TFE3-Rearranged Renal Cell Carcinoma: Understanding Your Pathology Report

Section Editor: Trevor Flood MD FRCPC
July 18, 2026

TFE3-rearranged renal cell carcinoma is a rare type of kidney cancer. It is caused by a single genetic accident: a gene called TFE3, which sits on the X chromosome, breaks and joins onto a different gene, producing a new hybrid gene that drives the cell to grow. Another name for this cancer is Xp11 translocation renal cell carcinoma, which refers to the exact spot on the X chromosome where the break occurs. Both names describe the same disease, and you may see either on your report.

This cancer stands out for who it affects. It accounts for roughly 4 out of every 10 kidney cancers in children and teenagers, making it the most common kidney cancer in young people, while making up only about 2 to 4 out of every 100 kidney cancers in adults. It is somewhat more common in women and girls than in men and boys.

This article will help you understand the findings in your pathology report for TFE3-rearranged renal cell carcinoma, what each term means, and why it matters for your care or the care of your child.

What causes TFE3-rearranged renal cell carcinoma?

TFE3-rearranged renal cell carcinoma, a rare kidney cancer, is caused by a translocation, an event in which two chromosomes break and swap pieces. The break occurs at a point on the X chromosome called Xp11.2, where the TFE3 gene is located. TFE3 normally makes a protein that switches other genes on and off at the right moments. When it joins onto a partner gene, the result is a fusion gene that makes a hybrid protein stuck permanently in the “on” position, and the cell keeps growing and dividing. More than twenty partner genes have been identified; the most common are ASPSCR1 (also called ASPL), PRCC, SFPQ, NONO, and RBM10. Which partner is involved can matter, as described in the biomarker section below.

Two points about causation are worth making clear, because they differ from what patients often expect.

This cancer is not inherited — the translocation occurs in a single kidney cell during a person’s lifetime. It is not present in the rest of the body; it was not passed down from a parent, and it cannot be passed on to children. This sets this cancer apart from other kidney cancers of the young, such as fumarate hydratase-deficient and succinate dehydrogenase-deficient renal cell carcinoma, which are usually inherited. Germline genetic testing is therefore not routinely offered for this diagnosis.
Prior chemotherapy is the one known risk factor — People treated with certain chemotherapy drugs for an earlier cancer, often in childhood, have a higher risk of developing this tumor years later. This accounts for a minority of cases. For everyone else, no cause has been identified, and nothing you did or did not do brought it about.

What are the symptoms of TFE3-rearranged renal cell carcinoma?

Many people with TFE3-rearranged renal cell carcinoma, a rare kidney cancer, have no symptoms, and the tumor is found by accident when an ultrasound, CT scan, or MRI is done for an unrelated reason. When symptoms do occur, they may include:

Blood in the urine, which can make the urine look red, pink, or brown.
Pain or a dull ache in the back or the side of the abdomen.
A lump or fullness in the abdomen or side.
Weight loss that was not intended, or fatigue.

This tumor is found at a more advanced stage more often than the common kidney cancers, and for some people the first sign is a symptom caused by spread to another part of the body (a process called metastasis) rather than by the kidney tumor itself.

How is the diagnosis made?

The diagnosis of TFE3-rearranged renal cell carcinoma is made when a pathologist examines kidney tissue under a microscope and a genetic test confirms the fusion. The tumor is usually first seen as a mass in the kidney on imaging. Tissue is most often obtained by surgery to remove the tumor, although a needle biopsy may be performed first when the cancer has already spread.

Under the microscope, the classic appearance is a tumor composed of papillae (finger-like projections) made of large cells with clear or pale pink cytoplasm, often containing psammoma bodies, which are tiny, round deposits of calcium. The difficulty is that this appearance overlaps heavily with the two most common kidney cancers: the clear cells resemble clear cell renal cell carcinoma, and the papillae resemble papillary renal cell carcinoma. Appearance alone cannot make this diagnosis, and it is likely that some of these tumors in adults have been classified as one of the common types. This is the main reason a pathologist reaches for additional testing, particularly in a young patient or when the appearance does not fit neatly into a familiar category.

The first additional test is usually immunohistochemistry, which uses special stains to detect proteins inside cells. In this tumor, the TFE3 protein accumulates in the cell nucleus, and the stain shows strong nuclear staining, described in reports as nuclear reactivity or nuclear expression. Two quirks of this tumor often show up alongside it: the cells may stain for markers usually associated with pigment cells, such as Melan-A and HMB-45, and for a protein called cathepsin K, while staining only weakly or not at all for cytokeratins, the proteins most carcinomas express strongly. PAX8, which confirms the tumor started in the kidney, is typically positive.

The TFE3 stain alone is not sufficient to make the diagnosis, which is an important point. The stain is technically difficult, results can be patchy or borderline, and a small number of ordinary clear cell renal cell carcinomas stain positive without having any fusion at all. Confirming the diagnosis requires a genetic test. Two are used. Fluorescence in situ hybridization (FISH) uses fluorescent probes to see whether the TFE3 gene has been broken apart. FISH is widely available but misses roughly 1 in 10 of these tumors because, in some cases, the gene rearranges within the X chromosome itself rather than swapping with another chromosome, and the probes cannot detect that. Next-generation sequencing of RNA reads the fusion directly, identifies the partner gene, and is the preferred confirmatory test when available. If your report describes a suspected TFE3-rearranged renal cell carcinoma with molecular testing pending, or mentions that FISH was negative but the appearance remains suspicious, this is why. Once the diagnosis is confirmed, imaging of the chest and abdomen is used to look for spread.

Histologic grade

Most kidney cancers are given a grade, a number from 1 to 4 describing how abnormal the cells look, using the WHO/ISUP system. The grade is based on how easily the nucleoli (small round structures inside the nucleus of each cell) can be seen under the microscope: at grade 1 they cannot be seen even at high magnification; at grade 2 they are visible at high magnification only; at grade 3 they are clearly visible at low magnification; and grade 4 covers tumors with extreme variation in cell size and shape, giant cells, or sarcomatoid or rhabdoid cells. This system replaced the older Fuhrman grading system, which you may still see on older reports.

A grade may or may not appear on your report for TFE3-rearranged renal cell carcinoma. The WHO/ISUP system was developed and validated for clear cell and papillary renal cell carcinoma, and how well the grade predicts behavior in this tumor is less well established, partly because the tumor is rare and partly because its behavior is driven by the fusion itself. Where a grade is reported, it is interpreted alongside the other findings rather than on its own. The findings described in the next section are clearer signals.

Sarcomatoid and rhabdoid features

Some TFE3-rearranged renal cell carcinomas contain areas where the tumor cells have changed their appearance completely. These changes, called sarcomatoid and rhabdoid features, identify tumors more likely to grow quickly and spread, and they can be found in any type of renal cell carcinoma.

Sarcomatoid features — The tumor cells are replaced by long, thin, spindle-shaped cells that resemble a soft tissue cancer rather than a carcinoma.
Rhabdoid features — The tumor cells become large and round with a bright pink center and an off-to-the-side nucleus, resembling muscle cells.

If either is present, your report will state the percentage of the tumor involved, and the tumor is placed in the highest grade category. Both are associated with a higher risk of the cancer returning or spreading. If your report does not mention them, they were not found.

Tumor size

Your pathology report will state the size of the TFE3-rearranged renal cell carcinoma, measured in centimeters, from the tissue removed at surgery. This measurement is more accurate than the size estimated on imaging beforehand, so the two numbers may not match exactly. Size determines part of the tumor stage (pT), and the thresholds are 4 cm, 7 cm, and 10 cm.

Multifocal tumors

When only one tumor is present, pathologists call it unifocal. When more than one tumor is found in the same kidney, it is called multifocal. Multiple tumors are uncommon in this cancer, which fits with the fact that it is not inherited: the genetic accident that causes it happens in one cell, not in every kidney cell from birth. If more than one tumor is found, each is described separately in your report, and the stage is based on the largest.

Tumor extension

Tumor extension describes whether a TFE3-rearranged renal cell carcinoma has grown outside the kidney and, if so, how far. The kidney is surrounded by a layer of fat, and outside that fat is a tough envelope called Gerota’s fascia. The adrenal gland sits on top of the kidney, and the renal vein carries blood away from the kidney into the largest vein in the body, the inferior vena cava. Your pathologist examines all of these structures in the tissue removed at surgery.

The report may describe growth into the fat around the kidney (perinephric fat), into the fat in the middle of the kidney where the blood vessels enter (renal sinus fat), into the collecting system that drains urine (the pelvicalyceal system), into the renal vein or the inferior vena cava, into the adrenal gland, or through Gerota’s fascia into other organs. Extension beyond the kidney raises the tumor stage and is associated with a higher risk of the cancer returning.

Lymphovascular invasion

Lymphovascular invasion means that cells from the TFE3-rearranged renal cell carcinoma are seen inside small blood vessels or lymphatic channels within or around the tumor. Blood vessels carry blood throughout the body, and lymphatic channels carry a fluid called lymph toward the lymph nodes. Tumor cells inside these vessels can be carried elsewhere, so lymphovascular invasion is associated with a higher risk of the cancer returning or spreading.

Lymphovascular invasion is not the same as growth into the renal vein, which is a large named vessel and is reported separately as part of tumor extension and stage. It does not change the pT stage on its own, but it is one of the findings your treatment team considers when deciding how closely to follow you after surgery.

Surgical margins

A margin is the cut edge of the tissue removed during surgery for TFE3-rearranged renal cell carcinoma. Your pathologist examines these edges under the microscope to see whether any tumor cells reach them. Which margins are examined depends on the operation. In a partial nephrectomy, where only the tumor and a rim of surrounding tissue are removed, the margins are the kidney tissue and fat around the tumor. In a radical nephrectomy, where the whole kidney is removed, the margins include the fat around the kidney, the renal vein, the ureter (the tube carrying urine to the bladder), and the blood vessels.

Negative margin — No tumor cells are seen at the cut edge. This suggests the whole tumor was removed and is associated with a low risk of the cancer coming back in the same place. Your report may also state the distance from the tumor to the nearest margin.
Positive margin — Tumor cells are present at the cut edge. This means tumor cells may have been left behind, and it is associated with a higher risk of the cancer returning at that site. A positive margin is one of the findings the surgical team uses when deciding whether more surgery or closer imaging follow-up should be considered.

Lymph nodes

Lymph nodes are small immune organs found throughout the body, including around the large blood vessels near the kidney. Cells from a TFE3-rearranged renal cell carcinoma can travel through lymphatic channels and settle in a lymph node. Lymph nodes are usually removed only when they look enlarged on imaging or feel abnormal during the operation. This tumor involves lymph nodes more often than the common kidney cancers do, so nodes are sampled more frequently here.

If lymph nodes were removed, your report will state how many were examined, how many contained cancer, and the size of the largest deposit of tumor within a node. It may also state whether extranodal extension is present, which means that cancer cells inside a lymph node have broken through the outer capsule of the node into the surrounding tissue. Cancer in a lymph node places the tumor in a higher stage group and generally signals a higher risk of the cancer returning. One qualification is specific to this cancer and worth knowing: in children and young people, tumors that have reached the lymph nodes have in some reports still done well after surgery, better than the same finding would predict in an adult. This is a question worth putting directly to the treatment team rather than reading across from general kidney cancer information.

Examination of the non-tumor kidney

When kidney tissue is removed for TFE3-rearranged renal cell carcinoma, your pathologist also examines the kidney tissue away from the tumor. This part of the report describes how well the remaining kidney is likely to work after surgery. Findings may include scarring of the small blood vessels from long-standing high blood pressure (arterionephrosclerosis) or damage to the filters from diabetes (diabetic nephropathy), although in younger patients the surrounding kidney is often normal. These findings do not describe the cancer. They are reported because they help predict kidney function after surgery.

Biomarker and molecular testing

Biomarkers are features of a tumor, usually proteins or gene changes, that provide information beyond the diagnosis itself. TFE3-rearranged renal cell carcinoma occupies an unusual position. The molecular finding is not optional here because it establishes the diagnosis, and the tests used to make it are described in the “How is the diagnosis made?” section above. What follows covers the additional information those tests provide and the other testing that may be done. No biomarker result currently selects an approved drug for this cancer.

The fusion partner

When the fusion is identified by RNA sequencing rather than FISH, the report names the partner gene that TFE3 joined onto, for example ASPSCR1::TFE3 or PRCC::TFE3. This detail is not used to choose treatment today, but it carries information. Tumors with an ASPSCR1 partner tend to be found at a more advanced stage and have the least favorable natural history, while some other partners are associated with more slowly growing tumors. Research suggests the partner may also influence how well drug treatment works, and studies that record the partner gene are ongoing. If your report names a partner, it is reasonable to ask your oncologist what is known about it.

Comprehensive genomic profiling (next-generation sequencing)

Next-generation sequencing reads many genes at once from the tumor tissue. In this cancer, the same test that confirms the diagnosis often reports other genetic changes at the same time. Beyond the fusion, these tumors carry relatively few mutations. Where the cancer has spread, sequencing is mainly used to look for changes that might open the door to a clinical trial. Reports may state which alterations were found, that no reportable alterations were identified, or that a change of uncertain significance was detected.

Mismatch repair, microsatellite instability, and tumor mutational burden

These tests identify tumors that respond to immunotherapy regardless of where the cancer started, an idea called a tumor-agnostic approval. Mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) are tested by immunohistochemistry and reported as intact or retained, which is the normal result, or as deficient (dMMR) when one or more proteins are lost. The related test for microsatellite instability is reported as stable (MSS) or high (MSI-H). Tumor mutational burden counts the number of mutations in the tumor and is reported as mutations per megabase, with 10 or more considered high. All three findings are uncommon in this cancer, so a normal result is expected. When one is present, it can make a person eligible for the immunotherapy drug pembrolizumab under approvals that apply across cancer types.

You can learn more about the tests described here in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage of a TFE3-rearranged renal cell carcinoma describes how far the cancer had grown at the time of surgery. It is written using the TNM system created by the American Joint Committee on Cancer (AJCC), currently in its 8th edition, and it is the same system used for all renal cell carcinomas. T describes the size of the tumor and how far it has grown outside the kidney, N describes whether cancer is found in nearby lymph nodes, and M describes whether the cancer has spread to a distant part of the body. The letter “p” in front means the category was assigned by a pathologist after examining the tissue. The M category is almost always determined by imaging rather than by the pathologist, so it may not appear on your report at all.

Tumor stage (pT)

pT1a — The tumor is 4 cm or smaller and remains inside the kidney.
pT1b — The tumor is larger than 4 cm but not more than 7 cm and remains inside the kidney.
pT2a — The tumor is larger than 7 cm but not more than 10 cm and remains inside the kidney.
pT2b — The tumor is larger than 10 cm and remains inside the kidney.
pT3a — The tumor has grown into the renal vein or one of its branches, into the fat around the kidney or in the renal sinus, or into the collecting system that drains urine, but not beyond Gerota’s fascia.
pT3b — The tumor has grown into the inferior vena cava below the diaphragm.
pT3c — The tumor has grown into the inferior vena cava above the diaphragm, or into the wall of the vena cava.
pT4 — The tumor has grown beyond Gerota’s fascia, including growth into the adrenal gland on the same side.

Nodal stage (pN)

pN0 — No cancer was found in any of the lymph nodes examined.
pN1 — Cancer was found in one or more nearby lymph nodes.
pNX — No lymph nodes were removed or they could not be assessed.

What is the prognosis?

Prognosis means the expected course of a disease. For TFE3-rearranged renal cell carcinoma, age matters more than it does for most cancers. In children and young people, this tumor has often followed a slow course, and many are cured by surgery even when lymph nodes are involved. In adults, it behaves less favorably: it is found at a more advanced stage more often, and survival in published series has been similar to clear cell renal cell carcinoma and worse than papillary renal cell carcinoma. Because the tumor is rare and was only recognized as its own disease relatively recently, the numbers come from small series and should be treated as a general guide rather than a prediction for any one person.

One feature of this cancer shapes follow-up more than any other: it can return very late. Spread has been reported many years, in some cases two decades or more, after the kidney was removed. This is well beyond the period over which most cancers are watched, and it is the reason follow-up here continues far longer than the standard kidney cancer schedule. The features on your report associated with a higher risk of the cancer returning include growth outside the kidney, cancer in lymph nodes, sarcomatoid or rhabdoid features, tumor necrosis (areas where tumor cells have died), lymphovascular invasion, a positive surgical margin, and larger tumor size.

What happens after the diagnosis?

Once TFE3-rearranged renal cell carcinoma has been confirmed, the findings on your pathology report, particularly the stage, the margin status, and whether lymph nodes are involved, shape the next steps. Care usually involves a urologist, a medical oncologist, a radiologist, and a pathologist, and for a child, a pediatric oncology team. Because the tumor is rare and the evidence base is thin, review at or in consultation with a center that sees it regularly is worth asking about, and this applies to adults as much as to children.

Surgery — For a tumor confined to the kidney, surgery is the main treatment and offers the best chance of cure. Whether part or all of the kidney is removed depends on the size and position of the tumor. Removing involved lymph nodes at the same time is often considered, since this tumor reaches them more often than the common kidney cancers.
Treatment after surgery (adjuvant therapy) — No drug treatment given after surgery has been shown to help in this cancer. The immunotherapy options approved after kidney cancer surgery, including pembrolizumab and the pembrolizumab and belzutifan combination approved in June 2026, were studied in and approved for renal cell carcinoma with a clear cell component and do not apply here. Follow-up is by imaging, and for a tumor at high risk of returning, a clinical trial may be discussed.
Treatment for cancer that has spread — No drug is approved specifically for this cancer, and no treatment has been tested in a trial devoted to it, so the options come from studies of kidney cancers other than clear cell and from series of patients with this diagnosis. On current evidence, treatment teams generally consider a combination of an immunotherapy drug with a drug that blocks blood vessel growth. Cabozantinib has the strongest supporting evidence among the individual drugs. Immunotherapy given alone appears less effective here than in clear cell renal cell carcinoma. Chemotherapy is not effective and is not used, except that a history of chemotherapy for an earlier cancer is relevant background for the team. Clinical trials are discussed more often in this cancer than in the common kidney cancers.
Follow-up — Imaging of the abdomen and chest continues on a schedule set by your treatment team, and because of the risk of late return it continues for many years. For a young person cured by surgery, this means a follow-up relationship that may last decades, and it is worth understanding early why it is being recommended.
Family members — Because this cancer is not inherited, relatives are not at increased risk and do not need genetic testing or kidney screening on account of this diagnosis.

Questions to ask your doctor

Was the fusion confirmed by a genetic test, and was it FISH or RNA sequencing?
If FISH was negative but the appearance was suspicious, will RNA sequencing be done?
Which partner gene was involved in the fusion, and is that known to matter?
How large was my tumor, and what was the pathologic stage (pT and pN)?
Were any lymph nodes removed, and did any contain cancer?
Did my tumor contain sarcomatoid or rhabdoid cells, and was necrosis seen?
Did the tumor grow outside the kidney, into the fat, the renal sinus, or the renal vein?
Were the surgical margins negative or positive, and if positive, where?
Was a grade reported for my tumor, and how much weight does it carry in this type of kidney cancer?
Given that this cancer can come back late, how long will my follow-up continue and what scans will be used?
Does my family need any testing or screening because of this diagnosis?
Should my care be reviewed at a center that specializes in rare kidney cancers?
If treatment beyond surgery is needed, what options apply to this specific type of kidney cancer?
Are there clinical trials open to me?