High-Grade Papillary Urothelial Carcinoma: Understanding Your Pathology Report

Section Editor: Trevor Flood MD FRCPC
October 9, 2026

High-grade papillary urothelial carcinoma is a type of cancer that starts in the urothelial cells that line the inside of the urinary tract. The word papillary means the tumor grows as finger-like projections that stick out from the lining. The term high grade means the tumor cells look very different from normal urothelial cells under the microscope.

High-grade papillary urothelial carcinoma most often starts in the bladder, but it can also start in the kidney, the ureters, or the urethra. Many of these tumors are found while the cancer cells are still confined to the lining, which is called non-invasive. Others have already grown beyond the lining into the bladder wall, which is called invasive. Compared with low-grade tumors, high-grade tumors are more likely to grow deeper into the bladder wall and to spread.

This article explains how high-grade papillary urothelial carcinoma is diagnosed and what your pathology report says about the grade, invasion, and stage of the tumor. It also explains why treatment and close follow-up are needed even when the cancer has not invaded.

Who gets high-grade papillary urothelial carcinoma?

High-grade papillary urothelial carcinoma is mainly a disease of older adults, and the typical age at diagnosis is in the early 70s. It is about four times more common in men than in women. It is uncommon before the age of 40.

What causes high-grade papillary urothelial carcinoma?

Smoking is the most important cause of high-grade papillary urothelial carcinoma, because chemicals from tobacco smoke are filtered into the urine and damage the lining of the bladder. Long-term exposure to certain industrial chemicals, such as aromatic amines once used in dye and rubber manufacturing, also increases risk. Other causes include arsenic in drinking water and earlier treatment with radiation to the pelvis or with the chemotherapy drug cyclophosphamide.

A small number of urothelial carcinomas are linked to an inherited condition called Lynch syndrome. This link is strongest for tumors that start in the kidney or ureter. Stopping smoking lowers the chance of new tumors forming in the bladder after treatment.

What are the symptoms of high-grade papillary urothelial carcinoma?

The most common symptom of high-grade papillary urothelial carcinoma is blood in the urine, which is usually painless and may come and go. Some people notice the blood themselves, while in others it is found only on a urine test. Other symptoms include burning during urination and needing to urinate often or urgently. Pain in the side or lower back can occur if a tumor blocks urine flow.

How is the diagnosis made?

The diagnosis of high-grade papillary urothelial carcinoma usually begins after blood is found in the urine. A doctor may send a urine sample for cytology, a test in which a pathologist looks for cancer cells. Urine cytology is good at finding high-grade cancer cells because they look so different from normal cells. Our article on cytology explains this type of test.

A urologist then looks inside the bladder with a thin camera, a procedure called cystoscopy. If a tumor is seen, it is removed through the urethra in a procedure called a transurethral resection of bladder tumor, or TURBT. Our article on the TURBT pathology report explains the procedure and what pathologists examine.

Under the microscope, a pathologist sees thin projections called papillae, each with a central stalk of tissue and blood vessels called a fibrovascular core. In high-grade papillary urothelial carcinoma, the cells covering these papillae are large, vary in shape, and are arranged in a disorderly way. Many of the cells are dividing. The pathologist then decides whether the cancer cells have grown below the lining.

The pathologist also checks whether the thick muscle layer of the bladder wall, called the muscularis propria, is present in the sample. For a high-grade tumor, this is especially important, because these tumors can reach the muscle. Your TURBT report will describe the muscle layer in one of these ways:

Not identified. No muscle was included in the sample, so the pathologist cannot tell whether the cancer has reached it. For a high-grade tumor, a second TURBT is usually done to sample the muscle.
Present, negative for tumor. The sample included muscle, and no cancer cells were seen.
Present, involved by tumor. Cancer cells have grown into the muscle, which means the cancer is muscle-invasive.
Cannot be determined. The pathologist could not tell with certainty, often because the tissue was damaged during removal.

Imaging, such as a CT scan, is often used to check the kidneys and ureters for other tumors. If the cancer is invasive, scans are also used to look for spread to lymph nodes and other organs.

Histologic grade

The grade of a papillary urothelial carcinoma describes how different the tumor cells look from normal urothelial cells. For high-grade papillary urothelial carcinoma, grade is one of the most important findings in your report. It helps predict tumor behavior, and your team uses it to plan treatment and follow-up. Papillary urothelial carcinoma has two grades:

Low grade. The tumor cells look only slightly different from normal urothelial cells. These tumors often come back but rarely grow into the muscle, and they are described in our article on low-grade papillary urothelial carcinoma.
High grade. The tumor cells look very different from normal urothelial cells. These tumors are more likely to recur, invade the bladder wall, and spread.

Some papillary urothelial carcinomas contain both low-grade and high-grade areas. Under the World Health Organization (WHO) classification, 5th edition (2022), the tumor is graded as high grade when the high-grade areas make up 5% or more of the tumor. Your report may describe the tumor as high grade even if most of it looks low grade.

Some reports, especially in Europe, also assign a grade from 1 to 3 using an older 1973 WHO system. This grade is optional, and it is given alongside the low and high grade rather than replacing it. Most high-grade tumors are grade 3 in the older system, and some are grade 2.

Non-invasive and invasive high-grade papillary urothelial carcinoma

For high-grade papillary urothelial carcinoma, the next most important finding after grade is whether the cancer cells have grown below the lining. This process is called invasion. Your report will name the deepest layer of the bladder wall that contains cancer cells.

Non-invasive papillary carcinoma. The cancer cells are confined to the lining and papillae, and none have grown into the underlying tissue. Your report may also use the term non-invasive. These tumors are staged as pTa.
Invades the lamina propria. The cancer cells have grown into the lamina propria, the thin layer of connective tissue just below the lining. These tumors are staged as pT1, and they are still called non-muscle-invasive bladder cancer.
Invades the muscularis propria. The cancer cells have grown into the bladder wall’s thick muscle layer. This is muscle-invasive bladder cancer, and it is described in our article on invasive urothelial carcinoma.
Cannot be determined. The pathologist often cannot tell whether invasion is present because the tissue is damaged or poorly oriented. A second TURBT may be done to answer the question.

When high-grade papillary urothelial carcinoma invades the lamina propria, the pathologist will usually describe how much of this layer is involved, if measurable. The report may give the size or depth of the invasive area in millimeters. It may also say whether the cancer is above or below a thin band of muscle within the lamina propria, called the muscularis mucosae. More extensive invasion is linked to a higher chance that the cancer will grow into the muscle later.

When a high-grade tumor is invasive, the pathologist will also look for subtypes of urothelial carcinoma, such as the micropapillary, nested, or plasmacytoid subtype. These subtypes are listed in the College of American Pathologists (CAP) protocol and the WHO classification. Finding one in a pT1 tumor places the cancer in a higher-risk group, and your team may discuss removing the bladder early. Our article on urothelial carcinoma describes each subtype.

Your report may also mention urothelial carcinoma in situ in the lining near the papillary tumor. This flat, high-grade, non-invasive form of the cancer is common alongside high-grade papillary tumors and can be hard to see during cystoscopy. When it is present, the risk of the cancer coming back or growing into the muscle is higher.

Lymphovascular invasion

Lymphovascular invasion means cells from the high-grade papillary urothelial carcinoma are seen inside a small blood vessel or a lymphatic channel. Your report may call this “lymphatic and/or vascular invasion,” and it is reported as present, not identified, or cannot be determined. It can only happen once the cancer has invaded below the lining, so it is not seen in non-invasive tumors. When it is present in a pT1 tumor, the risk of spread is higher, and your team may discuss removing the bladder early.

Margins

A TURBT removes high-grade papillary urothelial carcinoma in many small pieces, so the pathologist cannot tell which edges were cut during surgery. For this reason, we do not report margins on a TURBT specimen. A second TURBT is often done to make sure no tumor remains. If the bladder is later removed in an operation called a cystectomy, the margins are reported as described in our article on the radical cystectomy pathology report.

Biomarker and molecular testing

Biomarker testing for high-grade papillary urothelial carcinoma looks for features of the cancer cells that can guide treatment. Most reports do not include these tests for non-invasive or pT1 tumors. They are usually done only if the cancer becomes advanced, comes back after surgery, or if a clinical trial is being considered. They can be performed on tissue from an earlier TURBT.

FGFR3

FGFR3 is a gene that makes a protein involved in cell growth. Changes in FGFR3 are less common in high-grade than in low-grade papillary urothelial carcinoma, but they are still found in some tumors. Testing is done with a molecular test such as next-generation sequencing (NGS). The test looks for a mutation or a fusion with another gene.

Detected. An FGFR3 change was found. If the cancer is advanced, this can make a person eligible for erdafitinib. The FDA granted full approval to erdafitinib in January 2024 for advanced urothelial carcinoma with certain FGFR3 changes, after at least one earlier treatment.
Not detected. No FGFR3 change was found. This means FGFR3-targeted drugs are not an option, but other treatments remain available.

HER2

HER2 is a protein on the surface of some cancer cells that helps them grow. In urothelial carcinoma, clinicians test for it by immunohistochemistry, mainly when the cancer is advanced. Results are scored from 0 to 3+.

0 or 1+. The cancer cells make little or no HER2.
2+. This is an in-between result, and your oncologist can explain what it means in your situation.
3+. The cancer cells make a large amount of HER2. In April 2024, the FDA granted accelerated approval to trastuzumab deruxtecan for advanced solid tumors with a HER2 score of 3+, after earlier treatment.

PD-L1

PD-L1 is a protein that some cancer cells use to hide from the immune system. In urothelial carcinoma, it is tested by immunohistochemistry and usually reported as a combined positive score (CPS) or as positive or negative. For most current immunotherapy treatments for urothelial carcinoma, including those used for high-risk non-invasive tumors, a PD-L1 result is not required. If your report includes a PD-L1 result, your oncologist can explain whether it affects your treatment. Our article on PD-L1 testing in cancer explains how the test works.

Mismatch repair proteins

Mismatch repair proteins fix mistakes that happen when a cell copies its DNA. Testing looks for four proteins called MLH1, PMS2, MSH2, and MSH6. For high-grade papillary urothelial carcinoma, it is done most often on tumors from the kidney or ureter, because of their link to Lynch syndrome.

Intact, retained, or no loss of expression. All four proteins are present. This is the normal result, making Lynch syndrome unlikely.
Loss of expression. One or more proteins are missing. This result does not confirm Lynch syndrome, but it warrants referral for genetic counseling and a blood test. Advanced tumors with this result may also respond well to immunotherapy.

Our article on mismatch repair across cancer types explains these results in more detail. For more information on tumor testing, visit our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for high-grade papillary urothelial carcinoma of the bladder is assigned using the TNM system from the AJCC Cancer Staging Manual, 8th edition. The tumor stage (pT) describes how deeply the cancer has grown. The nodal stage (pN) describes spread to lymph nodes and is assigned only when lymph nodes are removed. Spread to distant organs (M) is usually determined by imaging rather than by the pathology report.

Tumor stage (pT)

pTa. The tumor is non-invasive papillary carcinoma.
pTis. The report shows flat urothelial carcinoma in situ. If it is found alongside a papillary tumor, your report may list both.
pT1. The tumor has grown into the lamina propria but not into the muscle layer.
pT2. The tumor has grown into the muscularis propria.
pT3. The tumor has grown through the muscle into the fat around the bladder.
pT4. The tumor has grown into a nearby organ, such as the prostate, uterus, or vagina, or into the wall of the pelvis or abdomen.

A TURBT can show whether the cancer has reached the muscle, but it cannot show stages pT3 or pT4. Those stages are assigned only after the bladder is removed.

Nodal stage (pN)

Lymph nodes are not removed during a TURBT, so most reports for high-grade papillary urothelial carcinoma do not include a nodal stage. If lymph nodes are removed during a cystectomy, the nodal stage is assigned as follows:

pN0. No cancer was found in the examined lymph nodes.
pN1. Cancer was found in a single pelvic lymph node.
pN2. Cancer was found in more than one lymph node in the pelvis.
pN3. Cancer was found in lymph nodes along the common iliac arteries, which are higher in the pelvis.

Tumors that start in the kidney or ureter are staged with slightly different definitions, because the wall of these organs is thinner than the wall of the bladder.

What is the prognosis?

The prognosis for high-grade papillary urothelial carcinoma depends mostly on whether the cancer has invaded and how deeply. When the cancer has not reached the muscle, most people do well with treatment. However, these tumors often recur, and some later invade the muscle, which is why close follow-up is needed.

Non-invasive tumors. About 98 in 100 people with non-invasive bladder cancer are alive five years after diagnosis, and about 2 in 100 are not. For a high-grade pTa tumor without carcinoma in situ, about 3 in 100 later develop cancer in the muscle.
High-risk tumors treated with BCG. This group includes many high-grade pT1 tumors. About 5 to 7 in 100 people develop cancer in the muscle within five years.
Very-high-risk tumors. These are high-grade tumors with several additional risk features. Even with BCG, about 15 to 17 in 100 develop cancer in the muscle within five years.
Tumors that have invaded the bladder wall but not spread. About 73 in 100 people are alive five years after diagnosis, and about 27 in 100 are not. This group includes tumors that have reached the muscle, which have a less favorable outlook than pT1 tumors.

These numbers are averages for large groups of people and don’t predict what will happen to you. Features in your report that are linked to a higher chance of the cancer coming back or growing deeper include:

Invasion of the lamina propria. A pT1 tumor, especially when the invasion is extensive or below the muscularis mucosae.
Carcinoma in situ. Flat cancer in the lining near the papillary tumor.
Lymphovascular invasion. Cancer cells inside small vessels, which can carry them to other parts of the body.
A subtype. A subtype such as micropapillary or plasmacytoid in an invasive tumor.
Cancer remaining at a second TURBT. Especially when the second TURBT shows invasion.
Several or large tumors. More than one tumor, or a tumor larger than 3 cm, as described by your urologist.

What happens after the diagnosis?

After a diagnosis of high-grade papillary urothelial carcinoma, your care team uses the depth of invasion and other findings in your report to plan treatment. Your urologist combines these findings with the number and size of the tumors. Most high-grade tumors that have not reached the muscle are placed in the high-risk group, which guides treatment and follow-up. A single small high-grade pTa tumor may instead be placed in the intermediate-risk group.

A second TURBT. For pT1 tumors, and for pTa tumors when muscle was not sampled, or removal was incomplete, a second TURBT is usually done within a few weeks. It checks that no tumor remains and that the cancer has not reached the muscle.
BCG. BCG is a weakened bacterium that stimulates the immune system. It is placed in the bladder through a catheter, usually weekly for six weeks, followed by maintenance treatments for up to three years.
Durvalumab with BCG. In May 2026, the FDA approved durvalumab, an immunotherapy drug, to be given with BCG to some people with high-risk tumors who have not received BCG before.
Early removal of the bladder. For pT1 tumors with very-high-risk features, such as lymphovascular invasion or a subtype, your team may discuss removing the bladder instead of BCG.
Tumors that come back after BCG. If a high-grade tumor returns despite BCG, removing the bladder is often discussed. Several newer medicines are FDA-approved for some people in this situation, mainly when carcinoma in situ is also present.
Muscle-invasive tumors. These are treated as invasive urothelial carcinoma, usually with chemotherapy and surgery or radiation.

Drug approval and access differ by country, and your care team can explain what applies where you live. Follow-up for high-grade papillary urothelial carcinoma includes cystoscopy and urine cytology every few months at first. Checks become less frequent over time if no new tumor is found, and doctors repeat imaging of the kidneys and ureters from time to time.

Questions to ask your doctor

Is the tumor non-invasive, or has it grown into the lamina propria?
If there is invasion, how extensive is it, and is it above or below the muscularis mucosae?
Did my TURBT sample include muscle?
Do I need a second TURBT, and when?
Was carcinoma in situ found in the lining near the tumor?
Was lymphovascular invasion found?
Does my tumor have a subtype, such as micropapillary?
What is the stage of my cancer, and is it high risk or very high risk?
Will I receive BCG, and how long will the treatment last?
Am I a candidate for durvalumab with BCG, or for a clinical trial?
Should removing my bladder be considered now?
Should my kidneys and ureters be checked for other tumors?
How often will I need cystoscopy and urine tests?