Introduction

The thymus is a primary lymphoid organ situated in the superior mediastinum. Largest during early life, the thymus gradually decreases in size after puberty and undergoes fibrofatty replacement, accompanied by diminished immunologic function.[1] Clinical relevance persists due to the organ’s proximity to major mediastinal structures and its association with pathological conditions such as myasthenia gravis and DiGeorge syndrome.[2]

Familiarity with thymic anatomy and function is essential for recognizing mediastinal masses, interpreting imaging studies, and diagnosing immunologic disorders and paraneoplastic syndromes linked to pathologies affecting this organ. Additionally, knowledge of the thymus supports safe surgical planning in the anterior mediastinum, particularly during thymectomy or cardiac procedures.

Structure and Function

Structure

The thymus is located in the superior portion of the retrosternal mediastinum. Although bilobed, the organ exhibits considerable morphological variation among individuals and typically measures 30 to 40 mm in length and 25 to 35 mm in width.[3] The thymus contains 2 histological subcomponents, the cortex and the medulla, and is composed of epithelial, dendritic, mesenchymal, and endothelial cells.[4][5] Unlike most other human organs, the thymus reaches full maturation in utero and undergoes progressive involution beginning around puberty. This process involves structural remodeling, during which organized parenchyma is gradually replaced by adipose tissue as immunologic activity declines.

Most of the organ occupies the anterior and anterosuperior mediastinum. The 2 lobes converge near the level of the sternal manubrium, from which cervical extensions may extend superiorly, sometimes reaching the inferior border of the thyroid gland. The thyrothymic ligament maintains this connection.[6] The right lobe lies between the right lung and the ascending aorta at its inferior extent. Posterior relations include the great vessels of the superior mediastinum, the trachea, and the anterior surface of the fibrous pericardium. Anteriorly, the manubrium, deep cervical fascia, and the sternohyoid and sternothyroid muscles border the thymus.[7] 

Function

The thymus is the primary site for the production and maturation of immune cells, particularly small lymphocytes that defend the body against foreign antigens. This organ supplies progenitor cells to peripheral lymphoid tissues and supports their maturation and functional competence.

T-cell development within the thymus involves both positive and negative selection. During positive selection, T-cells capable of recognizing self-antigens are retained for further screening, while those lacking appropriate receptor affinity undergo apoptosis. Approximately 95% of developing T-cells are eliminated at this stage due to self-reactivity. Surviving cells then undergo negative selection, during which those that bind self-antigens with high affinity are also removed to prevent autoimmunity.

Only lymphocytes that pass both selection processes exit the thymus. Once in the periphery, these mature T-cells become activated in response to pathogens such as bacteria and viruses. Clonal expansion follows activation. After pathogen clearance, most effector T-cells undergo apoptosis, while a subset persists as memory cells, facilitating rapid and robust responses upon reexposure to the same antigen.

Hassall corpuscles—structures unique to the thymus—contribute to the maturation of thymocytes and the clearance of apoptotic cells. These epithelial structures play an essential role in lymphopoiesis.

Embryology

Originally derived from the ventral 3rd pharyngeal pouch, the thymus enlarges from embryogenesis through approximately 3 years of age and then begins to regress during puberty. During development, the organ descends from the 3rd pharyngeal pouch into the superior mediastinum, settling posterior to the manubrium (see Image. The Thymus in a Full-Term Fetus).[8] The thymus is prominent in infants and young children, gradually coalescing and undergoing replacement by adipose tissue in early adulthood. Involution is thought to result from rising androgen levels in the circulation during puberty.[9]

Blood Supply and Lymphatics

The blood supply to the thymus is complex and highly variable. Arterial supply most commonly arises from the inferior thyroid, internal thoracic, pericardiacophrenic, or anterior intercostal arteries. In rare cases, the organ receives branches from the middle thyroid artery. Laterally, branches of the internal mammary artery, referred to as the "lateral thymic arteries," supply the organ. These vessels are asymmetric and variable in number.[10] Posterior thymic arteries, which may originate from the brachiocephalic artery or the aorta, are infrequently observed. Accessory arteries are diverse and have been reported to arise from the thyrocervical trunk, subclavian artery, or superior thyroid artery.

Venous drainage is also variable but most often involves tributaries of the left brachiocephalic and internal thoracic veins. Thymic veins travel within the interlobular septa, enter the capsule, and exit via a venous plexus located on the posterior surface of the organ. These vessels then converge and typically drain each lobe separately.

Nerves

Sympathetic innervation of the thymus arises from the superior cervical and stellate ganglia. These fibers form a perivascular plexus that follows major blood vessels before entering the thymic capsule. Direct parasympathetic innervation of the thymus is not supported by current anatomical evidence.[11] Rodent studies have demonstrated that thymocytes respond to various neurochemical stimuli, including norepinephrine, dopamine, acetylcholine, neuropeptide Y, vasoactive intestinal peptide, calcitonin gene-related peptide, and substance P.[12]

Muscles

The thymus is located in the mediastinum, directly posterior to the manubrium. Nearby are the paired sternohyoid and sternothyroid muscles, which attach to the sternum and function to depress the hyoid bone. The thyrohyoid and sternocleidomastoid muscles lie in proximity to any ectopic thymic tissue or superior extensions of the organ. Inferiorly, the thymus lies anterior to the pericardium and the cardiac muscle.

Physiologic Variants

Anatomic variation in the number of lobes, size, and location of the thymus is common. The most frequent variant involves a cervical extension reaching the thyroid gland, identified in approximately 1/3 of children undergoing routine neck ultrasonography.[13] Ectopic thymic tissue may become displaced during embryologic descent from the 3rd pharyngeal pouch. In a large review of thymectomy cases in patients with myasthenia gravis, ectopic tissue was most often located in the anterior mediastinal fat (33.2%), followed by the pericardiophrenic angles (13.6%), aortopulmonary window (10.4%), and pretracheal fat (7.5%).[14]

Surgical Considerations

The thymus presents surgical challenges due to its considerable variability in size and arterial supply. Imaging also has limited utility, as the gland is often difficult to visualize and rarely offers surgeons meaningful preoperative insight. On standard chest radiographs, the thymus is typically obscured by the cardiac silhouette. The organ appears more clearly in infants and young children, where it has smooth borders. Ultrasonography is primarily used to evaluate thymic parenchyma, while computed tomography provides a more reliable assessment of the organ’s location, size, shape, and relationship to adjacent structures (see Image. Thymus on Contrast-Enhanced Computed Tomography).[15][16]

Ectopic thymic tissue may be mistaken for lymphadenopathy or neoplasm. Because clinical differentiation is often inconclusive, the benign nature of such masses is typically confirmed only after resection. Ectopic tissue can compress nearby structures, leading to swelling, impaired perfusion, discomfort, and in some cases, thyroid dysfunction. Surgical excision may be complicated by adherence to the carotid sheath and proximity to critical structures, including the pharyngeal muscles and the phrenic nerve.[17]

Clinical Significance

Insulin plays a critical role in supporting thymic growth. Along with growth hormone and insulin-like growth factor, insulin promotes lymphocyte development and is detectable within the medulla of the thymus.[18] Thymic function is impaired in type 1 diabetes, contributing to immunodeficiency in addition to the endocrine and metabolic complications of the disease. Insulin supplementation may help preserve thymic structure and support immune system maturation.

Thymic hyperactivity, most commonly due to hyperplasia, is frequently associated with myasthenia gravis. Other causes include thymic epithelial tumors, lymphomas, systemic lupus erythematosus, and hyperthyroidism.[19][20][21] Clinical manifestations may include pallor, lymphadenopathy, rhinorrhea, and tonsillitis. Reported treatments have included supplementation with vitamins A and D, calcium, and iodine, as well as modalities such as thalassotherapy, thymic radiotherapy, and heliotherapy.

Myasthenia gravis is an autoimmune disorder characterized by muscle weakness resulting from impaired neuromuscular transmission.[22] The thymus contributes to disease pathogenesis by generating antibodies that disrupt acetylcholine signaling at the motor endplate. Muscle fatigue with repeated contractions is a hallmark clinical feature that helps distinguish myasthenia gravis from Lambert-Eaton syndrome. Thymic hyperplasia is common in myasthenia gravis and is considered a diagnostic criterion, along with the presence of circulating antibodies against acetylcholine receptors and anti-muscarinic antibodies. Magnetic resonance imaging or computed tomography may be used to assess thymic size and morphology.[23]

Treatment of myasthenia gravis depends on disease severity. Management options include immunosuppressive agents, corticosteroids, and surgical thymectomy. In some cases, symptom control is achieved with pyridostigmine bromide, a cholinesterase inhibitor that prolongs acetylcholine activity at the synapse. When treating patients with myasthenia gravis, clinicians must consider the risk of medication-induced exacerbation, particularly during acute illness or in the presence of comorbid conditions.

In contrast, thymic atrophy or agenesis is observed in several congenital immunodeficiency disorders. DiGeorge syndrome involves failure of thymic development during embryogenesis, resulting in T-cell deficiency and recurrent infections.[24] In severe combined immunodeficiency, the thymus involutes early in childhood, and both T- and B-cell populations are deficient. Affected children are highly susceptible to life-threatening infections.[25]

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Disclosure: Kailey Remien declares no relevant financial relationships with ineligible companies.

Disclosure: Felix Jozsa declares no relevant financial relationships with ineligible companies.

Disclosure: Arif Jan declares no relevant financial relationships with ineligible companies.