Timoma in adults and children

Among quite rare neoplasms, specialists distinguish thymoma, which is a tumor of the epithelial tissue of the thymus - one of the main lymphoid-glandular organs of the immune system.

Epidemiology

Among all cancers, the proportion of thymus tumors is less than 1%. The incidence of thymoma is estimated by WHO in 0.15 cases per 100 thousand people. And, for example, in China, the total incidence of malignant thymoma is 6.3 cases per 100 thousand people. [1]

Timoma of the anterior mediastinum, which accounts for 90% of all thymus tumors, accounts for 20% of tumors of this localization - in the upper chest, under the sternum.

In other cases (no more than 4%), the tumor can occur in other areas, and this is the mediastinal thymoma. 

Causes of the thymomas

The biology and classification of thymic neoplasias are complex medical issues, and she still does not know the exact causes of thymus thymoma. This tumor is detected with equal frequency in men and women, and thymoma is more often found in adult adults.

But a thymus tumor in young people, as well as thymoma in children, is rare. Although the  thymus (thymus gland) is  most active precisely in childhood, since the forming immune system requires a large number of T-lymphocytes, which are produced by this gland.

The thymus gland, reaching its greatest size in the puberty, gradually involves in adults (shrinking in size), and its functional activity is minimal.

More information in the material -  Physiology of the thymus gland (thymus)

Risk factors

Hereditary or environmental risk factors predisposing to the development of thymoma have not been identified either. And today, risk factors, confirmed by clinical statistics, are considered age and ethnicity.

The risk of this type of neoplasm grows with age: thymomas are more often observed in adults 40-50 years old, as well as after 70 years.

According to American oncologists, in the United States this tumor is most common among representatives of the Asian race, African Americans and people from the Pacific Islands; thymoma is least likely to be found in white-skinned and Hispanic. [2]

Pathogenesis

Like the causes, the pathogenesis of thymoma remains a mystery, but researchers do not lose hope of solving it and are considering various versions, including UV radiation and radiation.

The T-lymphocytes are produced by the thymus, their migration to peripheral lymphoid organs is ensured, and antibody production by B-lymphocytes is also induced. In addition, this lymphoid-glandular organ secretes hormones that regulate the differentiation of lymphocytes and the complex interactions of T cells in the thymus and tissues of other organs.

Timoma refers to epithelial tumors and grows slowly - with the proliferation of normal or modified medullary epithelial cells (similar to normal). Experts note that the epithelial cells that make up the malignant thymoma may not have typical signs of malignancy, which determines the cytological features of this tumor. And its malignant behavior, observed in 30-40% of cases, is an invasion of the surrounding organs and structures.

An analysis of the relationship of thymoma with other diseases showed that almost all of them are autoimmune in nature, which may indicate impaired tolerance of immunocompetent cells and the formation of a persistent autoimmune reaction (cellular auto-reactivity). The most common related condition (in a third of patients) is  myasthenia gravis  with thymoma. Myasthenia gravis is associated with the presence of autoantibodies to the acetylcholine receptors of neuromuscular synapses or to the enzyme muscle tyrosine kinase.

The correlation of tumors of this type with such simultaneously occurring autoimmune diseases as polymyositis and dermatomyositis, systemic lupus erythematosus, red blood cell aplasia (in half of the patients), hypogammaglobulinemia (in 10% of patients), bullous dermatoses (pemphigus), pernicious anemia or megal Addison’s disease), ulcerative colitis, Cushing’s disease, scleroderma, diffuse toxic goiter, Hashimoto thyroiditis, nonspecific aortoarteritis (Takayasu syndrome), Sjogren’s syndrome, hyperparaty rheoidism (excess parathyroid hormone), Simmonds disease (panhypopituitarism), Good's syndrome (combined B- and T-cell immunodeficiency).

Symptoms of the thymomas

In 30-50% of cases, there are no symptoms of a tumor growth of the thymic epithelial tissue, and, as radiologists note, thymoma is accidentally detected on the chest x-ray (or CT) - during an examination conducted for another reason.

If the tumor manifests itself, then the first signs are felt in the form of discomfort and pressure in the chest and chest cavity, to which shortness of breath, persistent cough, chest pain of an indefinite nature and other signs of the superior vena cava syndrome can join  .

Patients who have myasthenia gravis during thymoma complain of fatigue and weakness (for example, it is difficult for them to raise their hands to comb their hair), double vision (diplopia), difficulty swallowing (dysphagia), drooping upper eyelids (ptosis). [3], [4]

Stages

The growth of thymoma and the degree of its invasiveness is determined by the stages:

I - the tumor is completely encapsulated and does not grow into the adipose tissue of the mediastinum;

IIA - the presence of tumor cells outside the capsule - microscopic penetration through the capsule into the surrounding adipose tissue;

IIB - macroscopic invasion through the capsule;

III - macroscopic invasion of neighboring organs;

IVA - there are pleural or pericardial metastases;

IVB - the presence of lymph or hematogenous metastases in the extrathoracic region.

Forms

The behavior of these tumors is unpredictable, and most of them are able to develop like cancer and spread beyond the gland. So thymomas can be benign or malignant; malignant (or invasive) thymoma are tumors that behave aggressively. Most Western experts attribute thymoma to malignant neoplasia. [5]

By combining and systematizing the pre-existing classifications of thymic tumors, WHO experts divided all types of thymus according to their histological type.

Type A - medullary thymoma, consisting of tumor epithelial cells of the thymus (without nuclear atypia); in most cases, the tumor is encapsulated, oval.

Type AB is a mixed thymoma in which there is a mixture of spindle-shaped and rounded epithelial cells or lymphocytic and epithelial components.

Type B1 is a cortical thymoma consisting of cells similar to the epithelial cells of iron and its cortex, as well as areas similar to the medulla of the thymus.

Type B2 - cortical thymoma, the newly formed tissue of which has swollen epithelial reticular cells with vesiculate nuclei and arrays of T-cells and B-cell follicles. A tumor cell can accumulate near the vessels of the thymus.

Type B3 - epithelial or squamoid thymoma; consists of lamellarly growing polygonal epithelial cells with or without atypia, as well as non-tumor lymphocytes. It is considered a well-differentiated thymic carcinoma.

Type C - thymic carcinoma with histological atypia of cells.

When thymoma behaves aggressively with invasion, it is sometimes called malignant.

Complications and consequences

The consequences and complications of thymoma are due to the ability of these tumors to grow into nearby organs, which leads to a violation of their functions.

Metastases are usually limited to lymph nodes, pleura, pericardium or diaphragm, and extra thoracic (extrathoracic) metastasis - to the bones, skeletal muscles, liver, abdominal wall - is rarely observed.

In the presence of thymoma, the risk of developing cancer is almost four times higher, and secondary malignant neoplasms can be found in the lungs, thyroid gland, and lymph nodes.

In addition, thymoma - even after complete resection - may recur. As clinical practice shows, 10 years after removal, relapses of thymoma occur in 10-30% of cases.

Diagnostics of the thymomas

In addition to the anamnesis and examination, the diagnosis of thymoma includes a whole range of examinations. Assigned tests are aimed both at identifying related diseases and the presence of  paraneoplastic syndrome , and at determining the possible spread of the tumor. This is a general and complete clinical blood test, analysis for antibodies, for the level of thyroid hormones and parathyroid hormone, ACTH, etc. [6]

Instrumental diagnostics involves visualization by compulsory chest x-ray (in direct and lateral projection), ultrasound and computed tomography. It may also be necessary to perform thoracic MTR or PET (positron emission tomography).

The thymoma on the roentgenogram has the form of an oval evenly or slightly wavy outlined shadow - lobed density of soft tissues, slightly shifted to the side relative to the middle of the chest.

Timoma on CT has the appearance of a significant accumulation of neoplastic tissue in the mediastinum.

Using a fine-needle aspiration biopsy (under CT control), a tumor tissue sample is obtained for its histological examination. Although the ability to determine the type of neoplasm as accurately as possible is provided only by postoperative histology - after its removal: due to the histological heterogeneity of thymus, which complicates their classification to a certain type.

Differential diagnosis

Differential diagnosis should take into account the probability of the patient having: thymomegaly, thymus hyperplasia, thymolipoma, lymphoma, nodular form of retrosternal goiter, pericardial cyst or tuberculosis of the intrathoracic lymph nodes .

Treatment of the thymomas

As a rule, treatment of a thymus gland epithelial tumor of stage I begins with the operation to remove the thymoma (by means of a complete median sternotomy) with simultaneous resection of the thymus - thimectomy. [7]

Surgical treatment of a stage II tumor also consists in the complete removal of the thymus with possible adjuvant radiation therapy (for a high-risk neoplasm).

At stages IIIA-IIIB and IVA, the following are combined: surgery (including the removal of metastases in the pleural cavity or lungs) - before or after a  course of chemotherapy  or radiation. Perfusion chemotherapy, targeted and radiation therapy can be used in cases where removal of the tumor does not give the expected effect, or the tumor is especially invasive. [8]

For chemotherapy, Doxorubicin, Cisplatin, Vincristine, Sunitinib, Cyclophosphamide and other  cancer drugs are used . Chemotherapy is given to all inoperable patients. [9],  [10], [11]

Treatment of thymoma in stage IVB is carried out according to an individual plan, since general recommendations are not developed.

Forecast

Thymomas grow slowly, and the prospects for a successful cure are much higher when the neoplasm is detected in the early stages.

It is clear that for thymus stage III-IV - compared with stage I-II tumors - the prognosis is less favorable. According to the statistics of the American Cancer Society, if survival for five years at stage I is estimated at 100%, at stage II - at 90%, then at stage III thymomas leave 74%, and at stage IV less than 25%.