Diagnosis of Thyroid Cancer: Ultrasound, Scintigraphy, Fine-Needle Biopsy, and Lymph Nodes

Thyroid cancer is a rare, malignant form of cancer that affects the thyroid gland. In this condition, cells in the gland become abnormal and form a tumor. In medical terminology, thyroid cancer is referred to as thyroid carcinoma; the term “struma maligna” (“malignant goiter”) is also occasionally used.

Key Terms at a Glance

• Thyroid cancer / thyroid carcinoma: a malignant tumor in the thyroid gland
• Benign vs. malignant: Lumps or enlargements can be harmless, but cancer is not
• Organ: The thyroid gland produces thyroid hormones, among other things, and is located in the neck

Important distinction:
Not every change in the thyroid gland is cancer. Common causes of a goiter (enlarged thyroid) include iodine deficiency, an overactive thyroid (hyperthyroidism), an underactive thyroid (hypothyroidism), or benign cysts. Nodules in the thyroid are also often benign. Only in rare cases are they actually thyroid carcinoma.

Thyroid cancer can lead to an enlarged thyroid (goiter) © amazing studio | AdobeStock

Thyroid cancer is classified into four main types, depending on the tissue of origin of the tumor. These cancers differ in terms of growth, spread (metastasis), treatment, and prognosis.

• Papillary thyroid carcinoma (most common form)
  The peak incidence occurs between the ages of 40 and 50. There is often a single nodule or multiple foci (multifocal) in the thyroid gland. Metastasis occurs primarily via the lymphatic system; therefore, lymph node metastases are not uncommon. Overall, the prognosis for cure is very good. (= “papillary” type)
• Follicular thyroid carcinoma
  Originates from follicular cells, occurs more frequently between the ages of 50 and 60, and usually forms a single nodule. Tends to metastasize via the bloodstream (e.g., to the lungs or bones). It is also highly treatable. (= “follicular” type)
• Medullary thyroid carcinoma (C-cell carcinoma)
  Arises from C-cells, which produce calcitonin. It usually grows slowly but spreads early to lymph nodes in the neck and later to other organs; it is sometimes familial or genetically determined. (= “medullary” form)
• Anaplastic thyroid carcinoma (rare, highly malignant)
  Occurs predominantly in people over the age of 60, grows rapidly, and metastasizes early. In these cases, the disease is often already advanced, which complicates treatment.

Papillary and follicular variants are considered differentiated thyroid carcinomas with a generally more favorable prognosis; anaplastic carcinoma, on the other hand, has a significantly more aggressive course.

Papillary thyroid carcinoma is the most common type © bilderzwerg | AdobeStock

In Germany, approximately 5,000–6,000 people are diagnosed with thyroid cancer each year. Around 700–800 of those affected die from the disease; this corresponds to approximately 0.2–0.3% of cancer-related deaths.

• Ranking of new cases: 15th among men, 14th among women.
• Women are affected more than twice as often as men.
• The median age at diagnosis is approximately 55 years.
• Thyroid cancer can occur at any age, but is more common starting in middle age.
• Internationally, an increase is being observed across all age groups.
• Papillary carcinoma is by far the most common type of thyroid cancer.

Despite its generally rare occurrence, thyroid carcinoma is one of the most significant types of thyroid cancer.

Thyroid cancer is a malignant tumor of the endocrine organs and develops from abnormal thyroid cells within the thyroid tissue. Generally, two cell lines can be affected:

Causes of its development include, among others, genetic factors and previous exposure to radiation.

• Hormone-producing cells (follicular cells) that produce thyroid hormones—the basis of differentiated carcinomas (e.g., papillary, follicular).
• C cells, which produce calcitonin—the origin of medullary thyroid carcinoma.
• Nodules in the thyroid gland warrant special attention:
• In scintigraphic imaging, areas with reduced function appear as “cold nodules.”
• Such suspicious findings are frequently associated with a malignant tumor and require further evaluation.
• On ultrasound, high-risk lesions are often noticeable due to low echogenicity.
• The risk of thyroid cancer is increased by exposure to ionizing radiation during childhood and certain family histories.

Implications for clinical practice and treatment planning: The histological type of thyroid carcinoma significantly influences treatment and prognosis—ranging from well-treatable differentiated thyroid carcinomas to undifferentiated forms.

So-called “cold nodules” require further investigation © bilderzwerg | AdobeStock

Spread and Risk Factors 

Like any malignant tumor, thyroid cancer can invade surrounding tissue and adjacent organs. In advanced stages, metastases frequently develop:

• Lymphatic spread: initially to regional lymph nodes.
• Hematogenous spread: Distant metastases via the bloodstream, primarily to the lungs and bones.

Medullary thyroid carcinoma occurs in a significant proportion of cases with a family history and may be genetically determined. It is not uncommon for it to be associated with neoplasms of the adrenal medulla and the parathyroid glands.

Radiation exposure is considered a major risk factor:

• Ionizing/high-energy radiation, e.g., X-ray exposure to the neck region during childhood.
• Following radioactive incidents, an increased rate of thyroid cancer has been observed in exposed regions.

Important to note: An enlarged thyroid gland (goiter) alone is not a risk factor for cancer. Only tissue changes or newly developed nodules require a targeted medical evaluation.

An enlarged thyroid and palpable nodules are possible symptoms of thyroid cancer © medistock | AdobeStock

In most cases, a medical evaluation is necessary to distinguish a benign goiter from a carcinoma.

Early detection is crucial for the course of the disease and treatment. The process begins with a medical history and physical examination: Doctors document symptoms, their duration, family history, and possible exposure to ionizing radiation—especially during childhood and adolescence. The diagnosis of thyroid cancer is based on medical history, ultrasound, scintigraphy, and fine-needle aspiration biopsy.

Diagnostic methods:

• Physical examination of the neck (palpation of the thyroid gland and lymph nodes)
• Thyroid ultrasound (assessment of nodules, size, borders, and echogenicity)
• Scintigraphy (hot/cold nodules)
• Laboratory tests (including thyroid hormones; calcitonin if medullary thyroid cancer is suspected)
• Imaging as needed: X-ray, CT, MRI
• Fine-needle biopsy (cytological evaluation)
• Genetic analysis in appropriate cases

Palpation of the neck

The thyroid gland is examined with both hands to assess its size, surface, and mobility during swallowing. Firm lesions that are difficult to move or areas tender to pressure are findings that require further investigation. In addition, the neck is palpated for enlarged lymph nodes.

Ultrasound examination of the thyroid

If thyroid cancer is suspected following palpation, an ultrasound is performed. It provides information on the gland’s location, size, and borders, as well as any focal lesions present. Tissue changes reflect sound waves differently; terms such as “hypoechoic” or “hyperechoic” help in assessing risk.
Important: This method does not allow for a definitive distinction between benign and malignant lesions—further tests (e.g., fine-needle biopsy) are necessary for this.

Ultrasound examination of the thyroid © Alexander Raths | AdobeStock

Thyroid scintigraphy can distinguish between hyperfunctional and hypofunctional areas. For this purpose, a weakly radioactive substance (e.g., technetium) is administered; it accumulates in the thyroid tissue and provides information about metabolic activity.

• Hyperactive areas: increased activity, usually benign.
• Hypoactive areas: decreased or no activity—suspicious findings that require further evaluation (e.g., fine-needle biopsy).

In selected cases, a specialized scintigraphy (e.g., MiBi) can also help better classify abnormal areas.

Laboratory Tests

Blood tests provide additional clues regarding thyroid disorders and thyroid function:

• Thyroid hormones: Measurement of T3 (triiodothyronine) and T4 (thyroxine); TSH is also frequently measured.
• TSH is a hormone produced by the pituitary gland (hypophysis) and regulates thyroid activity.
• Tumor markers: Calcitonin is available as a marker for medullary thyroid carcinoma; abnormal values may be verified with specialized tests if necessary.

Important: Most thyroid carcinomas cannot be detected based on laboratory test results alone. A definitive diagnosis is based on a comprehensive evaluation of clinical findings, imaging, and (if necessary) fine-needle aspiration biopsy.

Physical examination of the thyroid gland and blood test for thyroid hormones © Peakstock | AdobeStock

Imaging Procedures

Depending on the clinical question, imaging procedures provide additional information for the diagnosis and treatment planning of thyroid cancer. They show the size and extent of the tumor, involvement of adjacent structures in the neck, and possible metastases.

• X-ray of the trachea/esophagus:
  Assesses whether the tumor is compressing these structures.
• Chest X-ray:
  Used to screen for lung metastases once a tumor has been confirmed and may reveal thyroid enlargement extending into the upper thoracic cavity.
• Computed Tomography (CT) & Magnetic Resonance Imaging (MRI):
  For larger or advanced tumors, these provide detailed information on invasion into surrounding tissue and adjacent organs; this is important for treatment decisions.
• Regional lymph node assessment:
  Regardless of the findings regarding the primary tumor, assessment of the lymph nodes (cervical/mediastinal) is crucial for evaluating lymphatic spread.

Fine-needle biopsy

A fine-needle biopsy determines whether suspicious lesions contain malignant cancer cells. Under ultrasound guidance, cells are extracted from abnormal areas and examined under a microscope.

• Objective: To confirm or rule out thyroid cancer at the cytological level (cell evaluation).
• Procedure: Puncture of hypoactive areas or structurally abnormal lesions; the sample is sent for cytological or, if necessary, histological evaluation.
• Limitations: Not every fine-needle aspiration allows for a definitive distinction between benign and malignant. In unclear cases, the final histological examination is performed after surgery (e.g., partial or complete removal of the thyroid gland) to definitively determine the nature of the tumor.

This combination of imaging and tissue sampling increases diagnostic certainty and guides further treatment planning.

Fine-needle aspiration of the thyroid gland to obtain a tissue sample for subsequent microscopic examination © bilderzwerg | AdobeStock

Genetics

Medullary thyroid carcinoma often arises from C-cells due to genetic factors and frequently occurs in families. Detection of a RET proto-oncogene mutation confirms a hereditary predisposition and allows for risk assessment for affected individuals and their relatives. In these cases, the condition is often classified as a form of multiple endocrine neoplasia (MEN2).

When is genetic testing recommended?

• In cases of confirmed medullary thyroid carcinoma (also known as medullary thyroid carcinoma).
• In cases of a family history of thyroid tumors.
• In cases of comorbidities such as tumors of the adrenal medulla (pheochromocytoma) or disorders of the parathyroid glands.

Benefits of Testing

• Determines whether a hereditary variant is present (RET mutation).
• Identifies relatives with an increased risk who should be monitored closely.
• Helps plan preventive care, as well as the timing and extent of treatment (including possible surgery).

This allows at-risk family members to undergo targeted screening for thyroid cancer; the results guide patient education, follow-up examinations, and management of the neck region (e.g., monitoring for lymph node involvement).

The treatment of thyroid cancer offers various options, depending on the tumor type and extent of spread. In thyroid cancer, the histological type determines the course of action; the goal of any treatment is to ensure effective tumor control and maintain a favorable prognosis.

Standard procedure:

• Surgery for thyroid cancer: partial resection or removal of the thyroid gland (thyroidectomy); often accompanied by the removal of regional lymph nodes in the neck.
• Histology: The removed tissue is examined to determine the type of thyroid cancer and the next course of action.
• Radioiodine therapy for thyroid cancer: Following surgery, radioactive iodine is often administered to destroy tumor cells or metastases—particularly any remaining tumor cells or metastases in the thyroid tissue.
• Hormone therapy: After surgery, the hormone L-thyroxine replaces the missing thyroid hormones; dose adjustments are made during follow-up care for thyroid cancer.
• Adjuvant treatments: Radiation therapy for residual tumors or in cases where the thyroid does not retain iodine; chemotherapy is used only in advanced, selected cases.

During surgery, part of the thyroid gland or the entire gland is removed © Bergringfoto | AdobeStock

The most promising treatment generally depends on the specific type of thyroid cancer.

Papillary thyroid carcinoma

This is the most common form of thyroid cancer. One or more lesions may be detected in the thyroid gland. If this tumor spreads, it first spreads via the lymphatic system to the surrounding lymph nodes. Papillary thyroid carcinoma has the best prognosis (10-year survival rate of approximately 93 percent).

In the case of a single small tumor up to 1 cm in size (microcarcinoma), a total thyroidectomy and removal of the cervical lymph nodes are not necessary.

Partial or total removal of the thyroid © bilderzwerg | AdobeStock

The most promising treatment always depends on the type and stage of thyroid carcinoma. Differentiated forms (papillary/follicular) generally respond very well to surgery and subsequent radioiodine therapy; involvement of regional lymph nodes is taken into account in treatment planning.

Papillary Thyroid Carcinoma

The papillary type is the most common form. It can occur in the thyroid as a single nodule or in multiple foci and tends to spread via the lymphatic system to the cervical lymph nodes. The prognosis is generally considered very favorable.

Standard approach:

• Surgery: hemithyroidectomy or total thyroidectomy, depending on the risk; additional lymph node dissection if there are clinical or ultrasound findings suggestive of involvement. In cases with higher-grade findings, the thyroid must be completely removed.
• Radioiodine therapy: risk-adapted, administered afterward to eliminate microscopic residual disease.
• Hormone therapy/follow-up: Hormone replacement and TSH suppression, with regular follow-up visits.

Low-Risk (Microcarcinoma ≤ 1 cm):

• In the case of a single small tumor, removal of the entire gland and systematic neck lymph node dissection are often not required; the approach is determined on an individual basis.

The anaplastic type is rare, highly malignant, and primarily affects older patients. Due to its very rapid, infiltrative growth and early metastasis, the disease is often already advanced at the time of diagnosis; curative surgery is therefore not always possible.

Treatment approach (focused on managing complications):

• Primarily radiation therapy to slow local tumor growth and prevent complications.
• Surgery—if considered at all—is only considered in select situations; in anaplastic thyroid carcinoma, it is often not curative.

Medullary thyroid carcinoma

Medullary thyroid carcinoma arises from C cells and is the only form with a readily usable tumor marker (calcitonin). Since these tumor cells do not store iodine, radioiodine therapy is not effective in this case.

Standard of care:

• Total thyroidectomy: the entire thyroid gland is surgically removed; regional lymph nodes in the neck are often removed as well.
• In cases of early lymph node involvement, an extended dissection extending into the chest area may be necessary. Only in cases of very advanced tumors is it necessary to resect adjacent organs as well.

Prognosis and Special Considerations:

• The average 10-year survival rate is approximately 75%. The prognosis is primarily determined by whether the cancer has spread beyond the thyroid gland and by the presence of metastases.
• In cases of medullary thyroid carcinoma, genetic analysis (RET testing) is often indicated, as the disease can run in families; the approach for family members is then based on an individualized treatment plan.

Because of the lack of iodine uptake, surgery is the treatment of choice for medullary thyroid carcinoma; depending on the findings, radiation therapy or other procedures may be used as adjunctive treatments, while chemotherapy is reserved for select cases.

The prognosis depends primarily on the tumor type and the stage at the time of diagnosis. As a general rule, the earlier a carcinoma is detected and treated, the better the outlook.

Key Factors

• Histology (papillary, follicular, medullary, anaplastic)
• Extent of spread in the neck (locally confined vs. invasive growth)
• Presence of metastases (lungs/bones)
• Completeness of the surgery and effectiveness of subsequent radioiodine therapy

Differentiated forms (papillary/follicular)

• Generally very good outcomes with early treatment involving surgery and radioiodine therapy.
• Papillary and follicular carcinomas rarely metastasize; cure rate approx. 80–90%.

Medullary carcinoma

• Prospects are comparably good with early detection; in cases of metastasis, the 5-year survival rate is about 50–60%.
• Key factors include, among others, excessive growth of the thyroid gland and the presence of metastases.

Anaplastic carcinoma

• Highly malignant with rapid progression; the 5-year survival rate is less than 10%.

Isolated lymph node involvement often has less of an impact on the prognosis than extrathyroidal tumor growth or distant metastases. Overall, structured follow-up care and individually tailored therapy improve long-term outcomes.

A thyroid specialist is a medical oncologist. As part of an interdisciplinary team with specialists from other fields (e.g., endocrine surgery, nuclear medicine), they plan and implement treatment.

Patients should seek treatment at specialized clinics for thyroid cancer. There, a high quality of care is guaranteed.

In addition, patients may be able to benefit from the latest therapies by participating in clinical trials.

Further information: German Cancer Aid & Federal Association for Thyroid Cancer