Anaplastic Thyroid Carcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
April 20, 2026

Anaplastic thyroid carcinoma is a rare and highly aggressive type of thyroid cancer. It starts from follicular cells, the cells that normally make thyroid hormone, but over time, these cells change so much that they no longer look or behave like thyroid cells. For this reason, anaplastic thyroid carcinoma is sometimes called undifferentiated thyroid carcinoma.

Anaplastic thyroid carcinoma grows very rapidly and often invades nearby structures in the neck within weeks. It most often affects adults over the age of 60 and is slightly more common in women. Because it grows so quickly, anaplastic thyroid carcinoma is considered a medical emergency, and urgent evaluation by a team of specialists is essential.

What are the symptoms of anaplastic thyroid carcinoma?

Because anaplastic thyroid carcinoma grows rapidly, symptoms usually develop over days to weeks rather than months. The most common symptoms include:

A rapidly growing lump or mass in the front of the neck.
Pain or pressure in the neck.
Difficulty swallowing.
Difficulty breathing.
Hoarseness or other changes in the voice.
A cough or a sense of fullness in the throat.

Some patients also have more general symptoms, such as fatigue, weight loss, or, less commonly, high blood calcium levels.

What causes anaplastic thyroid carcinoma?

The exact cause of anaplastic thyroid carcinoma is not known. In many cases, the tumor appears to develop from a pre-existing, slower-growing thyroid cancer, such as papillary thyroid carcinoma or follicular thyroid carcinoma, that has become more aggressive over time. This process is called dedifferentiation — the original cancer cells lose their mature features and begin to grow in a much more disorderly, aggressive way as they acquire additional genetic changes.

Known risk factors include:

A history of a long-standing goiter or thyroid nodule.
Previous radiation exposure to the neck.
Low iodine intake.
A previous diagnosis of a well-differentiated thyroid cancer, such as papillary or follicular thyroid carcinoma.

How is the diagnosis of anaplastic thyroid carcinoma made?

Because anaplastic thyroid carcinoma grows quickly, the diagnosis needs to be made urgently. A physical examination and imaging tests such as ultrasound, CT, or MRI are usually the first steps and show a large, rapidly growing mass in the thyroid that often invades nearby structures. A tissue sample is then obtained, either by fine-needle aspiration (FNA) or by core needle biopsy, so that a pathologist can examine the tumor cells under the microscope. Under the microscope, anaplastic thyroid carcinoma cells look very abnormal and bear little resemblance to normal thyroid cells, which is why additional tests are usually needed to confirm the diagnosis. Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins in the tumor cells; in anaplastic thyroid carcinoma, the tumor cells usually stain for cytokeratins (proteins found in many cancers that start from epithelial cells), often show abnormal (increased) p53 staining, and have a very high Ki-67 (a marker of how quickly cells are dividing). Thyroid-specific proteins such as thyroglobulin and TTF-1 are usually negative or only weakly positive, reflecting that these tumor cells have lost their thyroid features; PAX8 may still be positive in about half of cases and can help confirm that the tumor originated in the thyroid. Imaging is also used to look for spread to lymph nodes in the neck and to distant parts of the body, such as the lungs, bones, or brain. Because treatment decisions depend heavily on molecular testing (described in the biomarkers section below), tumor tissue is usually sent for urgent molecular testing at the same time that the diagnosis is being made.

What does anaplastic thyroid carcinoma look like under the microscope?

Under the microscope, anaplastic thyroid carcinoma shows features that reflect its highly aggressive and undifferentiated nature. The tumor may be made up of several different cell types, often mixed together in the same tumor:

Spindle-shaped cells. Long and thin cells arranged in sweeping bundles, often resembling the cells of a sarcoma (a cancer of soft tissue).
Epithelioid cells. Rounder, more closely packed cells that form clusters or sheets.
Giant cells. Very large tumor cells that often contain several nuclei. These are signs of high-grade, aggressive cancer.
Squamous cells. Flat, plate-like cells are seen when the tumor has a squamous growth pattern.

Other features commonly seen in anaplastic thyroid carcinoma include:

Very rapid cell division. Many cells can be seen dividing, and the dividing cells (called mitotic figures) often appear abnormal.
Tumor necrosis. Large areas of dead tumor cells are a sign that the tumor is growing so quickly that it outpaces its blood supply.
Marked variation in cell shape and size. Tumor cells and their nuclei vary widely in size and shape, another sign of a very aggressive, high-grade tumor.
Loss of normal structure. The tumor does not form the well-organized follicles seen in normal thyroid tissue; instead, it invades surrounding tissue in a disorganized, sheet-like pattern.
Inflammation. Immune cells, especially a type called neutrophils, are often mixed in with the tumor.

In some cases, small areas of a pre-existing well-differentiated thyroid carcinoma (such as papillary or follicular thyroid carcinoma) are also seen within the tumor. If present, these areas support the theory that the anaplastic tumor developed from a previously slower-growing thyroid cancer, and they will be mentioned in the pathology report.

Biomarkers in anaplastic thyroid carcinoma

Biomarkers are molecular features of a tumor that can help explain how it developed, how it may behave, and — most importantly in anaplastic thyroid carcinoma — whether targeted drug therapy may be effective. Because the outlook for anaplastic thyroid carcinoma has been transformed in recent years by the introduction of molecular targeted therapy, urgent biomarker testing is now considered standard of care for all patients. Molecular testing is usually performed on the tumor tissue using next-generation sequencing (NGS).

BRAF V600E mutation

The BRAF V600E mutation is the single most important biomarker in anaplastic thyroid carcinoma. It is found in about 20 to 40 percent of tumors, most often those that developed from a pre-existing papillary thyroid carcinoma. When this mutation is present, a combination of two targeted drugs — dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) — can dramatically shrink the tumor and is approved specifically for BRAF-mutant anaplastic thyroid carcinoma. For tumors that are initially too large to remove by surgery, this combination is sometimes given first to shrink the tumor enough that surgery becomes possible. Because of how much this finding can change treatment, BRAF testing should be done urgently in every patient with anaplastic thyroid carcinoma. For more information, see our dedicated article on BRAF mutations in thyroid cancer.

TP53 mutations

The TP53 gene is often called the “guardian of the genome” because it normally helps prevent cells with damaged DNA from dividing. Most anaplastic thyroid carcinomas carry a TP53 mutation, which is one of the main reasons these tumors behave so aggressively. There is no drug that directly targets mutated TP53, but the presence of a mutation supports the diagnosis and is a marker of aggressive disease.

TERT promoter mutations

The TERT promoter is a region of DNA that controls how much telomerase a cell produces. Telomerase helps cells maintain their chromosomes’ integrity during cell division. Mutations in the TERT promoter allow tumor cells to divide indefinitely. They are very common in anaplastic thyroid carcinoma and are associated with the most aggressive behavior, especially when they occur together with a BRAF or RAS mutation.

RAS mutations

The RAS family of genes (HRAS, KRAS, and NRAS) makes proteins that help control cell growth. RAS mutations are found in about 20 to 25 percent of anaplastic thyroid carcinomas and are more often seen in tumors that developed from a pre-existing follicular-pattern thyroid cancer. There is no standard RAS-targeted therapy for thyroid cancer, but RAS status helps explain how the tumor developed and is considered in treatment planning, particularly in clinical trials.

NTRK and RET fusions

A fusion happens when part of one gene becomes joined to part of another, creating an abnormal combined gene. Fusions involving NTRK or RET are uncommon in anaplastic thyroid carcinoma, but when they are found, they are highly actionable. Drugs such as larotrectinib and entrectinib are very effective against NTRK-fusion tumors, and drugs such as selpercatinib and pralsetinib are very effective against RET-fusion tumors. These fusions are a core reason that comprehensive molecular testing is now standard in anaplastic thyroid carcinoma. For more information, see our dedicated article on RET mutations and fusions in thyroid cancer.

Mismatch repair deficiency and tumor mutational burden

A small number of anaplastic thyroid carcinomas have lost the ability to properly repair DNA damage, a state called mismatch repair deficiency (dMMR). These tumors typically carry many more mutations than average, a feature called a high tumor mutational burden (TMB-high). Both findings may make the tumor eligible for immunotherapy drugs such as pembrolizumab, which help the immune system recognize and attack the cancer.

Tumor size

If the tumor is removed by surgery, it is measured in three dimensions, and the largest measurement is reported. Tumor size is important because larger tumors are more likely to invade nearby structures and more likely to have spread to distant parts of the body.

Extrathyroidal extension

Extrathyroidal extension means the cancer has spread beyond the thyroid gland into the surrounding neck tissues. This is a very common feature of anaplastic thyroid carcinoma and almost always indicates advanced disease. The tumor may invade nearby muscles, the voice box (larynx), windpipe (trachea), food pipe (esophagus), or major blood vessels, making complete surgical removal difficult or impossible.

Microscopic extrathyroidal extension. Tumor cells just beyond the thyroid that can only be seen under the microscope.
Gross (macroscopic) extrathyroidal extension. Tumor growth that is visible during surgery or on imaging. This is the more common form in anaplastic thyroid carcinoma and is associated with a worse prognosis.

Vascular invasion

Vascular invasion means that tumor cells have entered blood vessels in or around the tumor. Once tumor cells are inside a blood vessel, they can travel to distant parts of the body, such as the lungs, bones, or brain, where they can form new tumors (metastases). Vascular invasion is very common in anaplastic thyroid carcinoma and is another sign of aggressive, advanced disease.

Lymphatic invasion

Lymphatic invasion means that tumor cells have entered lymphatic channels, the tiny vessels that carry a fluid called lymph toward lymph nodes. From there, tumor cells can travel to lymph nodes in the neck and form new tumor deposits. Lymphatic invasion is often present in anaplastic thyroid carcinoma.

Margins

A margin is the edge of the tissue removed during surgery. The pathologist examines the margins to determine whether any cancer cells extend to the cut edge.

Negative margin. No cancer cells are seen at the edge. This suggests that the visible tumor was completely removed.
Positive margin. Cancer cells are seen at the edge, meaning some of the tumor is likely to remain in the body. Additional treatment is usually recommended.

Because anaplastic thyroid carcinoma often invades structures that cannot be removed safely (such as the windpipe, food pipe, or large blood vessels), positive margins are common even when the surgeon has done everything possible to remove the tumor.

Lymph nodes

Lymph nodes are small immune organs that filter lymph fluid. Cancer cells can travel from the thyroid through lymphatic channels to nearby lymph nodes. When lymph nodes are removed during surgery, the pathologist examines them under the microscope and reports the total number of lymph nodes examined and the number, if any, that contain cancer cells. Finding cancer cells in a lymph node raises the nodal stage (pN) and may influence decisions about additional treatment.

Neck dissection

A neck dissection is a surgical procedure in which lymph nodes are removed from specific regions of the neck. These regions are called levels (1 through 7). The central compartment of the neck, just around the thyroid, is called level 6; the area just below it, in the upper chest, is called level 7. Lymph nodes on the same side of the neck as the tumor are called ipsilateral (same side), while those on the opposite side are called contralateral (opposite side).

How lymph nodes are described in the report

If lymph nodes are removed, the pathologist will report:

The total number of lymph nodes examined.
The number of lymph nodes that contain cancer cells. These are called positive nodes.
The size of the largest deposit of cancer cells within a lymph node.
Whether extranodal extension is present. This means cancer cells have grown beyond the outer edge (capsule) of the lymph node into the surrounding tissue.

Pathologic stage (pTNM)

The pathologic stage for anaplastic thyroid carcinoma is based on the size and extent of the tumor (pT), whether cancer is found in nearby lymph nodes (pN), and whether the cancer has spread to distant parts of the body (pM). Unlike most other cancers, all cases of anaplastic thyroid carcinoma are considered stage IV because of how aggressively this cancer behaves. The exact substage (IVA, IVB, or IVC) depends on how far the tumor has spread.

Tumor stage (pT)

T1: Tumor 2 cm or smaller and still within the thyroid.
T2: Tumor larger than 2 cm but not larger than 4 cm and still within the thyroid.
T3: Tumor larger than 4 cm, or tumor of any size with growth into the strap muscles (the muscles just in front of the thyroid).
T4: Tumor with more extensive growth outside the thyroid.
- T4a: Tumor growing into the soft tissues under the skin, voice box (larynx), windpipe (trachea), food pipe (esophagus), or nearby nerves.
- T4b: Tumor growing into the tissue at the front of the spine or surrounding major blood vessels in the neck or chest.

Nodal stage (pN)

NX: No lymph nodes were submitted for examination.
N0: No cancer was found in any of the lymph nodes examined.
N1: Cancer was found in one or more lymph nodes.
- N1a: Cancer in lymph nodes in the central part of the neck (level 6) or upper chest (level 7).
- N1b: Cancer in lymph nodes on the side of the neck (levels 1 through 5).

What happens after the diagnosis?

Because anaplastic thyroid carcinoma grows so rapidly, treatment decisions must be made urgently — often within days of diagnosis. Care is best coordinated by a multidisciplinary team that may include an endocrinologist, a head and neck surgeon, a medical oncologist, a radiation oncologist, a pathologist, and sometimes a palliative care specialist. Protecting the airway is often the first priority, and a procedure to keep the airway open (tracheostomy) may be needed if the tumor is pressing on the windpipe.

The specific treatment plan depends on how far the tumor has spread and on the results of urgent biomarker testing. Options include:

Targeted therapy. For tumors with a BRAF V600E mutation, the combination of dabrafenib and trametinib is now standard of care and can dramatically shrink the tumor. Similar targeted drugs are available for less common tumors with NTRK or RET fusions.
Immunotherapy. For tumors with mismatch repair deficiency (dMMR) or a high tumor mutational burden (TMB-high), immunotherapy drugs such as pembrolizumab may be used, sometimes in combination with targeted therapy.
Surgery. When the tumor is limited to the thyroid or can be removed safely, surgery is performed, often followed by radiation. In tumors that are initially too large to remove, targeted therapy may be given first to shrink the tumor enough for surgery to become possible.
Radiation therapy. External-beam radiation is often used, either after surgery to reduce the risk of local recurrence or as the primary treatment when surgery is not possible.
Chemotherapy. Conventional chemotherapy may be combined with radiation or used in tumors without a targetable biomarker.
Clinical trials. Because new therapies for anaplastic thyroid carcinoma are being developed rapidly, clinical trial enrollment is strongly encouraged whenever possible.
Palliative care. Palliative care focuses on managing symptoms and supporting quality of life; it is an important part of care from the time of diagnosis, alongside any treatments directed at the cancer itself.

The outlook for anaplastic thyroid carcinoma remains serious. Historically, average survival was only a few months. However, outcomes have improved significantly for patients with BRAF-mutant tumors treated with targeted therapy, and a small but growing number of patients are now living considerably longer. Factors associated with better outcomes include smaller tumors confined to the thyroid, no distant spread, successful complete surgical removal of the tumor, and the presence of a targetable biomarker such as BRAF V600E.

Questions to ask your doctor

Has urgent molecular testing, including BRAF testing, been performed on my tumor?
Am I a candidate for targeted therapy (for example, dabrafenib plus trametinib)?
Am I a candidate for immunotherapy?
Has my cancer spread outside the thyroid or to distant parts of the body?
What is my pathologic stage?
Is surgery to remove the tumor possible? If not now, could it become possible after targeted therapy or radiation?
Do I need a tracheostomy to protect my airway?
What is the goal of treatment — to try to cure the cancer, to shrink it, or to control symptoms?
Should I consider enrolling in a clinical trial?
Is palliative care involved in my team?
How often will I need follow-up visits, imaging, and blood tests?