genes
• if lymph nodes have cancer in them
• if nearby blood vessels or lymph vessels have cancer in them (Lymphovascular invasion, LVI)
• if cancer has invaded nearby nerves (Perineural invasion, PNI)

Your doctor and care team will incorporate these findings when establishing your diagnosis/stage, prognosis, and treatment plan recommendations.