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The major clinical symptom of metastatic medullary thyroid carcinoma is diarrhea; occasionally a patient will have flushing episodes. Both occur particularly with liver metastasis, and either symptom may be the first manifestation of the disease. The flushing that occurs in medullary thyroid carcinoma is indistinguishable from that associated with carcinoid syndrome. In MTC, the flushing, diarrhea, and itching (pruritis) are all caused by elevated levels of calcitonin gene products (calcitonin or calcitonin gene-related peptide). Alternatively, the flushing and diarrhea observed in carcinoid syndrome is caused by elevated levels of circulating serotonin.
Medullary thyroid carcinoma may also produce a thyroid nodule and enlarged cervical lymph nodes.
Sites of spread of medullary thyroid carcinoma include local lymph nodes in the neck, lymph nodes in the central portion of the chest (mediastinum), liver, lung, and bone. Spread to other sites such as skin or brain occurs but is uncommon.
It is impossible to distinguish between follicular adenoma and carcinoma on cytological grounds. If fine needle aspiration cytology (FNAC) suggests follicular neoplasm, thyroid lobectomy should be performed to establish the histopathological 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 to lung and bone via the bloodstream.
- Papillary thyroid carcinoma commonly metastasizes to cervical lymph nodes.
HMGA2 has been proposed as a marker to identify malignant tumors.
Carcinoids most commonly affect the small bowel, particularly the ileum, and are the most common malignancy of the appendix. Many carcinoids are asymptomatic and are discovered only upon surgery for unrelated causes. These coincidental carcinoids are common; one study found that one person in ten has them. Many tumors do not cause symptoms even when they have metastasized. Other tumors even if very small can produce adverse effects by secreting hormones.
Ten per cent (10%) or less of carcinoids, primarily some midgut carcinoids, secrete excessive levels of a range of hormones, most notably serotonin (5-HT) or substance P, causing a constellation of symptoms called carcinoid syndrome:
- flushing
- diarrhea
- asthma or wheezing
- congestive heart failure (CHF)
- abdominal cramping
- peripheral edema
- heart palpitations
A carcinoid crisis with profound flushing, bronchospasm, tachycardia, and widely and rapidly fluctuating blood pressure can occur if large amounts of hormone are acutely secreted, which is occasionally triggered by factors such as diet, alcohol, surgery chemotherapy, embolization therapy or radiofrequency ablation.
Chronic exposure to high levels of serotonin causes thickening of the heart valves, particularly the tricuspid and the pulmonic valves, and over a long period can lead to congestive heart failure. However, valve replacement is rarely needed. The excessive outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency, and thus pellagra, which is associated with dermatitis, dementia, and diarrhea. Many other hormones can be secreted by some of these tumors, most commonly growth hormone that can cause acromegaly, or cortisol, that can cause Cushing's syndrome.
Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. Bowel obstruction can occur, sometimes due to fibrosing effects of NET secretory products with an intense desmoplastic reaction at the tumor site, or of the mesentery.
Conceptually, there are two main types of NET within this category: those which arise from the gastrointestinal (GI) system and those that arise from the pancreas. In usage, the term "carcinoid" has often been applied to both, although sometimes it is restrictively applied to NETs of GI origin (as herein), or alternatively to those tumors which secrete functional hormones or polypeptides associated with clinical symptoms, as discussed.
The Hürthle cell is named after German histologist Karl Hürthle, who investigated thyroid secretory function, particularly in dogs. However, this is a misnomer since Hürthle actually described parafollicular C cells. The cell known as the Hürthle cell was first described in 1898 by Max Askanazy, who noted it in patients with Graves' disease.
A Hürthle cell () or Askanazy cell () is a cell in the thyroid that is often associated with Hashimoto's thyroiditis as well as benign and malignant tumors (Hürthle cell adenoma and Hürthle cell carcinoma, a subtype of follicular thyroid cancer). This version is a relatively rare form of differentiated thyroid cancer, accounting for only 3-10% of all differentiated thyroid cancers. Oncocytes in the thyroid are often called Hürthle cells. Although the terms oncocyte, oxyphilic cell, and Hürthle cell are used interchangeably, Hürthle cell is used only to indicate cells of thyroid follicular origin.
Follicular thyroid cancer or follicular thyroid carcinoma accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.
Squamous epithelial cells are not found in normal thyroid, thus the origin of SCTC is not clear. However, it might be a derived from the embryonic remnants such as thyroglossal duct or branchial clefts. Often SCTC is diagnosed in one of the thyroid lobes, but not in the pyramidal lobe. Another possible way of SCTC development can be through the squamous metaplasia of cells. However, that theory is also controversial, since the Hashimoto's thyroiditis and chronic lymphocytic thyroiditis (neoplasms to be showed squamous metaplasia) are not associated with SCTC. Primary STCT is usually diagnosed in both lobes of thyroid gland. The histopathology of STCT shows a squamous differentiation of tumor cells.
Medullary thyroid cancer (MTC) is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.
Medullary tumors are the third most common of all thyroid cancers. They make up about 3% of all thyroid cancer cases.
Approximately 25% of medullary thyroid cancer is genetic in nature, caused by a mutation in the RET proto-oncogene. This form is classified as familial MTC. When MTC occurs by itself it is termed sporadic MTC. When it coexists with tumors of the parathyroid gland and medullary component of the adrenal glands (pheochromocytoma) it is called multiple endocrine neoplasia type 2 (MEN2).It was first characterized in 1959.
Papillary thyroid carcinoma is usually discovered on routine examination as an asymptomatic thyroid nodule that appears as a neck mass. In some instances, the mass may have produced local symptoms. This mass is normally referred to a fine needle aspiration biopsy (FNA) for investigation. FNA accuracy is very high and it is a process widely used in these cases. Other investigation methods include ultrasound imaging and nuclear scan. The ultrasound is a useful test to distinguish solid from cystic lesions and to identify calcifications. The thyroid ultrasound is also very effective to discover microcarcinomas, which refer to very small carcinomas (<1 cm).
Papillary thyroid carcinomas are also discovered when a hard nodule is found in multinodular goiter, when enlarged cervical lymph nodes are detected, or when there are unidentified metastatic lesions elsewhere in the body. Expanding lesions found in the thyroid gland, especially if they are painful, should be examined as they may indicate the presence of papillary thyroid carcinoma. Other clinical signs that could indicate papillary thyroid are fixation to the trachea, a firm neck mass, damage to recurrent laryngeal or cervical sympathetic nerves. Five percent of the population can have thyroid nodules, and the majority will be benign.
Appropriate workup includes an ultrasound of the neck, followed by lab studies. Patients will usually meet with both an endocrinologist and a surgeon (head and neck surgeon or endocrine surgeon).
Papillary thyroid cancer gets its name from the among its cells, visible on microscopy. Features include:
- Characteristic Orphan Annie eye nuclear inclusions (nuclei with uniform staining, which appear empty due to powdery chromatin and marginal micronucleoli) and psammoma bodies on light microscopy. The former is useful in identifying the follicular variant of papillary thyroid carcinomas.
- Lymphatic spread is more common than hematogenous spread
- Multifocality is common
- The so-called Lateral Aberrant Thyroid is actually a lymph node metastasis from papillary thyroid carcinoma.
- Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring less than or equal to 1 cm. The highest incidence of papillary thyroid microcarcinoma in an autopsy series was reported by Harach et al. in 1985, who found 36 of 101 consecutive autopsies to have an incidental microcarcinoma. Michael Pakdaman et al. report the highest incidence in a retrospective surgical series at 49.9 percent of 860 cases. Management strategies for incidental papillary microcarcinoma on ultrasound (and confirmed on FNAB) range from total thyroidectomy with radioactive iodine ablation to observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. It was Woolner et al. who first arbitrarily coined the term "occult papillary carcinoma" in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.
Several variants are recognized, although classical papillary thyroid carcinoma is the most frequent; microscopic, follicular variant, diffuse sclerosing variant, tall cell variant, columnar cell variant, hobnail variant, among others. The encapsulated follicular variant, specifically when noninvasive, has been newly reclassified as the noninvasive follicular thyroid neoplasm with papillary-like nuclear features.
Although papillary carcinoma has a propensity to invade lymphatics, it is less likely to invade blood vessels.
These kinds of tumors are most commonly unencapsulated, and they have a high tendency to metastasize locally to lymph nodes, which may produce cystic structures near the thyroid that are difficult to diagnose because of the paucity of malignant tissue. Furthermore, papillary tumors may metastasize to the lungs and produce a few nodules or the lung fields may exhibit a snowflake appearance throughout.
Other characteristics of the papillary carcinoma is that E.M. shows increased mitochondria, increased RER, as well as increased apical microvilli. Moreover, papillary carcinomas have an indolent growth, and 40 percent of cases spread out of the capsule.
The SCTC is biologically aggressive malignant neoplasm which is associated with rapid growth of neck mass followed by infiltration of thyroid-adjacent structures.
Patients usually demonstrate the dysphagia, dyspnea, and voice changes, as well as local pain in the neck.
Anaplastic tumors have a high mitotic rate and lymphovascular invasion. They rapidly invade surrounding tissues (such as the trachea). The presence of regional lymphadenopathy in older patients in whom needle aspiration biopsy reveals characteristic vesicular appearance of the nuclei would support a diagnosis of anaplastic carcinoma.
It is always considered as stage IV.
Anaplastic thyroid cancer (ATC) is a form of thyroid cancer which has a very poor prognosis due to its aggressive behavior and resistance to cancer treatments. Its anaplastic cells have poor differentiation, including dedifferentiation.
Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm (thyroid cancer), such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. The estimated number of new cases of thyroid cancer in the United States in 2010 is 44,670 compared to only 1,690 deaths. Of all thyroid nodules discovered, only about 5 percent are cancerous, and under 3 percent of those result in fatalities.
Hürthle cell adenoma is the benign analogue of Hürthle cell carcinoma. This adenoma is extremely rare; when it occurs, it usually occurs in women. Often the adenoma is harmless but is removed after detection because its future course cannot be trusted. This mass can be detected and removed before transformation and metastasis. The tumor is often detected by imaging such as ultrasound. The location and size of the tumor may cause pressure and pain to the patient. But often the tumor goes undetected. After detection, the mass is tested using an invasive fine-needle aspiration biopsy.
Thyroid cancers are mainly papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. Nearly 80 percent of thyroid cancer is papillary and about 15 percent is follicular; both types grow slowly and can be cured if caught early. Medullary thyroid cancer makes up about 3 percent of this cancer. It grows slowly and can be controlled if caught early. Anaplastic is the most deadly and makes up around 2 percent. This type grows quickly and is hard to control. The classification is determined by looking at the sample of cells under a microscope and by which type of thyroid cell is present.
Other thyroid malignancies include thyroid lymphoma, various types of thyroid sarcoma, smooth muscle tumors, teratoma, squamous cell thyroid carcinoma and other rare types of tumors.
Hürthle cell adenoma is a rare benign tumor, typically seen in women between the ages of 70 and 80 years old. This adenoma is characterized by a mass of benign Hürthle cells (Askanazy cells). Typically such a mass is removed because it is not easy to predict whether it will transform into the malignant counterpart, a subtype of follicular thyroid cancer called a Hürthle cell carcinoma.
Most often the first symptom of thyroid cancer is a nodule in the thyroid region of the neck. However, many adults have small nodules in their thyroids, but typically under 5% of these nodules are found to be cancerous. Sometimes the first sign is an enlarged lymph node. Later symptoms that can be present are pain in the anterior region of the neck and changes in voice due to an involvement of the recurrent laryngeal nerve.
Thyroid cancer is usually found in a euthyroid patient, but symptoms of hyperthyroidism or hypothyroidism may be associated with a large or metastatic well-differentiated tumor.
Thyroid nodules are of particular concern when they are found in those under the age of 20. The presentation of benign nodules at this age is less likely, and thus the potential for malignancy is far greater.
Patients typically present with a non-productive cough and weight loss.
Basophilic, bland cells similar to acinar cells. Growth pattern: solid - acinar cells, microcytic - small systic spaces mucinous or eosinophilic, papillary-cystic - large cystic lined by epithelium, follicular - similar to thyroid tissue.
These tumors which resemble serous acinar cells vary in their behavior from locally aggressive to blatantly malignant.
It can also appear in the breast. The pancreatic form of acinic cell carcinoma is a rare subtype of exocrine pancreatic cancer. Exocrine pancreatic cancers are the most common form of pancreatic cancer when compared to endocrine pancreatic cancer.
Acinic cell carcinomas arise most frequently in the parotid gland. Other sites of primary tumors have included the submandibular gland and other major and minor salivary glands. There have been rare cases of primary tumors involving the parapharyngeal space and the sublingual gland.
Most patients experience moderate to severe hypercalcemia and high parathyroid hormone levels. A large mass in the neck is often seen, and renal and bone abnormalities are common.
Acinic cell carcinoma appears in all age groups, but presents at a younger median age (approx. 52 years) than most other salivary gland cancers. Occurrences in children are quite common.
Medullary carcinoma may refer to one of several different tumors of epithelial origin. As the term "" is a generic anatomic descriptor for the mid-layer of various organ tissues, a medullary tumor usually arises from the "mid-layer tissues" of the relevant organ.
Medullary carcinoma most commonly refers to:
- Medullary thyroid cancer
- Medullary carcinoma of the breast
Medullary carcinoma may also refer to tumors of:
- Pancreas
- Ampulla of Vater
- Gallbladder
- Stomach
- Large intestine
- Kidney — Renal medullary carcinoma
Parathyroid carcinoma is a rare malignant neoplasm resulting in parathyroid adenoma to carcinoma progression. It forms in tissues of one or more of the parathyroid glands (four pea-sized glands in the neck that make parathyroid hormone, which helps the body store and use calcium).
It is rare, and much less common than parathyroid adenoma.
It can be difficult to excise.