Atypical Parathyroid Tumor: Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC
May 20, 2026

An atypical parathyroid tumor (APT) is an unusual growth of the parathyroid gland. It shows some microscopic features that raise concern for cancer, but does not meet all the criteria needed to diagnose parathyroid carcinoma. For this reason, pathologists describe an atypical parathyroid tumor as a neoplasm of uncertain malignant potential — a growth that sits between a typical parathyroid adenoma (benign) and parathyroid carcinoma (malignant). Atypical parathyroid tumors account for roughly 1 to 2 percent of all parathyroid neoplasms. Most patients with this diagnosis come to medical attention because of primary hyperparathyroidism, a condition in which one of the parathyroid glands produces too much parathyroid hormone.

The current World Health Organization (WHO) classification of endocrine and neuroendocrine tumors, published in 2022, uses the term atypical parathyroid tumor. This term replaced the older name, atypical parathyroid adenoma, to better reflect the uncertain nature of these growths. You may still see the older term on pathology reports during the transition between the two names. Both terms describe the same lesion.

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 an atypical parathyroid tumor?

Most atypical parathyroid tumors are sporadic, which means that doctors do not know why they develop. They are not caused by anything a person did, ate, or was exposed to. A smaller number arise in people who carry a genetic change that runs in families. The genetic syndromes most often linked to atypical parathyroid tumors are:

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome — Caused by an inherited change in a gene called CDC73. The CDC73 gene makes a protein called parafibromin that helps control cell growth. When the gene is altered, the protein is lost, and parathyroid cells can grow into a tumor. People with HPT-JT may also develop tumors of the jaw, kidney, and uterus.
Multiple endocrine neoplasia type 1 (MEN1) — Caused by an inherited change in the MEN1 gene, which makes a protein called menin. People with MEN1 are more likely to develop tumors of the parathyroid glands, the pituitary gland, and the pancreas.
Familial isolated hyperparathyroidism (FIHP) — A pattern in which several family members develop parathyroid tumors without the other features of MEN1 or HPT-JT.

Recognizing one of these syndromes is important because other family members may also carry the genetic change and may benefit from screening.

What are the symptoms of an atypical parathyroid tumor?

The symptoms of an atypical parathyroid tumor come from too much parathyroid hormone in the blood, a condition known as primary hyperparathyroidism. Parathyroid hormone raises blood calcium levels. When the calcium level becomes too high, a state called hypercalcemia, it affects many parts of the body. Symptoms can include:

Fatigue, weakness, or low mood.
Nausea, vomiting, loss of appetite, or constipation.
Increased thirst and increased urination.
Bone pain or fractures from weakened bones.
Kidney stones.
Confusion or trouble concentrating.
A lump that can be felt in the front of the neck (this is uncommon).

Compared with a typical parathyroid adenoma, patients with an atypical parathyroid tumor often have higher calcium levels, higher parathyroid hormone levels, and a larger tumor at the time of diagnosis. These features sometimes raise concern for parathyroid carcinoma before surgery, but the final answer comes from examining the tumor under the microscope.

How is the diagnosis made?

The work-up usually begins when a blood test shows a high calcium level. Additional blood tests then confirm that the parathyroid hormone level is also high, pointing to a parathyroid gland as the source of the problem. Imaging tests, most often a neck ultrasound and a sestamibi scan (a nuclear medicine test that highlights overactive parathyroid tissue), are then used to locate the abnormal gland. In some cases, four-dimensional CT or MRI of the neck is added.

Unlike thyroid nodules, parathyroid tumors are not usually sampled by needle biopsy before surgery. A needle biopsy can spread parathyroid cells along the needle track and make later surgery more difficult, so it is generally avoided. The diagnosis of an atypical parathyroid tumor is made after the entire gland is surgically removed in an operation called parathyroidectomy and sent to a pathologist for examination under the microscope.

Under the microscope, the pathologist evaluates the tumor for the features described by the WHO classification. The central task is to decide whether the tumor is a typical parathyroid adenoma, an atypical parathyroid tumor, or a parathyroid carcinoma. The diagnosis of carcinoma requires definite evidence that the tumor has invaded into surrounding tissue, into blood vessels, into nerves, or has spread to other organs. An atypical parathyroid tumor shows some worrisome features but does not show any of these definite signs of cancer. A typical parathyroid adenoma lacks these worrisome features altogether.

Two special tests called immunohistochemistry are often used to support the diagnosis. Immunohistochemistry uses antibodies that stick to specific proteins in tissue, producing a color change visible under the microscope. The two markers most often used in this setting are:

Parafibromin — The protein made by the CDC73 gene. In normal parathyroid cells and most benign adenomas, parafibromin is present inside the nucleus of every cell. Loss of parafibromin staining raises the possibility of an underlying CDC73 change, which may be sporadic or inherited as part of HPT-JT syndrome. Loss of parafibromin is more common in parathyroid carcinoma but can also be seen in some atypical parathyroid tumors.
Ki-67 — A protein that appears only in cells that are dividing. The pathologist counts the percentage of tumor cells that show Ki-67 staining; this number is called the Ki-67 labeling index. A Ki-67 labeling index above 5 percent is unusual in a typical adenoma and supports the impression that the tumor is more active than expected.

These stains do not make the diagnosis on their own. They are interpreted together with the microscopic findings to reach a final answer.

Atypical features that may be described in your report

The WHO classification lists several microscopic findings that, when present, allow a pathologist to call a parathyroid tumor “atypical.” Your report may mention one or more of the features below. None of these findings alone is enough to diagnose cancer, but together they distinguish an atypical parathyroid tumor from a typical adenoma.

Band-like fibrosis — Thick bands of scar-like tissue running through the tumor. This pattern is unusual in a typical adenoma.
Cellular nests within fibrous bands — Groups of tumor cells trapped inside the bands of fibrous tissue. The pathologist looks carefully to ensure the cells are not actually invading the bands, which would suggest carcinoma.
Trabecular growth pattern — Tumor cells are arranged in long, thin cords or ribbons rather than in the rounded groups typical of a benign adenoma.
Tumor cells within the capsule — A thin layer of fibrous tissue, called the capsule, normally surrounds a parathyroid tumor. Cells found inside the capsule but not breaking through it are an atypical feature. Cells passing all the way through the capsule would be considered invasion and would point toward carcinoma.
Adherence to nearby structures — The surgeon may note that the tumor stuck to nearby tissue, such as the thyroid gland or muscle, during the operation. If the pathologist does not find clear evidence of cells invading into that tissue, the finding is considered atypical rather than diagnostic of cancer.
Increased mitotic activity — A mitotic figure is a cell caught in the act of dividing. Most parathyroid adenomas show very few. An atypical parathyroid tumor often shows more than 5 mitotic figures per 10 square millimeters of tissue.
Atypical mitotic figures — Dividing cells with an abnormal shape or pattern. These are uncommon in benign growths and suggest a more active tumor.
Coagulative necrosis — Areas where tumor cells have died in a particular pattern called coagulative necrosis. This is uncommon in benign adenomas. The pathologist distinguishes true tumor necrosis from changes that can occur after surgery or imaging procedures.
Loss of parafibromin — Discussed above. This finding may prompt genetic testing.
Elevated Ki-67 labeling index — Discussed above. A value above 5 percent is considered atypical.

Your pathology report may list some of these features and not others. Whether a tumor is called atypical depends on the overall picture, not on any single feature.

Inherited syndromes and genetic testing

A meaningful minority of atypical parathyroid tumors are linked to an inherited genetic change. Loss of parafibromin staining on immunohistochemistry, a strong family history of parathyroid disease, a young age at diagnosis, or other features of MEN1 or HPT-JT may prompt the medical team to consider referral for genetic counseling. Genetic counseling is a conversation with a specialist who reviews the family history, explains the possible inherited causes, and helps decide whether a blood test for a germline mutation is appropriate. Identifying an inherited cause allows other family members to be offered testing and, if needed, regular screening for parathyroid and related tumors.

The findings on the pathology report help guide that decision but do not require it on their own. The surgical team, an endocrinologist, and (when needed) a genetic counselor work together to decide whether testing is appropriate.

Margins

A margin is the cut edge of the tissue removed at surgery. For parathyroid tumors, the surgical goal is to remove the involved gland in one piece with its capsule intact. The pathologist describes whether the tumor was completely contained within the removed specimen.

Negative margin — No tumor cells are seen at the cut edge or breaking through the capsule. This suggests the tumor was completely removed.
Positive margin — Tumor cells are seen at the cut edge, or the capsule was disrupted during surgery and tumor cells may have spilled into the surrounding tissue. A positive margin or capsular rupture increases the risk that the tumor will return at the same site over time.

The margin status is one of the factors the medical team considers when planning the surveillance schedule after surgery.

What is the prognosis?

The prognosis for an atypical parathyroid tumor is generally favorable, especially when the tumor was removed in one piece with the capsule intact and the calcium and parathyroid hormone levels return to normal after surgery. The vast majority of patients are cured by the operation alone. Compared with parathyroid carcinoma, atypical parathyroid tumors very rarely spread to lymph nodes or distant organs.

The most important concern is local recurrence — the tumor coming back in the same area of the neck — which is uncommon but happens more often than after a typical parathyroid adenoma. Reported recurrence rates vary across studies but are generally in the range of a few percent over many years of follow-up. Because recurrence can occur years or even decades after the first operation, long-term monitoring of calcium and parathyroid hormone levels is recommended.

Features that may be associated with a higher risk of recurrence include:

Loss of parafibromin staining — Suggests an underlying CDC73 change and a slightly higher risk of recurrence or future development of carcinoma.
Capsular rupture during surgery or a positive margin — Tumor cells may have been left behind in the surgical bed.
Large tumor size or very high preoperative calcium and parathyroid hormone levels — Have been linked to a slightly higher risk of recurrence in some studies.
Underlying genetic syndrome (HPT-JT or MEN1) — These patients are at a higher lifetime risk of developing additional parathyroid tumors over time.

What happens after this diagnosis?

The pathology findings shape the next steps in care rather than dictating a single treatment. After complete surgical removal of an atypical parathyroid tumor, the medical team typically considers:

Long-term monitoring of blood tests — Calcium and parathyroid hormone levels are checked at regular intervals, often for life, to look for early signs of recurrence.
Imaging if levels change — If calcium or parathyroid hormone levels rise again, neck ultrasound, sestamibi scanning, or 4D-CT may be used to look for a recurrence.
Referral for genetic counseling — Considered when parafibromin is lost on immunohistochemistry, when the patient is young, when other endocrine tumors are present, or when there is a relevant family history.
Bone density and kidney evaluation — Long-standing hyperparathyroidism can affect the bones and kidneys; these are often assessed and followed over time.
Multidisciplinary review — Endocrine surgeons, endocrinologists, and (when relevant) genetic counselors work together to plan follow-up. Radiation and chemotherapy are not part of standard care for an atypical parathyroid tumor.

The findings on your pathology report — the specific atypical features, the parafibromin and Ki-67 results, and the margin status — help your team decide how closely to follow you and whether to involve a genetic counselor.

Questions to ask your doctor

What was the size of the tumor, and which parathyroid gland was involved?
Which atypical features were seen under the microscope?
Was the tumor completely removed, and were the margins negative?
Was the capsule of the tumor intact during surgery?
What did the parafibromin and Ki-67 stains show?
Was there any evidence of invasion that would change the diagnosis to parathyroid carcinoma?
Should I be referred for genetic counseling or testing for HPT-JT, MEN1, or familial isolated hyperparathyroidism?
How will my calcium and parathyroid hormone levels be monitored after surgery?
How often will I need follow-up blood tests, and for how long?
What imaging tests will be used if my calcium or parathyroid hormone levels rise again?
What is the risk that this tumor will come back at the same site?
Do I need an assessment of my bones (bone density) or kidneys?
Should my family members be screened for parathyroid disease?