Ductal Adenocarcinoma of the Pancreas: Understanding Your Pathology Report

Jason Wasserman MD PhD FRCPC
June 15, 2026

Ductal adenocarcinoma is the most common type of pancreatic cancer. It starts from the cells that line the small tubes (ducts) inside the pancreas. These cells normally help carry digestive fluids made by the pancreas into the small intestine. In ductal adenocarcinoma, cells begin to grow abnormally and invade surrounding tissue. Over time, the cancer may spread to nearby organs or to distant parts of the body. About two-thirds of these tumors arise in the head of the pancreas (the part closest to the small intestine), and the rest start in the body or tail of the gland. Most people have a single tumor.

This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What causes ductal adenocarcinoma of the pancreas?

The most well-known risk factor is smoking. Other risk factors include obesity, long-standing diabetes, chronic pancreatitis (ongoing inflammation of the pancreas), and a family history of pancreatic cancer. Heavy alcohol use may also raise the risk. Some people inherit gene changes (mutations) that increase their risk of developing pancreatic cancer, including mutations in BRCA2, BRCA1, PALB2, CDKN2A, and mismatch repair genes linked to Lynch syndrome. Because some of these gene changes can be passed down through families, your healthcare team may recommend genetic counseling and testing, which can also help relatives understand their own risk.

What are the symptoms of ductal adenocarcinoma?

Many people with ductal adenocarcinoma have symptoms such as fatigue, loss of appetite, indigestion, weight loss, or pain in the upper abdomen or back. If the tumor blocks the bile duct, it can cause jaundice, which makes the skin and eyes look yellow. Some people are diagnosed after developing new-onset diabetes. When the cancer has spread to the liver or other organs, symptoms may come from those areas as well. Because early pancreatic cancer often causes few or no symptoms, many tumors are found only after they have grown or spread.

How is the diagnosis made?

The diagnosis is made after a tissue sample is examined under the microscope by a pathologist. The sample is most often obtained by a fine needle during an endoscopic ultrasound (EUS), a procedure in which a thin scope is passed through the mouth and stomach to reach the pancreas. In some cases, the tissue is obtained during surgery. After the diagnosis is confirmed on a small sample, surgery may later be performed to remove the entire tumor if the cancer is considered removable.

Under the microscope, ductal adenocarcinoma consists of abnormal glands that grow in a disorganized manner and invade the surrounding pancreatic tissue. The glands are often irregular in shape and size and may contain mucin, a jelly-like substance normally made by pancreatic duct cells. The tissue around the tumor usually shows a dense, scar-like reaction to the invading cancer. In higher-grade tumors, the cancer cells may lose their gland-forming pattern and instead form solid sheets, with marked variation in cell size and shape.

Pathologists often use a test called immunohistochemistry (IHC) to support the diagnosis. This test uses antibodies linked to colored dyes to highlight specific proteins inside cells, which helps confirm that the tumor started in the pancreas and helps rule out other cancers that can look similar. No single protein identifies pancreatic ductal adenocarcinoma on its own, but certain combinations are helpful. Most of these tumors produce proteins typically found in pancreatic duct cells, such as CK7 and CK19. Other markers, such as synaptophysin and chromogranin (seen in neuroendocrine tumors) or trypsin (seen in acinar cell carcinoma), are usually negative, which helps separate ductal adenocarcinoma from those other tumor types. Many ductal adenocarcinomas also show loss of proteins that normally help control cell growth, such as SMAD4 (also called DPC4), and an abnormal pattern of the p53 protein. These changes support a diagnosis of cancer rather than a benign condition. In difficult cases, the pathologist combines these results with the imaging studies and clinical information to reach the final diagnosis.

Once cancer is confirmed, imaging tests such as CT and MRI are used to measure the size of the tumor, see whether it involves nearby blood vessels, and check whether it has spread to other organs. This information helps the treatment team decide whether the tumor can be removed with surgery.

Histologic grade

Histologic grade describes how different the tumor cells look compared with the normal cells of the pancreas. To assign a grade, the pathologist looks at how well the tumor forms gland-like structures, how much mucin it produces, how many cells are actively dividing (mitosis), and how abnormal the nuclei (the control centers of the cells) appear. The grade helps predict how the tumor is likely to behave and is one of the factors the treatment team considers when planning care.

Ductal adenocarcinoma of the pancreas is divided into three grades:

Well differentiated — The tumor cells look similar to normal cells, form organized glands, and divide slowly. These tumors tend to grow and spread more slowly.
Moderately differentiated — The tumor cells look more abnormal, form less organized glands, and divide more often.
Poorly differentiated — The tumor cells look very abnormal, form few or no glands, and divide quickly. These tumors tend to grow and spread more readily.

If a tumor contains areas of different grades, the highest grade is used for the final diagnosis. Higher-grade tumors are linked to a higher chance of the cancer returning or spreading and may lead the treatment team to consider more intensive treatment.

Histologic subtypes of ductal adenocarcinoma

Histologic subtypes are different patterns that the cancer cells can form when examined under the microscope. The subtype matters because some types grow and spread more readily, respond differently to treatment, or carry a better or worse outlook than typical ductal adenocarcinoma.

Adenosquamous carcinoma and squamous cell carcinoma

Adenosquamous carcinoma contains two kinds of cancer cells: gland-forming (adenocarcinoma) cells and squamous cells. Squamous cells are not normally found in the pancreas. In this subtype, at least 30 percent of the tumor consists of squamous cells. This subtype tends to grow and spread more quickly than typical ductal adenocarcinoma. Pure squamous cell carcinoma of the pancreas is very rare, and when it is found, doctors first make sure the cancer has not spread from another part of the body, such as the lungs.

Colloid carcinoma

Colloid carcinoma is a rare subtype in which the tumor cells float in large pools of mucin rather than forming tightly packed glands. It is often linked to a non-invasive tumor called an intestinal-type intraductal papillary mucinous neoplasm (IPMN). Colloid carcinoma tends to have a better outlook than most other pancreatic cancers, with a higher five-year survival rate.

Hepatoid carcinoma

Hepatoid carcinoma is a very rare type of pancreatic cancer that looks like liver cancer under the microscope. The tumor cells are large with pink cytoplasm, similar to liver cells, and they may produce a protein called alpha-fetoprotein (AFP). Because several tumors can mimic liver cancer, this diagnosis requires special tests to confirm where the cancer started. These tumors may grow and spread quickly, but information on the outlook is limited because the subtype is so rare.

Medullary carcinoma

Medullary carcinoma is a rare subtype made up of sheets or nests of poorly differentiated tumor cells that grow with a pushing rather than an infiltrating border. These tumors often contain many immune cells. Although they are poorly differentiated, some patients with this subtype have a better outcome than expected. Medullary carcinoma is often associated with microsatellite instability (a change in the cell’s ability to repair DNA) and may respond to immunotherapy.

Invasive micropapillary carcinoma

In this subtype, at least half of the tumor consists of small clusters of cancer cells surrounded by clear spaces, forming what pathologists call a micropapillary pattern. Micropapillary carcinomas tend to grow and spread more readily and may reach the lymph nodes and other parts of the body.

Signet-ring cell carcinoma

Signet-ring cell carcinoma is a very rare form of pancreatic cancer. The tumor is composed of individual cells that contain mucin, which pushes the nucleus to one side and gives the cells a “signet-ring” appearance. This pattern is often linked to cancers from other organs, such as the stomach or breast, so doctors carefully rule out spread from another site before diagnosing it as a tumor that started in the pancreas. These tumors tend to grow and spread quickly.

Undifferentiated carcinoma

Undifferentiated carcinoma is a high-grade cancer in which the tumor cells no longer resemble normal cells and do not form a clear pattern. These tumors often grow as solid sheets of cells with little or no gland formation. Recognized patterns include anaplastic undifferentiated carcinoma (with large, irregular cells and sometimes bizarre giant cells), sarcomatoid undifferentiated carcinoma (with spindle-shaped cells), and carcinosarcoma (which contains both gland-forming and spindle-shaped components, each making up at least 30 percent of the tumor). Undifferentiated carcinomas generally carry a poor outlook and tend to grow and spread quickly.

Undifferentiated carcinoma with osteoclast-like giant cells

This rare tumor contains three kinds of cells: non-cancerous osteoclast-like giant cells (large cells with many nuclei), non-cancerous immune cells, and the cancer cells themselves. Despite the very abnormal appearance of the cancer cells, some tumors in this group behave less quickly than expected, and some patients live for years after diagnosis. This subtype is related to typical ductal adenocarcinoma and shares some of the same genetic changes.

Perineural invasion

Perineural invasion means that cancer cells are growing along or around nerves. It is very common in pancreatic ductal adenocarcinoma and is an important finding because it may increase the chance of the cancer spreading or returning after surgery. If it is present, it will be described in your pathology report.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells are present within blood or lymphatic vessels near the tumor. This finding raises the risk that the cancer may spread to lymph nodes or to other parts of the body.

Surgical margins

A margin is the edge of the tissue that is cut during surgery to remove the tumor. After surgery, the pathologist examines these edges under the microscope to see whether any cancer cells reach them.

Negative margin — No cancer cells are seen at the cut edge. This suggests the tumor was likely removed completely. The pathologist may also record the distance between the tumor and the closest margin, because a very close margin (for example, less than 1 mm) can still raise the risk of the cancer returning.
Positive margin — Cancer cells are seen right at the cut edge. This raises concern that some cancer may have been left behind, and it may lead the treatment team to consider further surgery or radiation therapy.

In pancreatic surgery, several specific margins are usually examined, and your report may name them:

Pancreatic transection margin — The edge where the pancreas was cut to remove the tumor. It is often the most important margin for tumors in the head or neck of the pancreas.
Common bile duct margin — The edge of the bile duct removed with the pancreas. The bile duct carries bile from the liver to the intestine and passes near the head of the pancreas.
Uncinate (retroperitoneal) margin — The deep tissue margin behind the pancreas, close to important blood vessels and nerves. It is one of the margins most often involved by tumor.
Duodenal and gastric margins — If part of the small intestine (duodenum) or stomach is removed, the cut edges of these organs are also examined.

Lymph nodes

Lymph nodes are small, bean-shaped organs that are part of the immune system, and they are often one of the first places pancreatic cancer spreads. During surgery, nearby lymph nodes are usually removed and examined under the microscope. Your pathology report may describe the total number of lymph nodes examined, the number that contain cancer, the location of the involved nodes, and the size of the largest deposit of cancer within a node.

The report may also note whether extranodal extension is present. Extranodal extension means that cancer cells have broken through the outer capsule of a lymph node into the surrounding tissue. In pancreatic cancer, this finding is linked to a higher risk of the cancer returning. The number of lymph nodes containing cancer is used to assign the nodal stage (pN), which is described in the staging section below.

Biomarker and molecular testing

Biomarkers are measurable changes in tumor cells, usually involving specific genes or proteins, that help the treatment team understand how a cancer behaves and which treatments may be effective. Biomarker testing is increasingly important in pancreatic ductal adenocarcinoma because some tumors carry genetic changes that affect outlook, point toward targeted therapy or immunotherapy, or signal an inherited condition that affects family members. Most testing is done using next-generation sequencing (NGS), a method that reads many genes at once, performed on a biopsy or surgical sample. Some tests, such as those for inherited gene changes, are done on a blood or saliva sample. Testing is often done when the cancer is advanced or has spread, and germline (inherited) testing is recommended for most people with pancreatic cancer.

KRAS

KRAS is the most commonly mutated gene in pancreatic cancer, found in roughly 90 percent of tumors. A KRAS mutation keeps growth signals switched on, which drives the cancer to grow. The most common change in pancreatic cancer is KRAS G12D, followed by G12V, G12R, and others. For many years KRAS could not be targeted with drugs, but this is changing: drugs that block the KRAS G12C change (sotorasib and adagrasib) are approved for some other cancers and are being studied in the small number of pancreatic cancers with that change, while drugs aimed at KRAS G12D and at KRAS more broadly are being tested in clinical trials. KRAS results also carry information about outlook. Testing is done by NGS or PCR. Your report will state whether a KRAS mutation was found (and usually which specific change, such as G12D) or whether the tumor is KRAS wild-type, meaning no mutation was found. Tumors that are KRAS wild-type are more likely to carry other targetable changes, such as the gene fusions described below.

Mismatch repair (MMR) and microsatellite instability (MSI)

Mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) help correct small errors during DNA replication. When these proteins are lost, the tumor is described as mismatch repair deficient (dMMR) or microsatellite unstable (MSI-high). This pattern is uncommon in pancreatic cancer (about 1 percent of tumors) but is important for two reasons: it may make immunotherapy (such as pembrolizumab) an option, and it can be a sign of Lynch syndrome, an inherited condition that raises the risk of several cancers and may warrant genetic counseling for the patient and their relatives. MMR proteins are tested by immunohistochemistry, and MSI can also be measured by PCR or NGS. Your report will describe the tumor as mismatch repair proficient (pMMR), meaning all proteins are present, or mismatch repair deficient (dMMR), meaning one or more are missing.

BRCA1, BRCA2, and PALB2

BRCA1, BRCA2, and PALB2 are genes that help repair damaged DNA. Changes in these genes can be inherited (germline) or arise only within the tumor (somatic). They are important because tumors with these changes may respond to a type of targeted therapy called a PARP inhibitor; olaparib is approved as maintenance treatment for people with an inherited BRCA mutation and metastatic pancreatic cancer whose disease has not progressed after platinum-based chemotherapy. An inherited change also has implications for family members, who may carry the same gene change. Related DNA repair genes, such as RAD51C, RAD51D, and ATM, are sometimes tested as well and may suggest similar treatments. Testing is done by NGS, often on both a blood sample (to look for inherited changes) and the tumor (to look for changes within the cancer). Your report will state whether a mutation was found, and may specify whether it is inherited or tumor-only, or whether no mutation was detected.

NRG1 fusions

An NRG1 fusion is formed when the NRG1 gene joins with another gene, creating an abnormal protein that drives tumor growth. NRG1 fusions are rare overall but are found more often in pancreatic cancers that are KRAS wild-type. They are important because a drug called zenocutuzumab is approved for advanced pancreatic cancer with an NRG1 fusion when the disease has worsened after earlier treatment. NRG1 fusions are best detected using RNA-based NGS. Your report will state whether an NRG1 fusion was detected.

NTRK fusions

An NTRK fusion is another type of gene fusion that produces a growth-driving protein. NTRK fusions are rare in pancreatic cancer, but when present they may be treated with drugs approved across cancer types regardless of where the cancer started, such as larotrectinib or entrectinib. Testing is done by NGS. Your report will state whether an NTRK fusion was detected.

RET fusions

A RET fusion produces an abnormal protein that promotes tumor growth. Although rare in pancreatic cancer, a RET fusion may make a tumor eligible for selpercatinib, a drug approved across cancer types for RET fusion-positive tumors. Testing is done by NGS or, in some cases, FISH. Your report will state whether a RET fusion was detected.

BRAF

BRAF is a gene involved in a growth pathway. The BRAF V600E change is uncommon in pancreatic cancer, but when present, it may make a tumor eligible for the combination of dabrafenib and trametinib, which is approved across cancer types. Other BRAF changes are sometimes found in KRAS wild-type tumors. Testing is done by NGS or PCR. Your report will state whether a BRAF mutation was found (and, if so, which one, such as V600E) or whether no mutation was detected.

HER2 (ERBB2)

HER2 (also called ERBB2) is a protein that promotes cell growth. In a small number of pancreatic cancers, HER2 is overactive because of extra copies of the gene (amplification). When HER2 is strongly positive, a tumor may be eligible for trastuzumab deruxtecan, a HER2-targeted drug approved across cancer types for tumors with strong HER2 staining. HER2 is tested first by immunohistochemistry and scored as 0, 1+, 2+, or 3+. Scores of 0 or 1+ are considered HER2-negative; 3+ is HER2-positive; and 2+ is uncertain and warrants additional testing (such as FISH or NGS) to assess for amplification.

Tumor mutational burden (TMB)

Tumor mutational burden measures the number of mutations present in the tumor’s DNA. A high TMB (10 or more mutations per million DNA bases) can make a tumor eligible for immunotherapy with pembrolizumab, which is approved across cancer types for TMB-high tumors that have worsened after other treatment. High TMB is uncommon in pancreatic cancer and often overlaps with mismatch repair deficiency. TMB is measured by NGS. Your report will state whether the tumor is TMB-high.

For more general information about the tests in this section, visit our Biomarkers section.

Pathologic stage (pTNM)

The pathologic stage describes how far the cancer has grown and spread, based on examination of the tissue removed during surgery. It uses the TNM system (8th edition of the American Joint Committee on Cancer, or AJCC), which combines the size and extension of the tumor (pT), the involvement of lymph nodes (pN), and spread to distant organs (pM). The M part is usually determined by imaging rather than by the pathologist. Ductal adenocarcinoma begins in the small ducts of the pancreas and, as it grows, can extend beyond the pancreas into nearby fat, nerves, blood vessels, and organs. Growth into major arteries is what separates the highest tumor stage from the others.

Tumor stage (pT)

pT0 — No tumor was found.
pTis — Carcinoma in situ. The abnormal cells are present only within the ducts and have not invaded the surrounding pancreatic tissue. This includes high-grade precancerous changes such as PanIN-3.
pT1 — The tumor is 2 cm or smaller. It may be further divided into pT1a (0.5 cm or smaller), pT1b (more than 0.5 cm up to 1 cm), and pT1c (more than 1 cm up to 2 cm).
pT2 — The tumor is larger than 2 cm but not more than 4 cm.
pT3 — The tumor is larger than 4 cm but has not grown into nearby major arteries.
pT4 — The tumor has grown into one or more major arteries, such as the celiac axis, superior mesenteric artery, or common hepatic artery. The size of the tumor does not matter at this stage.

Nodal stage (pN)

pNX — The lymph nodes could not be assessed, or no lymph nodes were submitted.
pN0 — No cancer was found in any of the lymph nodes examined.
pN1 — Cancer was found in one to three regional lymph nodes.
pN2 — Cancer was found in four or more regional lymph nodes.

The number of lymph nodes containing cancer is strongly linked to outlook. People with more involved lymph nodes are more likely to have the cancer return after surgery, and this information helps the treatment team decide whether additional treatment, such as chemotherapy, may be considered.

What is the prognosis?

Ductal adenocarcinoma is a fast-growing cancer with a meaningful chance of spreading or returning after treatment. Outlook depends most on the stage at diagnosis, whether the tumor was completely removed by surgery, and whether it has reached the lymph nodes or other organs. Across all stages, five-year survival is low, around 13 percent. However, the numbers are higher for tumors found early: for cancers that are confined to the pancreas and completely removed with clear margins and no involved lymph nodes, five-year survival is considerably better. Adding chemotherapy before or after surgery improves outcomes for many patients.

The following features, when present on the pathology report, are linked to a higher risk of the cancer returning or spreading:

Higher tumor stage (pT3 or pT4) — Larger tumors and tumors that involve major arteries are harder to remove completely.
Involved lymph nodes (pN1 or pN2) — Cancer in more lymph nodes is linked to a higher risk of recurrence.
Positive or close surgical margins — Cancer cells at or near the cut edge raise the risk that some cancer was left behind.
Higher histologic grade — Poorly differentiated tumors tend to grow and spread more readily.
Perineural and lymphovascular invasion — Cancer growing along nerves or within vessels is associated with a higher risk of spread.

What happens after the diagnosis?

Care for pancreatic ductal adenocarcinoma usually involves a team that may include a surgeon, a medical oncologist, a radiation oncologist, a gastroenterologist, a pathologist, and a genetic counselor. The findings in your pathology report help this team decide on the next steps.

If the tumor is considered removable, surgery (such as a Whipple procedure for tumors in the head of the pancreas, or a distal pancreatectomy for tumors in the body or tail) may be performed, with the goal of removing the tumor with clear margins. Chemotherapy is often given before surgery, after surgery, or both; common regimens include FOLFIRINOX and the combination of gemcitabine and nab-paclitaxel. The choice depends on factors such as the stage, the margin and lymph node findings, and a person’s overall health. Radiation therapy may be considered in some situations, such as when margins are positive. Biomarker results help the team decide whether targeted therapy or immunotherapy may be an option, and an inherited gene change found on testing may lead to a referral for genetic counseling for the patient and their family.

Supportive (palliative) care focuses on managing symptoms such as pain, jaundice, and weight loss, and on maintaining quality of life. It is offered alongside other treatments from the time of diagnosis and is a standard part of care, not only an end-of-life measure. After treatment, follow-up usually includes regular imaging and clinic visits to watch for any return of the cancer.

Questions to ask your doctor

Where in the pancreas did the cancer start, and what was the size of the tumor?
What is the histologic grade of my tumor, and is it a special subtype?
What is the pathologic stage (pT and pN) of my cancer?
How many lymph nodes were examined, and how many contained cancer?
Were the surgical margins negative, close, or positive?
Was perineural or lymphovascular invasion seen in my tumor?
Was extranodal extension found in any of the lymph nodes?
Was biomarker or molecular testing performed, and what did it show?
Should I have germline (inherited) genetic testing, and what would it mean for my family?
Based on my report, is my cancer removable with surgery?
What treatments are being considered based on these findings, and in what order?
What follow-up tests will I need to watch for the cancer returning?