Kimura's disease with unusual eosinophilic epithelioid granulomatous reaction: a finding possibly related to eosinophil apoptosis

We report and discuss a case of Kimura's disease with an unusual eosinophilic epithelioid granulomatous reaction. A 3-year-old Japanese boy with eosinophilia and a high concentration of IgE developed lymphadenopathy and multiple cervical masses. A lymph node biopsy demonstrated the infiltration of eosinophils in the stroma, which is consistent with the findings of Kimura's disease. Interestingly, a number of apoptotic eosinophils was detected in the infiltrating eosinophils. Multiple epithelioid granulomas with central eosinophilic abscesses and necrosis were also observed. Macrophages and giant cells had phagocytosed the apoptotic eosinophils at the edge of the granulomas. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay showed that the TUNEL-positive eosinophils were both in the macrophages and in the central eosinophilic abscesses of the granulomas. These findings suggest that the eosinophils had undergone an accelerated apoptosis in this case of Kimura's disease, and that the epithelioid granulomas were produced by phagocytosis of the apoptotic eosinophils by macrophages.     

Histopathologic findings in culture-positive secondary osteomyelitis

As peripheral vascular disease and diabetes mellitus are increasingly common, chronic wounds are often seen. Bone biopsies, with imaging and microbial cultures, are often obtained to evaluate for osteomyelitis. Because much of the historical literature describing the histology of osteomyelitis pertains to primary osteomyelitis, this study characterizes the histologic findings and provides correlation with culture results in secondary osteomyelitis.The histologic features of bone biopsies were assessed over a 5 year period. Concurrent laboratory and radiographic data were obtained and these data were compared with culture results.This study included 163 cases, of which 104 were culture-positive osteomyelitis. All culture-positive cases had been present longer than 28 days and had at least one of the following histologic features: neutrophilic inflammation, plasmacytic inflammation, or eosinophilic fibrosis. However, none of these findings were restricted to culture-positive cases. Overall, plasmacytic and neutrophilic inflammation provided similar specificity, and positive predictive values for osteomyelitis. Medullary fibrosis gave a sensitivity of 95%, the highest for any single feature, and the combination of fibrosis and neutrophilic inflammation had the greatest specificity of 96%. Additionally, neutrophilic inflammation correlated often with isolation of Staphylococcus aureus, while plasma cell predominance was found more frequently with other infectious agents.This study describes histologic features in secondary osteomyelitis, which may challenge the widespread inclination to equate a neutrophilic inflammation with ‘acute osteomyelitis’ and ‘chronic osteomyelitis’ with one rich in plasma cells. We report an early correlation between common histopathologic findings and specific culture isolates, which can be further refined with additional research.     

Clinicopathological findings of focal organizing pneumonia: a retrospective study of 37 cases

Background and objective: Focal organizing pneumonia (FOP) is an uncommon disease. The etiology, and in particular the disease’s relationship with infection and the incidence of idiopathic FOP, is relatively unknown. The aim of this study is to review clinical, radiological and pathological features of patients with organizing pneumonia (OP) presenting solitary lesions and to analyze possible causes. Methods: We retrospectively reviewed 37 surgical lung biopsy or resection cases of pathologically confirmed FOP over a period of 10 years. Results: Microscopically, 17 cases showed OP with neutrophilic infiltration or abscess, 11 with epithelioid cell granulomas or scattered multinucleated giant cells, 2 with greater eosinophilic infiltration, and the remaining 7 cases met the diagnostic criteria for pathological cryptogenic OP (COP). The 37 cases of FOP included 22 men and 15 women, aged 29-76 years, and 17 cases had a history of smoking. Cough, fever, sputum, chest or back pain and hemoptysis were the main symptoms. Seven cases were asymptomatic. The diameters of the lesions ranged from 0.2-6.0 cm (median, 3.0 cm). Fever (9/30), high-sensitivity C-reactive protein elevation (9/17) and abnormalities in pulmonary function test (8/24) existed in focal secondary OP (FSOP) patients, but these symptoms were rarely observed in focal COP (FCOP) (0/7, 1/7 and 0/7 cases, respectively). However, no statistically significant differences were found between the FSOP and FCOP. Conclusions: Histologically, secondary factors exist in the majority of FOP cases. Idiopathic FOP is found in a minority. With respect to secondary FOP, acute infection and granulomatous inflammation are the main causes. Surgical resection alone appears sufficient for the management of FOP.     

Renal cancer associated with Xp11.2 translocation/TFE3 gene fusion: Clinicopathological analysis of 13 cases

ObjectiveTo explore the clinicopathological characteristics, immunohistochemical phenotype, diagnosis and differential diagnosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion.MethodsThe clinical history, pathological morphology, immunohistochemical phenotype and related molecular test results of 13 cases of Xp11.2 translocation/TFE3 gene fusion-related renal cell carcinoma were retrospectively analyzed, and the relevant literature was reviewed.ResultsOf the 13 patients, 5 were males and 8 were females. The age of onset ranges from 8 to 73 years old, most of which were middle-aged and elderly patients. Among them, there were 3 cases of left kidney tumor and 10 cases of right kidney tumor. In the treatment method, 2 of the 13 patients underwent partial nephrectomy, and 11 underwent radical nephrectomy. Histopathological morphology showed papillary, nested, tubular and acinar structures. The cytoplasm was transparent or eosinophilic, and the interstitial fibrosis was accompanied by chronic inflammatory cell infiltration, hemosiderin deposition and foam cell aggregation. The immunohistochemical analysis of 13 patient specimens all expressed TFE3 antibody, and the expression intensity was strongly positive; gene FISH detection technology revealed the breakage and rearrangement of TFE3 gene in 12 assessable cases. One of thirteen patients had a metastasis at follow-up from 3 to 69 months.ConclusionsThis type of kidney cancer was a rare subtype. Because of its complex and changeable shape, it has a high degree of overlap with other kidney cancer subtypes, and the missed diagnosis rate and misdiagnosis rate are extremely high. The diagnosis is mainly based on pathomorphology and immunohistochemistry, TFE3 positive expression and TFE3 gene destruction and rearrangement.     

Eosinophilic products lead to myocardial damage

Eosinophils have been associated with endomyocardial fibrosis. However, their effect on the myocardium and the reactions they elicit have not been emphasized. We describe four patients with extensive myocardial eosinophilic infiltration with and without endomyocardial fibrosis. Patients with a short duration of disease had eosinophilic infiltrates, myocardial eosinophilic abscesses containing granular eosinophilic material, and/or Charcot-Leyden crystals with and without profuse histiocytic and giant cell reaction with granuloma formation. In the early phase, the granular eosinophilic material can be visualized by the Luna stain and/or by electron microscopic examination. In patients with a long duration of symptoms, well-developed granulomas and profuse fibrosis are seen and eosinophilic material may not be visualized. Toxic eosinophil granular protein may be involved in the development of these lesions.     

An unusual cause of granulomatous inflammation: eosinophilic abscess in Langerhans cell histiocytosis

Eosinophilic abscess inciting a granulomatous response has rarely been reported and appears not to have been described in the setting of a neoplasm. In this report, a case is described where a granulomatous response occurred around eosinophilic abscesses in a patient with Langerhans cell histiocytosis, an association which has not previously been documented. On histology, the excised lymph node showed the presence of eosinophilic abscess and necrosis surrounded by granulomas, which in turn were surrounded by Langerhans cells, a feature confirmed on immunohistochemistry. Although rare, this case highlights the importance of careful examination of eosinophilic abscess with granulomatous inflammation in order to exclude an underlying neoplasm.     

The spectrum of eosinophilic infiltration of the gastrointestinal tract and its relationship to other disorders of angiitis and granulomatosis.

Six cases of eosinophilic infiltration of the gastrointestinal tract were studied. Three cases were of the diffuse infiltrative variety (eosinophilic enteritis, two cases; eosinophilic peritonitis, one case), and three cases were of the circumscribed variety (so-called inflammatory fibroid polyp). Two of the infiltrative lesions showed necrotizing granulomas identical to those described by Churg and Strauss; one of the two also showed active vasculitis. One circumscribed lesion occurred in a patient with polyarteritis nodosa. Necrotizing eosinophilic granulomas were also noted in this lesion. Our observations suggest that the two forms of eosinophilic infiltration of the gastrointestinal tract are parts of a disease spectrum. Supporting evidence in the literature is presented. The relationship of this group of eosinophilic lesions to the hypereosinophilic syndrome, allergic granulomatosis and angiitis of Churg and Strauss, and polyarteritis nodosa is discussed.     

Algorithm for cytological diagnosis of nonneoplastic lesions of the salivary glands

The aim of this study was to formulate an algorithm for the cytologic diagnosis of nonneoplastic enlargements of the salivary gland.Smear cellularity and cytological features such as presence of epithelial cells and types of inflammation were assessed in a retrospective study of 201 aspirates. One hundred and forty-six were inflammatory, 19 were noninflammatory nonneoplastic, and 36 were cystic lesions. Of the cystic lesions, cytological evidence of retention cyst was seen in seven, while two aspirates with only hemosiderin-laden macrophages were hematomas. The remaining 27 defied subclassification. Noninflammatorynonneoplastic lesions included 5 fatty infiltrations, 2 sialadenosis, and 12 normal salivary glands. Forty-two lesions were acute inflammations, 89 were chronic, and 15 were granulomatous. Cytomorphologic patterns identified in samples with acute inflammation were 9 abscesses, 29 acute obstructive sialadenitis, and 4 acute infective sialadenitis. Three aspirates with chronic inflammation were lymphoepithelial lesions, 82 chronic sialadenitis, and 4 lymph node in salivary gland. Fifteen granulomatous lesions were 10 tuberculosis, 3 sarcoidosis, and 2 foreign body granulomas. Using the proposed algorithmic approach, nonneoplastic salivary gland enlargement could be placed into distinct, clinically relevant diagnostic categories.     

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.     

Murine allergic respiratory responses to the major house dust mite allergen Der p 1.

BACKGROUND: Although many studies have examined chronic asthma, limited data exist on acute immunopathogenic events induced by allergens. The aim of the study was to investigate the acute cellular, serologic and histopathologic events in airway inflammation produced by intranasal challenge of mice sensitised to the major house dust mite allergen Der p 1. METHODS: C57BL/6 mice were immunised subcutaneously with Der p 1 in alum. Mice were bled and challenged intranasally with Der p 1 on day 14 and killed on day 17. Lungs were fixed in situ, processed and stained with haematoxylin and eosin. The degree of inflammation and eosinophil infiltration was quantified by image analysis. Specific IgE was determined by passive cutaneous anaphylaxis. Cells from spleen and draining lymph nodes were cultured for 24 h with Der p 1, and IL-3/GM-CSF released into supernatants was measured by bioassay. RESULTS: Intranasal challenge of sensitised mice induced eosinophilic influx into the large and small airways and the alveolar regions of the lung, mucus plugging and in severe cases numerous Charcot-Leyden crystals. The quantitation of the inflammation induced by different sensitisation and challenge doses showed that optimal inflammation could be produced using only 1 microg of allergen for both sensitisation and challenge. The degree of inflammation was not related to the titre of IgE antibody and was indeed produced in its absence. T cell reactivity of spleen cells to the allergen was decreased suggesting cell migration or inactivation. CONCLUSIONS: Mice sensitised and challenged intranasally with as little as 1 microg of Der p 1 produced an extensive pulmonary eosinophilic inflammation which shared many of the features of the inflammation found in asthma. The small amount of allergens required and the use of intranasal challenge should provide a useful model.     

Diversion colitis in children: an iatrogenic appendix vermiformis?

AIMS: Diversion colitis (DC) is a localized, relatively benign, iatrogenic condition which occurs in almost 100% of diverted colonic segments in patients who undergo ileostomy/colostomy for various reasons. The aim of this study was to establish histological features of DC in children. METHODS AND RESULTS: Twenty-three cases of DC following colostomy for Hirschsprung's disease in young children were analysed. The distinguishing features included prominent follicular lymphoid hyperplasia (100%), chronic mucosal inflammation (100%), accompanied by a variable degree of acute inflammation (78%) and Paneth cell metaplasia (26%). Less frequent histological findings were as follows: mild goblet cell depletion (22%), foci of cryptitis (13%), crypt abscesses (13%) and mild architectural distortion (22%). A previously unrecognized feature was the presence of mucosal aggregates of eosinophils, found in 43% of cases. A striking similarity between the normal appearance of the vermiform appendix and pathological features in DC was noted and the possible relationship between the two is discussed. CONCLUSIONS: Histological features of DC in children are very similar to those described in adults. They should help to distinguish it from ulcerative colitis and Hirschsprung's-associated enterocolitis in order to prevent inappropriate therapy and follow-up. There are many similarities between DC and the normal appendix vermiformis.     

Severe Liver Disorder Following Liver Transplantation in STING-Associated Vasculopathy with Onset in Infancy

Purpose

STING-associated vasculopathy with onset in infancy (SAVI) is a type-I interferonopathy, characterized by systemic inflammation, peripheral vascular inflammation, and pulmonary manifestations. There are three reports of SAVI patients developing liver disease, but no report of a SAVI patient requiring liver transplantation. Therefore, the relevance of liver inflammation is unclear in SAVI. We report a SAVI patient who developed severe liver disorder following liver transplantation.

Methods

SAVI was diagnosed in a 4-year-old girl based on genetic analysis by whole-exome sequencing. We demonstrated clinical features, laboratory findings, and pathological examination of her original and transplanted livers.

Results

At 2 months of age, she developed bronchitis showing resistance to bronchodilators and antibiotics. At 10 months of age, she developed liver dysfunction with atypical cholangitis, which required liver transplantation at 1 year of age. At 2 years of age, multiple biliary cysts developed in the transplanted liver. At 3.9 years of age, SAVI was diagnosed by whole-exome sequencing. Inflammatory cells from the liver invaded the stomach wall directly, leading to fatal gastrointestinal bleeding unexpectedly at 4.6 years of age. In pathological findings, there were no typical findings of liver abscess, vasculitis, or graft rejection, but biliary cysts and infiltration of inflammatory cells, including plasmacytes around the bile duct area, in the transplanted liver were noted, which were findings similar to those of her original liver.

Conclusion

Although further studies to clarify the mechanisms of the various liver disorders described in SAVI patients are needed, inflammatory liver manifestations may be amplified in the context of SAVI.

     

Chronic eosinophilic leukemia with eosinophilic granulomas of the lung (author's transl)]

For the first time a report is given on a case of chronic eosinophilic leukemia with occurence of eosinophilic pulmonary granulomas. Even after enucleation of the granulomas eosinophilia remained in the peripheral blood and in the bone marrow, and over a period of 6 years lay at a value of above 50% of the granulocytes. The illness ended with sudden increase in the number of myeloblasts. The autopsy revealed destruction of the bone marrow by myeloblasts, immature and mature eosinophilic granulocytes as well as infiltration of the heart, liver, spleen and kidneys. On the basis of histological, cytological and histochemical examinations of the granulomas, the peripheral blood and the organs after dissection, particularly of the bone marrow, there was good reason to assume common pathogenesis of these changes; it was not however possible to completely exclude an allergically generated cause.     

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.     

Novel murine model of chronic granulomatous lung inflammation elicited by carbon nanotubes

Lung granulomas are associated with numerous conditions, including inflammatory disorders, exposure to environmental pollutants, and infection. Osteopontin is a chemotactic cytokine produced by macrophages, and is implicated in extracellular matrix remodeling. Furthermore, osteopontin is up-regulated in granulomatous disease, and osteopontin null mice exhibit reduced granuloma formation. Animal models currently used to investigate chronic lung granulomatous inflammation bear a pathological resemblance, but lack the chronic nature of human granulomatous disease. Carbon nanoparticles are generated as byproducts of combustion. Interestingly, experimental exposures to carbon nanoparticles induce pulmonary granuloma-like lesions. However, the recruited cellular populations and extracellular matrix gene expression profiles within these lesions have not been explored. Because of the rapid resolution of granulomas in current animal models, the mechanisms responsible for persistence have been elusive. To overcome the limitations of previous models, we investigated whether a model using multiwall carbon nanoparticles would resemble chronic human lung granulomatous inflammation. We hypothesized that pulmonary exposure to multiwall carbon nanoparticles would induce granulomas, elicit a macrophage and T-cell response, and mimic other granulomatous disorders with an up-regulation of osteopontin. This model demonstrates: (1) granulomatous inflammation, with macrophage and T-cell infiltration; (2) resemblance to the chronicity of human granulomas, with persistence up to 90 days; and (3) a marked elevation of osteopontin, metalloproteinases, and cell adhesion molecules in granulomatous foci isolated by laser-capture microdissection and in alveolar macrophages from bronchoalveolar lavage. The establishment of such a model provides an important platform for mechanistic studies on the persistence of granuloma.     

Erdheim–Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone

We report a patient with eosinophilic granuloma localized to the left mandible who was subsequently shown to have Erdheim–Chester disease involving the lower extremities, omentum and lung. The diagnosis of eosinophilic granuloma was based on the presence of typical CD1a⁺ Langerhans' cell granulomas in a biopsy of mandible. The diagnosis of Erdheim–Chester disease was established on the basis of the pattern of radioisotopic uptake by long bones, seen on a technetium bone scan, and the presence of characteristic histopathological features in biopsies of lung and peritoneum. The pathological findings in lung were compatible with the abnormalities observed by tomodensitometry, but strikingly different from those seen in Langerhans' cell granulomatosis. The differences in the histological features of pulmonary involvement seen in the two diseases, and the possible relationship between Langerhans' cell granulomatosis and Erdheim–Chester disease, are discussed.     

Experimental production of pulmonary granulomas. IV. Eosinophilic granuloma.

Pulmonary granulomas induced in rabbits by the endobronchial instillation of mycobacterial chemical fractions were re-examined for eosinophilic infiltration. Delayed type hypersensitivity reactions either of tuberculin type or of wax D type did not induce but rather suppressed eosinophilic infiltration in the inflamed area, although some peptidoglycans which are antigenic for the induction of immediate hypersensitivity and fatty acid fractions were weak stimulators of eosinophilic infiltration. Bacterial endotoxin, LPS, was a potent stimulator. It was found that some long chain fatty acids can cause severe eosinophilic infiltration in the induced granulomas. Arachidonic acid was the most active of those examined, so the activity of its metabolites was tested and PGE2 was found to be most active. As the eosinophilic infiltration was markedly suppressed in animals treated with a cyclooxygenase inhibitor (aspirin), the stimulators of eosinophilic infiltration were not fatty acids themselves but their metabolites, PGE2 and some others. The site of permeation of eosinophils from the circulation was found to be arteriolar in the inflamed lung. The granulomatous lesion with eosinophilic infiltration in rabbits is discussed to shed light on the aetiology of eosinophilic granuloma in the human lung.     

Pathologic findings in native infective endocarditis

BackgroundThere are few studies on the histologic findings in native infective endocarditis, especially regarding mimics of autoimmune valvulitis.MethodsWe prospectively studied 106 surgical specimens from 95 patients with a clinical diagnosis of infective endocarditis on native valves, and compared gross and histologic findings with culture results, underlying valve disease, risk factors and time interval from symptom onset to surgical intervention.ResultsThere were 41 (39%) aortic, 33 (31%) mitral, 9 (9%) tricuspid, 1(.9%) pulmonic and 11 (10%) multiple valve replacements. Underlying valve disease was present in 26 (27%) patients (non-calcified bicuspid aortic valve, 10 (38%) cases; mitral valve prolapse, 5 (19%) cases; calcified trileaflet aortic valve, 5 (19%) cases; calcified bicuspid aortic valve, 2 (8%) cases; post-rheumatic mitral valve disease, 2 (8%) cases; hypertrophic cardiomyopathy-related mitral valve disease, 1 (4%) case, trileaflet aortic insufficiency 1 (4%) case) and associated with streptococcal infection (p = .001). Absence of underlying valve disease was associated with intravenous drug abuse (p = .01) and dialysis dependent renal disease (p = .006). Intravenous drug abuse was associated with staphylococcal infection (p = .03). Vegetations were present in 80 (75%) of cases, and on the nonflow surface of the valve in 65 (81%) of these. Gram-stain positivity and neutrophilic microabscesses were associated with staphylococcal infection (p = .03). Epithelioid macrophages with palisading features mimicking necrobiotic granulomas were seen in 42 (40%) valves and more frequently associated with streptococcal infection (p = .03). As expected, the presence of valve necrosis and acute inflammation decreased with an increase in time with respect to symptomatic onset.ConclusionHistologic findings that mimic autoimmune inflammation are frequent in infective endocarditis and associated with streptococcal infection. Risk factors for infective endocarditis include calcific valve disease.     

An autopsy case of purulent mycobacterial meningitis in AIDS.

The patient was a 46-year-old male hemophiliac who died of acute mycobacterial meningitis associated with AIDS (acquired immune deficiency syndrome). Autopsy revealed severe basal meningitis which was characterized by an infiltration of numerous polymorphonuclear leukocytes. Severe mural inflammation of the subarachnoid arteries was noted, and innumerable acid-fast bacilli were demonstrated. Epithelioid cell granulomas were not found in the meningeal lesion. The lungs, liver, spleen, and bone marrow contained many epithelioid cell granulomas with caseous necrosis. Massive proliferation of swollen histiocytes could not be identified in any organ. The absence of epithelioid cell granulomas in the meningeal lesion indicate a severe impairment of cell-mediated immunity in the patient; this anergic type of lesion is one of the characteristics of tuberculosis occurring in association with terminal AIDS.