Cribriform morular thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
February 21, 2024

Cribriform morular thyroid carcinoma (CMTC) is a rare type of thyroid gland cancer. The thyroid is a butterfly-shaped gland in the neck that produces hormones important for metabolism. Cribriform morular thyroid carcinoma is unique due to its specific appearance under the microscope and its association with certain genetic conditions.

What are the symptoms of cribriform morular thyroid carcinoma?

Like other thyroid cancers, cribriform morular thyroid carcinoma often does not cause symptoms in the early stages. When symptoms do occur, they may include:

• A lump or swelling in the neck.
• Difficulty swallowing or breathing.
• Changes in voice, like hoarseness.

What causes cribriform morular thyroid carcinoma?

The exact cause of cribriform morular thyroid carcinoma is not fully understood. However, it is often associated with a genetic condition known as Familial Adenomatous Polyposis (FAP). In addition to cribriform morular thyroid carcinoma, people with FAP typically develop small growths throughout the digestive tract called polyps and are at high risk for developing colon cancer.

Cribriform morular thyroid carcinoma is linked with mutations in the APC gene, which is the same gene associated with FAP. These mutations can lead to abnormal cell growth in the thyroid gland, resulting in cancer.

Who is at risk for developing cribriform morular thyroid carcinoma?

The vast majority of patients diagnosed with cribriform morular thyroid carcinoma are females under 40 years of age. Women with FAP syndrome are also at higher risk for developing this type of cancer.

How is this diagnosis made?

Diagnosing cribriform morular thyroid carcinoma usually starts with a visit to your doctor, who might feel your neck for any unusual lumps. If they find something suspicious, they might order an ultrasound, which uses sound waves to create a picture of your thyroid gland. This helps them see if there are nodules (lumps) that need a closer look.

The gold standard for diagnosing cribriform morular thyroid carcinoma, however, is a fine needle aspiration biopsy (FNAB). This involves using a very thin needle to take a small tissue sample from the nodule. The sample is then examined under a microscope to check for cancer cells. After the diagnosis is made, your doctor may recommend surgery to remove part or all of the thyroid gland.

Microscopic features

When examined under the microscope cribriform morular carcinoma comprises large tumour cells showing various growth patterns. The term “cribriform” refers to groups of tumour cells surrounding small holes, similar to Swiss cheese. The term “morular” refers to small round groups of elongated or spindle-shaped tumour cells that resemble squamous cells. Other patterns of growth commonly seen in this tumour include solid, follicular, and papillary. In contrast to the cells normally found in the thyroid gland, the tumour cells in cribriform morular thyroid carcinoma do not produce a substance called colloid.

Immunohistochemistry

Immunohistochemistry (IHC) is a test that allows pathologists to see the types of proteins being made by individual cells in a tissue sample. When IHC is performed on cribriform morular thyroid carcinoma, the tumour cells are typically positive for pan-cytokeratins and TTF-1. The tumour cells also show abnormal nuclear expression of beta-catenin protein (in normal cells this protein is found in the membrane of the cells, not in the nucleus). The tumour cells are typically negative for thyroglobulin and PAX-8.

Tumour size

After the tumour is removed completely, it will be measured. The tumour is usually measured in three dimensions, but only the largest dimension is described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe the tumour as being 4.0 cm. The tumour size is important for cribriform morular thyroid carcinoma because it is used to determine the pathologic tumour stage (pT) and because larger tumours are more likely to spread to other parts of the body, such as lymph nodes.

Extrathyroidal extension

​Extrathyroidal extension means that tumour cells have spread outside of the thyroid gland and into the surrounding tissues. Pathologists divide extrathyroidal extension into two types:

• Microscopic extrathyroidal extension – The tumour cells outside of the thyroid gland could be seen only after the tumour was examined under the microscope. This type of extrathyroidal extension is not associated with a worse prognosis and it does not change the pathologic tumour stage (pT).
• Gross (macroscopic) extrathyroidal extension – The tumour could be seen spreading into surrounding tissues without the use of a microscope. Your doctor may see this type of extrathyroidal extension at the time of surgery or by the pathologist’s assistant performing the gross examination of the tissue sent to pathology. This type of extrathyroidal extension is important because these tumours are more likely to spread to other body parts. Gross extrathyroidal extension also increases the pathologic tumour stage (pT) to pT3b.

Vascular invasion (angioinvasion)

​Vascular invasion (also called angioinvasion) is the spread of tumour cells into a blood vessel. Blood vessels carry blood around the body. Vascular invasion is important because it increases the risk that tumour cells will spread to other parts of the body, such as the lungs or bones. Most reports will describe vascular invasion as negative if no tumour cells are seen inside a blood vessel or positive if tumour cells are seen inside at least one blood vessel.

Lymphatic invasion

​Lymphatic invasion means that tumour cells were seen inside a lymphatic vessel. Lymphatic vessels are small hollow tubes that allow the flow of a fluid called lymph from tissues to immune organs called lymph nodes. Lymphatic invasion is important because it increases the risk that tumour cells will spread to lymph nodes. If lymphatic invasion is seen, it will be called positive. If no lymphatic invasion is seen, it will be called negative.

Margins

​In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure, like an excision or resection, aimed at removing the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some tumour cells may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Tumour cells can spread from the primary tumour to lymph nodes through small lymphatic vessels. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of tumour cells from the tumour to another part of the body, such as a lymph node, is called metastasis.

Tumour cells typically spread first to lymph nodes close to the tumour, although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.

A neck dissection is a surgical procedure performed to remove lymph nodes from the neck. The lymph nodes removed usually come from different areas of the neck, and each area is called a level. The levels in the neck include 1, 2, 3, 4, and 5. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. “Positive” means that tumour cells were found in the lymph node. “Negative” means that no tumour cells were found. If tumour cells are found in a lymph node, the size of the largest group of tumour cells (often described as “focus” or “deposit”) may also be included in your report. Extranodal extension means that the tumour cells have broken through the capsule on the outside of the lymph node and have spread into the surrounding tissue.

The examination of lymph nodes is important for two reasons. First, this information determines the pathologic nodal stage (pN). Second, finding tumour cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as radioactive iodine, chemotherapy, radiation therapy, or immunotherapy is required.

Pathologic stage (pTNM)

The pathologic stage for cribriform morular thyroid carcinoma can only be determined after the entire tumour has been surgically removed and examined under the microscope by a pathologist. The stage is divided into three parts: tumour stage (pT) which describes the tumour, nodal stage (pN) which describes any lymph nodes examined, and metastatic stage (pM) which describes tumour cells that have spread to other parts of the body. Most pathology reports will include information about the tumour and nodal stages. The overall pathologic stage is important because it helps your doctor determine the best treatment plan and predict the outlook for recovery.

Tumour stage (pT)

• T0: No evidence of primary tumour.
• T1: The tumour is 2 cm (about 0.8 inches) or smaller in its greatest dimension and confined to the thyroid.
  • T1a: The tumour is 1 cm (about 0.4 inches) or smaller.
  • T1b: The tumour is larger than 1 cm but not larger than 2 cm.
• T2: The tumour is larger than 2 cm but not larger than 4 cm (about 1.6 inches) and is still inside the thyroid.
• T3: The tumour is larger than 4 cm or has minimal extension beyond the thyroid gland.
  • T3a: The tumour is larger than 4 cm but is still confined to the thyroid.
  • T3b: The tumour shows gross extrathyroidal extension (it has spread into the muscles outside of the thyroid).
• T4: This indicates advanced disease.
  • T4a: The tumour extends beyond the thyroid capsule to invade subcutaneous soft tissues, the larynx (voice box), trachea (wind-tumour, esophagus (food pipe), or recurrent laryngeal nerve (a nerve that controls the voice box).
  • T4b: The tumor invades poesophagusal space (area in front of the spinal column), and encases the carotid artery or the mediastinal vessels (major blood vessels).

Nodal stage (pN)

• N0: No regional lymph node metastasis (the cancer hasn’t spread to nearby lymph nodes).
• N1: There is metastasis to regional lymph nodes (near the thyroid).
  • N1a: Metastasis is limited to lymph nodes around the thyroid (pretracheal, paratracheal, prelaryngeal/Delphian, and/or perithyroidal lymph nodes).
  • N1b: Metastasis to other cervical (neck) or superior mediastinal lymph nodes (lymph nodes in the upper chest).

Other helpful resources

American Thyroid Association (ATA)

American Cancer Society

Learn more pathology

Atlas of Pathology