Microenvironments in the normal thymus and the thymus in myasthenia gravis.

The disposition of epithelial cells and extracellular matrix, in the thymus of 8 cases of myasthenia gravis (MG) and in controls (over a wide age range) was studied. In the controls, the subcapsular epithelium was strongly Leu-7-positive in the fetus, negative in childhood, and positive again in adults. Another antibody, RFD4, also labeled the subcapsular epithelium in childhood and adults, but not fetal samples. The samples from MG cases showed the same staining pattern as adult control samples. The medullary epithelium was also RFD4+, and at all ages. The most striking changes in the advanced cases of MG were the unusual arrangement and hypertrophic appearance of medullary epithelial cell areas, separated by laminin-positive basement membranes from the alternating multiple bands of peripheral lymph-node-like areas. The latter had regions resembling the paracortex of lymph nodes as well as germinal centers (GCs). The T-cell zones contained heavy deposits of fibronectin. These T-cell zones were unique to the thymus in MG and were absent in the two normal thymic samples with isolated GCs. In MG the laminin-containing basement membrane, which separated the medullary epithelial and peripheral lymph-node-like areas, was fenestrated at circumscribed points closest to the GCs, thus apparently permitting communication among the medullary epithelium, the T-cell zones, the GCs and the associated antigen-presenting cells. Large numbers of interdigitating cells and some lymphocytes of cortical thymocyte phenotype were also found at these special sites, where opportunities for autosensitization may persist in MG.     

Phenotypic characterization of the thymus microenvironment study of the human thymus architecture

Phenotypic characterization of the human thymic microenvironment shows the heterogeneity of the epithelial component. Using monoclonal antibody L191, we define here a new antigen common to the flat epithelial cells lining up the thymic capsule and septum, stellate epithelial cells from the subcapsular area and the medulla (M), but lacking on stellate epithelial cells from the inner cortex. Thus, this cell population can be characterized by a series of antigens (TE-4 and P19--shared with HTLV--previously described by B. Haynes et al.) which reflect a common differentiation program--including neuroendocrine specialization--with remarkable differences in the expression of these antigens, occurring during ontogeny and after birth. Another Ab we obtained shows particularities in the cytoskeletal organization of this cell population. Finally the organization of the mesenchymal component was also investigated with a third, anticollagen, antibody. A striking observation we made, using these antibodies, was the relationship between the thymic septum and flat epithelial cells with medullary and Hassal's body (HB) epithelial cells: septae deeply penetrate the medulla so that flat epithelial cells come into direct contact with medullary epithelial cells; in addition, HB are in close contact with the deepest portion of the septae, often separated solely by a single stellate cell. This architectural organization might be related to the differentiation--regeneration process of the thymic epithelium.     

Histopathology of the thymus

The thymus is a primary lymphoid organ that manifests dynamic physiological changes as animals age in addition to being exquisitely sensitive to stress and toxic insult. It is typically the first lymphoid tissue to respond to immunotoxic xenobiotics, with the first change being loss of cortical lymphocytes by apoptosis. This is followed by removal of the apoptotic cellular debris and, in the absence of recovery, may lead to loss of the cortico-medullary demarcation and organ atrophy. Nonneoplastic proliferative changes include focal lymphoid hyperplasia and proliferation of medullary epithelial cells, often with formation of ribbons, cords, or tubules. Thymomas are relatively rare tumors that exhibit a wide spectrum of morphologic types but do not metastasize. Thymic lymphomas are common in some mouse strains and can become leukemic with hematogenous spread throughout the body.     

Tumors of the thymus

Tumours of the thymus include heterogenic group of benign and malignant organ-specific (thymomas and carcinoma) and organ-nonspecific (neuroendocrine, germinogenic tumours, lymphomas and others) neoplasms. Histologic classifications are now the most useful for the correlation with prognosis and clinical manifestations. It is obligatory to do verification of the progression stage.     

In search of the origin of the thymus: the thymus and GALT may be evolutionarily related

The thymus is the major primary immune tissue for the production of functional T lymphocytes in vertebrates. However, its evolutionary origin is unknown. It has recently been shown that the generation of local T cells also occurs in gut-associated lymphoid tissues (GALT). This suggests that the thymus and GALT have similar functions and that they might be evolutionarily related. We discuss the possibility that the thymus may have evolved from mucosa-associated lymphoid tissues (MALT) located in the gill region in early vertebrates. Various facts supporting this proposal are summarized.     

Surgical pathology of the thymus and mediastinum

The thymus is an anterior mediastinal lymphoid organ important for immunological self-tolerance that comprises epithelial, lymphocytic, histiocytic and stromal elements with characteristic histological arrangements. Its complex embryological development means that dysgenesis and embryological remnants may be seen and rarely lead to sequelae such as tumours. Thymic biopsy or thymectomy may be performed for diagnostic reasons, although thymectomy is more commonly performed as a treatment, usually for myaesthenia gravis or tumours. The major categories of thymic pathology include cysts, hyperplasia, thymomas, haematopoietic neoplasms, primary and secondary carcinomas, neuroendocrine tumours, germ cell tumours and soft tissue tumours.     

Tumours of the thymus and their nomenclature

Conclusion During the past two decades, substantial progress has been made in the understanding of the biology of the thymus gland and, therefore, in the pathology and clinical behaviour of thymic tumours (Levine and Rosai 1978; Janossy et al. 1980; CIBA Foundation Symposium No. 84 1981; Otto 1984; Müller-Hermelink 1986; Hofmann et al. 1989). Thymic tumors are classified according to their morphological features and presumed histogenesis. They include tumors arising from thymic epithelial cells (thymomas, thymic carcinomas), neuroendocrine cells (carcinoid tumours of the thymus, neuroectodermal carcinomas), lymphoid cells (malignant non-Hodgkin's lymphomas of T- and B-cell types and Hodgkin's disease), and adipose tissue (thymolipomas). All other tumours (myoid and histiocytic) and tumour-like lesions (cysts, hyperplasia) are extremely rare.