Adenocarcinoma of the Colon: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
April 3, 2026

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Adenocarcinoma of the colon is the most common type of colon cancer. It starts in the gland-forming cells that line the inner surface of the colon. These cells normally produce mucus, which helps stool move through the large intestine. When these cells accumulate genetic changes and grow uncontrolled, they form a tumour called adenocarcinoma.

This article will help you understand the findings in your pathology report — what the terms mean, what the numbers indicate, and why each piece of information matters for your care.

What causes adenocarcinoma of the colon?

Most colon adenocarcinomas develop slowly over time as cells in the colon lining accumulate DNA damage. These changes can occur randomly, be influenced by lifestyle, or be inherited. In many cases, the cancer begins as a non-cancerous growth called an adenoma or polyp and then progresses to cancer over the years.

Important risk factors include a personal or family history of colorectal polyps or cancer, inherited conditions such as Lynch syndrome (which is caused by inherited mutations in mismatch repair genes and greatly increases colorectal cancer risk) or familial adenomatous polyposis (FAP) (which causes hundreds of polyps and a near-certain risk of cancer without treatment), and long-standing inflammation in the colon from conditions like ulcerative colitis or Crohn’s disease. Diets high in red or processed meat and low in fiber, limited physical activity, smoking, and heavy alcohol use also increase risk. If your tumour is found to have a mismatch repair deficiency (see Biomarker testing below), your doctor may recommend genetic counseling to evaluate whether Lynch syndrome is present, as this has implications for you and your family members.

What are the symptoms?

Colon adenocarcinoma often causes no symptoms in its early stages. As the tumour grows, symptoms can include a change in bowel habits such as constipation, diarrhea, or a change in stool shape; rectal bleeding or blood mixed with stool; abdominal discomfort, bloating, or pain; unexplained weight loss; and fatigue or weakness due to anemia (a low red blood cell count caused by slow, chronic bleeding from the tumour). Symptoms depend on the tumour’s size and location. Any persistent change in bowel habits or signs of bleeding should be discussed with your doctor.

How is the diagnosis made?

The diagnosis is made after a tissue sample is examined under the microscope by a pathologist. The sample is usually obtained during a colonoscopy, either as a biopsy of a suspicious area or as part of a polypectomy. Under the microscope, adenocarcinoma is identified when normal glandular structures are replaced by malignant-looking glands or tumour cells that invade deeper layers of the colon wall. The tumour cells typically have enlarged, irregular nuclei and may produce mucus.

Once a diagnosis is confirmed on a biopsy, imaging studies such as CT scans are used to determine whether the cancer has spread to lymph nodes or other organs before surgery is planned. If you had a biopsy or polypectomy during a colonoscopy, our guide to understanding your colonoscopy biopsy report may also be helpful.

Tumour grade

Tumour grade describes how closely the cancer cells resemble normal colon cells. It is determined by how much of the tumour forms recognizable gland-like structures under the microscope.

• Grade 1 (well differentiated) — More than 95% of the tumour forms glands. Closely resembles normal colon tissue.
• Grade 2 (moderately differentiated) — 50–95% of the tumour forms glands—some resemblance to normal tissue.
• Grade 3 (poorly differentiated) — Less than 50% of the tumour forms glands. Looks quite abnormal.
• Grade 4 (undifferentiated) — No gland formation at all.

Higher-grade tumors are more aggressive and more likely to spread. Some pathology reports use a simplified two-tier system in which grades 1 and 2 are grouped as low grade and grades 3 and 4 as high grade. Both systems describe the same thing, and your doctor will interpret the result in the context of all other findings.

Mucinous differentiation

Some colon adenocarcinomas produce large amounts of a gel-like substance called mucin. When more than 50% of the tumour is composed of mucin pools surrounding tumour cells, it is classified as a mucinous adenocarcinoma. This subtype has a somewhat distinct biology and is more commonly associated with mismatch repair deficiency. If your report describes mucinous features or mucinous differentiation, see the separate guide on mucinous adenocarcinoma for a detailed explanation.

Level of invasion

Invasion describes how deeply the tumour has grown into the wall of the colon. Adenocarcinoma starts in the innermost layer — the mucosa — and can spread into progressively deeper layers:

• Mucosa — the inner lining containing the epithelial cells where cancer begins
• Submucosa — a supportive layer of connective tissue just beneath the mucosa, containing blood vessels and lymphatic channels
• Muscularis propria — the thick muscle layer that contracts to move waste through the colon
• Pericolorectal tissues (subserosa/pericolic fat) — a thin layer of fat or connective tissue surrounding the outer muscle in parts of the colon
• Serosa — the smooth outer surface covering sections of the colon (not present in all parts)
• Adjacent organs — in advanced cases, the tumour may grow directly into nearby structures.

The deepest layer reached by the tumour is the level of invasion, which is used to determine the pathologic tumour stage (pT). As a tumour grows into deeper layers, the likelihood of spread to lymph nodes or distant organs increases.

Tumour budding

Tumour budding refers to single cancer cells or small clusters of up to four cells seen breaking away from the tumour at its advancing edge. The number of buds in the most active area under the microscope is counted and used to assign a score: low, intermediate, or high. A high tumour budding score is associated with a greater risk of lymph node involvement and cancer recurrence, and may influence decisions about additional treatment after surgery.

Lymphatic invasion

Lymphatic invasion means cancer cells are present inside lymphatic channels — tiny vessels that drain fluid toward nearby lymph nodes. Finding tumour cells inside these channels suggests a higher chance that cancer has spread, or could spread, to nearby lymph nodes. Pathologists may use immunohistochemistry with special stains to highlight these small channels and confirm their involvement.

Vascular invasion

Vascular invasion means cancer cells are present inside blood vessels. This can occur within the colon wall (intramural vascular invasion) or in the surrounding fatty tissue outside the wall (extramural vascular invasion). Both are associated with a higher risk of the cancer spreading to distant organs such as the liver or lungs. Still, extramural vascular invasion is considered particularly important and is specifically noted when present. Special stains may be used to confirm this finding.

Perineural invasion

Perineural invasion means cancer cells are growing along or around a nerve. This feature is more often seen in advanced tumors and is associated with a higher risk that the cancer will spread or recur after treatment. Your pathology report will state whether perineural invasion was identified.

Immune response

The body often mounts an immune response to a tumour by sending lymphocytes and other immune cells to surround and infiltrate it. A strong immune response in and around the tumour is generally a favorable sign and is associated with better outcomes. A specific pattern called a Crohn-like reaction — clusters of immune cells at the outer edge of the tumour — is also associated with a more favorable prognosis. These immune features are more commonly seen in tumors with mismatch repair deficiency.

Surgical margins

Margins are the cut edges of the tissue removed during surgery. The pathologist examines margins to determine whether the tumour was removed in its entirety.

• Negative margin — No cancer cells are seen at the cut edge. This is the goal of surgery and indicates the tumour was fully removed in that area.
• Positive margin — Cancer cells are present at the cut edge, suggesting some tumour may remain. This usually leads to a recommendation for additional treatment.

In colon surgery, the relevant margins include the proximal and distal margins (the two cut ends of the removed bowel segment), the mesocolic (mesenteric) margin (the soft-tissue surface along the blood supply), and — in rectal cancers — the circumferential resection margin (CRM), the closest non-mucosal surface to the tumour.

Treatment effect

Some patients receive chemotherapy or radiation therapy before surgery (called neoadjuvant treatment) to shrink the tumour. After surgery, the pathologist evaluates how much viable tumour remains and assigns a treatment response score:

• Score 0 — No viable cancer cells remain (complete response).
• Score 1 — Single cells or rare small groups of cancer cells remain (near-complete response).
• Score 2 — Residual cancer with evidence of regression, but more than just isolated cells (partial response).
• Score 3 — Extensive residual cancer with no evidence of regression (poor or no response).

A complete or near-complete response is associated with a better prognosis.

Tumour deposits

Tumour deposits are small nodules of cancer cells found in the fat surrounding the colon or rectum, outside the main tumour and not within a recognizable lymph node. They represent local spread and are an adverse prognostic feature. If tumour deposits are present but no lymph nodes contain cancer, the nodal stage is classified as pN1c. If positive lymph nodes are also present, the nodal stage is based on the number of involved nodes, with tumour deposits still recorded as they influence treatment decisions.

Lymph nodes

Lymph nodes are small immune organs that filter lymphatic fluid. During surgery, the lymph nodes in the fatty tissue attached to the removed colon segment (the mesentery) are examined by the pathologist. Your report will state the total number of lymph nodes examined and the number, if any, that contain cancer.

Lymph node involvement is one of the most important factors in determining the pathologic nodal stage (pN) and in deciding whether chemotherapy is recommended after surgery. When cancer is found in a lymph node, the report may also note the size of the largest deposit and whether the cancer has broken through the lymph node’s outer wall — a finding called extranodal extension, which carries a worse prognosis.

Biomarker and molecular testing

Biomarkers are measurable features of tumour cells — usually specific genes or proteins — that help doctors understand how the cancer behaves and how it is likely to respond to treatment. Biomarker testing is now a standard part of managing colorectal cancer, and the results directly influence treatment decisions. Testing is typically performed using immunohistochemistry (which detects proteins) and molecular tests such as PCR or next-generation sequencing (which analyze tumour DNA).

Mismatch repair (MMR) proteins: MLH1, PMS2, MSH2, MSH6

Mismatch repair proteins are part of the cell’s system for fixing small errors in DNA. When one or more of these proteins — MLH1, PMS2, MSH2, or MSH6 — are absent from tumour cells, the result is called mismatch repair-deficient (MMR-deficient or dMMR), also known as microsatellite instability-high (MSI-high). When all proteins are present, the result is MMR-proficient (pMMR).

This is one of the most clinically important biomarkers in colorectal cancer because MMR-deficient tumors may respond to immunotherapy (checkpoint inhibitor drugs such as pembrolizumab), whereas MMR-proficient tumors typically do not. MMR deficiency is also a signal to investigate whforynch syndrome, as an inherited mutation in one of these genes would have implications for the patient and family members. Further tests — including BRAF and MLH1 promoter hypermethylation testing — are usually performed to help determine whether the MMR deficiency is inherited or sporadic.

MLH1 promoter hypermethylation

When MLH1 and its partner PMS2 are lost, the most common explanation is a chemical silencing of the MLH1 gene called MLH1 promoter hypermethylation. This change is acquired in the tumour cells only and is not inherited — it is the most common cause of sporadic (non-inherited) MMR deficiency. Finding MLH1 hypermethylation usually means Lynch syndrome is unlikely, though a BRAF V600E mutation (see below) is typically also checked to confirm this.

KRAS and NRAS

KRAS and NRAS are genes that control cell growth signaling. Mutations in either gene keep growth signals permanently active and, critically, make tumours resistant to a class of targeted therapies called anti-EGFR drugs (such as cetuximab and panitumumab). KRAS and NRAS testing is therefore performed before these drugs are considered. About half of all colorectal cancers carry a KRAS or NRAS mutation. Your report will state whether each gene is mutated or wild-type (no mutation detected).

BRAF

The BRAF gene is part of the same growth pathway as KRAS and NRAS. The BRAF V600E mutation is found in approximately 8–10% of colorectal cancers and is associated with more aggressive behavior and a worse prognosis. Like KRAS/NRAS mutations, it predicts resistance to anti-EGFR therapy. Importantly, the BRAF V600E mutation is strongly associated with sporadic MLH1 hypermethylation and effectively rules out Lynch syndrome as the cause of MMR deficiency when present. BRAF-mutated tumors in advanced disease may also be candidates for BRAF-targeted combination therapies.

HER2 (ERBB2)

In a small subset of colorectal cancers — particularly those without KRAS, NRAS, or BRAF mutations — the HER2 gene can be amplified, resulting in excess HER2 protein on tumour cells. HER2-positive colorectal cancers may respond to HER2-targeted therapies, and HER2 testing is increasingly performed, particularly in advanced or metastatic disease when other treatment options have been exhausted. Results are reported as 0, 1+, 2+, or 3+, with 3+ considered positive. A 2+ result is equivocal and requires additional testing to confirm gene amplification.

PIK3CA and PTEN

PIK3CA mutations and PTEN loss both affect a growth-signaling pathway, potentially reducing the benefit of anti-EGFR therapy. PIK3CA mutations are found in approximately 10–20% of colorectal cancers; some studies suggest that patients with these mutations may benefit from taking aspirin after surgery, though this is not yet standard practice. PTEN loss can be detected by immunohistochemistry or molecular testing. These markers are more commonly assessed in advanced disease when treatment selection is complex.

PD-L1

PD-L1 is a protein that some tumour cells produce to evade immune attack. PD-L1 testing may be performed when immunotherapy is being considered. Results are often reported as a Combined Positive Score (CPS) reflecting expression across both tumour and immune cells. In colorectal cancer, MMR deficiency is generally the more reliable predictor of immunotherapy response, but PD-L1 results provide additional context in some clinical situations.

For detailed explanations of these and other biomarkers in colorectal cancer, visit our Biomarkers and Molecular Testing section.

Pathologic stage (pTNM)

Pathologic staging describes how far the cancer has spread based on examination of the surgical specimen. It uses the internationally recognized TNM system, considering the primary tumour (T), lymph node involvement (N), and distant metastasis (M). The pathologist determines the pT and pN stages; the M stage is typically determined by imaging.

Tumour stage (pT)

• pT1 — Cancer has grown into the submucosa but not the muscle layer.
• pT2 — Cancer has grown into the muscularis propria (muscle layer).
• pT3 — Cancer has grown through the muscle layer into the pericolorectal fat or tissue.
• pT4a — Cancer has reached the outer surface of the colon (serosa/visceral peritoneum) or has perforated through it.
• pT4b — Cancer has grown directly into a nearby organ or structure such as the bladder, uterus, or abdominal wall.

Nodal stage (pN)

• pN0 — No cancer found in any lymph nodes examined.
• pN1a — Cancer found in 1 lymph node.
• pN1b — Cancer found in 2 to 3 lymph nodes.
• pN1c — Tumour deposit(s) present in pericolorectal fat, but no cancer in lymph nodes.
• pN2a — Cancer found in 4 to 6 lymph nodes.
• pN2b — Cancer found in 7 or more lymph nodes.
• pNX — Lymph nodes were not assessed.

What is the prognosis for colon adenocarcinoma?

The prognosis for colon adenocarcinoma depends on several factors working together, and no single finding tells the complete picture. The most important are the pathologic stage — particularly whether the cancer is confined to the colon wall or has spread to lymph nodes or distant organs — and whether the tumour was completely removed with clear margins.

For localized disease (cancer confined to the colon wall with no lymph node involvement), outcomes are generally very good, with most patients achieving long-term cure after surgery. When lymph nodes are involved, the risk of recurrence is higher, and chemotherapy after surgery is often recommended. Advanced or metastatic disease requires systemic treatment, and outcomes are more variable but continue to improve as new therapies become available.

Additional factors that influence prognosis include tumour grade, the presence of lymphovascular or perineural invasion, high tumour budding score, extramural vascular invasion, and molecular features. MMR deficiency, for example, is generally associated with a more favorable prognosis in localized disease but is a strong predictor of immunotherapy benefit in advanced disease. Your treatment team will consider all of these factors together when discussing your outlook and planning your care.

What happens after diagnosis?

After diagnosis, your healthcare team uses your pathology report, imaging results, and overall health to plan treatment. The team typically includes a surgeon, a medical oncologist, a radiation oncologist, and a pathologist. Treatment depends on stage, tumour features, and biomarker results.

For most patients, surgery to remove the segment of colon containing the tumour and its nearby lymph nodes is the primary treatment. Chemotherapy after surgery (adjuvant chemotherapy) may be recommended if the stage or tumour features suggest a higher risk of recurrence. In some situations — especially for rectal cancers or locally advanced tumors — chemotherapy or radiation may be given before surgery to shrink the tumour first. If the tumour carries specific biomarkers such as MMR deficiency, HER2 amplification, or a BRAF mutation, your oncologist may discuss immunotherapy or targeted therapy as part of standard care or within a clinical trial.

After treatment, you will have regular follow-up, including clinic visits, blood tests (including CEA, a tumour marker), and periodic imaging. Colonoscopic surveillance is used to detect new polyps or early recurrence. If a significant portion of the colon was removed, your team will also monitor bowel function and nutritional status.

Questions to ask your doctor

Your pathology report contains important information that will guide your care. The following questions may help you prepare for your next appointment.

• What is the stage and grade of my tumour?
• Were the surgical margins negative? Was the tumour completely removed?
• Were lymph nodes involved, and if so, how many?
• Were any high-risk features found, such as extramural vascular invasion, perineural invasion, or high tumour budding?
• What were the results of MMR/MSI testing, and does my tumour qualify for immunotherapy?
• Should I be referred for genetic counseling to assess for Lynch syndrome?
• What were the results of KRAS, NRAS, BRAF, and HER2 testing, and how do they affect my treatment options?
• Do I need chemotherapy after surgery, and what regimen would you recommend?
• Are there clinical trials available for my stage and tumour type?
• What follow-up tests and appointments will I need, and how often?
• Should my family members be considered for colorectal cancer screening given my diagnosis?