Paraganglioma: Understanding Your Pathology Report

Section Editor: Bibianna Purgina MD FRCPC
May 29, 2026

Paraganglioma is a rare neuroendocrine tumor that arises from specialized cells called paraganglion cells. Paraganglion cells are part of the autonomic nervous system, which operates without conscious control. They normally help regulate blood pressure, heart rate, and the body’s response to stress, and some types release hormones called catecholamines (such as adrenaline and noradrenaline) into the bloodstream.

Paragangliomas can arise in many parts of the body. They have traditionally been divided into two groups:

Head and neck paragangliomas — Arise from parasympathetic paraganglion cells in the head and neck. Most do not produce catecholamines and tend to grow slowly.
Sympathetic paragangliomas — Arise from sympathetic paraganglion cells, most often in the chest, abdomen, or pelvis. These tumors more frequently produce catecholamines and are closely related to pheochromocytoma, the tumor of the adrenal medulla. Together, pheochromocytomas and paragangliomas are sometimes referred to as PPGLs.

The current World Health Organization (WHO) classification of endocrine and neuroendocrine tumors, published in 2022, no longer divides paragangliomas into “benign” and “malignant” categories. Instead, all paragangliomas are considered to have some risk of spreading to other parts of the body. The challenge for the pathologist is to estimate that risk based on the appearance of the tumor under the microscope and on additional tests.

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

Where is a paraganglioma found?

Paragangliomas can arise anywhere paraganglion cells are normally present. The most common locations include:

Head and neck — The carotid body (near the carotid artery in the neck), the middle ear region (jugulotympanic), along the vagus nerve, in the larynx, and less commonly in sites such as the parotid gland, nasal cavity, orbit, or skull base.
Chest, abdomen, and pelvis — Sympathetic paragangliomas most often arise in the area behind the abdominal organs (the retroperitoneum), near the major blood vessels of the abdomen, in the bladder wall, or along the chain of nerves running through the chest.

Some patients develop multiple paragangliomas at the same time or over many years. Tumors can occur on both sides of the body. Multiple or bilateral tumors raise the chance of an inherited cause and prompt a careful workup for hereditary syndromes.

What causes a paraganglioma?

Paragangliomas have one of the strongest inherited components of any tumor. About 30 to 40 percent of patients with paraganglioma carry an inherited (germline) genetic change. The proportion is even higher in children. Because the chance of an inherited cause is so high, current guidelines recommend that all patients with paraganglioma be offered genetic counseling and testing, even when there is no known family history.

The inherited syndromes most often linked to paraganglioma include:

Hereditary paraganglioma-pheochromocytoma syndromes — Caused by inherited changes in one of the succinate dehydrogenase genes (SDHA, SDHB, SDHC, SDHD, and SDHAF2). These genes make parts of an enzyme complex called succinate dehydrogenase, which helps cells produce energy. Tumors linked to SDHD are most often head and neck paragangliomas and are frequently multiple. Tumors linked to SDHB are more often abdominal paragangliomas and have the highest risk of spreading to other parts of the body.
Von Hippel-Lindau (VHL) syndrome — Caused by inherited changes in the VHL gene. People with VHL syndrome can develop paragangliomas along with pheochromocytomas, hemangioblastomas of the brain and retina, kidney cancer, and tumors of the pancreas and inner ear.
Multiple endocrine neoplasia type 2 (MEN2A and MEN2B) — Caused by inherited changes in the RET gene. People with MEN2 most often develop pheochromocytoma but can also develop paraganglioma.
Neurofibromatosis type 1 (NF1) — Caused by inherited changes in the NF1 gene. Paraganglioma is less common in NF1 than pheochromocytoma.
Other rarer hereditary causes — Including changes in the TMEM127, MAX, and FH genes.

The remaining patients have sporadic paragangliomas, which appear without a known trigger. Sporadic tumors can still have mutations in some of the same genes listed above, but the changes are found only in the tumor cells and cannot be passed on to children.

Environmental factors such as long-term low oxygen levels, including living at high altitude or having congenital heart disease, may raise the risk in genetically susceptible individuals.

What are the symptoms of a paraganglioma?

Symptoms depend on where the paraganglioma is located and whether it produces catecholamines.

Many head and neck paragangliomas do not produce catecholamines and present as a slow-growing, painless mass. A tumor in the carotid body may be felt as a lump in the side of the neck. A tumor in the middle ear region may cause a rhythmic whooshing sound in the ear (pulsatile tinnitus), hearing changes, or a feeling of fullness in the ear. Larger tumors or those involving cranial nerves may cause hoarseness, difficulty swallowing, tongue weakness, or other nerve-related symptoms.

Sympathetic paragangliomas (in the chest, abdomen, or pelvis) are more likely to produce excess catecholamines. The symptoms come from the release of these hormones into the bloodstream and are similar to those of pheochromocytoma. The classic pattern is episodes (called spells) of high blood pressure, pounding or racing heartbeat, headache, sweating, trembling, anxiety, and pale skin. Some sympathetic paragangliomas, especially those linked to certain genetic mutations, do not produce hormones and are biochemically silent. Bladder paragangliomas can cause symptoms during urination, such as headache, sweating, or palpitations, triggered by emptying the bladder.

A growing number of paragangliomas are discovered during screening of people known to carry an inherited genetic change, sometimes before any symptoms develop.

How is the diagnosis made?

The diagnosis of paraganglioma is made by combining clinical history, blood and urine tests, imaging, and pathology. Blood or urine tests measure breakdown products of catecholamines called metanephrines. Common tests include plasma-free metanephrines and 24-hour fractionated urine metanephrines. An additional marker, 3-methoxytyramine, may be measured in some cases, particularly when a tumor is suspected to primarily produce dopamine. Hormone tests are often performed even when the tumor is thought to be non-functioning, because biochemical findings can affect anesthesia planning if surgery is needed.

Imaging tests, most often CT and MRI, are used to locate the tumor and to look for spread. Specialized nuclear medicine scans can detect multiple tumors at once, identify spread, or help plan treatment. Gallium-68 DOTATATE PET-CT (which highlights cells that express somatostatin receptors) is especially sensitive for paraganglioma and has become a preferred imaging test in many centers. MIBG scintigraphy is another option, particularly when a different therapy plan is being considered.

Needle biopsy of a suspected paraganglioma is generally avoided. Sampling can cause bleeding because paragangliomas are highly vascular, and in catecholamine-producing tumors, biopsy can release a surge of hormones into the bloodstream and trigger a dangerous spike in blood pressure. The diagnosis is therefore made after the tumor is surgically removed and examined under the microscope by a pathologist.

Under the microscope, paragangliomas show a characteristic growth pattern called Zellballen, in which nests of tumor cells are surrounded by a delicate network of small blood vessels. The tumor cells, called chief cells, have moderate amounts of pink or pale cytoplasm and round-to-oval nuclei with a fine “salt-and-pepper” appearance. Each nest is surrounded by supporting cells called sustentacular cells. Mitotic figures (dividing cells) are usually rare, and the microscopic appearance alone cannot reliably predict how the tumor will behave. For this reason, pathologists apply structured scoring systems (PASS and GAPP, described in the next sections) and special tests to estimate the risk of spread.

Immunohistochemistry uses antibodies to detect specific proteins in tissue. Paragangliomas express neuroendocrine markers, including chromogranin A, synaptophysin, and INSM1, along with nuclear GATA3, and they do not express cytokeratins (which are seen in carcinomas of epithelial origin). Special stains such as S100 or SOX10 highlight the sustentacular cells surrounding the tumor nests. A stain called SDHB is particularly important and is discussed in the biomarker section below.

PASS score (Pheochromocytoma of the Adrenal Gland Scaled Score)

The PASS score was originally developed for pheochromocytoma but is sometimes applied to paragangliomas as well. It is a system that pathologists use to estimate the risk that a tumor will spread to other parts of the body. The pathologist examines the tumor for the following microscopic features. Each feature contributes one or two points, and the points are added together to give a total score:

Invasion into surrounding fat — Tumor cells have grown beyond the tumor into the nearby fat (2 points).
Vascular invasion — Tumor cells are seen inside blood vessels (1 point).
Capsular invasion — Tumor cells have grown into or through the fibrous capsule around the tumor (1 point).
Large nests or diffuse growth — Tumor cells grow in large sheets rather than the typical small rounded nests (2 points).
Necrosis — Areas of tumor cell death (2 points).
High cellularity — Tumor cells are densely packed together (2 points).
Cellular monotony — Tumor cells all look very similar to one another (2 points).
Spindle-shaped tumor cells — The cells are elongated rather than round (2 points).
Increased mitotic activity — More than 3 dividing cells in 10 high-power microscope fields (2 points).
Atypical mitotic figures — Dividing cells with an abnormal shape or pattern (2 points).
Marked nuclear variation — Tumor cell nuclei vary widely in size and shape (1 point).
Hyperchromatic nuclei — Tumor cell nuclei appear very dark because they contain extra genetic material (1 point).

In general, a PASS score of 3 or less suggests the tumor is likely to behave in a non-aggressive manner. A PASS score of 4 or higher suggests a higher risk of aggressive behavior, including spread to other parts of the body. The PASS score has known limitations, especially when applied to paraganglioma: different pathologists may score the same tumor slightly differently, and the system was designed for adrenal tumors. For this reason, the PASS score is interpreted together with the GAPP score, the SDHB result, the tumor location, the genetic testing findings, and imaging.

GAPP score (Grading of Adrenal Pheochromocytoma and Paraganglioma)

The GAPP score was developed specifically for both pheochromocytomas and paragangliomas and is increasingly used to estimate the risk of metastasis. It combines microscopic features with the type of hormone produced by the tumor and with the Ki-67 proliferation index (a measure of how many tumor cells are actively dividing).

The GAPP score is based on six features, with a maximum total of 10 points:

Growth pattern — Zellballen (typical nested) pattern = 0 points; large or irregular nests = 1 point; pseudorosettes (small ring-like structures of cells) = 1 point.
Cellularity — Low = 0 points; moderate = 1 point; high = 2 points.
Comedo-type necrosis — Areas of tumor cell death surrounded by living tumor cells. Absent = 0 points; present = 2 points.
Capsular or vascular invasion — Absent = 0 points; present = 1 point.
Ki-67 labeling index — Less than 1 percent = 0 points; 1 to 3 percent = 1 point; greater than 3 percent = 2 points.
Catecholamine type — Adrenergic (producing adrenaline) or non-functional = 0 points; noradrenergic (producing noradrenaline) = 1 point.

Based on the total score, the tumor is classified into one of three categories:

Well-differentiated (0 to 2 points) — Lowest risk of metastasis.
Moderately differentiated (3 to 6 points) — Intermediate risk.
Poorly differentiated (7 to 10 points) — Highest risk.

Loss of SDHB staining (described in the biomarker section) is sometimes added to the GAPP score to create a modified GAPP score, which improves the accuracy of risk estimates in patients with hereditary tumors. The GAPP score, like the PASS score, is not used alone; the treatment team considers it alongside other findings in the pathology report and the results of genetic testing.

Capsular and vascular invasion

Capsular invasion means that tumor cells are growing into or through the fibrous capsule that surrounds the tumor. Vascular invasion means that tumor cells are seen inside a blood vessel. Both findings are part of the PASS and GAPP scoring systems and are recorded separately on the pathology report.

Vascular invasion is the more important of the two because blood vessels can carry tumor cells to distant organs such as the lungs, liver, or bones. The pathologist is careful to distinguish true vascular invasion (tumor cells fixed inside a vessel and attached to the wall or mixed with blood clot material) from an artifact, in which tumor cells appear to be inside a vessel only because they were displaced during tissue handling.

Surgical margins

A margin is the cut edge of the tissue removed at surgery. The pathologist examines the margins to see whether the tumor was completely removed. For paraganglioma, the standard surgical approach is to remove the tumor in one piece together with its surrounding capsule when possible. This is sometimes more difficult than for tumors in other locations because paragangliomas can be deep, highly vascular, or wrapped around important blood vessels or nerves.

Negative margin — No tumor cells are seen at the cut edge. This suggests the tumor was completely removed.
Positive margin — Tumor cells reach the cut edge. A positive margin indicates that some tumor may have been left behind and is linked to a higher risk of local recurrence.
Capsular rupture during surgery — If the surface of the tumor was disrupted during the operation, tumor cells may have spilled into the surgical bed, even when the formal margin is negative.

Lymph nodes

Lymph nodes are small bean-shaped structures throughout the body that filter fluid and house immune cells. Routine removal of lymph nodes is not standard for every paraganglioma. The surgeon may remove suspicious lymph nodes when the tumor is large or when imaging suggests involvement. The pathology report will state how many lymph nodes were examined and how many contained tumor cells. Lymph node involvement is uncommon at the time of diagnosis but is associated with a higher pathologic stage and a higher risk of further spread.

Biomarker and molecular testing

Biomarker testing is an important part of the paraganglioma workup. The tests below help confirm the diagnosis, identify inherited causes, and estimate the risk of recurrence.

SDHB immunohistochemistry

Succinate dehydrogenase (SDH) is an enzyme complex inside cells that helps produce energy. It has four parts: SDHA, SDHB, SDHC, and SDHD. The pathologist uses immunohistochemistry to look for the SDHB protein in tumor cells. The result is described in one of two ways:

Retained (preserved) SDHB expression — Tumor cells show granular brown staining, similar to surrounding non-tumor cells. This pattern makes a hereditary SDH-related tumor less likely.
Loss of SDHB expression — Tumor cells do not stain for SDHB, while normal cells in the background still do. This pattern strongly suggests an SDH-deficient tumor.

Loss of SDHB staining is important because it:

Raises concern for an inherited change in one of the SDH genes (most often SDHB, but also SDHA, SDHC, SDHD, or SDHAF2), even in the absence of a family history.
Is associated with a higher lifetime risk of metastasis, especially in tumors linked to SDHB.
Triggers a recommendation for genetic counseling, germline (blood) testing, and long-term follow-up for the patient and (if applicable) for family members.

Ki-67 proliferation index

Ki-67 is a protein found only in cells that are actively dividing. The pathologist quantifies the percentage of tumor cells staining positive for Ki-67 in the most active area (the hot spot). The result is reported as a percentage. Most paragangliomas have a Ki-67 index below 3 percent. A higher Ki-67 index is one component of the GAPP score and is associated with a higher risk of recurrence and spread.

Genetic testing

Genetic testing is recommended for nearly all patients with paraganglioma, regardless of age or tumor location. Testing is usually arranged through a genetic counselor and involves a blood test that looks at the genes most often linked to paraganglioma (SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, RET, NF1, TMEM127, MAX, FH, and others). Results may show an inherited change, a tumor-only change, or no detectable change. An inherited change confirms a hereditary syndrome and prompts:

Screening of other family members who may carry the same change.
Long-term surveillance for other tumors associated with the syndrome.
More intensive follow-up of the patient for new pheochromocytomas, paragangliomas, or distant spread.

Molecular testing of the tumor itself is not required for diagnosis in most cases, but it can be helpful in selected situations to clarify the underlying mechanism.

For more information on biomarker testing in cancer, please visit our Biomarkers section.

Pathologic stage (pTNM)

Paragangliomas are staged using the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition. The staging system depends on the location of the tumor:

Sympathetic paragangliomas (chest, abdomen, pelvis) — Staged using the same chapter as pheochromocytoma. A sympathetic paraganglioma of any size, with no invasion into adjacent tissues, is classified as pT2. Tumors with invasion into adjacent organs are pT3. The pN category records whether regional lymph nodes contain tumor cells (pN0 = no spread, pN1 = spread). The pM category records distant spread.
Head and neck paragangliomas — Staged using a separate chapter that varies by exact location (carotid body, jugulotympanic, vagal, or laryngeal). The pT category is generally based on tumor size and whether it has invaded surrounding structures, such as the skull base or nearby nerves. The pN and pM categories follow the standard pattern.

The full stage grouping (Stages I to IV) combines pT, pN, and pM information. Your treatment team can explain the specific stage and what it means in your case.

Can paraganglioma spread?

Yes. The current WHO 2022 classification considers all paragangliomas to have some risk of metastasis, which is why the older labels “benign paraganglioma” and “malignant paraganglioma” are no longer used. Spread (metastasis) is diagnosed when tumor cells are found in places where paraganglion tissue does not normally occur, such as lymph nodes outside the typical drainage area, bones, liver, or lungs. Reported metastasis rates depend on tumor location: head and neck paragangliomas have a relatively low risk overall, while paragangliomas in the abdomen and retroperitoneum (especially those linked to SDHB) have a higher risk. Spread can occur many years (sometimes decades) after the original surgery, which is why long-term follow-up is essential.

What is the prognosis?

Most paragangliomas grow slowly, and overall outcomes are favorable for tumors that can be completely removed. Individual outcomes vary widely depending on tumor location, completeness of resection, and underlying genetic findings.

Pathologic and genetic features associated with a higher risk of recurrence or spread include:

Loss of SDHB staining or an inherited SDHB mutation — The strongest single predictor of metastatic disease in paraganglioma.
Tumor location outside the head and neck — Sympathetic paragangliomas in the chest, abdomen, or pelvis carry a higher risk of metastasis than head and neck paragangliomas.
Large tumor size and local invasion — Linked to higher recurrence and spread rates.
Higher PASS score (4 or greater) — Associated with more aggressive behavior, with the limitations described above.
Higher GAPP score (moderately or poorly differentiated category) — Linked to higher risk of metastasis.
High Ki-67 proliferation index — Linked to a higher risk of recurrence.
Invasion into surrounding fat, blood vessels, or adjacent organs — Markers of more aggressive local behavior.
Lymph node involvement or distant metastasis at diagnosis — Indicates more advanced disease.
Positive surgical margin or capsular rupture during surgery — Linked to higher risk of local recurrence.

What happens after this diagnosis?

The pathology findings guide the next steps in care rather than dictating a single treatment. After complete staging and recovery from surgery, the treatment team typically considers:

Hormone monitoring — Catecholamines and metanephrines are checked after surgery to confirm that the tumor has been removed and that hormone levels have normalized. These tests are then repeated at regular intervals as part of long-term follow-up.
Imaging surveillance — Repeat CT, MRI, or specialized nuclear medicine scans (often gallium-68 DOTATATE PET-CT) are used to look for new tumors or evidence of recurrence. The interval depends on tumor location, scoring system results, SDHB status, and genetic findings. Patients with inherited syndromes need lifelong surveillance because new tumors can develop years or decades after the first.
Genetic counseling and testing — Recommended for nearly all patients with paraganglioma. The results guide screening for other family members and long-term surveillance for other tumors associated with the inherited syndrome.
Treatment of recurrence or metastatic disease — When the tumor returns or has spread, options can include further surgery (when the disease can be safely removed), targeted radionuclide therapy (such as 131I-MIBG or lutetium-177 DOTATATE), external beam radiation for symptom control, and systemic chemotherapy. Choice of treatment depends on the location of the disease, the patient’s symptoms, and the genetic findings.
Alpha-blockade before any further surgery — Patients with active catecholamine production are usually treated with medications called alpha-blockers (and sometimes beta-blockers) for several days before any operation to prevent dangerous swings in blood pressure.
Multidisciplinary care — Endocrine surgery, endocrinology, head and neck surgery (for head and neck tumors), medical oncology, nuclear medicine, and genetics work together to plan follow-up. Care is often coordinated through a specialized center with experience in paraganglioma and pheochromocytoma.

Questions to ask your doctor

Where is my paraganglioma located, and is it sympathetic or parasympathetic?
What was the size of my tumor, and was it completely removed?
Does my tumor produce catecholamines, and if so, which ones?
What was my PASS score, and what does it mean?
Was a GAPP score reported, and what category did my tumor fall into?
What did the SDHB immunohistochemistry test show?
Was capsular or vascular invasion identified?
What was the Ki-67 proliferation index?
How many lymph nodes were examined, and were any involved by tumor?
What is my pathologic stage (pT, pN, and pM)?
Should I have genetic testing, and which genes should be tested?
If I have an inherited cause, what other tumors am I at risk for, and how will I be screened?
Should my family members be offered genetic counseling and testing?
How often will I need follow-up blood tests and imaging, and for how long?
Would referral to a specialized center experienced in paraganglioma and pheochromocytoma help guide my care?