The word thymus originates from the Greek word thymos, which has dual meaning. Although it is synonymous with heroic character characterized by soul, spirit, courage, power, will, heart, and anger, it is also related to the herb thyme and to the thyme flower. Rufus (98 to 117 CE), who lived in Ephesus, a center of learning on the western shore of modern-day Turkey, is acknowledged as the first person to refer to the thymus gland in humans.

The thymus gland gained clinical importance once it was linked by the Swiss physician Platter in 1614 to the sudden death of a 5-month-old boy from suffocation. An autopsy was performed at the request of the father as two other sons had died similarly. This revealed a highly vascular mass compressing the mediastinal structures. This condition was subsequently called “mors thymica or thymic death.” More than two centuries later, Sir Astley Cooper in 1832 described the death of a 19-year-old woman from a malignant thymic tumor invading the major veins of superior mediastinum and compressing the trachea.

The finding of thymic tumors in autopsies in 1889 by Oppenheim and in 1901 by Weigert first suggested an interrelation between the thymus and MG. Contemporaneous invention of X-rays by Wilhelm Roentgen in 1895 allowed diagnostic imaging of enlarged mediastinal structures. The first thymectomy for MG was performed in 1911 by Ernst Ferdinand Sauerbruch from Zurich. He used a radiogram to diagnose thymic enlargement, associated it with the patient’s MG symptoms, and performed a successful transcervical thymectomy on a 19-year-old woman.

In 1936, Alfred Blalock became the first person to perform a transsternal thymectomy in a 19-year-old woman with persistent, severe MG and an anterior–superior mediastinal tumor that had only partially responded to three courses of radiotherapy. Beginning with this case, and encouraged by the neurologist Ford, Blalock also demonstrated the relation between MG and nonthymomatous thymus glands.

Sir Geoffrey Keynes followed Blalock in 1942 when he performed a thymectomy and completion thyroidectomy on one of his previous patients with severe MG and recurrent thyrotoxicosis 12 years after removal of a goiter. The subsequent smooth postoperative period encouraged Keynes, who reported a series of 281 thymectomies by 1956. His contributions to the evolution of thymectomy included the separate evaluation of the operative results of patients with thymomatous and nonthymomatous glands, and the precise documentation of surgical thymic anatomy.

The transsternal approach remained the “gold standard” for thymectomy until the early 1960s. After Carlens described mediastinoscopy in 1959, Crile in 1964 and Akakura in 1965 reported their experience with 24 cases of transcervical thymectomy. In addition to MG, the indications for thymectomy were extended to resection of thymic cysts or suppression of rejection in renal transplant recipients. In 1969, Kirschner reported on 21 cases with only 1 death, and suggested that transcervical thymectomy be adopted as the preferred approach to resection, exclusive of thymomas.

Other clinicians remained skeptical regarding completeness of transcervical thymectomy. Reported clinical failures following cervical excisions, in some cases necessitating a reresection, fueled the ongoing debate of the optimal approach to thymectomy for MG. These discussions became more complicated after the reports of Masaoka et al. in 1975 and Jaretzki in 1988 demonstrating the presence of extraglandular thymic tissue in 74% of the cases. Investigators at the University of Pennsylvania have reported comparable results with transcervical thymectomy to transsternal thymectomy after using a specially designed sternal retractor that allowed extended dissection through the limited cervical incision. With this report, the scale again tipped in favor of less-invasive surgery in the debate of thymectomy for MG.

The thymus gland, together with the inferior parathyroid glands, arises from the third pair of pharyngeal pouches (Fig. 1). Although the fourth pharyngeal pouches also give rise to a small amount of thymic tissue, these are usually vestigial masses and these latter primordia in humans are usually either absent or rudimentary. In the 6th week of gestation, epithelium of the third pouch proliferates to form a dorsal bulbar component, later becoming the inferior parathyroid gland, and an elongated ventral portion, which is destined to become a thymic lobe. The entire third pouch separates from the pharynx during the 7th week. These thymic primordia migrate in a caudal and medial direction. Originally hollow, thymic primordia rapidly become solid epithelial bars, and during the 8th week, the caudal ends of the paired components of the thymus fuse together to form what is generally a four-lobed gland that attaches to the anterior pericardium. The organ, then being attached to the growing pericardium, descends into the mediastinum behind the sternum and anterior to the great vessels. Incomplete migration may potentially leave islands of thymus anywhere along the course of the primordia. The lower capsule tends to be less distinct, and thymic corpuscles, as well as abundant lymphocytes, trail off into the surrounding mediastinal fat and nodal tissue. Because of either premature arrest of migration or deviation from its natural tract, the thymus gland itself may be found anywhere between the hyoid bone cranially and the xiphoid process of sternum caudally.

Although the thyroid, parathyroid, and thymus glands arise from the pouches of the same primordial pharynx, they separate in later stages of embryonic life. As the thymus descends caudally, the parathyroid glands normally remain settled at the same level with and posterior to the lower poles of thyroid. The parathyroid glands are also called parathymic glands. In autopsy studies, as many as 20% of inferior parathyroid glands are found within the thymic capsule in the neck or in the mediastinum. Although more common for parathyroid tissue, thyroid tissue may also be present within the thymus gland.

In the newborn, the thymus weighs 10 to 12 g and continues to grow until puberty. Steinmann reported an average weight of 27.3 g with a standard deviation of 16.4 g within the 1st year of life. At puberty, the gland reaches its maximum weight of 20 to 50 g. Thereafter it enters a gradual involution state, decreasing in mass to only 5 to 15 g in the elderly. At this time, the parenchyma is mostly replaced by fibrofatty tissue.

The thymus is a bilobed glandular structure; however, its two lobes are rarely symmetrical. The thymus is located predominantly in the anterior–superior mediastinum, where it anteriorly covers the great vessels, pericardium, and the base of the heart. It is also in close proximity with the anterior surface of the innominate vein as it runs obliquely across the superior mediastinum to join the right brachiocephalic vein to form the superior vena cava (SVC; Fig. 2). The thymus may sometimes lie adjacent to either SVC on the right or the pulmonary artery on the left. One or both lobes may also lie behind the left innominate vein instead of in front of it. The two thymic lobes are fused in the midline, giving the gland its H-shaped configuration. The upper poles of each lobe reach into the neck where they join the thyroid gland by the thyrothymic ligaments on both sides. The lower poles lie on the pericardium anterior to the heart.

The arterial supply of the thymus is chiefly derived from the internal thoracic arteries, although it receives branches from inferior thyroid arteries and
pericardiophrenic arteries as well. There may be small draining veins traveling with the arteries from any of the three sources. However, the main venous drainage is through one or two major trunks, formed by convergence of multiple tributaries from both lobes, running posteriorly between the lobes and draining into the anterior surface of the innominate vein. Although it is a major lymphatic tissue, unlike a lymph node, the thymus gland lacks afferent lymph channels. There are efferent lymph channels, which only drain the capsule and fibrous septa of the gland and drain into anterior mediastinal, pulmonary hilar, and internal mammary lymph nodes. Both sympathetic and parasympathetic nerve fibers are found in the thymus.

Numerous islets of thymic tissue, both macroscopic and microscopic, may be found in the neck, middle mediastinum, both pulmonary hili, aortopulmonic window, retrocarinal fat, diaphragm, and even within the pulmonary parenchyma. Masaoka et al. reported 72% of extracapsular microscopic collections of thymic tissue in the anterior mediastinum in 1975, and Fukai et al. came up with the same findings in 51.8% of cases in 1991. Jaretzki documented the variations of extraglandular thymic tissue found in different mediastinal locations in 1997. These publications form the basis for the ongoing debate on completeness and adequacy of thymectomy via various incisions.

The thymus is a complex organ with epithelial and lymphoid components. During infancy, the thymus is essential for the development of cellular immunity. It is the main site for maturation of null lymphocytes into T cells. The majority of cells in the thymus are T lymphocytes and epithelial cells. These cells comprise the two main structural layers of the gland, the cortex and the medulla, respectively. Occasional lymphoid follicles with B cells and germinal centers can also be found. Although rare, myoid cells may be a part of histologic picture in the thymus. These cells act like skeletal muscle cells, including expression of the acetylcholine receptors (AChRs), and may be involved in the pathophysiology of MG.

The proper function of the immune system depends on the normal simultaneous development of cellular and humoral components, and normal interaction between them. Although thymus-centered T-cell population is responsible for differentiating self-antigens from intruders and producing cell-mediated immune reactions, as seen in delayed hypersensitivity reactions, the bursa-dependent system, formed by the bursa, lymphoid follicles, and plasma cells, is responsible for the production of immunoglobulins (A, G, and M) and specific antibodies. Any disturbance in development of either system may lead to one of the various immunologic deficiency syndromes. Interestingly, some of these syndromes have been associated with various neoplasms of the thymus as well as with congenital thymic hypoplasias and agenesis. Some morphologic changes that the thymus can display have also been linked to hyperplasia, abnormal development, and infections.

Symptoms related to thymic disease are categorized as the ones arising directly from the thymic lesion by either compression or invasion, symptoms associated with a previously described clinical syndrome (i.e.,
MG, red cell aplasia, or hypogammaglobulinemia), or nonspecific systemic symptoms such as anorexia and fatigue. Developmental anomalies can involve the location of the thymus or its development. Failure of the thymus to descend into the anterior mediastinum might account for cervical thymic tissue, which can be mistaken for neoplasm, lymphadenopathy, or an enlarged parathyroid. This aberrant tissue can cause compressive symptoms such as stridor or dysphagia. Lymphocyte count and tests of immunologic capacity may be diminished by thymectomy; however, no particular clinical problems have developed to correlate with these laboratory observations.

The epithelial subset of thymic neoplasms, namely, thymoma, is the most common tumor of the anterior mediastinum. It is fundamental in oncology that a successful therapeutic approach to a neoplasm be based on a definitive and prognostically reproducible classification and staging system. However, the classification of thymic tumors has been one of the most debated subjects of modern thoracic surgery and oncology. There have been several classification proposals, focusing on one or more of histology, embryology, and biology of the tumors, in an attempt to establish an agreed-on nomenclature. Although lymphomas are far more common than thymomas in children and adolescents, the only role for surgery in their treatment is for diagnostic and staging purposes. Mesenchymal and germ cell tumors of the thymus are uncommon. The most common type is teratoma. Seminomas and nonseminomatous germ cell tumors also occur in the thymus, almost exclusively in men. Thymic carcinoids are extremely rare, often associated with endocrinopathies such as Cushing syndrome or inappropriate secretion of the antidiuretic hormone. They are typically invasive, often recur, are associated with extrathoracic metastases, and have a poor prognosis. The thymus can rarely be a site for metastasis as well.

The original description of MG dates back to the case report of the physiologist Sir Thomas Willis in 1672. The real recognition of the clinical syndrome came after the report by Wilks in 1877, in which he described a young woman who died of a respiratory paralysis. Autopsy did not reveal any central nervous system pathology that would explain the problem. In 1895, Jolly described the test now bearing his name, disclosing the easy fatigability in the affected muscle following repetitive stimuli. He then proposed the name myasthenia gravis pseudoparalytica for the disease. In 1899, the Berlin Society for Neurology and Psychiatry shortened the name to myasthenia gravis. However, only during the last two decades has the pathophysiology of this disorder become well elucidated as the experiments revealed the microstructure, physiology, and molecular composition of the nicotinic AChR.

The prevalence of MG has been estimated at 43 to 64 per million population. It has a predilection for females with a ratio of 3:2. Its peak age is 20 to 30 in women and more than 50 years in men. The disease is usually nonfamilial. The common presenting symptom of the disease is an insidious onset of generalized weakness. This is seen in 85% of the patients. It is usually symmetrical and becomes more intense at the end of the day. Muscles innervated by cranial nerves are often the first to be affected; however, any striated muscle in the body may be involved. Some patients may present with external ocular symptoms only, such as ptosis and diplopia. These symptoms may either spread to other muscle groups or remain confined to the eye, and may be so subtle that patients may go through several eyeglass prescriptions before they are diagnosed with MG. The worst type of disease occurs when the bulbar muscles are involved. The symptoms may include dysarthria with nasal tones caused
by palatal paresis, diminished voice, and dysphonia. Often, patients can bite on the food but as they continue to eat, the mastication muscles weaken until they can no longer chew or close their jaws. Dysphagia may be associated with nasal regurgitation of liquids. Weakening of neck and back muscles may necessitate manual support of the head. Pelvic weakness may result in waddling gait. The most dreaded complication, however, is respiratory involvement. Weakness of respiratory muscles with paresis of intercostal muscles and the diaphragm may necessitate emergent medical attention. The Osserman and Genkins classification of MG is still very useful and widely adopted (Table 5). Standardized preoperative clinical staging has been recommended by applying the Myasthenia Gravis Foundation of America (MGFA) clinical classification (Table 6). Postoperative assessment can be monitored again in a standardized schema by following the De Filippi classification (Table 7).