Minimally invasive follicular thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
July 3, 2025

Minimally invasive follicular thyroid carcinoma is a type of thyroid cancer that starts from follicular cells—the cells in the thyroid gland responsible for producing thyroid hormones. This tumour is classified as a well-differentiated carcinoma, which means the cancer cells still resemble normal thyroid cells when examined under the microscope.

The term minimally invasive means that the tumour has started to grow through the capsule (a thin layer of tissue that surrounds it), but has not spread into blood vessels. This limited invasion is what distinguishes it from a follicular adenoma (a benign tumour with no invasion) and from more aggressive forms of follicular thyroid carcinoma that invade blood vessels or surrounding thyroid tissue.

Minimally invasive follicular thyroid carcinoma generally grows slowly, and when completely removed, it has an excellent prognosis.

What are the symptoms of minimally invasive follicular thyroid carcinoma?

In most cases, people with minimally invasive follicular thyroid carcinoma do not have symptoms, and the tumour is found during a routine physical examination, imaging study, or evaluation of a thyroid nodule.

When symptoms are present, they may include:

• A painless lump in the front of the neck.

• A feeling of pressure in the neck.

• Difficulty swallowing (in rare cases).

Because this tumour usually does not spread to lymph nodes and does not cause hormone overproduction, symptoms of thyroid dysfunction or widespread disease are uncommon.

What causes minimally invasive follicular thyroid carcinoma?

The exact cause is unknown, but certain factors may increase the risk:

• Iodine deficiency, which has been linked to higher rates of follicular thyroid cancer.

• Radiation exposure, especially in childhood.

• Genetic conditions, including PTEN hamartoma tumour syndrome (Cowden syndrome), DICER1 syndrome, Werner syndrome, and Carney complex.

Most cases, however, are sporadic, meaning they occur by chance and are not inherited.

How is minimally invasive follicular thyroid carcinoma diagnosed?

The diagnosis cannot be made from a fine-needle aspiration biopsy (FNAB) alone. That’s because the key feature of cancer—capsular invasion—can only be seen when the entire tumour is removed and examined under the microscope.

Before surgery, the tumour may be labeled as a follicular neoplasm or suspicious for follicular neoplasm based on biopsy results. After surgery, a pathologist will examine the tumour to see if the cancer cells have broken through the capsule. If they have, but there is no invasion into blood vessels, the diagnosis is minimally invasive follicular thyroid carcinoma.

What does minimally invasive follicular thyroid carcinoma look like under the microscope?

When viewed under the microscope, this tumour:

• Is surrounded by a thin or thick capsule.

• Shows one or more areas where tumour cells penetrate through the capsule.

• Does not invade nearby blood vessels.

• Is made of follicular cells arranged in round follicles, solid areas, or trabecular (cord-like) patterns.

• Has uniform nuclei without the nuclear features seen in papillary thyroid carcinoma.

• Has low mitotic activity, meaning few dividing cells.

• Does not show tumour necrosis (areas of dead cancer cells).

To confirm the diagnosis, the pathologist carefully examines the capsule and may take multiple sections to look for signs of invasion.

Immunohistochemistry

Immunohistochemistry is a special test that pathologists use to help diagnose and classify tumours. It works by using antibodies to detect specific proteins made by the tumour cells. These proteins can help confirm that the tumour started in the thyroid and may also provide clues about how the tumour is likely to behave.

For minimally invasive follicular thyroid carcinoma, immunohistochemistry typically shows the following:

• Thyroglobulin: This protein is made by normal thyroid cells and is usually found in the cytoplasm (the inside of the cell). Most follicular thyroid carcinomas are positive for thyroglobulin, which confirms that the tumour came from thyroid follicular cells.

• Thyroid transcription factor 1 (TTF-1) and PAX8: These are nuclear proteins that are also commonly found in thyroid cells. Most follicular thyroid carcinomas show strong nuclear staining for both.

• Cytokeratins (CAM5.2, CK7): These proteins help support the structure of cells and are usually present in follicular thyroid carcinoma. They help distinguish thyroid tumours from other types of cancer.

• Calcitonin and CK20: These markers are negative in follicular thyroid carcinoma, which helps rule out other types of thyroid cancer (such as medullary thyroid carcinoma or metastatic cancers).

• Ki-67: This protein helps measure how quickly the tumour cells are dividing. Most follicular thyroid carcinomas have a low Ki-67 index (less than 5%), indicating that the tumour cells are not dividing rapidly. A higher Ki-67 index may suggest a more aggressive tumour or raise concern for a different type of cancer, such as poorly differentiated thyroid carcinoma.

These tests help pathologists confirm that the tumour started in the thyroid and rule out other possibilities. However, they do not reliably distinguish between follicular adenoma (a benign tumour) and minimally invasive follicular thyroid carcinoma because both may show similar staining. The final diagnosis still depends on whether the tumour has invaded surrounding tissue or blood vessels, which must be seen under the microscope.

Molecular testing

Molecular testing looks for changes (mutations or rearrangements) in the DNA of the tumour cells. These tests are often done using a method called next-generation sequencing (NGS), which allows many genes to be tested at once. Molecular testing is sometimes used to help understand how a thyroid tumour developed and how it might behave.

In minimally invasive follicular thyroid carcinoma, the most common molecular findings include:

• RAS mutations: Found in up to 30% of follicular thyroid carcinomas. These mutations affect genes that control cell growth (such as NRAS, HRAS, or KRAS). RAS mutations are common in both benign and malignant follicular-patterned thyroid tumours and are not specific for cancer.

• PAX8::PPARG gene rearrangement: This abnormal fusion between two genes is found in 10–40% of follicular thyroid carcinomas. Tumours with this change may occur in younger patients and may be more likely to show aggressive behaviour.

• TERT promoter mutations: Found in about 15% of follicular thyroid carcinomas, especially those with distant metastases (spread to other organs). These mutations are linked to more advanced disease and worse prognosis.

• PIK3CA and PTEN mutations: These are part of a signaling pathway that helps control cell growth. These mutations are more common in follicular thyroid carcinoma than in benign thyroid tumours.

• EIF1AX mutations: Found in a small number of cases, often in combination with RAS mutations.

• DICER1 and NF1 mutations: Rare but may be seen in tumours related to inherited syndromes.

• TSHR (thyroid-stimulating hormone receptor) mutations: Rarely seen, especially in tumours that produce excess thyroid hormone (causing hyperthyroidism).

It’s important to know that no single genetic mutation confirms the diagnosis of minimally invasive follicular thyroid carcinoma. The diagnosis is still made by carefully examining the tumour under the microscope. Molecular testing provides additional information that may help predict the behaviour of the tumour and guide future treatment.

What is the treatment for minimally invasive follicular thyroid carcinoma?

The most common treatment is surgery. Depending on the size and appearance of the tumour, your doctor may recommend:

• Lobectomy (removal of the affected half of the thyroid).

• Total thyroidectomy (removal of the entire thyroid gland), especially if there are multiple nodules or risk factors for recurrence.

Most patients do not need radioactive iodine therapy, especially if the tumour is small, fully removed, and shows only limited capsular invasion.

After surgery, your doctor may prescribe thyroid hormone replacement therapy to maintain normal hormone levels and help prevent the growth of any remaining thyroid tissue.

What is the prognosis for minimally invasive follicular thyroid carcinoma?

The prognosis is excellent. In most cases, surgery is curative, and the risk of recurrence or spread is very low. Long-term survival rates are greater than 95%. Patients with this diagnosis rarely develop distant metastases (cancer spread to other parts of the body), especially if the tumour has been completely removed and there is no blood vessel invasion. Regular follow-up with blood tests (such as thyroglobulin levels) and imaging may be recommended to monitor for recurrence, but ongoing treatment beyond surgery is often not needed.

Questions to ask your doctor

• What type of thyroid carcinoma do I have?

• Was there any invasion into blood vessels?

• Will I need further treatment after surgery?

• Do I need radioactive iodine therapy?

• Will I need thyroid hormone replacement?

• How often should I have follow-up testing?