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Thymoma

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Introduction
Thymoma, the most common neoplasm of the anterior mediastinum, originates within the epithelial cells of the thymus.

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The thymus is a lymphoid organ located in the anterior mediastinum. In early life, the thymus is responsible for the development and maturation of cell-mediated immunological functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T lymphocytes. The thymus gland is located behind the sternum in front of the great vessels; it reaches its maximum weight at puberty and undergoes involution thereafter.

In human anatomy, the thymus is an organ located in the upper anterior portion of the chest cavity just behind the sternum. The main function of the thymus is to provide an area for T cell maturation, and is vital in protecting against autoimmunity.

Etiology:-
The etiology of thymomas has not been elucidated; however, it has been associated with various systemic syndromes. As many as 30-40% of patients who have a thymoma experience symptoms suggestive of MG. An additional 5% of patients who have a thymoma have other systemic syndromes, including red cell aplasia, dermatomyositis, systemic lupus erythematous, Cushing syndrome, and syndrome of inappropriate antidiuretic hormone secretion.

History:-
The thymus was known to the Ancient Greeks, and its name comes from the Greek word ??µ?? (thumos), meaning heart, soul, desire, life – possibly because of its location in the chest, near where emotions are subjectively felt; or else the name comes from the herb thyme (also in Greek ??µ??), which became the name for a “warty excrescence”, possibly due to its resemblance to a bunch of thyme.

Galen was the first to note that the size of the organ changed over the duration of a person’s life.

Due to the large numbers of apoptotic lymphocytes, the thymus was originally dismissed as a “lymphocyte graveyard”, without functional importance. The importance of the thymus in the immune system was discovered in 1961 by Jacques Miller, by surgically removing the thymus from three day old mice, and observing the subsequent deficiency in a lymphocyte population, subsequently named T cells after the organ of their origin. Recently, advances in immunology have allowed the function of the thymus in T cell maturation to be more fully understood.

Function:-
In the two thymic lobes, lymphocyte precursors from the bone-marrow become thymocytes, and subsequently mature into T cells. Once mature, T cells emigrate from the thymus and constitute the peripheral T cell repertoire responsible for directing many facets of the adaptive immune system. Loss of the thymus at an early age through genetic mutation (as in DiGeorge Syndrome) or surgical removal results in severe immunodeficiency and a high susceptibility to infection.

The stock of T-lymphocytes is built up in early life, so the function of the thymus is diminished in adults. It is largely degenerated in elderly adults and is barely identifiable, consisting mostly of fatty tissue, but it continues to function as an endocrine gland important in stimulating the immune system.[8] Involution of the thymus has been linked to loss of immune function in the elderly, susceptibility to infection and to cancer.

The ability of T cells to recognize foreign antigens is mediated by the T cell receptor. The T cell receptor undergoes genetic rearrangement during thymocyte maturation, resulting in each T cell bearing a unique T cell receptor, specific to a limited set of peptide:MHC combinations. The random nature of the genetic rearrangement results in a requirement of central tolerance mechanisms to remove or inactivate those T cells which bear a T cell receptor with the ability to recognise self-peptides.

Iodine, thymus and immunity:-
Iodine has important actions in the immune system. The high iodide-concentration of thymus suggests an anatomical rationale for this role of iodine in immune system.

Phases of thymocyte maturation:-
The generation of T cells expressing distinct T cell receptors occurs within the thymus, and can be conceptually divided into three phases:

1.A rare population of hematopoietic progenitor cells enter the thymus from the blood, and expands by cell division to generate a large population of immature thymocytes.

2.Immature thymocytes each make distinct T cell receptors by a process of gene rearrangement. This process is error-prone, and some thymocytes fail to make functional T cell receptors, whereas other thymocytes make T cell receptors that are autoreactive. Growth factors include thymopoietin and thymosin.

3.Immature thymocytes undergo a process of selection, based on the specificity of their T cell receptors. This involves selection of T cells that are functional (positive selection), and elimination of T cells that are autoreactive (negative selection).

Anatomy:
The thymus is of a pinkish-gray color, soft, and lobulated on its surfaces. At birth it is about 5 cm in length, 4 cm in breadth, and about 6 mm in thickness. The organ enlarges during childhood, and atrophies at puberty. Unlike the liver, kidney and heart, for instance, the thymus is at its largest in children. The thymus reaches maximum weight (20 to 37 grams) by the time of puberty. It remains active only until puberty. Then with growing age, it starts to shrink. The thymus gland of older people is scarcely distinguishable from surrounding fatty tissue. As one ages the thymus slowly shrinks, eventually degenerating into tiny islands of fatty tissue. By the age of 75 years, the thymus gland weighs only 6 grams. In children the thymus is grayish-pink in colour and in adults it is yellow.
Presentation:-
Peak incidence of thymoma occurs in the fourth to fifth decade of life; mean age of patients is 52 years. No sexual predilection exists. Although development of a thymoma in childhood is rare, children are more likely than adults to have symptoms. Several explanations for the prevalence of symptoms in children have been proposed, including the following: (1) children are more likely to have malignancy, (2) lesions are more likely to cause symptoms by compression or invasion in the smaller thoracic cavity of a child, and (3) the most common location for mediastinal tumors in children is near the trachea, resulting in respiratory symptoms.

Four cases of patients who presented with severe chest pain secondary to infarction or hemorrhage of the tumor have been reported. Cases of invasion into the superior vena cava resulting in venous obstruction have also been reported.2  The clinician should be aware of these rare presentations of a thymoma.

The thymus will, if examined when its growth is most active, be found to consist of two lateral lobes placed in close contact along the middle line, situated partly in the thorax, partly in the neck, and extending from the fourth costal cartilage upward, as high as the lower border of the thyroid gland. It is covered by the sternum, and by the origins of the sternohyoidei and sternothyreoidei. Below, it rests upon the pericardium, being separated from the aortic arch and great vessels by a layer of fascia. In the neck, it lies on the front and sides of the trachea, behind the sternohyoidei and sternothyreoidei. The two lobes differ in size and may be united or separated

Problem:-
No clear histologic distinction between benign and malignant thymomas exists. The propensity of a thymoma to be malignant is determined by the invasiveness of the thymoma. Malignant thymomas can invade the vasculature, lymphatics, and adjacent structures within the mediastinum. The 15-year survival rate of a person with an invasive thymoma is 12.5%, and it is 47% for a person with a noninvasive thymoma. Death usually occurs from cardiac tamponade or other cardiorespiratory complications.

Frequency:-
Thymoma, the most common neoplasm of the anterior mediastinum, accounts for 20-25% of all mediastinal tumors and 50% of anterior mediastinal masses

Two primary forms of tumours originate in the thymus.

Tumours originating from the thymic epithelial cells are called thymomas, and are found in about 10-15% of patients with myasthenia gravis. Symptoms are sometimes confused with bronchitis or a strong cough because the tumor presses on the recurrent laryngeal nerve. All thymomas are potentially cancerous, but they can vary a great deal. Some grow very slowly. Others grow rapidly and can spread to surrounding tissues. Treatment of thymomas often requires surgery to remove the entire thymus. Tumours originating from the thymocytes are called thymic lymphomas.

Radiation Induced:-
People with enlarged thymus glands, particularly children, were treated with intense radiation in the years before 1950. There is an elevated incidence of thyroid cancer and leukemia in treated individuals.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://emedicine.medscape.com/article/193809-overview
http://en.wikipedia.org/wiki/Thymus

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