Thymoma is a heterogeneous group of neoplasms, different in histogenesis and degree of maturity, originating from the epithelial tissue of the thymus gland. Variants of the clinical course of thymoma can be different: from asymptomatic to pronounced (compression, pain, myasthenic, intoxication syndrome). Topographic-anatomical and etiological diagnosis is established using radiation methods (radiography, CT of the mediastinum), transthoracic puncture, mediastinoscopy, biopsy examination. Surgical treatment: removal of thymoma together with the thymus gland and adipose tissue of the anterior mediastinum, supplemented by chemoradiotherapy according to indications.
Meaning
Thymoma is an organ–specific tumor of the mediastinum, originating from the cellular elements of the cerebral and cortical substance of the thymus. The term “thymoma” was coined in 1900 by researchers Grandhomme and Scminke to refer to various tumors of the thymus gland. Thymomas account for 10-20% of all neoplasms of the mediastinal space. In 65-70% of cases, thymomas have a benign course; invasive growth with sprouting of the pleura and pericardium is noted in 30% of patients, distant metastasis – in 5%. Thymomas develop somewhat more often in women, mostly 40-60-year-olds suffer. Children account for less than 8% of thymus tumors.
The causes of thymus gland tumors are unknown. It is assumed that thymomas may have an embryonic origin, be associated with a violation of thymopoietin synthesis or immune homeostasis. Infectious diseases, radiation exposure, mediastinal injuries can serve as factors provoking the growth and development of a tumor. It has been noted that thymomas are often combined with various endocrine and autoimmune syndromes (myasthenia gravis, dermatomyositis, SLE, diffuse toxic goiter, Itsenko-Cushing syndrome, etc.).
Structure and functions of the thymus gland
The thymus gland, or thymus, is located in the lower part of the neck and the anterior part of the upper mediastinum. The organ is formed by two asymmetric lobes – the right and the left. In turn, each lobe is represented by a set of lobules consisting of cortical and medullary matter and enclosed in a connective tissue stroma. There are two types of tissue in the thymus gland – epithelial and lymphoid. Epithelial cells secrete thymic hormones (thymulin, a-, b-thymosins, thymopoietins, etc.), lymphoid tissue consists of T-lymphocytes of varying degrees of maturity and functional activity.
Thus, the thymus gland is both an internal secretion gland and an immune organ that ensures the interaction of the endocrine and immune systems. After 20 years, the thymus undergoes age-related involution; after 50 years, the parenchyma of the thymus is 90% replaced by adipose and connective tissue, preserved as separate islands lying in the mediastinal fiber.
Classification
In oncology, there are three types of thyma: benign, malignant type 1 thyma (with signs of atypia, but relatively benign course) and malignant type 2 thyma (with invasive growth).
- Benign thymoma (50-70% of thymus tumors) macroscopically, it looks like a single encapsulated node with a diameter of no more than 5 cm. Taking into account histogenesis, medullary (type A), mixed (type AB) and predominantly cortical (type B1) tima are distinguished within this group.
- Thymoma type A (medullary) accounts for 4-7% of benign tumors of the thymus gland. Depending on the structure, it can be solid and spindle-celled-large-celled, almost always has a capsule. The prognosis is favorable, the 15-year survival rate is 100%.
- Thymoma of type AB (corticomedullary) occurs in 28-34% of patients. It combines foci of cortical and medullary differentiation. Has a satisfactory prognosis; 15-year survival rate is more than 90%.
- Thymoma type B1 (mainly cortical) occurs in 9-20% of cases. Often has a pronounced lymphocytic infiltration. More than half of the patients are accompanied by myasthenic syndrome. The prognosis is satisfactory; the 20-year survival rate is more than 90%.
- Malignant thymoma type 1 (20-25% of cases) is a single or multiple lobular nodes without a clear capsule. The size of the tumor often does not exceed 4-5 cm, but sometimes there are neoplasms of large sizes. It is characterized by invasive growth within the gland. Histologically, it is represented by cortical thymoma (type B2) and highly differentiated carcinoma.
- Thymoma type B2 (cortical) is about 20-36% tim. Histological varieties are variable: dark-cell, light-cell, watery-cell, etc. In most cases, it occurs with myasthenia gravis. Prognostically less favorable: less than 60% of patients live for 20 years.
- Thymoma type B3 (epithelial) develops in 10-14% of patients. It often has hormonal activity. The prognosis is worse than with the cortical variety; the 20-year survival rate is less than 40%.
- Type 2 malignant thymoma (thymus cancer, type C thymoma) accounts for up to 5% of all cases. It is characterized by pronounced invasive growth, high metastatic activity (it gives metastases to the pleura, lungs, pericardium, liver, bones, adrenal glands). There are 6 histological types of thymus cancer: squamous, fusiform, light-cell, lymphoepithelial, undifferentiated, mucoepidermoid.
Depending on the specific gravity of the lymphoid component in the thymoma, lymphoid (more than 2/3 of all tumor cells are represented by T-lymphocytes), lymphoepithelial (T-lymphocytes make up from 2/3 to 1/3 cells) and epithelial thymomas (less than 1/3 of all cells are represented by T-lymphocytes) are differentiated.
Based on the degree of invasive growth, there are 4 stages of thymoma:
- Stage I – encapsulated thymoma without mediastinal adipose tissue germination
- Stage II – germination of tumor elements into mediastinal tissue
- Stage III – invasion of the pleura, lung, pericardium, large vessels
- Stage IV – the presence of implantation, hematogenic or lymphogenic metastases.
Symptoms
The clinical manifestations and course of thymoma depend on its type, hormonal activity, and size. In more than half of cases, the tumor develops latently and is detected during a preventive X-ray examination.
Invasive thymomas cause compression mediastinal syndrome, which is accompanied by pain behind the sternum, dry cough, shortness of breath. Compression of the trachea and large bronchi is manifested by stridor, cyanosis, respiratory failure. With compression syndrome of the superior vena cava, puffiness of the face, cyanosis of the upper half of the trunk, swelling of the cervical veins occurs. The pressure of a growing tumor on the nerve nodes causes the development of Gorner syndrome, hoarseness of the voice, elevation of the diaphragm dome. Compression of the esophagus is accompanied by a swallowing disorder – dysphagia.
According to various data, from 10 to 40% of tim are combined with myasthenic syndrome. Patients note a decrease in muscle strength, fatigue, weakness of facial muscles, double vision, choking, voice disorders. In severe cases, a myasthenic crisis may develop, requiring a transition to a ventilator and probe nutrition.
In the late stages of malignant thymoma, signs of cancer intoxication appear: fever, anorexia, weight loss. Often, thymoma is accompanied by various hematological and immunodeficiency syndromes: aplastic anemia, thrombocytopenic purpura, hypogammaglobulinemia.
Diagnostics
Diagnosis of thymoma is carried out by thoracic surgeons with the involvement of oncologists, radiologists, endocrinologists, neurologists. A clinical examination may reveal the expansion of the chest veins, swelling of the sternum in the projection of the tumor; enlargement of the cervical, supraclavicular, subclavian lymph nodes; signs of compression syndrome and myasthenia gravis. Physical examination reveals expansion of mediastinal boundaries, tachycardia, wheezing.
On the chest X-ray, the thymoma has the appearance of an irregularly shaped volumetric formation located in the anterior mediastinum. CT of the chest significantly expands the amount of information obtained during primary X-ray diagnostics and in some cases allows you to make a morphological diagnosis. Clarification of the localization and relationship of the neoplasm with neighboring organs during CT of the mediastinum allows further transthoracic puncture of the mediastinal tumor, which is extremely important for histological confirmation of the diagnosis and verification of the histological type of thymoma.
For visual examination of the mediastinum and performing a direct biopsy, diagnostic mediastinoscopy, parasternal thoracotomy or thoracoscopy is performed. The diagnosis of myasthenia gravis is clarified by electromyography with the introduction of anticholinesterase drugs. Differential diagnostic measures make it possible to exclude other volumetric processes in the mediastinum: retrosternal goiter, dermoid cysts and mediastinal teratomas.
Treatment
Treatment of tumors of the thymus gland is carried out in the departments of thoracic surgery and oncology. The surgical method is the main one in the treatment of thymoma, since only thymectomy provides satisfactory long-term results. In benign thymomas, surgical intervention consists in removing the tumor together with the thymus gland (thymomymectomy), fatty tissue and lymph nodes of the mediastinum. Such a volume of resection is dictated by a high risk of tumor recurrence and myasthenia gravis. The operation is performed from the median sternotomic access.
In case of malignant neoplasms of the thymus, the operation can be supplemented by resection of the lung, pericardium, main vessels, and diaphragmatic nerve. Postoperative radiation therapy is indicated for stages II and III of thymoma. In addition, irradiation is the leading method of treatment of inoperable stage IV malignant tumors. Currently, three-stage treatment, including neoadjuvant chemotherapy, tumor resection and radiation therapy, is of greater importance in the treatment of invasive tim.
In the postoperative period, myasthenic crisis may occur in patients who have undergone thymectomy, which requires intensive therapy, tracheostomy, ventilation, and long-term administration of anticholinesterase drugs.
Long-term results of treatment of benign tim are good. After removal of the tumor, the symptoms of myasthenia gravis disappear or significantly decrease. In patients with malignant thymoma operated on in the early stages, the 5-year survival rate reaches 90%, at stage III – 60-70%. Inoperable forms of cancer have a poor prognosis with a mortality rate of 90% over the next 5 years.