Parathyroid Carcinoma: Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC
May 21, 2026

Parathyroid carcinoma is a rare cancer of the parathyroid gland. The parathyroid glands are small endocrine organs in the front of the neck that produce parathyroid hormone, which helps regulate blood calcium levels. Parathyroid carcinoma develops when cells in one of these glands grow uncontrollably and invade nearby tissue or spread to other parts of the body. Most parathyroid carcinomas continue to produce parathyroid hormone, which causes the blood calcium level to rise to abnormal and sometimes dangerous levels.

Parathyroid carcinoma is extremely uncommon. It accounts for less than 1 percent of cases of primary hyperparathyroidism (a condition in which one or more of the parathyroid glands produce too much parathyroid hormone) and less than one in every 100,000 cancers diagnosed worldwide. Because it shares many features with the much more common parathyroid adenoma, the diagnosis is often made or confirmed only after the tumor has been surgically removed and examined under the microscope.

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

What causes parathyroid carcinoma?

For most patients, doctors do not know the exact cause of parathyroid carcinoma. These tumors are described as sporadic, meaning they appear without a known trigger and are not caused by anything the person did, ate, or was exposed to. A meaningful minority, however, are linked to inherited genetic changes that run in families:

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome — Caused by an inherited change in a gene called CDC73. This gene makes a protein called parafibromin, which normally helps control cell growth. People with HPT-JT have a substantially higher lifetime risk of developing parathyroid carcinoma, along with tumors of the jaw, kidney, and uterus. Even outside of HPT-JT, changes in the CDC73 gene (whether inherited or acquired only in the tumor) are found in the majority of parathyroid carcinomas.
Multiple endocrine neoplasia type 1 (MEN1) — Caused by inherited changes in the MEN1 gene. People with MEN1 most often develop parathyroid adenomas, but parathyroid carcinoma can occasionally arise in this setting.
Familial isolated hyperparathyroidism (FIHP) — A pattern in which several family members develop parathyroid tumors without the other features of MEN1 or HPT-JT.

Long-standing kidney failure (which leads to secondary or tertiary hyperparathyroidism) and a history of radiation to the neck have both been described as possible risk factors, but the evidence linking them to parathyroid carcinoma is limited.

What are the symptoms of parathyroid carcinoma?

Most symptoms result from the very high levels of blood calcium produced by the tumor. This state is called hypercalcemia. Compared with patients who have a benign parathyroid adenoma, patients with parathyroid carcinoma often have:

Much higher calcium levels.
Much higher parathyroid hormone levels (often more than five times the upper limit of normal).
More severe symptoms of hypercalcemia, including fatigue, muscle weakness, nausea, vomiting, increased thirst and urination, constipation, and confusion.
Bone pain or fractures from weakened bones.
Kidney stones or reduced kidney function.
A firm lump that can be felt in the front of the neck. This is much more common in parathyroid carcinoma than in adenomas.
Hoarseness or a change in voice, if the tumor presses on or invades the nerve to the voice box (the recurrent laryngeal nerve).

Severe hypercalcemia, very high parathyroid hormone levels, and a palpable neck mass together raise concern for parathyroid carcinoma before surgery, although the final diagnosis can only be made after the tumor is examined under the microscope.

How is the diagnosis made?

The workup usually begins when a blood test shows elevated calcium and parathyroid hormone levels. Imaging tests, including neck ultrasound, sestamibi scintigraphy (a nuclear medicine scan that highlights overactive parathyroid tissue), and sometimes four-dimensional CT or MRI, are used to locate the abnormal gland and look for signs of invasion into surrounding tissue.

Unlike thyroid lesions, parathyroid tumors are not usually sampled by needle biopsy before surgery. A needle biopsy can spread parathyroid cells along the needle track, making later surgery more difficult, so it is generally avoided when carcinoma is suspected. The diagnosis is made on the tissue removed at surgery and examined under the microscope.

The decisive question for the pathologist is whether the tumor shows definite evidence of invasive growth. According to the current World Health Organization (WHO) classification of endocrine and neuroendocrine tumors (published in 2022), a tumor is diagnosed as parathyroid carcinoma only when at least one of the following features is identified:

Tumor cells invading into a blood vessel (vascular invasion).
Tumor cells invading into a lymphatic vessel (lymphatic invasion).
Tumor cells invading around or into a nerve (perineural invasion).
Tumor cells invading directly into an adjacent organ or structure, such as the thyroid gland, neck muscles, trachea, or esophagus.
Spread of the tumor to a lymph node or to a distant organ (metastasis).

When none of these features is present, the diagnosis is not parathyroid carcinoma, even if the tumor looks worrisome under the microscope. Worrisome tumors that do not meet these criteria are instead diagnosed as atypical parathyroid tumor, a separate category described in a different article. The pathologist also uses immunohistochemistry, a laboratory test that stains specific proteins in the tissue, to support the diagnosis. The most useful stains in this setting are parafibromin and Ki-67, both of which are discussed in more detail in the biomarker section below.

Because the diagnosis of parathyroid carcinoma can be subtle, the pathologist often examines multiple tissue sections from different parts of the tumor to detect small areas of invasion. In difficult cases, the slides may be reviewed by a second pathologist with special expertise in parathyroid tumors.

Invasion into adjacent structures

Direct invasion into tissue around the parathyroid gland is one of the most important findings the pathologist looks for. The structures most commonly affected are:

Thyroid gland — The parathyroid glands sit very close to the thyroid. Tumor cells growing across the boundary into the thyroid are clear evidence of invasion. This affects the pathologic tumor stage (see the staging section below).
Neck muscles, trachea, or esophagus — Invasion into these structures indicates more advanced local disease and raises the pathologic tumor stage further.
Recurrent laryngeal nerve — The nerve that controls the voice box runs alongside the thyroid. Invasion into this nerve can cause hoarseness and is also a feature of more advanced local disease.
Major blood vessels or the spine — Rare, but represents the most advanced local stage.

The pathologist distinguishes true invasion (tumor cells growing through the capsule into surrounding tissue) from adherence alone (tumor stuck to nearby tissue without crossing into it). Only true invasion supports the diagnosis of carcinoma.

Perineural invasion

Perineural invasion means that tumor cells are seen growing around or into a nerve. Nerves are thin structures that carry signals between the brain and the rest of the body. In parathyroid tumors, perineural invasion is one of the findings that confirms the diagnosis of carcinoma under the WHO 2022 criteria. It is uncommon in parathyroid tumors overall and almost never seen in benign adenomas or atypical parathyroid tumors. When present, perineural invasion may also explain symptoms such as hoarseness if the affected nerve controls the voice box.

Lymphovascular invasion

Lymphovascular invasion means that tumor cells are seen inside small blood vessels or lymphatic channels. These vessels can serve as pathways that allow tumor cells to travel to nearby lymph nodes or to distant organs such as the lungs, liver, or bones. In parathyroid tumors, lymphovascular invasion is the single most important finding that confirms the diagnosis of carcinoma. Vascular invasion specifically (tumor cells inside a blood vessel) is the most frequently identified of the WHO essential diagnostic criteria, and pathologists often examine multiple tissue sections to look for it. The pathologist is also careful to distinguish true vascular invasion from artifacts (tumor cells displaced into a vessel during tissue handling), which do not support a diagnosis of cancer.

Surgical margins

A margin is the cut edge of the tissue removed at surgery. The pathologist examines the margins to see whether tumor cells reach the edge. The standard surgical approach for parathyroid carcinoma is called en bloc resection: removing the involved parathyroid gland together with the nearby thyroid lobe and any other tissue stuck to the tumor, in one piece, with the capsule of the tumor intact. The goal is to avoid spilling tumor cells into the surgical bed during the operation.

Negative margin — No tumor cells are seen at the cut edge of the specimen. This is the most favorable result and is the strongest single predictor of long-term cure.
Positive margin — Tumor cells reach the cut edge. A positive margin increases the risk that tumor cells were left behind in the neck and that the cancer will return at the same site. Further surgery may be considered when feasible.
Capsular rupture during surgery — If the capsule of the tumor was disrupted at the time of operation, tumor cells may have spilled into the surrounding tissue, even when the formal margins are negative. This is also linked to a higher risk of local recurrence.

Lymph nodes

Lymph nodes are small bean-shaped structures throughout the body, including the neck, that filter fluid and trap immune cells. The pathology report will state how many lymph nodes were examined and how many contained tumor cells. Routine removal of all neck lymph nodes (called central neck dissection) is not standard for every patient with parathyroid carcinoma. The surgeon removes nearby lymph nodes when there is concern for spread, when nodes appear abnormal on imaging or during surgery, or when the tumor is large. Reported rates of lymph node involvement at the time of diagnosis vary widely but are generally low, ranging from 5 to 25 percent of cases.

The pathologist also looks for extranodal extension, which means that tumor cells have broken through the outer capsule of a lymph node into the surrounding tissue. When present, extranodal extension is an adverse finding and may influence decisions about further treatment.

Biomarker and molecular testing

Biomarker testing is an important part of the parathyroid carcinoma workup. The tests below are used to support the diagnosis, to identify patients who may have an inherited cause for their cancer, and to help estimate the risk of recurrence.

Parafibromin

Parafibromin is the protein made by the CDC73 gene. In normal parathyroid cells and in most benign adenomas, parafibromin is present in the nucleus of every cell. In parathyroid carcinoma, parafibromin staining is lost in approximately 60-70% of cases, reflecting an underlying change in the CDC73 gene. The test is performed using immunohistochemistry, which uses antibodies to detect specific proteins inside cells. Loss of parafibromin on immunohistochemistry has two important implications:

It supports the diagnosis of parathyroid carcinoma in cases that are difficult under the microscope alone, particularly when the tumor shows worrisome features, but invasion is not clearly seen.
It identifies patients who may carry an inherited CDC73 change (HPT-JT syndrome) and helps decide who should be offered genetic testing and counseling. Identifying an inherited cause is important because other family members may also carry the change and can be offered screening.

Ki-67

Ki-67 is a protein that appears only in cells that are actively dividing. The pathologist counts the percentage of tumor cells with Ki-67 staining; this number is called the Ki-67 labeling index. In parathyroid carcinoma, the Ki-67 labeling index is usually above 5 percent, often much higher than in a benign adenoma. Ki-67 is not used to make the diagnosis on its own, but a high index supports the impression of an aggressive tumor when invasion is also present. Some studies have linked a higher Ki-67 index to an increased risk of recurrence after surgery.

CDC73 gene testing

When parafibromin is lost on immunohistochemistry, when the patient is young at diagnosis, or when there is a family history of parathyroid disease, jaw tumors, or kidney or uterine tumors, blood testing for an inherited change in the CDC73 gene may be recommended. This is usually arranged through a genetic counselor. Identifying a germline (inherited) change supports a diagnosis of HPT-JT syndrome and informs decisions about screening other family members. About one in three patients with parathyroid carcinoma carries a germline CDC73 change.

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

Pathologic stage (pTNM)

The pathologic stage describes how far the cancer has spread. Parathyroid carcinoma is staged using the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, currently in its 8th edition. The system has three parts: tumor (pT), nodal (pN), and metastasis (pM). For parathyroid carcinoma, the AJCC publishes pT and pN categories only; there is no formal stage grouping (Stage I, II, III, IV) for this cancer because too few cases have been studied to define one. The M category (whether the cancer has spread to distant organs) is determined by imaging rather than by pathology.

Tumor stage (pT)

pT1 — The tumor is confined to the parathyroid gland, possibly with extension into the immediately surrounding soft tissue.
pT2 — The tumor invades directly into the thyroid gland.
pT3 — The tumor invades into the recurrent laryngeal nerve, esophagus, trachea, neck muscles, adjacent lymph nodes, or thymus.
pT4 — The tumor invades into a major blood vessel or into the spine.

Nodal stage (pN)

pN0 — No tumor cells in any lymph nodes examined.
pN1a — Tumor cells in central neck (level VI) or upper mediastinal (level VII) lymph nodes.
pN1b — Tumor cells in lymph nodes on one or both sides of the neck other than the central neck, or in lymph nodes behind the throat.

What is the prognosis?

The prognosis of parathyroid carcinoma is highly variable. Many patients live for decades after diagnosis, and the disease often follows a slow course. At the same time, recurrence is common, and patients require lifelong follow-up. Published survival data vary across studies, but the most commonly cited figures are:

Five-year overall survival of approximately 75 to 85 percent.
Ten-year overall survival of approximately 50 to 75 percent.
Lifetime recurrence rates of approximately 40 to 60 percent.
Distant spread (to lung, liver, or bone) in fewer than 5 percent of patients at the time of diagnosis.

The most common cause of death is uncontrolled hypercalcemia from recurrent or metastatic tumor, rather than the tumor bulk itself. For this reason, calcium and parathyroid hormone levels are followed closely throughout life and are the earliest signs that the cancer may have returned.

Pathologic features associated with a higher risk of recurrence or worse outcome include:

Positive surgical margin or capsular rupture during surgery — Tumor cells may have been left behind in the neck.
Vascular invasion — Especially when extensive or involving larger vessels.
Lymph node involvement at diagnosis — Linked to worse overall survival.
Distant metastasis at diagnosis — Associated with shorter survival, although patients can still live for years with controlled disease.
Tumor size greater than 4 centimeters — Linked to higher recurrence and lower survival in registry studies.
Loss of parafibromin on immunohistochemistry — Suggests an underlying CDC73 change and has been associated with more aggressive behavior in some studies.
Recurrence within 36 months of the first operation — Linked to shorter overall survival than later recurrence.

What happens after this diagnosis?

The pathology findings guide the next steps in care. The treatment team typically considers the following based on the report:

Completeness of resection — Negative margins and an intact capsule suggest that no further surgery is needed at this time. A positive margin or capsular rupture may prompt the surgical team to consider re-operation when feasible.
Long-term monitoring of calcium and parathyroid hormone — Blood tests are checked at regular intervals, often for life, to look for the earliest sign of recurrence. A rising parathyroid hormone level is usually the first clue.
Imaging surveillance — Neck ultrasound, sestamibi scanning, CT, or MRI may be used when calcium or parathyroid hormone levels rise, or to evaluate the chest and abdomen if distant spread is suspected.
Genetic counseling and CDC73 testing — Considered when parafibromin is lost on immunohistochemistry, when the patient is young, when other endocrine or jaw tumors are present, or when the family history suggests HPT-JT or MEN1.
Management of hypercalcemia — If calcium remains high after surgery or recurs later, medications (such as cinacalcet, bisphosphonates, or denosumab) may be considered by the endocrinology team to bring the calcium level down.
Treatment of recurrence — When the cancer returns, repeat surgery to remove the recurrent tumor is generally the preferred approach when the disease can be safely resected.
Radiation therapy — Not part of standard postoperative care after a complete resection. It may be considered in selected cases, such as a positive margin in a location where re-operation is not feasible, or for symptomatic distant disease, and is usually discussed by the radiation oncology team.
Systemic therapy — Chemotherapy and targeted therapy are not standard treatments for parathyroid carcinoma. Their use is generally limited to advanced disease that cannot be controlled with surgery and is best discussed in the context of a referral to a specialized center or a clinical trial.
Multidisciplinary care — Endocrine surgery, endocrinology, medical oncology, radiation oncology, and (where relevant) genetics work together to plan follow-up. Palliative care is sometimes involved alongside other treatments to help manage symptoms such as bone pain and severe hypercalcemia.

Questions to ask your doctor

Which parathyroid gland was involved, and what was the size of the tumor?
Which features confirmed the diagnosis of parathyroid carcinoma (vascular invasion, perineural invasion, invasion into adjacent organs, lymph node spread, or distant spread)?
Did the surgery achieve negative margins, and was the capsule intact?
Was the thyroid gland or other neck tissue invaded by the tumor?
How many lymph nodes were examined, and were any involved by tumor?
What were the results of the parafibromin and Ki-67 stains?
Should I be referred for genetic counseling and testing for an inherited cause such as HPT-JT or MEN1?
What is my pathologic stage (pT and pN)?
How often will my calcium and parathyroid hormone levels be checked, and for how long?
What imaging will be used if my calcium or parathyroid hormone rises again?
What is the risk that the cancer will come back?
Is additional treatment, such as further surgery or radiation, being considered based on my pathology findings?
Should my family members be screened for parathyroid disease or related conditions?
Would a referral to a center with experience in parathyroid carcinoma be helpful for my ongoing care?