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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.

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.

Fresh thymus tissue from 31 infants and from three adults was examined by indirect immunofluorescenc-e using antisera from active cases of pemphigus vulgaris. This sera contained specific antibodies for squamous epithelial intercellular substance. Fluorescent staining was seen in Hassall's corpuscles in all cases. This finding is immunological support confirming the morphologic, ultrastructural and histochemical evidence that these bodies are squamous epithelial in nature.

Hassall's corpuscles are regular structures in the medulla of the normal thymus and in non-neoplastic thymic conditions, e.g. in multilocular thymic cysts. In thymomas, however, they are inconsistently found, and are believed to indicate medullary differentiation of WHO type B1-3 thymomas. We present five organotypical thymomas resembling WHO type B2 and B3 thymomas, but with an abundance of Hassall's corpuscles. We wonder whether this exceedingly rare observation might herald a distinct entity. Four tumors were asymptomatic, incidental findings and of low Masaoka stage (I or II) [20] . One patient suffered from myasthenia gravis which disappeared upon surgical removal of the thymus, while all other patients had no concomitant autoimmune disease. Two patients had a relapse-free follow-up of 12 and 2 years, respectively, upon curative surgery, and another tumor was an autopsy finding; follow-up data of two more recent cases was not yet available. The neoplastic epithelium other than Hassall's corpuscles was arranged either in a cortical type B2 pattern or in type B3 solid cords. In all examples, there was cyst formation, inflammatory reaction and repair, indicative of a long-standing condition. Immature T cells were present in all instances. “Corpuscular thymomas” morphologically resemble WHO type B2 and B3 thymomas, but appear biologically indolent and are rarely associated with myasthenia gravis. Whether they qualify for a separate entity has to be proven by larger series, including genetic studies.

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.

Twenty-eight healthy fetuses between 11-40 weeks were selected to study the histological and morphological growth of Hassall's corpuscles. We were found that Hassall's corpuscle appreciated earliest at 14th weeks and seen as two to three cells nest in area having degenerated tissues. Later, as the age of fetus advanced the size and shape of Hassall's corpuscles rapidly increasing by additions of more apoptotic cells and aggregation of reticulo-epithelial cells. Near 28th week these corpuscles showed spurt of growth and initially corpuscles were distant from each other, they started to come together e.g. reducing inter-corpuscular distance. In late stage (near term) these corpuscles fused together giving variable shapes and sizes.

The aim of this study is to assess Hassall’s corpuscles in lamb. Thymus samples were harvested from 10 lambs (3 months old) and histologically processed. From the harvested samples, 5 I¼m seriated sections were made, stained with Goldner’s trichrome method and examined under light microscope. In the medulla of the thymic lobules there are on average 7-8 highly polymorphic Hassall’s corpuscles. The majority of the corpuscles (80%) have a diameter between 5 and 50 I¼m, 15% between 50 and 100 I¼m and only 5% have a diameter of over 100 I¼m. Only 20-25% among them have a typical „onion-like” structure, 40-45% present different keratinization degrees and 3-5% are cavitary corpuscles, containing degenerated cell fragments. Hassall’s corpuscles in lamb are numerous and highly polymorphic.

The thymus is implicated as an organ that contributes to autoimmunity in myasthenia gravis (MG) patients. Hassall's corpuscles (HCs) are assumed to represent the terminally differentiated stage of medullary thymic epithelial cells (mTECs). By using multicolor immunohistofluorescence analysis, we examined HCs in thymuses that were therapeutically excised from MG (+) and MG (-) patients. We found that the number of HCs per unit area of the thymic medulla was significantly elevated in the thymuses of MG (+) patients with thymic hyperplasia. CCL21 expression increased in the hyperplastic MG thymuses. We speculate that the altered differentiation of mTECs is associated with the thymic hyperplasia and the onset of MG.

Human immunodeficiency virus type 1 (HIV-1) was immunohistochemically and ultrastructurally localized in human thymus implants in SCID-hu mice 3 weeks after intravenous (i.v.) inoculation of the virus. A viral antigen (gp120) was predominantly distributed in and around the epithelial cells in Hassall's corpuscles as demonstrated by fluorescence immunohistochemistry. Occasional solitary round cells positive for the viral antigen but negative for cytokeratin were detected in the perivascular areas. Ultrastructural examinations clearly revealed a number of mature viral particles in the intercellular spaces of the Hassall's corpuscles. Thus the present study indicates the possibility that thymic epithelial cells in Hassall's corpuscles act as a target and/or reservoir in an early stage of HIV infection.

We encountered three cases of the intra-thyroidal ectopic thymus at autopsy and also performed three autopsy cases consisted of mothers and children, and children with severe stress. The morphological and immune histochemical characteristics of the Hassall’s corpuscles were examined in those in ectopic and normal positioned thymus, and in the thymuses obtained from mothers and children, and children with severe stress. The Hassall’s corpuscles obtained from ectopic and normal positioned thymus showed resemble morphology and stainability with antibodies. These results indicate the Hassall’s corpuscles in the intra-thyroidal ectopic thymuses also possess the biological significance.

International audience; 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.

A highly malignant case of intrathyroidal thymic carcinoma showing morphological and biochemical evidence identical with mediastinal thymoma is presented. A 32-year-old female, who had previously undergone total colectomy with ileo-proctostomy due to familial adenomatous polypnosis, was operated on for a tumor (3.4 x 4.5 cm) originating from the left thyroid lobe. A minute focus (diam. 0.8 cm) of papillary adenocarcinoma also existed in the upper pole of the right lobe. The main tumor was morphologically an epithelial thymoma with scanty lymphocyte intermixing and showed medullary differentiation with apparent Hassall's corpuscles. Mitosis was frequent and numerous tumor thrombi were in the subcapsular veins. Five months after the total thyroidectomy and lymph node dissection, a subcutaneous recurrence of the tumour (diam. 2.3 cm) appeared in the anterior cervical region. The cystic contents of the recurrent tumor revealed a high titer of thymosin alpha 1-Other organs, including thymus, lungs, and adrenals, had all been free of neoplastic changes clinically and radiologically for 5 months after her first admission until the local tumor recurrence.

General and histochemical observations of the thymus were carried out in guinea pigs after injection of cyclophosphamide (280 mg/kg). Acute involution of the thymus induced by cyclophosphamide was accompanied by marked enlargement of Hassall's corpuscles in the first week after injection. However, the markedly enlarged Hassall's corpuscles disappeared entirely by the fourth week. Large cells characterized by pale nuclei with one or two prominent nucleoli became aggregated in the enlarged Hassall's corpuscles by the second week. Their cytoplasm frequently was foamy or vesicular in appearance. Histochemical observations revealed strong activities of nonspecific esterase, acid phosphatase and beta-glucuronidase in these cells. Staining for these lysosomal hydrolytic enzymes was evident not only intracellularly but also extracellularly, indicating the dissolution of Hassall's corpuscles by intensive extracellular enzyme release.

A 7-year-old leukemic girl developed pancytopenia following chemotherapy and was given several transfusions of nonirradiated blood. Within 2 weeks she developed a maculopapular rash, fever, abnormal liver function, diarrhea, and wasting. She became septic and died 6 weeks later. Transfusion-associated graft-versus-host disease (GVHD) was suspected clinically. At autopsy, changes diagnostic of GVHD were present in the skin and liver. The remarkable feature of the case was the histopathology of the thymus, which was morphologically "dysplastic," i.e., minute, lymphoid depleted, devoid of a corticomedullary demarcation, and completely lacking in Hassall's corpuscles. These changes were virtually identical to those seen in the thymus of children with severe combined immunodeficiency disease (SCID). There was no evidence of preexisting immune deficiency. There is compelling experimental evidence that GVHD can produce changes in the thymus that are identical to those of "thymic dysplasia." These observations have led to the hypothesis that immunodeficiency associated with GVHD may stem, in part, from injury to thymic epithelium resulting in defective T cell maturation. As a corollary of this hypothesis, it has been suggested that the pathogenesis of some forms of SCID may involve GVHD-associated injury to the thymus by a maternal allograft acquired in utero. This report further documents thymic pathology in human GVHD and discusses these changes in the light of these ideas.

Morphological changes in Hassall's corpuscles were studied in guinea pigs during regeneration of the thymus, after local and general x-irradiation. The structural changes in the cells i.e. swelling, extrusion of chromatin droplets from the nucleus, vacuolization of the cytoplasm, cornification, and other signs, represented an ordered reconstruction of the stratified epithelium. They were destructive in character, and should not be regarded as representing a secretory process.

1. Regeneration of a thymus transplant is characterized by hypertrophy and hyperplasia of the reticulum cells, leading to the formation of small and large atypical Hassall bodies during the early stages. 2. Regeneration is usually complete by the 3rd week, when the newly formed lobules show differentiation into cortical and medullary zones, and typical Hassall bodies appear. 3. Typical Hassall's corpuscles are also derived from the reticulum epithelial cells. 4. These corpuscles have no function, being aggregates of spent reticulum cells. 5. The thymus reticulum cells are actively phagocytic, and react rapidly when noxious influences are exerted on the gland.

The results indicated that i.v. injection of fresh BCG induced in the guinea-pig thymus a transient increase of lymphocyte mitosis associated with an epithelial hyperplasia in the cortex on day 10. Changes in the medulla were more obvious on day 15. The hyperplasia of Hassall's corpuscles and epithelial cells in the medulla reached its maximum level at a time when many lymphocyte masses appeared in the splenic red pulp and in the T area of the spleen. Evidence suggesting an active secretory function in their external cells was recorded. These findings were consistent with the hypothesis that BCG produces an increase of new lymphocytes input into the T lymphocyte cycle.

Hassall's corpuscles represent a subset of medullary thymic epithelial cells whose origin and function within the thymus still remain largely unknown. The present study shows that Hassall's corpuscles can be defined by their intracellular content in specific keratin subunits. Two monoclonal anti-keratin antibodies were used: KL1, directed to high molecular weight keratins, and KL4, specific for high and medium molecular weight polypeptides. In vivo, KL1 exclusively binds to Hassall's corpuscles of five mammalian species including mouse, rat, guinea-pig, rabbit and pig. Thus KL1 appears as an exclusive marker of Hassall's corpuscles in a large number of mammals. In vitro, thymic epithelial cells gave rise in certain species to Hassall's corpuscles. In contrast to its in vivo reactivity, KL1 never labelled Hassall's corpuscles developed in vitro. These data strongly support the following conclusions: (1) Hassall's corpuscles derive from medullary epithelial cells; (2) they represent advanced stages of thymic epithelial maturation; (3) thymic epithelial cell differentiation is impaired in vitro. Furthermore, this study provides additional evidence that thymic epithelium heterogeneity reflects different stages in epithelial maturation.

In the monolayer of an established epithelial cell line from the rat thymus, IT-26R21, characteristic cell aggregates quite similar to Hassall's corpuscles were formed. These aggregates were examined by light and electron microscopy, and immunohistochemically. Their interpretation as Hassall's corpuscles is based n the following observations: (1) The aggregates are formed in the monolayer of cells that greatly resemble medullary epithelial cells of the thymus. (2) They consist of flattened epithelial cells in a concentric pattern with one or ore degenerating cells in the center. (3) Loss of microvilli suggests that these cells are keratinizing. (4) The aggregates show strongly positive reactions in immunofluorescent staining with antikeratin and antiprekeratin. When Hassall's corpuscles increase in size, cellular proliferation is somewhat suppressed. Both in vivo and in vitro, they may be interpreted as an expression of a changing growth pattern in confined spaces and thus seem to have little immunological function.

The Hassall’s corpuscles of man and other mammals have been deeply stained by a histochemical method that demonstrates bound histidine. We have employed a polyclonal anti-filaggrin antibody on thymus sections to verify whether this positivity was due to filaggrin and profilaggrin, its polymeric precursor, like in the skin. The immunohistochemical reaction has confirmed the presence of filaggrin in human Hassall’s corpuscles as well as in other species. Different patterns have been obtained for corpuscles at different developmental stages.

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.

The germinal centers of lymphatic tissue, the Hassall’s corpuscle of the thymus, and the tubercle of epithelioid granulation tissue are three unique histologic entities that may have a common biological significance. All three structures morphologically show a superficial similarity, and we sometimes refer to atrophic germinal centers depleted of their parenchymal cells as pseudotubercles or pseudo-Hassall’s corpuscles [1, 2]. Separating the structures from the point of view of diagnostic pathology has not been a major issue [2]. Shared functional properties, however, would be of considerable interest and would explain the anatomical similarity.

HASSALI's corpuscles in the guinea-pig thymus take up carbon1,2 and Evans blue3,4 from the circulation. In man, these corpuscles contain gamma globulin5–7. We therefore studied the localization in the thymus of albumin and globulin injected into the circulation by autoradiography and compared it with that in other lymphoid tissues.

Thirteen human thymuses and one thymoma were morphologically and immunohistologically investigated to define the histogenesis of Hassall's corpuscles (HCs). The following monoclonal antibodies: antisquamous cytokeratin on paraffin sections and TE-4 and TE-8 on frozen sections, were used to show the distribution of the epithelial components; PAL-E on frozen and anti-CD31 and anti-CD34 on paraffin sections detected the endothelial cell distribution. In the thymoma, epithelial onion-like structures, looking like true HCs, were found to originate from the perivascular epithelium lining dilatated spaces and some of them partially obliterated the space where the blood capillary showed thickened wall and endothelial regressive changes. Antisquamous cytokeratin stained: (1) in the thymus: subcapsular, medullary, and HC epithelial cells; (2) in the thymoma: epithelial cells lining the perivascular spaces and forming HCs. TE-4 stained: (1) in the thymus: the subcapsular and medullary epithelium; (2) in the thymoma: the epithelium lining the perivascular spaces and epithelial cells forming HCs. TE-8 stained: (1) in the thymus: HCs only; (2) in the thymoma: HCs and perivascular epithelial cells. PAL-E, CD31, and CD34, which specifically react with endothelial cells, stained remnants of capillary structures in the core of some HCs. The results indicate that: (1) corpuscular structures in thymoma originate from perivascular epithelium; (2) thymus medullary epithelial cells stained by cytokeratin and TE-4 correspond to perivascular epithelial cells whose staining is well documented in thymoma; (3) the subcapsular-perivascular epithelium and HCs represent different steps of differentiation of a single ectodermal cell lineage; (4) the PAL-E-, CD31-, and CD34-positive reaction in the core of some HCs suggests that the perivascular epithelium would be stimulated to transform into HCs as a consequence of endothelial changes with fragmentation of the capillary included in the perivascular space.