Urothelial Carcinoma of the Renal Pelvis and Ureter: Understanding Your Pathology Report

Section Editor: Trevor Flood MD FRCPC
October 28, 2026

Urothelial carcinoma of the renal pelvis and ureter is a cancer that starts in the lining of the upper urinary tract. The renal pelvis is the funnel-shaped space inside the kidney where urine collects. The ureter is the tube that carries urine from the kidney to the bladder. Both are lined by urothelial cells, the same cells that line the bladder. Doctors often call this cancer upper tract urothelial carcinoma, or UTUC.

This article explains how doctors diagnose upper tract urothelial carcinoma and what the grade, stage, margins, and lymph node results in your pathology report mean. It also explains the biomarker tests, including mismatch repair testing for Lynch syndrome, and the treatments your care team may discuss.

Who gets urothelial carcinoma of the renal pelvis and ureter?

Upper tract urothelial carcinoma is an uncommon cancer. It makes up about 5 to 10 out of every 100 urothelial carcinomas, while most of the rest start in the bladder. It is more common in older adults, and the risk rises with age. Tumors in the renal pelvis are more common than tumors in the ureter.

What causes urothelial carcinoma of the renal pelvis and ureter?

Several factors increase the risk of upper tract urothelial carcinoma. The most important are:

Smoking. The kidneys filter chemicals from tobacco smoke into the urine, where they damage the urothelial lining.
Aristolochic acid. This plant toxin is found in some herbal remedies and in contaminated grain in parts of the Balkans and Asia.
Lynch syndrome. This inherited condition results from a change in one of the mismatch repair genes. The College of American Pathologists (CAP) notes that people with Lynch syndrome have a risk of upper tract urothelial carcinoma of up to 28 in 100.

An inherited cause is found in about 5 to 9 out of every 100 people with this cancer who go through genetic screening. This is why the workup includes testing for Lynch syndrome, as described in the biomarker section below.

What are the symptoms of urothelial carcinoma of the renal pelvis and ureter?

The most common symptom of upper tract urothelial carcinoma is blood in the urine, which may be visible or found only on a urine test. Some people have pain in the side or back, which can happen when the tumor or a blood clot blocks urine flow from the kidney. Some tumors are found on imaging done for another reason.

How is the diagnosis made?

Upper tract urothelial carcinoma is usually first seen on a CT urogram, a CT scan that shows the kidneys, ureters, and bladder after a contrast dye is injected. A cystoscopy, which uses a thin camera to look inside the bladder, can also check for bladder tumors. Urine may also be sent for cytology, a test that looks for cancer cells shed into the urine. Our article on cytology reports explains how this test is reported.

Tissue for diagnosis is usually taken during a ureteroscopy. A thin scope is passed through the bladder and up the ureter, and small pieces of the tumor are removed for a biopsy. A pathologist then examines the tissue under the microscope. The pathologist looks for abnormal urothelial cells and decides whether the tumor is low grade or high grade. Ureteroscopy biopsies are very small, so they often cannot show how deeply the tumor has grown. Surgeons usually determine the final grade and stage after removing the tumor.

What are the different types?

Urothelial carcinoma of the renal pelvis and ureter is described by how it grows. The World Health Organization (WHO) classification, 5th edition (2022), and the CAP ureter and renal pelvis protocol (version 2.4.0.0) recognize these main forms:

Noninvasive papillary urothelial carcinoma. The tumor grows as finger-like projections into the open space of the renal pelvis or ureter, without growing into the wall. Our articles on low-grade and high-grade papillary urothelial carcinoma explain this form in more detail.
Urothelial carcinoma in situ. Flat, high-grade cancer cells are confined to the lining. Our article on urothelial carcinoma in situ explains this form.
Invasive urothelial carcinoma. Cancer cells have grown beyond the lining into the wall of the renal pelvis or ureter, or beyond it.

About 1 in 4 upper tract urothelial carcinomas contain a subtype or divergent differentiation. This means part of the tumor looks different from the usual pattern. Examples include micropapillary, nested, plasmacytoid, and sarcomatoid subtypes, as well as areas that resemble squamous or glandular cancer. The European Association of Urology (EAU) treats the presence of a subtype as a high-risk feature.

Histologic grade

Urothelial carcinoma of the renal pelvis and ureter is given one of two grades, based on how abnormal the cancer cells look under the microscope. The grade helps predict how the tumor will behave and guides treatment decisions.

Low grade. The cancer cells look only slightly different from normal urothelial cells. Low-grade tumors are usually noninvasive and tend to grow slowly, although they often come back.
High grade. The cancer cells look very abnormal, and high-grade tumors are more likely to grow into the wall and spread.

Carcinoma in situ is always high grade, and most invasive cancers are high grade. A high-grade result on a ureteroscopy biopsy places a tumor in the high-risk group, which affects the treatment options discussed.

Lymphovascular invasion

In upper tract urothelial carcinoma, lymphovascular invasion means cancer cells are seen inside a lymphatic channel or blood vessel. These vessels can carry cancer cells to lymph nodes and other organs. The CAP protocol requires reporting this finding as present or not identified. When present, it is associated with a higher risk of the cancer coming back.

Surgical margins

A margin is the cut edge of tissue removed during surgery for upper tract urothelial carcinoma. The CAP protocol names several margins. These are the ureteral margins, the bladder cuff margin where the ureter enters the bladder, and the soft tissue margin around the kidney and ureter. Your report will describe the margins in one of these ways:

Negative margin. No cancer cells are seen at any cut edge, which suggests the tumor was completely removed. Some reports also give the distance between the cancer and the closest margin.
Positive margin for invasive carcinoma. Invasive cancer cells are present at a cut edge, which raises the chance that cancer remains and may lead your care team to consider additional treatment.
Carcinoma in situ or noninvasive carcinoma at the margin. Flat or papillary cancer that has not invaded is present at a ureteral or bladder cuff margin. The report states whether it is low-grade or high-grade.

Lymph nodes

Lymph nodes near the kidney and ureter may be removed during surgery for upper tract urothelial carcinoma and checked for cancer cells. For the renal pelvis, these include nodes around the kidney’s blood vessels, the aorta, and the vena cava. For the ureter, they also include nodes along the iliac vessels in the pelvis. Your report will list the number of nodes examined and how many contain cancer. It will also give the size of the largest cancer deposit in a node.

Some reports state whether extranodal extension is present. This means cancer cells have broken through the lymph node’s outer capsule into surrounding tissue. Cancer in the lymph nodes increases the stage and is one finding that prompts discussion of additional treatment after surgery.

Biomarker and molecular testing

Biomarker testing for upper tract urothelial carcinoma has two purposes. It checks for Lynch syndrome, and it identifies features that make a person eligible for specific drugs if the cancer is advanced. Some of these results are reported separately and may come back after the main pathology report.

Mismatch repair (MMR) and microsatellite instability (MSI)

Mismatch repair proteins fix small mistakes made when a cell copies its DNA. Four genes make them: MLH1, PMS2, MSH2, and MSH6. When one of these proteins is lost, mistakes build up, a change called microsatellite instability. In upper tract urothelial carcinoma, MMR testing matters for two reasons. A loss may point to Lynch syndrome, which affects family members. It also makes a person eligible for immunotherapy if the cancer is advanced. The FDA granted pembrolizumab full approval in 2023 for advanced MSI-high or MMR-deficient solid tumors that have grown after earlier treatment.

MMR is usually tested by immunohistochemistry, which uses stains to show whether each protein is present. MSI can also be tested from tumor DNA. The EAU guideline (2026) recommends a family history for everyone and germline testing when Lynch syndrome is suspected. It also suggests offering MMR or MSI testing to people without those warning signs. Your report may describe the result in one of these ways:

MMR proficient, intact, or retained. All four proteins are present, which is the most common result. If MSI testing is done, the result is microsatellite stable (MSS).
MMR deficient, or loss of expression. One or more proteins are missing, and MSI testing, if done, reports MSI-high. Genetic counseling and blood testing for Lynch syndrome are usually offered.

Our article on Lynch syndrome explains the inherited condition in more detail.

FGFR3

FGFR3 is a gene that makes a protein that helps control cell growth. Changes in FGFR3, such as mutations or fusions, are common in urothelial carcinoma. In January 2024, the FDA granted full approval to erdafitinib for advanced urothelial carcinoma with FGFR3 changes found by an approved test. It is used after at least one prior treatment and is not recommended for patients who could still receive immunotherapy first. The EAU guideline (2026) recommends FGFR testing when the cancer has spread. FGFR3 is usually tested using next-generation sequencing or a PCR-based test. Your report will say either that an FGFR3 alteration was detected, naming the change, or that no alteration was detected.

HER2

HER2 is a protein on the surface of some cancer cells that helps them grow. In April 2024, the FDA granted accelerated approval to trastuzumab deruxtecan for advanced solid tumors of any type that are HER2-positive (IHC 3+) after earlier treatment. HER2 is tested by immunohistochemistry and scored from 0 to 3+. A score of 3+ is positive, while scores of 0, 1+, and 2+ do not qualify under this approval.

PD-L1

PD-L1 is a protein that helps cancer cells hide from the immune system. In the United States, PD-L1 testing is not required for adjuvant nivolumab after surgery. The EAU guideline (2026) considers adjuvant immunotherapy mainly for people whose tumors are PD-L1-positive and who cannot have or decline chemotherapy. The result is reported as a score or a percentage of stained cells. Positive means the score is at or above the test’s cut-off, and negative means it is below.

Our Biomarkers and Genetic Testing section has more information about these tests.

Pathologic stage (pTNM)

The pathologic stage of upper tract urothelial carcinoma describes how far the cancer has grown and whether it has spread to lymph nodes. It uses the TNM system from the AJCC Cancer Staging Manual, 8th edition, which is still current for this cancer. The M category, for spread to distant organs, is usually decided by imaging rather than by the pathologist.

Tumor stage (pT)

pTa. Noninvasive papillary carcinoma that has not grown into the wall.
pTis. Carcinoma in situ, in which flat, high-grade cancer cells are found only in the lining.
pT1. The cancer has grown into the connective tissue just below the lining.
pT2. The cancer has grown into the wall’s muscle layer.
pT3. The cancer has grown through the muscle layer. In the renal pelvis, it has reached the fat around the pelvis or the kidney tissue. In the ureter, it has reached the fat around the ureter.
pT4. The cancer has grown into nearby organs or, through the kidney, into the fat around the kidney.

Nodal stage (pN)

pN0. No cancer was found in the examined lymph nodes.
pN1. Cancer was found in a single lymph node, and the deposit is 2 cm or smaller.
pN2. Cancer was found in a single lymph node with a deposit larger than 2 cm, or in more than one lymph node.
pNX. Lymph nodes were not removed or could not be assessed, and some reports say “pN not assigned” instead.

What is the prognosis?

The prognosis for upper tract urothelial carcinoma depends most on the pathologic stage. Noninvasive low-grade tumors have a much better outlook, although they often come back in the upper tract or bladder. A large United States study of more than 7,000 people treated with nephroureterectomy reported the following approximate 5-year cancer-specific survival rates. These describe how many people had not died of this cancer 5 years after surgery.

pT1. About 75 to 90 in 100 people.
pT2. About 75 to 80 in 100 people.
pT3. About 60 in 100 people.
pT4. About 20 to 40 in 100 people.
Cancer in the lymph nodes. About 40 in 100 people.

Other features linked with a higher risk of the cancer coming back include high grade, lymphovascular invasion, a positive margin, and the presence of a subtype. After treatment for upper tract urothelial carcinoma, new tumors often develop in the bladder, so regular cystoscopy is part of follow-up.

What happens after the diagnosis?

After upper tract urothelial carcinoma is diagnosed, the next steps depend on whether the tumor is low risk or high risk. The EAU guideline (2026) defines low risk as a single, low-grade tumor smaller than 2 cm, with no high-grade cells on urine cytology and no invasion on CT. All other upper tract urothelial carcinomas are treated as high risk. A team of urologists, medical oncologists, radiologists, and pathologists usually discusses these cases.

Kidney-sparing treatment for low-risk tumors. The tumor may be destroyed with a laser through a ureteroscope, or part of the ureter may be removed. The FDA approved a gel form of mitomycin, a chemotherapy drug placed into the upper tract, in 2020 for low-grade tumors.
Radical nephroureterectomy for high-risk tumors. Surgery removes the kidney, the whole ureter, and a small cuff of bladder. Surgeons may remove nearby lymph nodes at the same time.
A single dose of chemotherapy into the bladder. This is given soon after surgery to lower the chance of a new tumor in the bladder.
Chemotherapy after surgery. The EAU guideline recommends offering platinum-based chemotherapy to people whose report shows pT2 to pT4 cancer or cancer in the lymph nodes.
Immunotherapy after surgery. The FDA approved nivolumab in 2021 for urothelial carcinoma at high risk of coming back after surgery, including cancer of the renal pelvis and ureter.
Cancer treatment that has spread. The EAU guideline recommends enfortumab vedotin plus pembrolizumab as first-line treatment. Other options for advanced cancer depend on the biomarker results described above.

Follow-up includes regular cystoscopy and urine cytology, and CT scans for high-risk tumors. After removal of a kidney, your doctor will also monitor your kidney function.

Questions to ask your doctor

Was the tumor in my renal pelvis, my ureter, or both?
Is the cancer low-grade or high-grade?
Is the tumor noninvasive, or has it invaded the wall?
Was a subtype, such as micropapillary or plasmacytoid, found?
Does my tumor count as low risk or high risk?
Is kidney-sparing treatment an option for me?
What is the pathologic stage (pT and pN)?
Were the margins negative, including the bladder cuff margin?
Was lymphovascular invasion present?
How many lymph nodes were removed, and did any contain cancer?
Was my tumor tested for mismatch repair, and should I see a genetic counselor?
Would chemotherapy or immunotherapy after surgery help in my situation?
Has my tumor been tested for FGFR3 or HER2?
How often will I need cystoscopy and imaging?