Thymoma
Encyclopedia
Thymoma is a tumor
originating from the epithelial cells of the thymus
. Thymoma is an uncommon tumor, best known for its association with the neuromuscular disorder myasthenia gravis
. Thymoma is found in 15% of patients with myasthenia gravis
. Once diagnosed, thymomas may be removed surgically. In the rare case of a malignant tumor, chemotherapy
may be used.
, dysphagia
(difficulty swallowing), cough
, or chest pain
.
One-third of patients have their tumors discovered because they have an associated autoimmune disorder. As mentioned earlier, the most common of those conditions is myasthenia gravis
(MG); 10-15% of patients with MG have a thymoma and, conversely, 30-45% of patients with thymomas have MG. Additional associated autoimmune conditions include pure red cell aplasia and Good's syndrome (thymoma with combined immunodeficiency and hypogammaglobulinemia
). Other reported disease associations are with acute pericarditis
, Addison's disease
, agranulocytosis
, alopecia areata
, ulcerative colitis
, Cushing's disease
, hemolytic anemia
, limbic encephalopathy, myocarditis
, nephrotic syndrome
, panhypopituitarism, pernicious anemia
, polymyositis
, rheumatoid arthritis
, sarcoidosis
, scleroderma
, sensorimotor radiculopathy, stiff person syndrome
, systemic lupus erythematosus
and thyroiditis
.
One-third to one-half of all persons with thymoma have no symptoms at all, and the mass is identified on a chest X-ray
or CT/CAT scan performed for an unrelated problem.
When a thymoma is suspected, a CT/CAT scan is generally performed to estimate the size and extent of the tumor, and the lesion is sampled with a CT-guided needle biopsy
. Increased vascular enhancement on CT scans can be indicative of malignancy, as can be pleural deposits. Limited biopsies are associated with a very small risk of pneumomediastinum
or mediastinitis
and an even-lower risk of damaging the heart
or large blood vessels. The diagnosis is made via histologic examination by a pathologist, after obtaining a tissue sample of the mass. Final tumor classification and staging is accomplished pathologically after formal surgical removal of the thymic tumor
Selected laboratory tests can be used to look for associated problems or possible tumor spread. These include: full blood count, protein electrophoresis
, antibodies to the acetylcholine receptor
(indicative of myasthenia), electrolyte
s, liver enzymes and renal function
.
cell population in the thymus, and several microscopic subtypes are now recognized. There are three principal histological types of thymoma, depending on the appearance of the cells by microscopy:
thymic cortical epithelial cells have abundant cytoplasm ,vesicular nucleus with finely divided chromatin and small nucleoli and cytoplasmic filaments contact adjacent cells.
thymic medullary epithelial cells in contrast are spindle shaped with oval dense nucleus and scant cytoplasm
thymoma if recapitulates cortical cell features more, is thought to be less benign.
, doxorubicin
and cisplatin
).
, generally to pleura, bone
s, liver
or brain
in approximately 7% of cases. Patients with stage III and IV tumors may nonetheless survive for several years with appropriate oncological management.
Patients who have undergone thymectomy for thymoma should be warned of possible severe side effects after yellow fever vaccination. This is probably caused by inadequate T-cell response to live attenuated yellow fever vaccine. Deaths have been reported.
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
originating from the epithelial cells of the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
. Thymoma is an uncommon tumor, best known for its association with the neuromuscular disorder myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
. Thymoma is found in 15% of patients with myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
. Once diagnosed, thymomas may be removed surgically. In the rare case of a malignant tumor, chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
may be used.
Signs and symptoms
A third of all people with a thymoma have symptoms caused by compression of the surrounding organs by an expansive mass. These problems may take the form of superior vena cava syndromeSuperior vena cava syndrome
Superior vena cava syndrome , or superior vena cava obstruction , is usually the result of the direct obstruction of the superior vena cava by malignancies such as compression of the vessel wall by right upper lobe tumors or thymoma and/or mediastinal lymphadenopathy. The most common malignancies...
, dysphagia
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....
(difficulty swallowing), cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, or chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...
.
One-third of patients have their tumors discovered because they have an associated autoimmune disorder. As mentioned earlier, the most common of those conditions is myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
(MG); 10-15% of patients with MG have a thymoma and, conversely, 30-45% of patients with thymomas have MG. Additional associated autoimmune conditions include pure red cell aplasia and Good's syndrome (thymoma with combined immunodeficiency and hypogammaglobulinemia
Hypogammaglobulinemia
Hypogammaglobulinemia is a type of immune disorder characterized by a reduction in all types of gamma globulins.Hypogammaglobulinemia is a characteristic of common variable immunodeficiency.-Terminology:...
). Other reported disease associations are with acute pericarditis
Acute pericarditis
Acute pericarditis is a type of pericarditis usually lasting 1.5 µg/L. Coronary angiography in those patients should indicated normal vascular perfusion. The elevation of these biomarkers are typically transient and should return to normal within a week. Persistence may indicated...
, Addison's disease
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
, agranulocytosis
Agranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
, alopecia areata
Alopecia areata
Alopecia areata is a medical condition in which hair is lost from some or all areas of the body, usually from the scalp. Because it causes bald spots on the scalp, especially in the first stages, it is sometimes called spot baldness. In 1–2% of cases, the condition can spread to the entire scalp ...
, ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
, Cushing's disease
Cushing's disease
Cushing's disease is a cause of Cushing's Syndrome characterised by increased secretion of adrenocorticotropic hormone from the anterior pituitary. This is most often as a result of a pituitary adenoma...
, hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
, limbic encephalopathy, myocarditis
Myocarditis
Myocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a...
, nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
, panhypopituitarism, pernicious anemia
Pernicious anemia
Pernicious anemia is one of many types of the larger family of megaloblastic anemias...
, polymyositis
Polymyositis
Polymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
, scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
, sensorimotor radiculopathy, stiff person syndrome
Stiff person syndrome
Stiff person syndrome is a rare neurologic disorder of unknown etiology characterized by progressive rigidity and stiffness, primarily of the axial musculature, that is superimposed by spasms, resulting in postural deformities...
, systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
and thyroiditis
Thyroiditis
Thyroiditis is the inflammation of the thyroid gland. The thyroid gland is located on the front of the neck below the laryngeal prominence, and makes hormones that control metabolism.-Classification:...
.
One-third to one-half of all persons with thymoma have no symptoms at all, and the mass is identified on a chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
or CT/CAT scan performed for an unrelated problem.
Diagnosis
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
. Increased vascular enhancement on CT scans can be indicative of malignancy, as can be pleural deposits. Limited biopsies are associated with a very small risk of pneumomediastinum
Pneumomediastinum
Pneumomediastinum is a condition in which air is present in the mediastinum...
or mediastinitis
Mediastinitis
Mediastinitis is inflammation of the tissues in the mid-chest, or mediastinum. It can be either acute or chronic.Acute mediastinitis is usually bacterial and due to rupture of organs in the mediastinum. As the infection can progress rapidly, this is considered a serious condition...
and an even-lower risk of damaging the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
or large blood vessels. The diagnosis is made via histologic examination by a pathologist, after obtaining a tissue sample of the mass. Final tumor classification and staging is accomplished pathologically after formal surgical removal of the thymic tumor
Selected laboratory tests can be used to look for associated problems or possible tumor spread. These include: full blood count, protein electrophoresis
Protein electrophoresis
Protein electrophoresis is a method for analysing the proteins in a fluid or an extract. The electrophoresis may be performed with a small volume of sample in a number of alternative ways with or without a supporting medium: SDS polyacrylamide gel electrophoresis Protein electrophoresis is a method...
, antibodies to the acetylcholine receptor
Acetylcholine receptor
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...
(indicative of myasthenia), electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s, liver enzymes and renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
.
Pathology
Thymoma originates from the epithelialEpithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
cell population in the thymus, and several microscopic subtypes are now recognized. There are three principal histological types of thymoma, depending on the appearance of the cells by microscopy:
- Type A if the epithelial cells have an oval or fusiform shape;(less lymphocyte count)
- Type B if they have an epithelioid shape (Type B has three subtypes B1 (lymphocyte-rich), B2 (cortical) and B3 (epithelial).);
- Type AB if the tumor contains a combination of both cell types.
thymic cortical epithelial cells have abundant cytoplasm ,vesicular nucleus with finely divided chromatin and small nucleoli and cytoplasmic filaments contact adjacent cells.
thymic medullary epithelial cells in contrast are spindle shaped with oval dense nucleus and scant cytoplasm
thymoma if recapitulates cortical cell features more, is thought to be less benign.
Staging
The Masaoka Staging System is used widely and is based on the anatomic extent of disease at the time of surgery:- I: Completely encapsulated
- IIA: Microscopic invasion through the capsule into surrounding fatty tissue
- IIB: Macroscopic invasion into capsule
- III: Macroscopic invasion into adjacent organs
- IVA: Pleural or pericardial implants
- IVB: Lymphogenous or hematogenous metastasis to distant (extrathoracic) sites
Treatment
Surgery is the mainstay of treatment for thymoma. If the tumor is apparently invasive and large, preoperative (neoadjuvant) chemotherapy and/or may be used to decrease the size and improve resectability, before surgery is attempted. When the tumor is an early stage (Masaoka I through IIB) no further therapy is necessary. Removal of the thymus in adults does not appear to induce immune deficiency. In children, however, postoperative immunity may be abnormal and vaccinations for several infectious agents are recommended. Invasive thymomas may require additional treatment with radiotherapy and chemotherapy (cyclophosphamideCyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
and cisplatin
Cisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
).
Prognosis
Prognosis is much worse for stage III or IV thymomas as compared with stage I and II tumors. Invasive thymomas uncommonly can also metastasizeMetastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
, generally to pleura, bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
or brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
in approximately 7% of cases. Patients with stage III and IV tumors may nonetheless survive for several years with appropriate oncological management.
Patients who have undergone thymectomy for thymoma should be warned of possible severe side effects after yellow fever vaccination. This is probably caused by inadequate T-cell response to live attenuated yellow fever vaccine. Deaths have been reported.