Your pathology report for widely invasive follicular thyroid carcinoma

by Jason Wasserman MD PhD FRCPC
July 3, 2025

Widely invasive follicular thyroid carcinoma is a rare but more aggressive type of thyroid cancer that starts from follicular cells, the cells in the thyroid gland that produce thyroid hormones. It is considered a well-differentiated carcinoma, meaning that the cancer cells retain a somewhat normal appearance under the microscope. However, unlike less aggressive forms of follicular carcinoma, this tumour invades widely into the surrounding thyroid tissue and often into nearby blood vessels or soft tissue.

This type of cancer is more likely to spread to other parts of the body, such as the lungs or bones, and usually requires more intensive treatment than other subtypes of follicular thyroid carcinoma.

What are the symptoms of widely invasive follicular thyroid carcinoma?

People with this type of cancer may notice:

  • A rapidly growing or firm lump in the neck.

  • Pressure or discomfort in the neck.

  • Difficulty swallowing or breathing.

  • Hoarseness or voice changes (if nearby nerves are affected).

In some cases, symptoms are caused by metastases, meaning the cancer has already spread to distant organs such as the lungs or bones. These symptoms may include bone pain or a persistent cough.

What causes widely invasive follicular thyroid carcinoma?

The exact cause is not known, but several risk factors have been associated with follicular thyroid carcinoma in general:

  • Iodine deficiency: Areas with low iodine in the diet have higher rates of this cancer.
  • Radiation exposure: Especially during childhood.
  • Genetic syndromes: Some inherited conditions, such as PTEN hamartoma tumour syndrome (Cowden syndrome), DICER1 syndrome, Werner syndrome, and Carney complex.

These inherited conditions may increase the risk of thyroid tumours, including widely invasive types. Most cases, however, are sporadic, meaning they occur by chance without a family history.

How is widely invasive follicular thyroid carcinoma diagnosed?

Diagnosis is usually made after surgery when the entire tumour is removed and examined under the microscope. A fine-needle aspiration biopsy (FNAB) done before surgery may suggest a follicular neoplasm. Still, it cannot confirm whether the tumour is benign or malignant or determine the degree of invasion.

Widely invasive follicular thyroid carcinoma is diagnosed when the tumour:

  • Extensively invades the surrounding thyroid tissue.

  • Frequently invades blood vessels.

  • Spreads beyond the thyroid into adjacent soft tissues or organs.

The diagnosis is based on these invasive features, which are seen during a careful examination of multiple sections of the tumour.

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

When examined under the microscope, widely invasive follicular carcinoma typically shows:

  • Irregular growth through the thyroid gland and possibly into surrounding tissues.

  • Multiple areas of vascular invasion, where tumour cells are seen inside blood vessels.

  • Tumour cells arranged in follicular, solid, or trabecular patterns.

  • Round nuclei with coarse chromatin, but lacking the nuclear features seen in papillary thyroid carcinoma.

  • Low to moderate mitotic activity, depending on the tumour.

  • No tumour necrosis (areas of dead tumour cells), although biopsy-related changes may be present.

These tumours are generally larger than other subtypes and often lack a clearly defined capsule. Pathologists may also look for signs that the tumour has invaded into fat, muscle, or blood vessels beyond the thyroid.

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 widely invasive follicular 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 follicular 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 conducted using a method called next-generation sequencing (NGS), which enables the simultaneous testing of multiple genes. Molecular testing is sometimes used to help understand how a thyroid tumour developed and how it might behave.

In widely 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 signalling 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 widely 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 widely invasive follicular thyroid carcinoma?

Treatment usually involves total thyroidectomy, meaning surgical removal of the entire thyroid gland. Because these tumours are more likely to spread, treatment often also includes:

  • Radioactive iodine therapy is used to destroy any remaining thyroid tissue or cancer cells.

  • Thyroid hormone replacement to maintain normal hormone levels and suppress the growth of any residual tumour.

  • External beam radiation or systemic therapy may be used in rare cases, particularly if the cancer has spread and cannot be removed completely.

  • Long-term follow-up with blood tests and imaging to monitor for recurrence or metastasis.

What is the prognosis for widely invasive follicular thyroid carcinoma?

The prognosis for a patient diagnosed with widely invasive follicular carcinoma depends on several factors:

  • Whether the cancer has spread beyond the thyroid gland.

  • The number of blood vessels invaded.

  • The presence of distant metastases, such as in the lungs or bones.

  • The presence of aggressive genetic changes, like TERT promoter mutations.

Compared to other types of follicular thyroid carcinoma, widely invasive tumours have a higher risk of recurrence and distant spread. Still, many patients respond well to treatment, especially if the tumour is detected early and removed completely.

Studies have shown that disease-free survival is significantly lower in widely invasive tumours than in minimally invasive or encapsulated angioinvasive types; however, long-term outcomes can still be favourable in many cases with proper treatment and monitoring.

Questions to ask your doctor

  • How invasive was the tumour? Did it invade blood vessels or tissues outside the thyroid?

  • Has the cancer spread to other parts of the body?

  • What treatments will I need after surgery?

  • Will I receive radioactive iodine therapy?

  • What follow-up tests will I need?

  • Are there any genetic mutations in my tumour that affect my prognosis?

  • Should I consider genetic counselling or testing for a hereditary cancer syndrome?

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