A
paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). About 97% are benign and cured by surgical removal; the remaining 3% are malignant because they are able to produce distant
metastasesMetastasis , or metastatic disease, sometimes abbreviated mets, is the spread of a disease from one organ or part to another non-adjacent organ or part...
. Paragangliomas are still sometimes referred to using older, obsolete terminology (for example as "chemodectomas" or "glomus tumours", the latter not to be confused with glomus tumours of the skin).
Paragangliomas originate from chromaffine-negative
glomus cellA glomus cell is a peripheral chemoreceptor, located in the carotid bodies and aortic bodies, that helps the body regulate breathing. When there is a decrease in the blood's pH, a decrease in oxygen , or an increase in carbon dioxide , the carotid bodies and the aortic bodies signal the medulla...
s derived from the
embryonicAn embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
neural crestThe neural crest, a transient component of the ectoderm, is located in between the neural tube and the epidermis of an embryo during neural tube formation...
, functioning as part of the
sympathetic nervous systemThe Sympathetic Nervous System is a branch of the autonomic nervous system along with the enteric nervous system and parasympathetic nervous system. It is always active at a basal level and becomes more active during times of stress...
(a branch of the
autonomic nervous systemThe autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
).
A
paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). About 97% are benign and cured by surgical removal; the remaining 3% are malignant because they are able to produce distant
metastasesMetastasis , or metastatic disease, sometimes abbreviated mets, is the spread of a disease from one organ or part to another non-adjacent organ or part...
. Paragangliomas are still sometimes referred to using older, obsolete terminology (for example as "chemodectomas" or "glomus tumours", the latter not to be confused with glomus tumours of the skin).
Cellular origin and classification
Paragangliomas originate from chromaffine-negative
glomus cellA glomus cell is a peripheral chemoreceptor, located in the carotid bodies and aortic bodies, that helps the body regulate breathing. When there is a decrease in the blood's pH, a decrease in oxygen , or an increase in carbon dioxide , the carotid bodies and the aortic bodies signal the medulla...
s derived from the
embryonicAn embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
neural crestThe neural crest, a transient component of the ectoderm, is located in between the neural tube and the epidermis of an embryo during neural tube formation...
, functioning as part of the
sympathetic nervous systemThe Sympathetic Nervous System is a branch of the autonomic nervous system along with the enteric nervous system and parasympathetic nervous system. It is always active at a basal level and becomes more active during times of stress...
(a branch of the
autonomic nervous systemThe autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
). These cells normally act as special chemoreceptors located along blood vessels, particularly in the
carotid bodiesThe carotid body is a small cluster of chemoreceptors and supporting cells located near the fork of the carotid artery ....
(at the bifurcation of the common carotid artery in the neck) and in
aortic bodiesIn the human heart, the aortic body is one of several small clusters of chemoreceptors, baroreceptors, and supporting cells located along the aortic arch.-Function:...
(near the
aortic archThe aorta is the largest artery in the body, originating from the left ventricle of the heart and bringing oxygenated blood to all parts of the body in the systemic circulation....
).
Accordingly, paragangliomas are categorised as originating from a neural cell line in the
World Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health...
classification of
neuroendocrine tumorsNeuroendocrine tumors, or more properly gastro-entero-pancreatic or gastroenteropancreatic neuroendocrine tumors , are cancers of the interface between the endocrine system and the nervous system....
. In the categorization proposed by Wick, paragangliomas belong to group II. Given the fact that they originate from cells of the orthosympathetic system, paragangliomas are closely related to phaeochromocytomas, which however are chromaffine-positive.
Clinical presentation
Most paragangliomas are either asymptomatic or present as a painless mass. While all contain neurosecretory granules, only in 1–3% of cases secretion of hormones such as catecholamines is abundant enough to be clinically significant; in that case manifestations often resemble those of phaeochromocytomas.
Inheritance
About 75% of paragangliomas are sporadic; the remaining 25% are hereditary (and have an increased likelihood of being multiple and of developing at an earlier age). Mutations of the genes
SDHDSDHD, which stands for succinate dehydrogenase complex subunit D, is one of the two transmembrane subunits of the four-subunit succinate dehydrogenase protein complex that resides in the inner mitochondrial membrane. It also refers to the gene that codes for this protein. The other transmembrane...
(previously known as PGL1),
PGL2PGL2 is a gene that is one cause of familial paraganglioma, also known as glomus tumors. Its locus is at 11q13.1.-External links:*...
, and
SDHCSDHC is an abbreviation for succinate dehydrogenase complex subunit C.The term SDHC can refer to;* The protein subunit itself.* The gene that codes for this protein....
(previously PGL3) have been identified as causing familial head and neck paragangliomas. Mutations of
SDHBSDHB is an acronym for succinate dehydrogenase complex subunit B.The term SDHB can refer to:* The protein subunit itself.* The gene that codes for this protein....
play an important role in familial adrenal pheochromocytoma and extra-adrenal paraganglioma (of abdomen and thorax), although there is considerable overlap in the types of tumors associated with SDHB and SDHD gene mutations. Paragangliomas may also occur in
MENThe term multiple endocrine neoplasia encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign...
type 2A and 2B.
Pathology
The paragangliomas appear grossly as sharply circumscribed polypoid masses and they have a firm to rubbery consistency. They are highly
vascular tumorVascular tumor may mean:* tumor of vascular origin, a growth formed from blood vessels; for example, hemangioma, hemangioendothelioma, Kaposi sarcoma, angiosarcoma, etc....
s and may have a deep red color.
On microscopic inspection, the tumor cells are readily recognized. Individual tumor cells are polygonal to oval and are arranged in distinctive cell balls, called
Zellballen. These cell balls are separated by fibrovascular stroma and surrounded by sustentacular cells.
By light microscopy, the differential diagnosis includes related neuroendocrine tumors, such as carcinoid tumor, neuroendocrine carcinoma, and medullary carcinoma of the thyroid; middle ear
adenomaAn adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...
; and meningioma.
With
immunohistochemistryImmunohistochemistry or IHC refers to the process of localizing antigens in cells of a tissue section exploiting the principle of antibodies binding specifically to antigens in biological tissues. It takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
, the chief cells located in the cell balls are positive for
chromograninThe chromogranin/secretogranin are a family of regulated secretory proteins ubiquitously found in the cores of amine and peptide hormone and neurotransmitter dense-core secretory vesicles.- Function :...
,
synaptophysinSynaptophysin can refer both to the vesicle membrane protein as well as the gene that encodes it.-Genomics:The gene is located on the short arm of X chromosome . It is 12,406 bases in length and lies on the Crick strand...
, neuron specific enolase,
serotoninSerotonin is a monoamine neurotransmitter. It is found extensively in the gastrointestinal tract of animals, and about 80 to 90 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements...
,
neurofilamentNeurofilaments are the 10 nanometer or intermediate filaments found specifically in neurons. The subunits of neurofilaments are related structurally to the 10nm or intermediate filaments of other tissues such as the keratin subunits, which make 10nm filaments expressed specifically in...
and
Neural cell adhesion moleculeNeural Cell Adhesion Molecule is a homophilic binding glycoprotein expressed on the surface of neurons, glia, skeletal muscle and natural killer cells...
; they are
S-100 proteinS-100 protein is a family of low molecular weight protein found in vertebrates characterized by two calcium binding sites of the helix-loop-helix conformation. There are at least 21 different types of S100 proteins...
negative. The sustentacular cells are S-100 positive and focally positive for glial fibrillary acid protein. By histochemistry, the paraganglioma cells are argyrophilic, periodic acid Schiff negative, mucicarmine negative, and
argentaffinArgentaffin refers to cells which take up silver stain. Enteroendocrine cells are sometimes called "argentaffins", because they take up this stain....
negative.
Sites of origin
About 85% of paragangliomas develop in the abdomen; only 12% develop in the chest and 3% in the head and neck region (the latter are the most likely to be symptomatic). While most are single, rare multiple cases occur (usually in a hereditary syndrome). Paragangliomas are described by their site of origin and are often given special names:-
- Carotid paraganglioma (carotid body
The carotid body is a small cluster of chemoreceptors and supporting cells located near the fork of the carotid artery ....
tumor): Is the most common of the head and neck paragangliomas. It usually presents as a painless neck mass, but larger tumors may cause cranial nerve palsies, usually of the vagus nerveThe vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves, and is the only nerve that starts in the brainstem...
and hypoglossal nerveThe hypoglossal nerve is the twelfth cranial nerve , leading to the tongue. The nerve arises from the hypoglossal nucleus and emerges from the medulla oblongata in the preolivary sulcus separating the olive and the pyramid. It then passes through the hypoglossal canal...
.
- Glomus tympanicum and Glomus jugulare: Both commonly present as a middle ear mass resulting in tinnitus
Tinnitus is the perception of sound within the human ear in the absence of corresponding external sound....
(in 80%) and hearing loss (in 60%). The cranial nerves of the jugular foramenThe jugular foramen, a large aperture in the base of the skull. It is located behind the carotid canal and is formed in front by the petrous portion of the temporal, and behind by the occipital; it is generally larger on the right than on the left side...
may be compressed, resulting swallowing difficulty. These patients present with a reddish bulge behind an intact ear drum. This condition is also known as the "Red drum". On application of pressure to the external ear canal with the help of a pneumatic ear speculum the mass could be seen to blanch. This sign is known as "Brown's sign".
- Vagal paraganglioma: These are the least common of the head and neck paragangliomas. They usually present as a painless neck mass, but may result in dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
and hoarseness.
- Pulmonary paraglioma: These occur in the lung
The lung or pulmonary system is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart...
and may be either single or multiple.
- Other sites: Rare sites of involvement are the larynx
The larynx , colloquially known as the voicebox, is an organ in the neck of mammals involved in protection of the trachea and sound production...
, nasal cavity, paranasal sinuses, thyroidThe thyroid is one of the largest endocrine glands in the body. This gland is found in the neck inferior to the thyroid cartilage and at approximately the same level as the cricoid cartilage...
gland, and the thoracic inlet, as well as the bladder in extremely rare cases.
External links