Thyroid cancer

The essentials in brief

The most common types of thyroid tumors are differentiated thyroid carcinomas, including papillary and follicular thyroid carcinomas.

Other types include poorly differentiated thyroid carcinoma, medullary thyroid carcinoma, and rarely squamous cell carcinomas, sarcomas, hemangiosarcomas, or metastases from other tumors.

Papillary thyroid carcinoma

Papillary thyroid carcinoma is the most prevalent malignant thyroid neoplasm, comprising 60-80% of cases.

Papillary thyroid carcinomas primarily affect children and young adults, with females being more affected than males.

Differentiated thyroid carcinomas have a very good prognosis, with a five-year survival rate of 93% in women and 88% in men.

Papillary microcarcinomas, smaller than 10 mm, have a 100% long-term survival rate and do not always require complete removal of the thyroid gland.

For papillary thyroid carcinomas larger than 10 mm, a complete thyroidectomy is usually recommended.

Surgical procedure followed by Radioiodine therapy are common treatments for thyroid cancer, and regular thyroglobulin monitoring is essential for detecting possible metastasis.

Hormone replacement therapy with levothyroxine is used for patients after treatment.

Ultrasound examinations are commonly used for early detection of thyroid carcinomas.

Follicular Thyroid Carcinoma

  • Prevalence: Accounts for 10-15% of thyroid cancers; more common in women (5:1 ratio), typically in the fifth decade of life.
  • Minimally Invasive: Comprises two-thirds of cases, difficult to distinguish from benign adenomas without histological examination. Prognosis is good with a 10-year survival rate over 90%. Routine thyroidectomy not recommended unless vascular invasion is present.
  • Widely Invasive: Has an indistinct boundary and significant invasion into surrounding tissue. Poorer prognosis with early metastasis through the bloodstream, requiring total thyroidectomy and radioiodine therapy. 10-year survival rate is 30-50%.
  • Diagnosis and Treatment: Requires detailed histological examination to determine cell appearance and invasion. Total thyroidectomy and radioiodine therapy necessary for widely invasive types; minimally invasive types may not always need extensive surgery. Risk of lymph node metastasis increases with nodules over 2 cm.

Oncocytic Follicular Thyroid Carcinoma

  • Rare with high rates of lymph node and distant metastases.
  • Requires total thyroidectomy followed by radioiodine therapy.

Poorly Differentiated Thyroid Cancer (PDTC)

  • Develops from differentiated thyroid carcinomas, representing 4-7% of cases.
  • Requires thyroidectomy and radioiodine therapy.
  • Two-thirds survive the first five years; about one-third develop distant metastases.
  • Prognosis is generally poorer compared to other differentiated thyroid carcinomas.

Anaplastic Thyroid Carcinoma

  • Accounts for 2-15% of malignant thyroid tumors, mostly in individuals over 60.
  • Highly malignant, undifferentiated, and often arising from differentiated carcinomas.
  • Rapidly growing with early lymphatic and hematogenous spread.
  • Requires thyroidectomy and radical neck dissection; radioiodine therapy is ineffective.
  • Very poor prognosis with most patients dying within the first year; 2-year survival rate is less than 10%.

Medullary Thyroid Carcinoma

  • Represents 2-12% of thyroid cancers, with 80% sporadic and 20% familial (MEN 2).
  • Originates from C-cells producing calcitonin; elevated calcitonin and CEA are key markers.
  • Metastasizes early to lymph nodes and later to lungs, liver, and bones.
  • Requires careful preoperative diagnostics and should be treated in specialized centers.
  • Surgical removal is the only curative therapy; prognosis depends heavily on initial surgery.

Differentiated Thyroid Carcinoma

The most common tumors in the thyroid are the differentiated thyroid carcinomas, the papillary, and the follicular thyroid carcinoma. The World Health Organization has also introduced poorly differentiated thyroid carcinoma, which lies biologically and histologically between the differentiated thyroid carcinomas and undifferentiated (anaplastic) thyroid carcinomas. Medullary thyroid carcinoma can arise from the calcitonin-producing cells (C cells). Additionally, in rare cases, squamous cell carcinomas, sarcomas, hemangiosarcomas, or metastases from other tumors can occur in the thyroid.When examining the thyroid under the microscope, it consists of small vesicles called thyroid follicles. These follicles are made up of cells called thyrocytes, which produce the thyroid hormones T3 and T4. The arrangement of cells is single-layered, and they surround the interior (lumen) of the follicles. Single-layered cells are called epithelial cells. Differentiated thyroid carcinomas arise from follicular epithelial cells. Among the differentiated thyroid carcinomas, there are papillary and follicular thyroid carcinomas. Differentiated thyroid carcinomas are the most common endocrine carcinomas (1-2%). The number of thyroid carcinomas is increasing significantly worldwide. Differentiated thyroid carcinomas have a very good prognosis. The five-year survival rate for differentiated thyroid carcinomas is 93% in women and 88% in men. Only in older patients with distant metastases are the survival rates lower. Differentiated thyroid carcinomas are most commonly detected as incidental findings during an ultrasound examination.

 

Papillary Thyroid Carcinoma

Papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid, accounting for 60-80% of cases. The carcinoma originates from thyroid cells, thyrocytes, and forms finger-like, branching (papillary) structures. Children and adolescents almost exclusively have papillary thyroid carcinomas. Adult women are four times more likely to be affected than men.

Papillary thyroid carcinomas metastasize (spread) to the surrounding lymph nodes. Microcarcinomas are very common and have a very good prognosis. A complete removal of the thyroid gland (thyroidectomy) is not necessary for papillary microcarcinomas smaller than 10 mm.

For papillary thyroid carcinomas larger than 10 mm, a complete removal of the thyroid gland should always be performed. If there is no suspicion of metastasis, the surrounding compartments do not need to be cleared. If lymph node metastases are found in the central compartment, it should be cleared. The central compartment includes the soft tissue in front of and behind the thyroid gland. It is bounded on both sides by the carotid artery. The two carotid arteries arise from the aortic arch. This represents the left lower boundary, and the right lower boundary is the origin of the right and left jugular veins. The upper boundary of the central compartment is the hyoid bone.

Clearing the other compartments is only necessary if there is a suspicion of metastasis. Papillary microcarcinomas have a 100% long-term survival rate. The average 10-year survival rate for larger papillary carcinomas is 80-90%.

Follicular Thyroid Carcinoma

Follicular Thyroid Carcinoma

Follicular thyroid carcinoma is less common, accounting for 10-15% of thyroid cancers. Like other types, this carcinoma originates from the thyroid cells. The structure of a mature and normally developed thyroid is maintained in this type. It affects women five times more often than men, with the peak incidence in the fifth decade of life.

Two-thirds of follicular thyroid carcinomas are minimally invasive. These minimally invasive follicular thyroid carcinomas cannot be distinguished cytologically or through intraoperative frozen section analysis from benign follicular adenomas. The diagnosis is only possible through detailed histological examination. The appearance of the cells and the presence of capsule or vascular invasion are critical factors. Minimally invasive follicular thyroid carcinomas have a good prognosis, with a 10-year survival rate of over 90%. Therefore, a routine thyroidectomy is not recommended if this type is found incidentally in histology. Depending on the evidence of vascular invasion (angioinvasion), it must be decided whether a total thyroidectomy followed by radioiodine therapy is necessary. There is a risk of lymph node metastasis only for nodules larger than 2 cm.

A widely invasive follicular thyroid carcinoma has an indistinct boundary and significant invasion into the surrounding thyroid tissue. The prognosis is poorer for this type, as metastases are often already present. Metastasis occurs through the bloodstream, leading to distant metastases. For this carcinoma, a total thyroidectomy followed by radioiodine therapy is always necessary. The 10-year survival rate is only 30-50%.

Oncocytic Follicular Thyroid Carcinoma

Oncocytic follicular thyroid carcinoma is a rare disease with an increased rate of lymph node and distant metastases. It always requires a total thyroidectomy followed by radioiodine therapy.

Poorly Differentiated Thyroid Cancer (PDTC)

Poorly Differentiated Thyroid Cancer (PDTC)

Differentiated thyroid carcinomas generally have a very good prognosis, with the exception of poorly differentiated thyroid carcinoma. Approximately one-third of patients die from this disease. Poorly differentiated thyroid carcinoma originates from follicular cells and primarily develops from differentiated carcinomas, with a frequency of 4-7%.

A poorly differentiated thyroid carcinoma always requires a thyroidectomy followed by radioiodine therapy. Two-thirds of patients survive the first five years, over 80% do not have local metastases in the neck, but one-third develop distant metastases.

Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma accounts for 2-15% of malignant thyroid tumors. It occurs in less than 5% of cases before the age of 50 and most commonly appears in individuals over 60 years old. Often, there has been a long-standing goiter, which suddenly enlarges, causing swallowing and breathing difficulties.

Anaplastic thyroid carcinoma likely originates from follicular cells, and the tumors are undifferentiated and highly malignant. They may develop either from differentiated carcinomas or de novo. In immunohistochemical examination with antibodies against thyroglobulin, no thyroglobulin can be detected in these tumors.

For anaplastic thyroid carcinoma, a thyroidectomy is always pursued, and affected lymph nodes in the surrounding area should also be removed (radical neck dissection). Radioiodine therapy is not effective for anaplastic thyroid carcinoma because the tumor cells do not take up radioactive iodine.

Anaplastic thyroid carcinoma spreads early through the lymphatic system (lymphogenously) and through the bloodstream (hematogenously). It has a very poor prognosis. Most patients die within the first year after diagnosis. The 2-year survival rate is less than 10%.

Medullary Thyroid Carcinoma

Medullary Thyroid Carcinoma

The incidence of medullary thyroid carcinoma varies regionally and accounts for 2-12% of thyroid cancers. In 80% of cases, medullary thyroid carcinoma occurs sporadically. In 20% of cases, it is familial (inherited in an autosomal dominant manner) and occurs as part of multiple endocrine neoplasia type 2 (MEN 2). For medullary thyroid carcinoma, a germline mutation should always be ruled out by determining the RET proto-oncogene. In familial cases associated with MEN 2, other tumors may be present: pheochromocytomas (50%) and parathyroid adenomas (15-20%) with hyperparathyroidism.

In MEN-3 syndrome (formerly MEN-2B syndrome), in addition to thyroid carcinoma and pheochromocytoma, neuromas (tumors of the nerves) of the mucous membranes are found. Medullary thyroid carcinoma develops from the C-cells of the thyroid. In the familial form, the carcinoma develops from C-cell hyperplasia. C-cells produce calcitonin. Therefore, for any sonographically suspicious thyroid nodule, a single calcitonin measurement should be performed. Besides calcitonin, the tumor marker CEA is also elevated in medullary thyroid carcinoma.

Medullary thyroid carcinoma metastasizes early to the surrounding lymph nodes and later hematogenously to the lungs, liver, and bones. Therefore, preoperative careful diagnostics with thin-section CT of the neck and mediastinum is necessary. Additionally, distant metastases should be searched for. The operation should only be performed in a recognized center for endocrine surgery. The prognosis highly depends on the initial surgery. The surgical removal of the tumor and its metastases is the only possible curative therapy.

A radioiodine therapy is ineffective for medullary thyroid carcinoma because the C-cells do not absorb radioactive iodine.

Postoperative follow-up is conducted at regular intervals, including ultrasound examinations of the neck and measurement of calcitonin and CEA levels. If either tumor marker increases, further imaging diagnostics for metastases must be performed. Surgical therapy remains the primary and most important treatment approach.

Sporadic medullary thyroid carcinoma without lymph node metastases has a good prognosis with cure rates between 80% and 100%. If lymph node metastases are present, the 10-year survival rate is only 40%. In MEN2, medullary thyroid carcinoma often occurs before the age of 30. Family members must be tested for RET proto-oncogene mutations. If a mutation is present, early thyroidectomy