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Introduction: The thymus is located in the superior mediastinum and anterior part of the inferior mediastinum. It plays a crucial role in the development, differentiation, and clonal expansion of T lymphocytes. In forensic cases involving foetal death, accurate estimation of foetal age is essential. When the foetus is extensively damaged, other organs can be used to estimate age. The thymus, being retrosternal and well-protected, is easily accessible during dissection. Therefore, studying the gross features and histogenesis of the thymus can be helpful in estimating gestational age in cases of severely mutilated foetal specimens. Aim: To examine the morphological features and histogenesis of the thymus in aborted and stillborn foetuses from normal pregnancies. Materials and Methods: A pilot study was conducted using a cross-sectional design at the Department of Anatomy, BLDEDU's Shri BM Patil Medical College, Vijayapura, Karnataka, India, from May 2016 to April 2018. The dimensions and histogenesis of the thymus were studied in a total of 50 human foetal thymus specimens, collected from normal pregnancies across different gestational age groups ranging from 12 to 40 weeks. The specimens were obtained from the Department of Pathology and the Department of Obstetrics and Gynaecology. The dimensions and weight of the thymus were recorded during autopsy. Slides were prepared, stained with Haematoxylin and Eosin (H&E), and examined under a compound microscope. The histogenesis of the thymus was studied to observe its maturation. Results: Foetal weight increased from 134.6±58.3 g at 12 weeks to 1942±598 g at 40 weeks. The weight of the thymus ranged from 0.2 g at 12 weeks to 5.9 g at 40 weeks. Crown rump length varied from 10.7 cm to 29.9 cm. The length of the thymus measured between 0.5 cm and 3.3 cm, breadth between 0.4 cm and 2.3 cm, and height between 0.2 cm and 0.9 cm from 12 to 40 weeks of gestation. Microscopic features observed in the present study at different gestational ages included a well-formed thick capsule at 17 weeks, lobulation starting at 19 weeks, cortico-medullary differentiation beginning at 17 weeks, appearance of epithelial cells around 19 weeks, and initial appearance of Hassal's corpuscles at 17 weeks, with more numbers observed later on. Conclusion: The thymus can be used in forensic investigations to estimate the gestational age of mutilated foetuses. It exhibits varying features at different gestational ages, which can aid in thymectomy procedures. Additionally, these findings can be considered during prenatal imaging studies. [ABSTRACT FROM AUTHOR]

Recently, the effects of exposure to clothianidin (CLO) on the thymus and gut microbiota have become clear, but no report has examined its next-generation impacts. Pregnant C57BL/6N mice were administered a no-observed-adverse-effect-level dose of CLO until weaning. We examined CLO's effects on the gut microbiota and immune organs of dams and their 3- and 10-week-old male offspring. CLO administration led to several alterations of the top 30 bacterial genera in the gut microbiota in dams and 3-week-old mice. Compared to controls, 10-week-old mice had more thymic Hassall's corpuscles, and both dams and 10-week-old mice had fewer macrophages. These results suggest that fetal and lactational CLO exposure may affect the immune system and gut microbiota of the next generation. [ABSTRACT FROM AUTHOR]

While there is convincing evidence on the role of Aire-positive medullary thymic epithelial cells (mTEC) in the induction of central tolerance, the nature and function of post-Aire mTECs and Hassall’s corpuscles have remained enigmatic. Here we summarize the existing data on these late stages of mTEC differentiation with special focus on their potential to contribute to central tolerance induction by triggering the unique pro-inflammatory microenvironment in the thymus. In order to complement the existing evidence that has been obtained from mouse models, we performed proteomic analysis on microdissected samples from human thymic medullary areas at different differentiation stages. The analysis confirms that at the post-Aire stages, the mTECs lose their nuclei but maintain machinery required for translation and exocytosis and also upregulate proteins specific to keratinocyte differentiation and cornification. In addition, at the late stages of differentiation, the human mTECs display a distinct pro-inflammatory signature, including upregulation of the potent endogenous TLR4 agonist S100A8/S100A9. Collectively, the study suggests a novel mechanism by which the post-Aire mTECs and Hassall’s corpuscles contribute to the thymic microenvironment with potential cues on the induction of central tolerance.

While there is convincing evidence on the role of Aire-positive medullary thymic epithelial cells (mTEC) in the induction of central tolerance, the nature and function of post-Aire mTECs and Hassall's corpuscles have remained enigmatic. Here we summarize the existing data on these late stages of mTEC differentiation with special focus on their potential to contribute to central tolerance induction by triggering the unique pro-inflammatory microenvironment in the thymus. In order to complement the existing evidence that has been obtained from mouse models, we performed proteomic analysis on microdissected samples from human thymic medullary areas at different differentiation stages. The analysis confirms that at the post-Aire stages, the mTECs lose their nuclei but maintain machinery required for translation and exocytosis and also upregulate proteins specific to keratinocyte differentiation and cornification. In addition, at the late stages of differentiation, the human mTECs display a distinct pro-inflammatory signature, including upregulation of the potent endogenous TLR4 agonist S100A8/S100A9. Collectively, the study suggests a novel mechanism by which the post-Aire mTECs and Hassall's corpuscles contribute to the thymic microenvironment with potential cues on the induction of central tolerance. [ABSTRACT FROM AUTHOR]

The features of the thymic morphology in hens and ducks were studied. Samples were obtained from 3 adult birds of each species. They were studied by light microscopy using classical methods of morphological research. The tissue samples were fixed in 10% neutral buffered formalin and embedded in paraffin block and finally the sections were cut at 5-10 μm thickness using sliding microtome and stained with hematoxylin and eosin, according to Van Gizon and Weigert and impregnated with silver nitrate according to Kelemen. It was established that the thymus of birds was represented by isolated cervical parts, which, in the form of strands, were located under the skin on the lateral surfaces of the neck, along the trachea, along the course of the neurovascular bundle, and consisted of individual lobes. In hens 5 to 8 lobes were included in each thymus and extended from the 3-cervical vertebra to the start of the thoraco-abdominal cavity. Thymus of ducks consisted of 3-4 lobes and was located in the posterior third of the neck. Its cranial end was at the level of 10-11 cervical vertebrae, and caudal end reached 12 cervical vertebra. Individual lobes of duck's thymus had a greater absolute mass than the lobes of hen's thymus. They were also more separated from each other. Lobes of hen's and duck's thymus had a variety of shapes. Among them, there were mainly oval, convex-oval, beanshaped, rounded, flat and, sometimes, sickle-shaped. Morphofunctional units of the thymus were lobules, which consisted of a cortex and a medulla. In birds the medulla occupied a larger area than the cortex. In the medulla, there were Hassall's corpuscles, that were better developed in ducks. [ABSTRACT FROM AUTHOR]

Hassall's corpuscles (HCs) are characteristic components of the medulla of the mammalian thymus and thymoma with an abundance of HCs is even more rare, with only five cases having been reported in the literature, to the best of our knowledge. Furthermore, their morphology usually resembles World Health Organization (WHO) type B2 or B3 thymoma. The biological behavior appears indolent and is rarely associated with myasthenia gravis. However, whether it is a separate entity or a variant of organotypical thymoma WHO B2 or B3 remains to be elucidated. The present case report reports a type B2 thymoma with a large presence of HCs from a 58‑year‑old Chinese woman, and investigates its histopathological characteristics, immunological features and biological behavior. Notably, the present case appeared biologically more aggressive compared with the cases reported previously. The aim of describing this rare case of thymoma with an abundance of HCs is so that it can be recognized and classified by pathologists. [ABSTRACT FROM AUTHOR]

Hassall’s corpuscles are the most prominent structures in the human thymus. However, relatively few analyses have been performed to determine their function and cellular origins during development. In this study, we evaluated the cellular microenvironment of human thymic Hassall’s corpuscles using histochemistry, immunohistochemistry, and transmission electron microscopy. We examined 95 human thymic tissue samples, which were perioperatively obtained from children undergoing cardiac surgery. To characterize the complex cellular microenvironment of human thymic corpuscles, we used a panel of 14 different antibodies to identify discrete cell types. We also utilized various histochemical methods (PAS reaction, alcian blue staining, alkaline phosphatase and acid phosphatase activity staining, von Kossa staining of calcified particles) and transmission electron microscopy to visualize these structures. Considerable variation in the sizes, shapes, and numbers of Hassall’s corpuscles was observed, even amongst children of the same age. Inside the largest Hassall’s corpuscles, cystic dilatation with an accumulation of cellular debris was found. These morphological observations might be associated with disruptions in the formation, migration, or differentiation of cardiac neural crest cells, which are essential for heart and thymus development. Immunohistochemical staining and electron microscopy revealed that Hassall’s corpuscles resemble other types of stratified squamous epithelia. Most Hassall’s corpuscles are heterocellular, consisting of thymic epithelial cells, macrophages, interdigitating dendritic cells, myoid cells, and, occasionally, mast cells and lymphocytes. To explore the potential functions of Hassall’s corpuscles, we found that the concentrations of B-lymphocytes and BCL2-positive lymphocytes suggested a role in regulation of lymphopoiesis. We also found that these structures do not originate from the perivascular epithelium as previously proposed, nor could we identify blood or lymph endothelial cells in close proximity. This leaves the origins of Hassall’s corpuscles an open question. [ABSTRACT FROM AUTHOR]

A comparative morphological study on Hassall's corpuscles of different maturity in vertebrate animals and humans with consideration of the age was carried out by light microscopy. It was found that the number and size of Hassall's corpuscles of different maturity depend on age, as well as the environmental conditions. Conclusions on the functional role of Hassall's corpuscles were drawn based on the present study. [ABSTRACT FROM AUTHOR]

Sodium valproate (VPA) was shown to inhibit cell growth mechanisms such as cell cycle arrest, proliferation suppression, increase of apoptosis. Many aspects of the contribution of the VPA pharmacological mechanisms and their significance in gender-related processes have not been investigated. In our study, we have tested hypothesis that the influence of VPA on thymus weight and structure might be gender-related. The thymus of Wistar rats of both genders aged 8 weeks was investigated in the following groups ( n = 6 each): controls, treated with VPA, castrated male and female treated with VPA, and the castrated control of both genders. The thymus weight, structural changes and area of cortical and medullar parts of the gland in slides stained with hematoxylin and eosin and immunohistochemically were assessed. A comparison of thymus weight of castrated male and of castrated VPA-treated male rats showed a significant thymus weight loss after VPA treatment (0.66 ± 0.04 g vs. 0.43 ± 0.03 g, p < 0.05). The treatment with VPA caused an about 6-fold (0.39 ± 0.12 vs. 0.07 ± 0.03) increase of Hassall‘s corpuscles (HCs) numbers per 1 mm 2 in male and more than 4-fold increase (0.46 ± 0.07 vs. 0.10 ± 0.04) in female rats. In castrated males and females, the HCs number was also increased, but this increase was statistically significant only in male animals vs. controls (0.46 ± 0.10 vs. 0.07 ± 0.03, p < 0.001 in males; 0.29 ± 0.13 vs. 0.10 ± 0.04, p > 0.05 in females). When castrated male and female rats were treated with VPA, further increase of HC numbers was found. In our study, VPA has inhibited the proliferative capacity of thymocytes by diminishing the thymus weight and inducing a differentiation of thymic medullar epithelial cells into HCs. The diminishing of the gl. thymus weight under the influence of VPA was significant in castrated male rats. The number of HCs increased in animals of both genders under the influence of VPA. Gender differences in HCs development were noted in castrated animals. [ABSTRACT FROM AUTHOR]

Background: Hassall's corpuscles (HC) are commonly used as diagnostic features for identifying human thymus and are still present in thymuses undergoing fatty degeneration in young adults. However, few studies have been performed on human fetuses. Aim: A cross-sectional study was done, to study the morphology of HC in human fetuses. Materials and Methods: Twenty-eight thymuses were collected from fetuses of gestational age ranging from 11 to 40 weeks. Thymuses were processed by paraffin embedding methods and hematoxylin and eosin staining. Results: The size of HC varied from very small (100 microns) to very large corpuscles (> 900 microns). A high level of polymorphism was also observed, from round to unusual or odd shapes corpuscles. The degenerated reticulo-epithelial cells represented the starting point in HC formation. The growth of HC was rapid, especially near 28 weeks, and the level of HC polymorphism was significantly greater after 28 weeks of gestation. In advanced stages of gestation, the increase in size of some corpuscles reduced the spaces between them, and some patterns strongly supported the hypothesis that some HC had fused in a single and larger corpuscle. Conclusion: The rapid rise in number and size of HC around 28 weeks of gestation would fit with their role in the negative selection process of thymocytes. [ABSTRACT FROM AUTHOR]

The anatomy, histology and ultrastructure of the thymus of a dipnoan, the Australian lungfish, Neoceratodus forsteri, was studied by light and transmission electron microscopy. The thymic tissue showed clear demarcation into a cortex and medulla with ample vascularization. Large cells including foamy and giant multinucleated cells with periodic acid Schiff/Alcian blue positive staining properties were localized mainly in the medulla. The major cellular components were epithelial cells and lymphoid cells. The epithelial cells were classified by location and ultrastructure into six sub-populations: capsular cells, cortical and medullary reticular cells, perivascular endothelial cells, intermediate cells, nurse-like cells and Hassall-like corpuscles. Myoid cells were found mainly in the cortico-medullary boundary and medulla. Macrophages and secretory-like cells were also present. These findings will provide a base of knowledge about the cellular immune system of lungfish. [ABSTRACT FROM AUTHOR]

We characterized herein the microarchitecture of the equine thymus along with post-natal development (6 months→18 years). Thymuses showed an involutional process, beginning before the puberty and defined by five histological grades, which consider the progressive cortical thymocyte depletion, shrinkage and rearrangement of the epithelial network and increase in extracellular matrix (ECM).A second feature of the equine thymus was the presence of eosinopoiesis, erythropoiesis, mastocytopoiesis and plasmacytogenesis. Additionally, lymphatic vessels, full of lymphocytes, were particularly prominent.Distribution of ECM proteins was heterogeneous, being denser in the medulla, as well as basement membranes of capsule, septa and perivascular spaces, thus similar to the patterns seen in other mammals. In vitro, horse thymic nurse cells produce ECM proteins, which are relevant in thymocyte/epithelial cell interactions.In conclusion, the equine thymus presents morphological and involutional characteristics similar to other mammals, exhibiting particular features, as prominent non-lymphoid hematopoiesis and lymphatic vessels. [Copyright &y& Elsevier]

Summary: Tight junctions (TJs), hallmark structures of one-layered epithelia and of endothelia, are of central biological importance as intramembranous “fences” and as hydrophobic “barriers” between lumina represented by liquid- or gas-filled spaces on the one hand and the mesenchymal space on the other. They have long been thought to be absent from stratified epithelia. Recently, however, constitutive TJ proteins and TJ-related structures have also been identified in squamous stratified epithelia, including the epidermis, where they occur in special positions, most prominently in the uppermost living epidermal cell layer, the stratum granulosum. Much to our surprise, however, we have now also discovered several major TJ proteins (claudins 1 and 4, occludin, cingulin, symplekin, protein ZO-1) and TJ-related structures in specific positions of formations of epithelium-derived tissues that lack any lumen and do not border on luminal or body surfaces. Using immunohistochemistry and electron microscopy we have localized TJ proteins and structures in peripheral cells of the Hassall''s corpuscles of human and bovine thymi as well as in specific central formations of tumor nests in squamous cell carcinomas, including the so-called “horn pearls”. Such structures have even been found in carcinoma metastases. In carcinomas, they often seem to separate certain tumor regions from others or from stroma. The structural significance and the possible functional relevance of the locally restricted synthesis of TJ proteins and of the formations of TJ-related structures are discussed. It is proposed to include the determination of the presence or absence of such proteins and structures in the diagnostic program of tumor pathology. [Copyright &y& Elsevier]

Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, plays an important role in various physiological functions including T cell activation. This enzyme is a target molecule for the immunosuppressants, cyclosporin A and FK506. In the present study, we investigated immunohistochemical localization of calcineurin and FKBP12, an FK506-binding protein, in human thymus and epidermis. The catalytic subunit (calcineurin A) of calcineurin was abundantly expressed in Hassall's corpuscles which were localized in the thymic medulla and represented the terminal stages of thymic medullary epithelium. The regulatory subunit (calcineurin B) of calcineurin was also expressed in high amounts in Hassall's corpuscles. In the epidermis, which shows similarities to Hassall's corpuscles, both subunits were also abundantly expressed, and their expression increased with the differentiation of keratinocytes. FKBP12 was observed to be expressed abundantly, both in Hassall's corpuscles and the entire epidermis. These findings suggest that the differentiated forms of the two cell types, which are the thymic medullary epithelial cell and the keratinocyte, are the target for pharmacological actions of FK506. [ABSTRACT FROM AUTHOR]

The janus kinases (JAK) and signal transducers and activators of transcription (STAT) pathway has been shown to play a key role in cytokine-mediated signal transduction, and to regulate growth, differentiation, and death of both normal and transformed cells. In the present study, we investigated immunohistochemically the distribution of the JAK-STAT pathway in the human thymus. Various elements of the pathway were abundantly expressed in Hassall's corpuscles, located in the thymus medulla and representing terminal stages of the thymic medullary epithelium. Furthermore, the elements of the pathway showed distinct localization in Hassall's corpuscles. JAK1, JAK2, and TYK2 were expressed in high amounts in the entirety of Hassall's corpuscles, whereas JAK3 was in the outer layer. STAT1, STAT2, and STAT6 were abundantly expressed in the entire Hassall's corpuscles, whereas STAT5 was in the outer layer. These findings strongly suggest that the JAK-STAT pathway may play a role in thymic medullary epithelial maturation. [ABSTRACT FROM AUTHOR]

The dissolution of Hassall's corpuscles by macrophages has been demonstrated in the sheep thymus. The findings indicate that enlarged Hassall's corpuscles are rapidly broken down by macrophages at the end of gestation or immediately after birth and replaced by newly formed corpuscles, and that these cyclic changes in Hassall's corpuscles persist, under normal physiological conditions, throughout life. [ABSTRACT FROM AUTHOR]