Thyroid carcinomas C73

Malignant epithelial neoplasm of the thyroid gland. Most common endocrine neoplasia.

There is an increased risk of thyroid cancer:

• in patients with rapidly growing thyroid nodules who are < 20 or > 60 years old
• for family members in whose families thyroid carcinomas have occurred.
• in familial medullary thyroid carcinoma (especially if MEN 2 syndrome is detected; (MEN = multiple endocrine neoplasia).
• in the case of iodine deficiency and TSH - increase
• in persons who were treated as children or adolescents with X-ray radiation in the neck area (e.g. when treating Hodgkin lymphoma or infant hemangioma in the neck area).
• in persons who have been exposed to high levels of radiation from radioactive iodine (e.g. as a result of the reactor disaster in Chernobyl) The incidence of disease in children is 25 times higher after irradiation and can occur many decades after radiation exposure.

Differentiated carcinomas

• Papillary carcinoma (60% of all thyroid carcinomas; in children and adolescents 1.5%-3% of all pediatric malignant tumors (Palaniappan R et al.2018)
• Follicular carcinoma (30% of all thyroid carcinomas)

Low differentiated carcinoma (rare)

Undifferentiated (anaplastic) carcinoma (rare)

Medullary carcinoma (derived from the calcitonin-producing C-cells; 5% of all thyroid carcinomas)

Other (<1% of all thyroid malignancies): Malignant lymphomas, thyroid sarcomas, metastases

Incidence: 5/100.000 people/year (about 1% of all cancer cases in Germany). Incidences have remained constant over the last two decades.

Increased risk for the development of thyroid carcinoma:

• Ionizing radiation exposure of the thyroid gland.
• Exposure to radiation in childhood significantly increases the risk of developing papillary thyroid carcinoma. The time of exposure is decisive. Children (especially children < 4 years) react many times more sensitively than adults. After the atomic bombs were dropped in Japan and the Chernobyl reactor accident, the rate of thyroid carcinoma increased in Japan and Europe, both in children and adults. The time interval from the time of exposure to radiation to the development of carcinoma is on average about 10 - 15 years.
• An iodine deficiency favours the development of follicular thyroid carcinoma.
• Some follicular thyroid carcinomas have an oncogenic chromosome translocation (fusion of two genes: PAX8 and PPARγ1).
• Genetic factors: medullary thyroid carcinomas in MEN syndrome have a mutation of the RET protooncogene. Such somatic mutations can also be detected in medullary thyroid carcinoma.
• Rosacea also appears to have an increased risk of thyroid carcinoma (LI WQ et al. 2015)

w:m=2/3:1 (refers to the differentiated carcinomas (papillary SD carcinoma, follicular SD carcinoma); in the case of anaplastic and C-cell carcinoma the ratio m/w is balanced. Men have a worse prognosis than women.

Thyroid carcinoma can occur at any age. Papillary carcinomas peak between the ages of 35 and 60, follicular carcinomas between the ages of 40 and 50. Anaplastic carcinomas are rare before the age of 40; the incidence peak is between the ages of 70 and 80. The age of patients with medullary thyroid carcinoma is highly variable; no peak in the age distribution can be detected.

In many cases, however, affected patients do not show any characteristic signs of disease. The diagnosis is often a sonographic incidental finding. Clinically, rapidly growing hard nodules within a few weeks are already indicative. Advanced thyroid carcinomas are conspicuous by their displacing, infiltrating and metastatic growth:

• Feeling of pressure in the throat area
• Difficulty swallowing
• Dyspnea
• Hoarseness and coughing stimuli (recurrent laryngeal nerve).
• Furthermore, palpable or visible enlarged lymph nodes in the neck area can be detected.
• Far advanced thyroid carcinomas cause stridor, Horner's syndrome and/or upper influence congestion.

Sonography: The sonography (ultrasound) of the thyroid gland is the basic examination and is nowadays considered the leading method in thyroid diagnostics. It should be used for all suspected or proven nodules, enlargements or functional disorders of the thyroid gland. As a simple, fast and less stressful procedure (important: no radiation exposure), sonography is particularly suitable for screening, follow-up and aftercare.

Elastography: Method for measuring the elasticity of tissue. Elastography is a newer imaging technique and a further development of ultrasound diagnostics. Similar to manual palpation (examination by touch), elastography makes use of the fact that tumour tissue often has a different consistency (firmer, coarser) than the surrounding healthy tissue.

Scintigraphy: For sonographically detected thyroid nodules > 1 cm, thyroid scintigraphy is recommended. The scintigraphy complements the morphological information provided by the image as a primarily function-oriented procedure. Due to the storage behaviour of the radioactive tracer used (technetium or iodine), non-storing ("cold") nodes can be identified which have a higher probability of carcinoma and therefore require further clarification.

Serum markers allow the detection of a residual or recurrent disease(thyroglobulin in differentiated thyroid carcinoma (papillary SDC and follicular SDC), calcitonin in medullary thyroid carcinoma). To assess thyroid function, the hormones TSH as well as fT3 and fT4 are determined. If an autoimmune disease of the thyroid gland is suspected (e.g. Basedow/Hashimoto's thyroiditis) the analysis of thyroid antibodies is necessary. Note: Calcitonin in blood is a very sensitive and specific marker for medullary thyroid carcinoma (MTC). The hormone should be determined at least once for each thyroid node to exclude MTC. After a complete thyroidectomy and radioiodine therapy, thyroglobulin is determined regularly (see below for follow-up).

Clinic, anamnesis (family screening), imaging (sonography, scintigraphy (cold nodules), CT, MRI - neck region, possibly PET = positron emission tomography), targeted fine needle aspiration biopsy, laboratory (calcitonin determination: values increased in medullary thyroid carcinoma)

Fine needle aspiration biopsy: in this procedure, thyroid nodes can be punctured under ultrasound control using a thin needle. The histological examination of the cell material thus obtained allows a statement to be made about the dignity of the tissue.

Combines surgical, radiotherapy, nuclear medicine, oncology (tumour conference) in specialised centres.

Surgery: Total thyroidectomy + lymph node dissection with preservation of the recurrent nerve and preservation of at least 1 parathyroid gland. The surgical strategy depends mainly on the type of tumor and the stage of the disease and should always be discussed individually with the patient.

Ablative radioiodine therapy: In the case of follicular and papillary thyroid carcinomas, 131I radioiodine therapy is administered after 4-6 weeks following surgery. The aim of this treatment is the selective destruction of remaining thyroid (tumor) cells and any metastases that may be present. Radioiodine therapy is the treatment of choice if metastases are detected postoperatively. Note: Medullary and anaplastic thyroid carcinomas do not store iodine and are therefore not suitable for radioiodine therapy. NW: Passagere radiation thyroiditis, gastritis, sialadenitis. Risk of later acute leukemia is <1%.

External radiation therapy (percutaneous radiotherapy): Patients with unfavourable prognostic parameters and a very high risk of recurrence (anaplastic thyroid carcinoma) may benefit from percutaneous radiotherapy (Brierley J et al.2012). Note: C-cell carcinomas are resistant to radiation (total thyroidectomy is therapy of choice).

Palliative chemotherapy for inoperable, non-radioiodine storing thyroid carcinomas. Therapies in controlled trials (tyrosine kinase inhibitors such as imatinib, vandetanib, levantinib, carbozantinib) and as mTOR inhibitor everolimus.

The chances of recovery are good if thyroid cancer is detected in time. The average 5-year survival rate is 94% for women and 87% for men.

10 year survival rates:

• Papillary thyroid carcinoma: >90%
• Papillary microcarcinoma (≤ 10 mm): often incidental finding after thyroid surgery. Favourable prognosis. After surgical R0 resection normal life expectancy according to age.
• Medullary thyroid carcinoma: minimally invasive: >95%; broadly invasive: 50%
• Follicular carcinoma of the thyroid gland: 50%.
• Anaplastic thyroid carcinoma: 0.5 years (!)

Staging (according to the international TNM classification - T stands for tumor, N for regional lymph node metastases, M for distant metastases):

• pT1: tumour < 2cm in size, is restricted to the thyroid gland.
• pT1a <= 1cm, limited to the thyroid gland
• pT1b >1-2 cm, restricted to the thyroid gland
• pT2: >2-4 cm, restricted to the thyroid gland.
• pT3a: > 4 cm, limited to the thyroid gland
• pT3b: any size with macroscopic extrathyroid invasion of the short straight neck muscles (sternohyoid, sternothyroid, thyrohyoid, omohyoid muscles).
• pT4a: spread to subcutis, larynx, trachea, esophagus, recurrens nerve
• T4b: Prevertebral fascia, mediastinal vessels, A. carotis
• N0: No evidence of regional lymph node metastases
• N1: Detection of regional lymph node metastases
  • N1a: The lymph node metastases are located in the lymph nodes in the middle of the neck.
  • N1b: The lymph node metastases can be located in the neck area or already in the upper thoracic region.
• M0: No detection of distant metastases.
• M1: Detection of distant metastases.

Special features of the pT classification for anaplastic/undifferentiated carcinoma

• T4a: restricted to the thyroid gland
• T4b: Spread beyond the thyroid capsule

In clinical practice, a stage classification of thyroid carcinomas based on TNM classification, patient age and histological type is also common.

Papillary/follicular SD carcinoma (age 45 years and > 45 years)

• Stage I: T1a, T1b, N0, M0
• Stage II: T2, N0, M0
• Stage III: T3, N0, N1a, M0 or T1, T2, T3, N1a, M0
• Stage IVA: T1, T2, T3, N1b, M0 or T4, N0/N1, M0
• Stage IVB: T4b, each N, M0
• Stage IVC: every T, every N, M1

Papillary/follicular SD carcinomas (age under 45 years)

• Stage I: every T, every N, M0
• Stage II: every T, every N, M1

Medullary thyroid carcinomas

• Stage I: T1a, T1b, N0, M0
• Stage II: T2, T3, N0, M0
• Stage III: T1, T2, T3, N1a, M0
• Stage IVA: T1, T2, T3, N1b, Mo or T4a, each N, M0
• Stage IVB: T4b, each N, M0
• Stage IVC; every T, every N, M1

Anaplastic SD carcinomas

• all cases are stage IV

Lifelong aftercare necessary. Local clinical and sonographic findings. Control of the thyroglobulin value (after radical thyroidectomy, no functional thyroid gland tissue present, no thyroglobulin value production. A renewed increase in the thyroglobulin value indicates a tumour recurrence.

1. Brierley J et al(2012) The role of external beam radiation and targeted therapy in thyroid cancer. Semin Radiat Oncol 22:254-262.
2. Dralle H et al. (2018) The new TNM classification of thyroid carcinomas. The surgeon 89:389-389
3. Hahn JM (2013) Diseases of endocrine organs. In: Checklist Internal Medicine, Hahn JM, published by Thieme Verlag Stuttgart-New York. S534-535
4. Li WQ et al (2015) Personal history of rosacea and risk of incident cancer among women in the US. Br J Cancer 113:520-523.
5. Palaniappan R et al (2018) Management outcomes of pediatric and adolescent papillary thyroid cancers with a brief review of literature. Indian J Cancer 55:105-110.
6. Wine RO et al (2011) Anaplastic thyroid carcinoma: palliation or treatment? Curr Opin Otolaryngol Head Neck Surg 19:113-118.