Anaplastic thyroid cancer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

In 1811, the first thyroid cancer case was reported. Thyroid cancer was first described by William Stewart Halsted, an American surgeon in the late nineteenth century. Anaplastic thyroid cancer arises from cells of thyroid, which are normally involved in production and secretion of thyroid hormones, thyroxine (T4) and triiodothyronine (T3) and is always considered as stage IV. Genes involved in the pathogenesis of follicular thyroid cancer include P53 and BRAF. Anaplastic thyroid cancer must be differentiated from other diseases that cause neck masses such as goiter, Grave’s disease, Hurthle cell carcinoma, follicular thyroid cancer, papillary thyroid carcinoma, follicular adenoma, sarcoma, and medullary thyroid carcinoma.^[1]. Depending on the extent of the tumor at the time of diagnosis, the prognosis of anaplastic thyroid cancer may vary. However, the prognosis is generally regarded as poor. The presence of metastasis is associated with a particularly poor prognosis among patients with anaplastic thyroid cancer. According to the American Joint Committee on Cancer (AJCC)^[2] there are 4 stages of anaplastic thyroid cancer based on the clinical features and findings on imaging. Each stage is assigned a letter and a number that designate the tumor size, number of lymph node regions involved, and metastasis. The hallmark of anaplastic thyroid cancer is swelling in the neck. A positive history of irradiation of head and neck, rapid growth of the nodule, and family history of anaplastic thyroid carcinoma is suggestive of anaplastic thyroid cancer. The most common symptoms of anaplastic thyroid cancer include swelling in the neck, pain in the front of the neck, and hoarseness of voice. Surgery is the mainstay of treatment for anaplastic thyroid cancer.

In 1811, the first thyroid cancer case was reported. Thyroid cancer was first described by William Stewart Halsted, an American surgeon in the late nineteenth century.

Anaplastic thyroid cancer arises from cells of thyroid, which are secretory cells that are normally involved in production and secretion of thyroid hormones, thyroxine (T4) and triiodothyronine (T3) and is always considered as stage IV. Genes involved in the pathogenesis of follicular thyroid cancer include P53 and BRAF.

Genetic mutation is suspected to be the main cause of anaplastic thyroid cancer.

Anaplastic thyroid cancer must be differentiated from other diseases that cause neck masses such as goiter, Grave’s disease, Hurthle cell carcinoma, follicular thyroid cancer, papillary thyroid carcinoma, follicular adenoma, sarcoma, and medullary thyroid carcinoma.^[3]

Females are more commonly affected with follicular thyroid cancer than males. The incidence of follicular thyroid cancer increases with age; the median age at diagnosis is 6th to 7th decades.

Common risk factors in the development of anaplastic thyroid cancer are iodine deficiency, family history of thyroid cancer, and radiation exposure.

Depending on the extent of the tumor at the time of diagnosis, the prognosis of anaplastic thyroid cancer may vary. However, the prognosis is generally regarded as poor. The presence of metastasis is associated with a particularly poor prognosis among patients with anaplastic thyroid cancer.

According to the American Joint Committee on Cancer (AJCC)^[4] there are 4 stages of anaplastic thyroid cancer based on the clinical features and findings on imaging. Each stage is assigned a letter and a number that designate the tumor size, number of lymph node regions involved, and metastasis.

The hallmark of anaplastic thyroid cancer is swelling in the neck. A positive history of irradiation of head and neck, rapid growth of the nodule, and family history of anaplastic thyroid carcinoma is suggestive of anaplastic thyroid cancer. The most common symptoms of anaplastic thyroid cancer include swelling in the neck, pain in the front of the neck, and hoarseness of voice.

Patients with anaplastic thyroid cancer usually appear thin and cachectic. Physical examination of patients with anaplastic thyroid cancer is usually remarkable for thyromegaly, lymphadenopathy and anxiety.

Laboratory findings consistent with the diagnosis of anaplastic thyroid cancer include elevated T3, elevated T4, and decreased thyroid stimulating hormone.

Chest x ray may be helpful in the diagnosis of anaplastic thyroid cancer.

CT scan may be helpful in the diagnosis of anaplastic thyroid cancer.

MRI may be helpful in the diagnosis of anaplastic thyroid cancer. MRI may also be performed to detect metastases of anaplastic thyroid cancer to brain and bones.

Neck ultrasound may be performed to detect anaplastic thyroid cancer.

PET may be helpful in the diagnosis of anaplastic thyroid cancer. PET may also be performed to detect metastases of anaplastic thyroid cancer to brain and bones.^[5]

Other diagnostic studies for anaplastic thyroid cancer include laryngoscopy, which demonstrates vocal cord immobility.

On biopsy, anaplastic thyroid cancer is characterized by trabecular or solid follicular tumor cells that invade tumor capsule and surrounding vascular structures.

Pharmacologic medical therapies for anaplastic thyroid cancer include radioactive iodine therapy and adjuvant radiotherapy.

Surgery is the mainstay of treatment for anaplastic thyroid cancer.

Effective measures for the prevention of anaplastic thyroid cancer include avoidance of diets low in iodine and avoidance of ultraviolet exposure.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

In 1811, the first thyroid cancer case was reported. Thyroid cancer was first described by William Stewart Halsted, an American surgeon in the late nineteenth century.

• The first case of thyroid cancer was described by William Stewart Halsted.^[1]
• In 1951, head and neck irradiation was demonstrated to cause thyroid cancer in children.

• In 1884, thyroidectomies were introduced to successfully treat thyroid disorders.
• Theodore Kocher (1841-1917) was considered an expert in thyroidectomy in Switzerland.
• Charles Horace Mayo was considered as an expert in thyroidectomies in United States.
• Murray discovered that patients with hypothyroidism respond well to injecting thyroid extracts to them.

• William Rehnquist, Chief Justice of the United States (1986-2005) passed away on September 3, 2005 from anaplastic thyroid cancer.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Anaplastic thyroid cancer arises from cells of the thyroid, which are normally involved in production and secretion of thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Anaplastic thyroid tumor is always considered as stage IV. Genes involved in the pathogenesis of follicular thyroid cancer include P53 and BRAF.

• Anaplastic tumors have a high mitotic rate and lymphovascular invasion. It rapidly invades surrounding tissues (such as the trachea).
• Most patients with anaplastic thyroid cancer have distant metastasis at the time of diagnosis because of the rapid growth and aggressive nature of this type of cancer.
• Common sites of metastasis include the lungs, pleura, bones, and brain.

• Anaplastic thyroid cancer has been associated with the following genetic mutations:^[1][2]
  • TP53
  • BRAF

• Anaplastic thyroid cancer may be associated with the following conditions:
  • Papillary thyroid cancer

• Macroscopic features of anaplastic thyroid cancer include:
  • Unencapsulated, fleshy, tan-white tumor
  • Soft-tissue infiltration of the neck

• Three types of histologic variety will be expected in anaplastic thyroid cancer:

• Spindle cell
• Giant cell
• Squamoid cell

• Features include:
  • Cytologically malignant:
  • Huge nuclear-cytoplasmic ratio
  • Mitoses
  • Presence or absence of necrosis

• Anaplastic thyroid cancer may be positive for the following markers:
  • Pankeratin (AE1/AE3)
  • High molecular weight keratins
  • TTF-1
  • PAX8
  • P53
  • B-catenin

• 
  Anaplastic thyroid carcinoma with a component of PTC. (WC)

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

• Genetic mutation is suspected to be the main cause of anaplastic thyroid cancer. Genes involved in the pathogenesis of follicular thyroid cancer include P53 and BRAF.

• Genetic mutations are suspected to be the main cause of anaplastic thyroid cancer. Genes involved in the pathogenesis of follicular thyroid cancer include P53 and BRAF.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Anaplastic thyroid cancer must be differentiated from other diseases that cause neck masses such as goiter, Grave’s disease, Hurthle cell carcinoma, follicular thyroid cancer, papillary thyroid carcinoma, follicular adenoma, sarcoma, and medullary thyroid carcinoma.^[1]

Thyroid cancers should be differentiated from one another and from various other diseases:

Disease Name	Age of Onset	Gender Preponderance	Signs/Symptoms	Imaging Feature(s)	Macroscopic Feature(s)	Microscopic Feature(s)	Laboratory Findings(s)	Other Feature(s)	Microscopic Appearance
Anaplastic Thyroid Cancer[2][3][4]	More common among older individuals Mean age at diagnosis is 65 years	More commonly affects women	Rapidly enlarging thyroid mass May manifest with compressive symptoms Can present with signs/symptoms of metastasis Constitutional symptoms may be present Hard nodular goiter without tenderness	On ultrasound: Solid hypoechoic nodule with a peripheral halo indicating fibrous capsule Irregular margin Imaging features are not characteristic of this cancer	Solid tumor with areas of necrosis and hemorrhage Infiltrative pattern	Undifferentiated, devastatingly aggressive variant of papillary/follicular thyroid cancer	Normal thyroid function tests	Poor prognosis May be associated with TP53 mutation
Papillary Thyroid Cancer[5][6][7]	More common in the middle aged (30 – 50 years of age)	More commonly affects women	Asymptomatic thyroid mass or nodule Compressive symptoms, such as: Difficulty swallowing/breathing Persistent cough Stridor Vocal chord paralysis Rapid enlarging mass	On ultrasound Solitary mass with an irregular outline Located in the sub-capsular region High vascularity Imaging features are not characteristic of this cancer	Solitary hypoechogenic nodule with lobulated margin which may extend into adjacent tissues Calcification may be present or not	Empty-appearing nuclei with central clearing (Orphan Annie eye) Psammoma bodies	Thyroid function tests can be normal Serum thyroglobulin can be used as a tumor marker	History of radiation to the head and neck BRAF and/or RET mutation may be present The most common type of thyroid cancer
Follicular Thyroid Cancer[6][7][8]	Peak incidence at 40 – 60 years of age	More commonly affects women	Asymptomatic thyroid mass or nodule Compressive symptoms, such as: Difficulty swallowing/breathing Persistent cough Stridor Vocal chord paralysis Rapid enlarging mass	On ultrasound: Solid hypoechoic nodule with a peripheral halo indicating fibrous capsule Irregular margin Imaging features are not characteristic of this cancer	Single encapsulated nodule Thick and irregular capsule Can be cystic or hemorrhagic in appearance	Invades thyroid capsule and vasculature Uniform follicles	Thyroid function tests can be normal Serum thyroglobulin can be used as a tumor marker	RAS mutation may be present PAX8–PPARγ translocations
Medullary Thyroid Cancer[9][10][11][7]	Incidence increases with age More common in the 3rd to 4th decades of life	Both genders are affected equally	Solitary thyroid nodule Mostly affects upper lobe of thyroid gland Possible systemic symptoms due to hormonal secretion by the tumor Cervical lymphadenopathy	On ultrasound: Solitary hypoechoic nodule with or without calcification Imaging features are not characteristic of this cancer	Single non-encapsulated mass Gray-tan color	Sheets of cells in an amyloid stroma	Secretes calcitonin Normal thyroid function tests Carcinoembryonic antigen (CEA) may be used as a tumor marker Rarely negative for calcitonin	Can be part of MEN 2A and 2B syndrome Can be associated with RET mutation
Follicular Adenoma[12]	More commonly affects individuals older than 50 years of age	More commonly affects women	Asymptomatic or symptoms of hyperthyroidism	Solitary nodule which may show echogenicity or not	Solitary, spherical, and encapsulated lesion Well demarcated from the surrounding parenchyma	Uniform follicles Absence of capsular or vascular invasion	Functional adenoma: Elevated T3, T4 Decreased TSH	May be considered functional or hot May be considered non-functional or cold
Multinodular Goiter[13]	Commonly affects individuals older than 60 years of age	More commonly affects women	Thyroid enlargement Signs/symptoms of hypo/hyperthyroidism	Multiple nodules with different echogenicity Calcification may be present	Multiple thyroid nodules	Variable sized follicles Some may show papillary projections without nuclear characteristics of papillary thyroid cancer	Classified as toxic and non-toxic Toxic: Hyperthyroidism Non-toxic: Normal thyroid function tests	Benign condition
Thyroid Lymphoma[14] [15][16][17]	Affects adults or elderly	More common among women	Rapidly enlarging mass/nodule of thyroid Compressive symptoms may be present Constitiutional symptoms can be present in 10% P/E:Firm, hard thyroid Fixed to the nearby structures Immobile even during swallowing Cervical or supraclavicular lymphadenopathy may be present	On ultrasound: Hypoechogenic appearance Difficult to distinguish from chronic thyroiditis	Thyroid nodule/mass Fixed to adjacent tissue Firm texture	It is of B cell lineage in the majority of cases Dffuse, large B-cell lymphomas is the most common subtype Marginal zone lymphoma is the second most common type	No specific test Some patients may have hypothyroidism Patients can also have antibodies against thyroid peroxidase or thyroglobulin	Preexisting chronic autoimmune (Hashimoto’s) thyroiditis is a known risk factor for this condition

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

The incidence of follicular thyroid cancer increases with age; the median age at diagnosis is 6th to 7th decades. Females are more commonly affected with anaplastic thyroid cancer than males.

• The incidence of anaplastic thyroid cancer is approximately 1.2-3.8 per 100,000 individuals world wide.
• The incidence of anaplastic thyroid cancer is approximately .01 per 100,000 individuals in United States.

• Anaplastic thyroid cancer typically occurs in the elderly (peak incidence in 6th to 7th decades).^[1]
• The incidence of anaplastic thyroid cancer increases with age; the median age at diagnosis is 65 years.

• Females are more affected with anaplastic thyroid cancer than males.
• The female to male ratio is approximately 1.5 to 1.^[2]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Common risk factors in the development of anaplastic thyroid cancer are iodine deficiency, family history of thyroid cancer, and radiation exposure.

• Patients with a history of radiation administered in infancy and childhood for benign conditions of the head and neck, such as enlarged thymus, acne, or tonsillar or adenoidal enlargement, have an increased risk of cancer as well as other abnormalities of the thyroid gland. Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.
• Other risk factors for the development of thyroid cancer include the following:

• A history of goiter
• Family history of thyroid disease
• Female gender
• Asian race^[1]

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Depending on the extent of the tumor at the time of diagnosis, the prognosis of anaplastic thyroid cancer may vary. However, the prognosis is generally regarded as poor. The presence of metastasis is associated with a particularly poor prognosis among patients with anaplastic thyroid cancer.

Anaplastic thyroid cancer is very aggressive and can invade directly into adjacent organs, such as the trachea, larynx, esophagus, blood vessel and muscle, resulting in suffocation, vocal cord paralysis, dyspnea or dysphagia. Most patients die a few months after diagnosis because of uncontrolled neck mass and metastases, and long-term survivors are rare.^[1]

• Common complications of anaplastic thyroid cancer are:

• Dyspnea
• Metastasis
• Hoarseness of voice

• The overall 5-year survival rate of anaplastic thyroid cancer has been given as 7%^[2] or 14%,^[3] although the latter has been criticized as being overestimated. Death is attributable to upper airway obstruction and suffocation in half of patients, and to a combination of complications from either local and distant disease or therapy, or both in the remainder.^[4]
• Anaplastic thyroid cancer is extremely aggressive; in most cases death occurs in less than 1 year as a result of aggressive local growth and compromise of vital structures in the neck. Anaplastic thyroid cancer in most series has a median survival of 4 to 5 months from the time of diagnosis, with rare long-term survivors.^[5]

Template:WikiDoc Sources