Follicular Thyroid Carcinoma
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Follicular thyroid cancer accounts for 15% of
thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...
and occurs more commonly in women over 50 years of age.
Thyroglobulin Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...
(Tg) can be used as a
tumor marker A tumor marker is a biomarker found in blood, urine, or body tissues that can be elevated by the presence of one or more types of cancer. There are many different tumor markers, each indicative of a particular disease process, and they are used in ...
for well-differentiated follicular thyroid cancer.
Thyroid follicular cells The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
are the thyroid cells responsible for the production and secretion of
thyroid hormones File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...
.


Cause


Associated mutations

Approximately one-half of follicular thyroid carcinomas have mutations in the Ras subfamily of oncogenes, most notably
HRAS GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the gene. The ''HRAS'' gene is located on the short (p) arm of chromosome 11 at position 15.5, from base pair 522,241 ...
, NRAS, and
KRAS ''KRAS'' ( Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cel ...
.Chapter 20 in: 8th edition. Mutations in MINPP1 have likewise been observed, as well as germline
PTEN gene Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the ''PTEN'' gene. Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate ca ...
mutations responsible for Cowden syndrome of which follicular thyroid cancer is a feature. Also, a
chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...
specific for follicular thyroid carcinomas is one between paired box gene 8 (PAX-8), a gene important in thyroid development, and the gene encoding peroxisome proliferator-activated receptor γ 1 (PPARγ1), a nuclear hormone receptor contributing to terminal differentiation of cells. The PAX8-PPARγ1 fusion is present in approximately one-third of follicular thyroid carcinomas, specifically those cancers with a t(2;3)(q13;p25) translocation, permitting juxtaposition of portions of both genes.
Tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
tend carry either a RAS mutation or a PAX8-PPARγ1 fusion, and only rarely are both genetic abnormalities present in the same case. Thus, follicular thyroid carcinomas seem to arise by two distinct and virtually nonoverlapping molecular pathways.


Hurthle cell variant

Hurthle cell thyroid cancer is often considered a variant of follicular cell carcinoma. Hurthle cell forms are more likely than follicular carcinomas to be bilateral and multifocal and to metastasize to lymph nodes. Like follicular carcinoma, unilateral hemithyroidectomy is performed for non-invasive disease, and total thyroidectomy for invasive disease.


Diagnosis

It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions.


Classification

It is impossible to distinguish between follicular adenoma and carcinoma on cytological grounds. If
fine needle aspiration cytology Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, aft ...
(FNAC) suggests follicular neoplasm, thyroid lobectomy should be performed to establish the
histopathological Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
diagnosis. Features ''sine qua non'' for the diagnosis of follicular carcinoma are capsular invasion and vascular invasion by tumor cells. Still, focuses of the capsular invasion should be carefully evaluated and discriminated from the capsular rupture due to FNA penetration resulting in WHAFFT (''worrisome histologic alterations following FNA of thyroid''). * Follicular carcinoma tends to
metastasize Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
to lung and
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
via the bloodstream. *
Papillary thyroid carcinoma Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases.Chapter 20 in: 8th edition. It occurs more frequently in women and presents in th ...
commonly metastasizes to
cervical lymph nodes Cervical lymph nodes are lymph nodes found in the neck. Of the 800 lymph nodes in the human body, 300 are in the neck. Cervical lymph nodes are subject to a number of different pathological conditions including tumours, infection and inflammati ...
.
HMGA2 High-mobility group AT-hook 2, also known as HMGA2, is a protein that, in humans, is encoded by the ''HMGA2'' gene. Function This gene encodes a protein that belongs to the non-histone chromosomal high-mobility group (HMG) protein family. HMG ...
has been proposed as a marker to identify malignant tumors.


Treatment

Treatment is usually
surgical Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
, followed by radioiodine.


Initial treatment

*If follicular cells are found on cytological testing, it is common to carry out ''
hemithyroidectomy A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. In general surgery, endocrine or head and neck surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condit ...
'' to distinguish between follicular adenoma and follicular carcinoma on histopathological examination, proceeding to ''completion thyroidectomy'' and postoperative radioiodine ablation where carcinoma is confirmed. This way total thyroidectomy is not carried out unnecessarily. *''
Thyroidectomy A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. In general surgery, endocrine or head and neck surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other conditio ...
'' is invariably followed by
radioiodine There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element. Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million year ...
treatment at levels from 50 to 200 millicuries following two weeks of a low iodine diet (LID). Occasionally treatment must be repeated if annual scans indicate remaining cancerous tissue. Some physicians favor administering the maximum safe dose (calculated based on a number of factors), while others favor administering smaller doses, which may still be effective in ablating all thyroid tissue. I-131 is used for ablation of the thyroid tissue. **
Minimally invasive Minimally invasive procedures (also known as minimally invasive surgeries) encompass Surgery, surgical techniques that limit the size of incisions needed, thereby reducing wound healing time, associated pain, and risk of infection. Surgery by d ...
thyroidectomy has been used in recent years in cases where the nodules are small.


Finding disease recurrence

Some studies have shown that thyroglobulin (Tg) testing combined with neck
ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...
is more productive in finding disease recurrence than full- or whole-body scans (WBS) using radioactive iodine. However, current protocol (in the USA) suggests a small number of clean annual WBS are required before relying on Tg testing plus neck ultrasound. When needed, whole body scans consist of withdrawal from thyroxine medication and/or injection of recombinant human
Thyroid stimulating hormone Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of ...
(TSH). In both cases, a low iodine diet regimen must also be followed to optimize the takeup of the radioactive iodine dose. Low dose radioiodine of a few millicuries is administered. Full body
nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is " radiology done inside out" because it records radiation emi ...
scan follows using a
gamma camera A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
. Scan doses of radioactive iodine may be I131 or I123. Recombinant human TSH, commercial name Thyrogen, is produced in cell culture from genetically engineered
hamster Hamsters are rodents (order Rodentia) belonging to the subfamily Cricetinae, which contains 19 species classified in seven genera.Fox, Sue. 2006. ''Hamsters''. T.F.H. Publications Inc. They have become established as popular small pets. The ...
cells.


Prognosis

The overall 5-year survival rate for follicular thyroid cancer is 91%, and the 10-year survival rate is 85%.Numbers from National Cancer Database in the US, fro
Page 10
in: (Note:Book also states that the 14% 10-year survival for anaplastic thyroid cancer was overestimated
By overall
cancer staging Cancer staging is the process of determining the extent to which a cancer has developed by growing and spreading. Contemporary practice is to assign a number from I to IV to a cancer, with I being an isolated cancer and IV being a cancer that ha ...
into stages I to IV, follicular thyroid cancer has a 5-year survival rate of 100% for stages I and II, 71% for stage III, and 50% for stage IV.cancer.org > Thyroid Cancer
By the American Cancer Society. In turn citing: AJCC Cancer Staging Manual (7th ed).
Compared to other variants of Follicular cell derived thyroid cancer, bone metastases are commonly associated with follicular carcinoma. In the present study a high rate of bone metastases of 34% was observed.


References


External links


Thyroid cancer at DMOZ

Cancer Management Handbook: Thyroid and Parathyroid Cancers

Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Taskforce (2015).
{{Endocrine gland neoplasia Thyroid cancer