A clinicopathological study of Kimura's disease and epithelioid hemangioma

The clinicopathological features of 9 cases of Kimura's disease and 5 cases of epithelioid hemangioma(EH) were reviewed. Patients with Kimura's disease presented with multiple or solitary large tumors occurring in the thigh, arms as well as parotid gland. Histologically, the lesions were characterized by numerous lymphoid follicles with proliferation of post-capillary venules lined by plump endothelium and a marked eosinophilic infiltration. Patients with EH were older than those with Kimura's disease and presented papular nodular lesions, less than 1 cm in size. Microscopically, there was proliferation of blood vessels lined by epithelioid endothelium with infiltration by lymphocytes and eosinophils. Although there may occasionally be clinicopathological overlap between Kimura's disease and EH, we consider that these two disorders can be recognized as separate entities.     

Allergic granulomatosis secondary to a limited form of Churg-Strauss syndrome.

Allergic granulomatosis is a disorder of obscure etiology characterized by infiltration of lymph nodes with histiocytic granulomas and eosinophils. In this report, we describe a case of allergic granulomatosis that is consistent with Churg-Strauss disease limited to lymph nodes. The histologic findings of this patient's lymph nodes demonstrated eosinophilic abscesses and ring-shaped necrotizing and nonnecrotizing granulomas surrounding hyperplastic germinal centers. We report herein a rare type of reactive lymphadenopathy and present its histologic, immunohistochemical, and flow cytometric findings, which may allow its distinction from other lymphadenopathies.     

Hepatic pathology of chronic granulomatous disease of childhood.

We reviewed the hepatic pathology of seven cases of chronic granulomatous disease of childhood. All patients were male, with an age range of 5 to 41 years. Hepatic biopsy with drainage or wedge resection was performed in five cases to remove abscesses. Autopsy was performed in three cases. Presentation was typical of infection (fever, leukocytosis) with an elevated serum alkaline phosphatase level. Histologically, the most consistent feature was the presence of foamy macrophages that contained a finely granular golden brown pigment, seen in all seven cases. These were present as small collections predominantly in the portal tracts but were also found in the lobules. Palisading granulomas with central necrosis and associated giant cells were seen in four cases, one of which also had occasional lobular epithelioid granulomas. One case showed hyalinized portal and lobular granulomas. Four cases that showed palisading granulomas cultured positive for Staphylococcus aureus. One case cultured Pseudomonas cepacia, and one case cultured Streptococcus intermedius. Although palisading granulomas are typical of chronic granulomatous disease, they are not seen in all cases. These granulomas are similar to granulomas that are seen with Candida and other fungal infections and therefore are not specific for chronic granulomatous disease of childhood. The pigmented macrophages appear to be a consequence of the primary defect of the disease and are not secondary to infection and associated inflammation.     

Eosinophilic myositis due to Sarcocystis hominis in a beef cow

A case of eosinophilic myositis (EM) in an 8-year-old beef cow was investigated. The animal originated from a herd in which a high incidence of the disease had been observed in slaughtered adult females over a period of 2 years. Histologically, the lesions in the muscles were characterized as granulomas with a central core of degenerate eosinophils and remnants of necrotic muscle fibres, surrounded by a rim of epithelioid cells and fibrous tissue with an infiltrate consisting predominantly of eosinophils radiating outwards. Degenerate sarcocysts with a thick (7-9 microm) wall were present in the suppurative centre of most lesions. Intact sarcocysts with similar morphology were present in adjacent muscle fibres but without an associated inflammatory reaction. By transmission electron microscopy the sarcocysts were identified as Sarcocystis hominis, based on the morphology of villar protrusions of the sarcocyst wall, which were broad-based and cylindrical, with a blunt distal end, and contained numerous long microfilaments. Circumstantial evidence indicated a human source of infection, human faecal material having been spread on the pasture grazed by the cattle. The findings supported a causal relationship between S. hominis infection and EM in cattle.     

超声诊断木村病的临床价值

目的 探讨超声诊断木村病的临床价值。方法 回顾性分析2009年7月~2017年1月经我院穿刺活检或手术病理证实的22例木村病患者临床资料,分析其临床表现、超声声像图特点及病理学表现。结果 22例患者中,17例为男性。35个病灶中,29个位于头颈部,4个位于上臂,1个位于腹股沟,1个位于腋窝。16例多发,6例单发。17例表现为低回声,3例为稍高回声,2例为混合回声。7例患者内病灶血流较丰富为Ⅱ~Ⅲ级,4例血流为Ⅲ,3例血流为Ⅱ,6例血流为Ⅰ级,1例血流为0级,1例血流为Ⅰ~Ⅱ级。血常规检查中,6例患者白细胞增高, 16例患者在正常范围。17例患者嗜酸性粒细胞及嗜酸性粒细胞绝对值计数增加。10例行血清IgE检查,血清IgE升高9例。各部位病灶主体及淋巴结镜下病变呈分叶状,可见增生的淋巴组织,淋巴组织内可见淋巴滤泡结构,生发中心及套区结构清楚,滤泡间区淋巴细胞间散在分布大量嗜酸性粒细胞,小血管增生明显,但未见上皮样血管内皮增生,嗜酸性粒细胞局部呈嗜酸性脓肿样改变。结论 根据木村病的超声特有表现,多发于男性,病程较长,超声于头颈部皮下软组织内发现淋巴结肿大或边界不清的“斑块状”团块,血供较丰富,实验室检查外周血嗜酸性粒细胞增多,血清IgE升高,结合病史和实验室检查有助于木村病的提示诊断和鉴别诊断,并利用超声检查重复性好等优势随时观察病情变化及临床治疗效果。     

Granulomatous inflammation in normal and athymic mice infected with schistosoma mansoni: an ultrastructural study.

Inflammatory cell types and their interrelationships were studied in hepatic schistosome egg granulomas by correlated light and electron microscopy in thymus-intact and athymic mice. Intact animals developed large granulomas composed of phagocytes, stimulated macrophages, epithelioid cells, eosinophils and mast cells. The lesions peaked in size between 10--14 weeks after infection and tended to heal after 16 weeks. In athymic mice only phagocytes, stimulated macrophages and possible epithelioid cells appeared in the granulomas which were much smaller and less well organised than in intact mice. Virtually no eosinophils or mast cells entered the granulomas. These findings support the idea that development of granulomatous inflammation per se is not determined by CMI, but T cell co-operation seems to be required for its full expression in schistosomiasis. Since CMI closely regulates ingress of eosinophils and mast cells into the granuloma, the nature of T cell co-operation probably occurs at several levels in this complex infectious granuloma.     

Immunohistological findings of suppurative granulomas of Yersinia enterocolitica appendicitis: a report of two cases

We report on the histopathologic and immunohistologic findings of two cases of suppurative granulomatous appendicitis of Yersinia enterocolitica (Y. ent.). Using formalin-fixed, paraffin-embedded materials, polymerase chain reaction revealed Y. ent. in both cases. Histologically, the epithelioid cell granulomas (EPGs) were transmural in both cases. The EPGs were predominantly nonsuppurative, and were surrounded by a lymphoid cuff composed of small lymphocytes. A portion of EPGs contained suppuration of the centers of the granulomas (central microabscesses). The EPGs were composed of numerous histiocytes with or without epithelioid cell features, along with scattered small T-lymphocytes and plasmacytoid monocytes. None of the EPGs contained monocytoid B-cells. Immunohistochemical study demonstrated that EPGs were usually surrounded by surface IgM/D+ small mantle zone lymphocytes. Moreover, CNA.42 immunostaining occasionally demonstrated residual follicular dendritic cells in the center of the EPGs. The overall histomorphologic and immunohistochemical findings demonstrated that the EPGs with Y. ent. are of the B-cell negative hypersensitivity type and occur in reactive germinal centers. In one case, regional lymph nodes contained EPGs showing the same histologic and immunohistologic findings as those of the appendix. The present study indicates that among abscesses forming epithelioid granulomatous lesions, EPGs with Y. ent. were B-cell negative granulomas, and it demonstrates histopathologic and immunohistochemical findings different from those of cat scratch disease and lymphogranuloma venerum, which contain numerous monocytoid B-cells.     

Effects of dexamethasone on apoptosis of eosinophils infiltrated into bronchoalveolar lavage fluid after Sephadex bead treatment in rat]

Eosinophilic inflammation of the airways is a key characteristic of asthma. Glucocorticoids can suppress the inflammatory response in part by promotion of eosinophilic apoptosis. We investigated the effects of glucocorticoids on leukocyte infiltration and apoptotic resolution of eosinophils and neutrophils in Sephadex-treated rat lung. Sephadex beads were injected intravenously, followed 24 h later by i.p. administration of dexamethasone (DEX, 0.1 mg/kg) or its vehicle. At 24 h post-DEX treatment, the bronchoalveolar lavage fluid (BALF) was collected. Differential leukocyte counts and the numbers of apoptotic eosinophils and neutrophils, and macrophages with engulfed eosinophils or neutrophils in BALF were determined microscopically from Diff-Quik stained cytospin preparations. Sephadex beads markedly increased cell counts of eosinophils and neutrophils in BALF. Compared with a vehicle-treated group, the DEX treatment significantly decreased the number of eosinophils, but not neutrophils, in BALF. Dexamethasone in BALF also significantly increased eosinophilic apoptosis and engulfment of apoptotic eosinophils by macrophages, but had no effect on neutrophilic apoptosis and engulfment of apoptotic neutrophils by macrophages. These results suggest that the increased clearance of eosinophils from airways by glucocorticoids may be partly due to the promotion of eosinophilic apoptosis.     

Macrophage populations in L-cysteine-induced rat sperm granulomas

Histopathologically, sperm granulomas consist of a central mass of degenerating spermatozoa surrounded by many epithelioid macrophages and lymphocytes. Using monoclonal antibodies (ED1, ED2, and OX6), the authors investigated immunohistochemically the participation of different macrophage populations in epididymal sperm granulomas induced in pubertal rats by repeated injection of L-cysteine. Monocyte-like and epithelioid macrophages expressed the ED1 antigen found on activated lysosomal membranes in rat blood monocytes and exudate macrophages, but did not express the ED2 antigen found on the membrane antigens of rat resident macrophages. Cells expressing MHC class II antigens (as detected by the OX6 antibody) were present in the granulomas in moderate numbers, particularly in the early stages. Ultrastructurally, fragmented spermatozoa were observed in the cytoplasm of epithelioid macrophages. These findings suggest that macrophages appearing in rat sperm granulomas originate mainly from blood monocytes, and that they have a high phagocytic activity and a potential for antigen presentation.     

A method for the detection of eosinophilic granulocytes in colonoscopic biopsies from IBD patients

Eosinophilic granulocytes were found to be autofluorescent when Giemsa-stained sections were stimulated with indirect light fluorescence (ILF). The frequency of autofluorescent eosinophils was assessed in areas with diffuse and focal inflammation in 76 consecutive colonoscopic biopsies from patients with inflammatory bowel disease (IBD), Crohn's disease (CD = 32), ulcerative colitis (UC = 30), and collagenous colitis (CC = 7). All IBD cases had moderate to severe pancolitis. In areas with diffuse inflammation, severe eosinophilia was recorded in 39.6% or in 38 of 96 high power fields investigated in patients affected by CD, and in 3.3% or in 3 of 90 high power fields examined in patients with UC. In areas with focal inflammation, the mean percentage of eosinophils in CD was 57% (range 44-70%), and 9% in UC (range 6-26%). No focal inflammation was present in CC. In the submucosa of some CD patients, a large number of autofluorescent eosinophils and many autofluorescent cell-free granules were seen. It was inferred that these autofluorescent granules had been released from eosinophils, and that the eosinophilic granulocytes from which these granules had originated were no longer discernible. Focal eosinophilic mucosal infiltration in CD is more common than epithelioid cell granulomas, and emerges as an important parameter in the histologic differential diagnosis between colonic CD and UC.     

Increased expression of fas ligand in human tuberculosis and leprosy lesions: a potential novel mechanism of immune evasion in mycobacterial infection

To study the location and mechanism of apoptosis within the human tuberculosis (TB) and leprosy lesions, parallel sections were analyzed for mycobacterial antigens (M.Ag), Fas ligand (FasL), Fas, CD68 and Mac387 by immunohistochemistry, and apoptotic cells by the terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling method. Cutaneous leishmaniasis and foreign body granulomas were analyzed for comparison. The heavily infected macrophages in multibacillary TB and leprosy granulomas very strongly expressed FasL, indicating that a mycobacterial infection can induce an increased expression of FasL in a population of infected macrophages, which may protect them from the attack of Fas-expressing lymphocytes. However, macrophages with high levels of leishmania amastigotes did not selectively express FasL, suggesting that this phenomenon is specific for the mycobacteria. Interestingly, in the well-formed TB granulomas, 84% of the multinucleated giant cells strongly expressed FasL. The expression of Fas was weak (34%) or absent. A higher number (33%) of epithelioid cells expressed FasL than Fas (23%). Lymphocytes were scanty among the epithelioid cells. The frequency of apoptotic cells was higher in the epithelioid cells (0.25%) than the mononuclear cells in the mantle zone (0.14%). Thus, the epithelioid cells and the multinucleated giant cells by virtue of the increased expression of FasL may make these granulomas an immune privileged site for mycobacteria.     

Eosinophilic myocarditis in a patient with idiopathic hypereosinophilic syndrome: insights into mechanisms of myocardial cell death

Idiopathic hypereosinophilic syndrome (HES) consists of a prolonged state of eosinophilia of unknown origin with organ involvement. We describe the case of a patient who developed fatal eosinophilic myocarditis. A 23-year-old woman with an 8-month history of eosinophilia presented with symptoms of myocarditis. Histological evaluation of an endomyocardial biopsy specimen revealed marked endomyocardial eosinophilic infiltration with eosinophil-rich granulomas and areas of myocyte necrosis. A terminal deoxynucleotidil transferase assay revealed apoptosis in several cardiomyocytes and vascular cells, mainly in the myocardial areas with higher eosinophil density. Evaluation of an endomyocardial biopsy specimen obtained after steroid therapy demonstrated that the eosinophils had disappeared, but there was marked myocardiosclerosis and scattered apoptotic cells. The patient slowly developed heart failure and died of sudden arrhythmic death. HES can cause severe myocarditis with extensive myocyte loss, probably due to both necrosis and apoptosis. Myocardial fibrosis may occur despite treatment, and patients may be at risk for fatal arrhythmias.     

Juvenile temporal arteritis associated with Kimura's disease

A case of juvenile temporal arteritis, which is a rare vascular lesion in children and young adults, associated with Kimura's disease in a healthy 23-year-old asymptomatic man is described. The patient presented with a painless 2.5 cm nodule with eosinophilia and normal erythrocyte sedimentation rate. Histologically, the left superficial artery showed marked intimal thickening with moderate eosinophilic infiltrates, constriction of the vascular lumen, focal disruptions of the internal elastic lamina and media, moderate eosinophilic infiltrates in the adventia, and absence of giant cells. The subcutaneous tissue surrounding the artery was characterized by lymphofollicular hyperplasia, marked eosinophilic infiltrates in the intra- and extra-follicles with abscess, capillary proliferations, lymphocytic, plasma cell and mast cell infiltrates, and fibrosis in the interfollicular region. Immunohistochemically, reticular, positive IgE staining was observed in the germinal centers. Clinically and histologically, the lesion was consistent with juvenile temporal arteritis associated with Kimura's disease. The findings indicate that both entities are closely related and juvenile temporal arteritis may be secondary to Kimura's disease.     

Severe eosinophilic cholangitis with parenchymal destruction of the left hepatic lobe due to hydatid disease

Hydatid cysts of the liver are known to occasionally rupture into the bile ducts and cause cholangitis. The histological features of this complication have not been adequately described in the literature. Herein is reported a case of severe eosinophilic cholangitis of the left hepatic lobe, occurring in a 24-year-old man with a large (16 cm) hydatid cyst, which obstructed and eroded the left hepatic duct. The patient presented with upper abdominal discomfort and low-grade fever of 3 weeks' duration. Sections of the left lobectomy specimen showed marked inflammatory infiltrates in the portal tracts, predominantly composed of eosinophils, extensively involving bile ducts of all sizes. Occasional small bile ducts were replaced by epithelioid cell granulomas surrounding eosinophilic microabscesses. The inflammatory infiltrates extended into the lobules, resulting in marked hepatocyte loss. This case demonstrates that echinococcosis may cause severe eosinophilic cholangitis with extensive parenchymal destruction, apparently resulting from a hypersensitivity reaction to parasitic antigens.     

Degranulation patterns of eosinophils in advanced gastric carcinoma: an electron microscopic study

Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and degranulation patterns of eosinophils in the tumor stroma. Seven cases of advanced gastric carcinomas were found to be massively infiltrated by eosinophils and studied by light and electron microscopy. Gastric carcinomas, despite having similar numbers of tissue eosinophils, exhibited markedly different degranulation patterns. In 2 cases, resting nondegranulating eosinophils were found. Piecemeal degranulation was the predominant mode of secretion from eosinophils localized within the tumor stroma in 4 cases. Eosinophil exocytosis and cytolysis were rarely observed. In 1 case, crystals morphologically similar to Charcot-Leyden crystals were observed at the extracellular level as well as in phagosomes of tissue macrophages, confirming active sequestrations of eosinophil Charcot-Leyden protein by macrophages in vivo. In the same case, eosinophils showed characteristic features of early and late apoptotic changes, such as condensed chromatin, focal dilatation of nuclear envelope, and preserved plasma membrane. Morphological association between apoptotic eosinophils and deposition of granules in the tumor stroma was found. Extracellular deposition of intact granules from apoptotic eosinophils was distinct from eosinophilic (necrotic) cytolysis, and has reported previously in experimental studies in vitro. To the knowledge of the authors, this case represents the first report of late apoptotic eosinophils that release their granules within the tumor stroma in a human gastric carcinoma.     

Immunohistochemical observation of lysozyme in macrophages and giant cells in human granulomas.

Lysozyme activity of macrophages and giant cells in various human granulomas were examined with immunoperoxidase bridge method in tissue sections. Various numbers of epithelioid cells and giant cells of epithelioid cell granulomas of tuberculosis, sarcoidosis and Crohn's disease exhibited intense granular cytoplasmic lysozyme activity. Foreign body granulomas induced with various substances showed negative or faintly positive lysozyme stain. Macrophages and giant cells of aspergillus granuloma associated with thymus hypoplasia and T-cell depression contained no lysozyme. The results suggest that cell-mediated immunology plays an important role for the lysozyme synthesis of macrophages in granuloma.     

Serum IgE and IgE antibody levels in patients with bronchial asthma, atopic dermatitis, eosinophilic granulomas of the soft tissue (Kimura's disease) and other diseases

Hyper-IgE immunoglobulinemia was observed in bronchial asthma, atopic dermatitis, eosinophilic granuloma of the soft tissue (Kimura's disease), disseminated visceral eosinophilic granulomas (Zuelzer-Apt syndrome) and disseminated eosinophilic collagen disease, IgE antibodies to environmental allergens (Dermatophagoides farinae mites, Aspergillus fumigatus, mountain cedar pollen, and Candida albicans) were found in bronchial asthma, atopic dermatitis and combinations of the two, but were not significantly detected in the latter three diseases. Hyper-IgE immunoglobulinemia may be divided into two groups on the basis of the presence of specific IgE antibodies directed to environmental allergens. The presence of antimite IgE antibodies in atopic dermatitis sera was confirmed by radioimmunoelectrophoresis. Anti-mite IgE antibodies in atopic dermatitis were heterogeneous in their specificity and the allergenic moieties to which IgE antibodies were directed varied from one case to another.     

Epithelioid haemangioma (angiolymphoid hyperplasia with eosinophilia) and Kimura''s disease in Chinese

Although Kimura's disease has often been considered to be identical to angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma), recent studies suggest that they are different clinicopathological entities. In this study, we have made a detailed morphological comparison of 10 cases of epithelioid haemangioma and 40 cases of Kimura's disease occurring in the Chinese population. The epithelioid haemangiomas occurred in the subcutaneous tissue, skin and maxillary antrum, whereas Kimura's disease affected the subcutaneous tissue, major salivary glands and lymph nodes. Distinctive features of epithelioid haemangiomas were exuberant proliferation of vessels lined by cuboidal to hobnail endothelial cells with irregular nuclei and cytoplasmic vacuoles, fibromyxoid matrix, involvement of muscular coat of blood vessels and zonation of inflammatory infiltrate towards the peripheral portion of the lesion. Distinctive features of Kimura's disease were florid lymphoid infiltrate with prominent lymphoid follicles, vascularization of germinal centres, germinal centre necrosis, marked eosinophilia with or without eosinophil abscess formation, proliferation of high endothelial venules, and sclerosis. The histological features suggest that epithelioid haemangioma is a proliferation of atypical endothelial cells, possibly neoplastic, that is associated with a variable inflammatory infiltrate, whereas Kimura's disease is primarily an inflammatory condition in which high endothelial venules are usually found.     

IMMUNOHISTOCHEMICAL OBSERVATION OF LYSOZYME IN MACROPHAGES AND GIANT CELLS IN HUMAN GRANULOMAS

Lysozyme activity of macrophages and giant cells in various human granulomas were examined with immunoperoxidase bridge method in tissue sections. Various numbers of epithelioid cells and giant cells of epithelioid cell granulomas of tuberculosis, sarcoidosis and Crohn's disease exhibited intense granular cytoplasmic lysozyme activity. Foreign body granulomas induced with various substances showed negative or faintly positive lysozyme stain. Macrophages and giant cells of aspergillus granuloma associated with thymus hypoplasia and T-cell depression contained no lysozyme. The results suggest that cell-mediated immunology plays an important role for the lysozyme synthesis of macrophages in granuloma.     

Eosinophil chemotactic factors from granuloma of Kimura's disease, with special reference to T lymphocyte-derived factors

The granuloma of patients with Kimura's disease characterized by tissue and peripheral blood eosinophilia was reviewed with respect to eosinophil infiltration. An infiltrate of inflammatory cells with histiocytes and a sprinkling of eosinophils were observed in the fibrous stroma surrounding the newly formed vessels. Mast cells were rarely seen in the areas where eosinophils were grouped together. Three different eosinophil chemotactic factors (ECF) were isolated from the granulomas of Kimura's disease. They were termed as low molecular weight (LMW), intermediate molecular weight (IMW), and high molecular weight (HMW)-ECF according to the profile on gel filtration (LMW-ECF, about 500; IMW-ECF, about 12,500; HMW-ECF, 45,000-70,000). In terms of their activity when extracted from the granuloma, LMW-ECF and HMW-ECF seemed to be major natural mediators for the tissue eosinophilia, whereas IMW-ECF was a minor one. In an in vitro system, it was shown that granuloma lymphoid cells produce spontaneously at least two ECF having similar properties to LMW- and HMW-ECF, respectively. By analysis with monoclonal antibodies, granuloma T cells, probably OKT4-positive cells, were shown to be responsible for the production of those two ECF. It was thus suggested that prolonged synthesis of LMW- and HMW-ECF by OKT4-positive T cells plays a crucial role in the local eosinophilia of Kimura's disease.