IFN-gamma role in granuloma formation in experimental subcutaneous cysticercosis.

Cysticercosis is an infection caused by the metacestode larval stage of Taenia parasites in tissues and elicits a host-parasite reaction in which the immune response may be decisive in the disease development. The aim of this study was to evaluate the role of IFNγ (IFN-gamma) in the experimental model of subcutaneous infection with Taenia crassiceps (T. crassiceps) cysticerci using IFNγ knockout mice. Male C57BL/6 and C57BL/6 KO IFNγ mice 8-12 weeks of age were inoculated with T. crassiceps cysticerci into the subcutaneous tissue of the dorsum. At 7 and 30 (acute phase), 60 and 90 (chronic phase) days post infection, animals from each group had their blood and the subcutaneous tissues collected for serologic and pathological studies. IFNγ and IL-4 were dosed and the histopathological analysis was performed. In the presence of IFNγ there was the establishment of a mixed Th1/Th2 systemic immune profile. This profile also locally induced the granuloma formation which was constituted by cells that played important roles in the parasitary destruction and that were likely associated to the Th1 axis of mixed immune response. On the other hand, the absence of IFNγ appears to favor the parasitary growth which may be related to the development of a systemic Th2 immune response. This profile influenced the granuloma formation with immunoregulatory properties and appears to be important in the collagen synthesis.

The Dacryocystorhinostomy Ostium Granulomas: Classification, Indications for Treatment, Management Modalities and Outcomes.

AIM: Ostium granulomas following dacryocystorhinostomy (DCR) have not been studied in detail previously. This study aims to classify the DCR-related granulomas based on their ostial locations and to assess the outcomes of their management. METHODS: A retrospective consecutive case series of 47 ostial granulomas evaluated over a period of 2 years were included in this study. All patients underwent detailed endoscopic examination to assess the granuloma locations and their response to initial topical steroids treatment. Persistent granulomas either underwent further management with excision or intralesional steroids based on their location. Patients were followed up for a minimum of 6 months. The primary outcome measure was resolution of granuloma. RESULTS: The mean age at presentation was 45 years with a female preponderance (68%). 70% (33/47) of granulomas were following external DCR and 30% (14/47) occurred in the setting of endonasal DCR. The most common location was an edge granuloma in 46.8% (22/47) followed by a combined granuloma in 21.2% (10/47). 91.4% (43/47) underwent initial treatment with topical nasal steroids. The remaining 4 (8.5%) underwent primary excision. Among those treated with topical steroids (n = 43), 9.3% (4/43) underwent further treatment with intralesional triamcinolone. Overall, 4.2% (2/47) recurred in 6 weeks following resolution and were treated with excision. CONCLUSION: We recommend routine endoscopic evaluation of all the DCR ostia. Detection of granulomas in early stages and appropriate management as per guidelines proposed may aid in better outcomes.

[Myositides]. / Myositiden.

Idiopathic inflammatory myopathies (IIM) are diseases that are potentially amenable to immunomodulatory therapy. The challenge for the neuropathologist consists in distinguishing these myopathies from secondary inflammatory myopathies, especially in the context of some muscular dystrophies and metabolic diseases that may also show inflammatory infiltrates. There are generalized IIMs (dermatomyositis, polymyositis, sporadic inclusion body myositis) and focal ones (e.g., proliferative myositis, macrophagic myofasciitis). This review provides diagnostic criteria for each of these and includes pathogenetic mechanisms where available.

[Effect of N-acetylcysteine on the egg granuloma in hepatic tissue of mice with Schistosomosis japonica].

OBJECTIVE: To study the effect of N-acetylcysteine (NAC) on the egg granuloma in hepatic tissue of mice infected with Schistosoma japonicum. METHODS: 36 mice were randomly divided into normal group, infected group and NAC group, each with 12 mice. The mice in the latter two groups were each infected with 25+/-2 cercariae of S. japonicum through the skin of abdomen. NAC solution was orally given to the mice of NAC group, 200 mg/kg, 2 times/d from the day of infection through to the 42nd day. Mice in the other 2 groups were given 2 ml normal saline daily. The mice were all sacrificed at the end of the 42nd day and their livers were collected for pathologic observation. Area of the egg granuloma was measured with computer image analysis software. Concentration of nitric oxide (NO) and reduced glutathione hormone (GSH), and the activity of glutathione peroxidase (GSH-PX) in serum and hepatic tissue, and the activity of inducible nitric oxide synthase (iNOS) in the hepatic tissue were all detected. RESULTS: Number of the single egg granuloma of "+,++,+++" grade were 1.80+/-0.25, 1.37+/-0.23 and 0.53+/-0.15 respectively in NAC treated group, which were less than those of infected group (3.70+/-0.28, 2.77+/-0.25 and 2.00+/-0.14 respectively) (P<0.05). The serum NO and GSH concentration was 0.53+/-0.17 and 229.66+/-9.47 respectively in NAC group, lower than those of infected group (2.64+/-0.31 and 312.47+/-18.55 respectively) (P<0.05), but its GSH-PX activity was 1101.99+/-140.81, higher than that of infected group (663.66+/-25.59) (P<0.05). The concentration of NO and GSH, and the activity of iNOS and GSH-PX in hepatic tissue of NAC group were 6.85+/-0.30, 13.44+/-0.40, 358.40+/-19.15 and 110.84+/-10.93 respectively, lower than those in infected group (8.26+/-1.69, 28.40+/-0.56, 1132.44+/-52.82 and 226.26+/-16.25 respectively) (P<0.05). CONCLUSION: NAC may have the effect of retarding pathological change of the liver, which may associate with the decrease of NO and GSH in serum and hepatic tissue and iNOS activity in the tissue.

Disseminated hyaline ring granuloma in the omentum of a dog.

BACKGROUND: Hyaline ring granuloma (HRG) is an uncommon histopathologic finding of unsolved etiopathogenesis. According to the exogenous theory, HRG develops due to implantation of foreign material, most probably indigestible plant fragments. HRG is a comparatively rare condition in humans, mostly involving the oral cavity with very rare extraoral locations. CASE PRESENTATION: An 1-year-old mixed-breed dog in good condition was presented for routine ovariohysterectomy. Disseminated HGR were accidentally found in the omental adipose tissue during surgery. Histopathology revealed the presence of ring-like hyaline structures surrounded by granulomatous inflammation including foreign body-type multinucleated giant cells. The histochemical examinations indicated the exogenous plant origin of the foreign material. CONCLUSIONS: The lesions were similar to the findings in humans with HRG. The definitive diagnosis remains largely based on histopathological examination supported by special histochemical stains. To the best of our knowledge, this is the first case of hyaline ring granuloma reported in a non-human species. Moreover, the omentum is an uncommon location for this condition.

Immunohistochemical expression of interferon-γ in different types of granulomatous lesions associated with bovine paratuberculosis.

Animals infected with Mycobacterium avium subsp. paratuberculosis (Map) show a variety of lesions, from focal forms, seen in subclinical stages to diffuse lesions in clinical cases. The purpose of this study was to evaluate the local expression of IFN-γ by immunohistochemistry in relation with the type of lesion in naturally Map-infected cows. The number of immunolabelled cells, -the majority morphologically consistent with lymphocytes-, was higher in focal and diffuse paucibacillary forms than in diffuse multibacillary lesions, where they appeared closely related to epithelioid cells. Diffuse multibacillary lesions had the lowest numbers, but higher than controls, and positive cells were intermingled among the macrophages. The peripheral IFN-γ production was higher in all Map infected cows and a positive correlation was found with the number of immunolabelled cells in the intestine. The findings of this study show that IFN-γ would play a role in the development of the different types of lesions in paratuberculosis, and also points out the importance of adequate sampling of lymphoid tissue containing samples when studying the local immune response in which IFN-γ expression may be involved, especially in cases where focal lesions are present.

[Examination of granuloma of revised cemented or cementless total hip arthroplasties using inductively coupled plasma atomic emission spectrometry (ICP-OES)]. / Atomemissionsspektralanalyse mit induktiv gekoppeltem Plasma (ICP-OES) von Granulomen zementierter und zementfreier Hüftendoprothesen.

INTRODUCTION: Aseptic loosening is the most common problem in total hip arthroplasty (THA). One main aspect is inflammatory reaction against wear particles of the prosthesis materials. Analysing failure mechanisms in THA analysis of the particles and their element distribution of revised granulomatous tissue is essential to improve materials used in THA. MATERIALS AND METHODS: 23 granulomas of revised THA due to aseptic loosening, 13 of which with metal on metal bearing (M/M), were analysed using inductively coupled plasma atomic emission spectrometry (ICP-OES). RESULTS: Elements Cr, Mn, Ni, Al, Cu, Zn, Cd, Ti, V, Zr, Nb and Fe could be detected. The maximum value of Cr was 23.88 ppb (parts per billion), Al 191.02 ppb, Ni 64.95 ppb and Zr 9.96 ppb. The highest value of Al could be found in cementless implants. The maximum value of the elements Cr and Ni could be detected in M/M. In cemented implants the highest value of Zr was found. DISCUSSION: The origin of Zr was the used bone cement in cemented THA. The elements Cr and Ni were significantly higher in M/M bearings. The highest value of Al was detected in granulomas of revised corund rough blasted cementless implants. The histopathologic findings of the revised M/M bearings have been published recently. Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-OES) could not show any differences of the alloying constituents in cases with or without allergic reactions. ICP-OES analysis seems to be not useful examination of histologic sections using SEM with cryotransfer unit.

Reactive Granulomatous Dermatitis: A Review of Palisaded Neutrophilic and Granulomatous Dermatitis, Interstitial Granulomatous Dermatitis, Interstitial Granulomatous Drug Reaction, and a Proposed Reclassification.

The terms "palisaded neutrophilic and granulomatous dermatitis," "interstitial granulomatous dermatitis," and the subset "interstitial granulomatous drug reaction" are a source of confusion. There exists substantial overlap among the entities with few strict distinguishing features. We review the literature and highlight areas of distinction and overlap, and propose a streamlined diagnostic workup for patients presenting with this cutaneous reaction pattern. Because the systemic disease associations and requisite workup are similar, and the etiopathogenesis is poorly understood but likely similar among these entities, we propose the simplified unifying term "reactive granulomatous dermatitis" to encompass these entities.

Hepatic granulomas following liver transplantation. Clinicopathologic features in 42 patients.

Liver granulomas have long been known to pose diagnostic problems for pathologists; however, their prevalence and associated etiologic factors have not been studied in liver transplant patients. We reviewed 3632 liver biopsy specimens from 563 patients at two institutions and identified 42 patients with posttransplant granulomas. A possible or probable etiologic factor was identified in 30 (71%) cases. Most were epithelioid granulomas and microgranulomas located in the parenchyma associated with hepatocyte necrosis (21 cases, 50%). Portal-based granulomas were associated with recurrent primary biliary cirrhosis (5 cases, 12%), acute cellular rejection (2 cases, 4.8%), and a foreign body-type reaction (1 case, 2.4%). One case was associated with tuberculosis (2.4%), 4 cases occurred in a fatty liver (9.5%), and 8 patients had liver granulomas but no other significant abnormality. The granulomas were most frequent in the first 7 months after transplantation when the patients were biopsied more often and underwent episodes of rejection or acute hepatitis. Portal-based granulomas in this period were usually associated with acute cellular rejection. After 7 months, the frequency of granulomas as well as the number of biopsies decreased and portal-based granulomas associated with recurrent primary biliary cirrhosis were most common (5 cases, 12%). Rare, late-appearing parenchymal granulomas were also seen (3 cases) and consisted of 1 lipogranuloma and 2 cases of epithelioid granuloma. The latter were thought, in 1 patient, to be associated with parenchymal hepatocyte necrosis; the others were of unknown etiology.

Granulomatous inflammation--a review.

The granulomatous inflammatory response is a special type of chronic inflammation characterised by often focal collections of macrophages, epithelioid cells and multinucleated giant cells. In this review the characteristics of these cells of the mononuclear phagocyte series are considered, with particular reference to the properties of epithelioid cells and the formation of multinucleated giant cells. The initiation and development of granulomatous inflammation is discussed, stressing the importance of persistence of the inciting agent and the complex role of the immune system, not only in the perpetuation of the granulomatous response but also in the development of necrosis and fibrosis.

Pyelonephritis and interstitial nephritis--clinical-pathological correlations.

AIMS: The relation between histological and clinical parameters were studied in 54 consecutive patients with acute interstitial nephritis or pyelonephritis without primary glomerular disorders, in all of whom percutaneous renal core biopsy had been performed. PATIENTS AND METHODS: Based on clinical criteria and without detailed knowledge of the appearance of the biopsy, the material was divided into 4 main groups: patients with septic and/or tubulotoxic conditions, hypersensitivity reactions (eosinophilic nephritis), ascending infections and other specified conditions. RESULTS: The overall correlation between the histological and the clinical diagnoses was good, but there were large overlaps between the histological findings in 3 of the groups, making classification of individual cases difficult. The histological and paraclinical findings were poorly correlated. Histologically, ascending infections were characterized by the presence of leukocyte casts and an increased number of neutrophilic granulocytes. CONCLUSION: The material justifies the present rough classification of the conditions mentioned above. By kidney biopsy, the interstitial conditions can be separated from glomerular and other conditions, but the biopsy offers little information about the clinical severity or the prognosis.

Xanthogranulomatous cholecystitis. Histopathological study and classification.

Xanthogranulomatous cholecystitis (XC) is a chronic inflammatory lesion of the gallbladder histologically characterized by the presence of varying amounts of foamy histiocytes in the inflammatory infiltrate. In this study a review of 63 cases selected from 1207 surgically removed gallbladder is presented; the percentage found (5.2%) is slightly higher than that of previous reports showing that XC is less uncommon than generally believed. A detailed microscopic study is performed: the authors observed according to the histological features particularly the different patterns of distribution of the inflammatory infiltrate and postulate the existence of three subtypes of XC: multinodular, focal and diffuse XC. Finally, the main etiopathogenetic hypotheses are briefly discussed.

Description and classification of different types of lesion associated with natural paratuberculosis infection in sheep.

Paratuberculosis lesions in naturally infected sheep were classified histologically. Adult sheep (n = 166) culled for various reasons, from four flocks in which clinical cases of the disease had occurred, were studied. Eight-two sheep (49.4%) showed lesions that could be divided into three main categories. Type 1 lesions, found in 24.1% of these animals, consisted of small granulomata formed by macrophages and were located exclusively in the ileocaecal Peyer's patch. In type 2 lesions, found in 4.8% of the sheep, granulomata were also observed in the mucosa associated with Peyer's patches. Type 3 lesions were characterized by granulomata in areas of the mucosa associated with, and also distinct from, the Peyer's patches. Three subtypes of type 3 lesions were recognized. In subtype 3a, found in 4.2% of the sheep, multifocal granulomata appeared in different areas of the lamina propria; they were not apparently associated with lymphoid tissue, and neither did they modify the morphology of the affected areas. Subtype 3b, found in 13.9% of animals, consisted of large numbers of macrophages, widespread in the lamina propria; in subtype 3c (2.4% of sheep) lymphocytes were the main inflammatory cell, with some macrophages scattered amongst them. In subtypes 3a and b, villi were distended and the mucosa appeared thickened. Mycobacteria could be demonstrated in tissue sections from all the samples with subtype 3b lesions and in almost all of those with type 2 and 3a lesions; these organisms were absent or sparse, however, in type 1 and 3c lesions. Macroscopical lesions were clearly visible only in sheep with type 3b and 3c lesions. Mycobacterium paratuberculosis was cultured from all the animals with type 3 lesions, from 87.5% of those with type 2 lesions, and from 47.5% of those with type 1. Type 3b lesions resembled the "borderline-lepromatous" form of mycobacterial lesions, whereas type 3c lesions resembled the "borderline-tuberculoid" form. The relationship between intestinal lymphoid tissue and paratuberculosis lesions is discussed, and the diagnostic importance of histological examination of the ileocaecal valve emphasized.

Endodontic classification.

Clinical and histopathologic findings are mixed in current endodontic classifications. A new system, based on symptomatology, may be more useful in clincial practice. The classifications are vital asymptomatic, hypersensitive dentin, inflamed-reversible, inflamed/dengenerating without area-irreversible, inflamed/degenerating with area-irreversible, necrotic without area, and necrotic with area.

Primary nasal tuberculosis: a case report.

During the past 2 decades, tuberculosis--both pulmonary and extrapulmonary--has re-emerged as a major health problem worldwide. Nasal tuberculosis--either primary or secondary to pulmonary tuberculosis or facial lupus--is rare, but it should be considered in the differential diagnosis of nasal granulomas. We describe a case of primary nasal tuberculosis in an adult male who presented with a polypoid lesion in one nasal cavity. The diagnosis was based on histopathology and the patient's successful response to antituberculous drug treatment. Given the rising incidence of tuberculosis, it is prudent that otolaryngologists remain cognizant of this infection as a potential cause of unusual lesions in the head and neck.

A new morphological concept and classification of granulomatous inflammation: the polar granulomas.

An historical analysis of granulomas and a new morphological concept and classification of granulomatous inflammation, the polar-granulomas, are presented. The historical analysis of the concept of granulomas reveals that the still proclaimed confusion concerning the process was due more to Virchow's comparison of granulomas to ordinary granulation tissue than to tumors and to objections of pathologists to Metchnikoff's theory of phagocytosis. And it is strange to verify that differences between granulomas and granulation tissue, although already established in the end of the 19th Century, were overlooked by the majority of pathologists. In this Century , the knowledge of granulomatous inflammation was greatly improved by Aschoff 's concept of reticulum endothelial system, Mitsuda test for types of leprosy, Jadassohn- Lewandowsky law, South American classification of leprosy into polar forms, and Forbus contribution to histogenesis and morphological classification of granulomas. The best model for the study of granulomatous inflammation is leprosy, because this disease is characterized by two different clinical polar forms, each one having particular types of phagocytosis (complete or incomplete) and of granulomas (tuberculoid or non tuberculoid). Based on the phenomenon of phagocytosis, polar forms of leprosy, Jadassohn- Lewandowsky law, metamorphosis of macrophages and nature of the etiologic agent, granulomas can be defined as a reactional hyperplasia of macrophages towards inanimate agents and towards animate agents of low virulence. Also based in the same data, a morphological classification of granulomas into polar types, tuberculoid and non tuberculoid, is proposed. The polar tuberculoid type follows the Jadassohn- Lewandowsky law, its etiologic agent is absent or scarce (complete phagocytosis) - and comprise two sub-types: tubercle-like and sarcoid-like. The polar non tuberculoid type does not follow the Jadassohn- Lewandowsky law, its etiologic agent is always present or copious (incomplete phagocytosis) and comprises two sub-types: giant cell and persistent macrophage. In the latter case, macrophages behave as a culture medium cell or as a storage cell. When both polar tuberculoid and non tuberculoid structures are found together in the same disease, granuloma can be called interpolar . If both types occur simultaneously in the same disease, granuloma would be bipolar. It seems that the proposed definition of granulomas combines morphology with functional activity of macrophages, easily observed in routine histopathological examination by optical microscopy. This morphological classification into polar granulomas (ABSTRACT TRUNCATED AT 250 WORDS)

[O'Brien's actinic granuloma, Three cases (author's transl)]. / Le granulome actinique de O'Brien. A propos de 3 observations.

We report three cases of 54, 58 and 65-year-old patients presenting annular lesions with centrifugal migratory extension. They occur exclusively on sun-exposed areas. In two cases, the lesions were multiple. In the third case, the lesion was single and mimicked an erythema annulare centrifugum. The past history ranged from 18 months to 8 years. Microscopic examination of the central part showed a disappearance of elastic fibers in upper reticular dermis. Examination of the ring showed in upper reticular dermis an histiocytic granulomatous infiltration with many giant cells, lymphocytes and patterns of elastic fibers phagocytosis. Similar features were found by electronmicroscopy. These three cases illustrate the typical features of O'Brien's actinic granuloma. Relationship between this actinic granuloma and granuloma annulare occurring on sun-exposed areas on one side, and necrobiosis lipoidica, Miescher's granuloma and granuloma multiforme on the other side, are discussed. On the basis of some clinical and histological patterns, the autonomy of O'Brien's actinic granuloma appears to be established.

[Bacterial granulomatous hepatitis]. / Le epatiti granulomatose batteriche.

The liver may react to different infectious and non- infectious agents, developing granulomatous lesions which characterize granulomatous hepatitis. Granulomas of the liver are circumscribed inflammatory lesions (size from 50 to 300 mm) composed of epithelioid cells, varied numbers of mononuclear cells and eosinophils and multinucleated giant cells. They represent a specialized cell-mediated immune response to a wide variety of etiological factors. A broad spectrum of microorganisms may trigger hepatic granulomas. M. tuberculosis is the more frequent agent (~ 44%). Granulomatous hepatitis is characterized by a febrile illness with systemic signs and symptoms such as fatigue, sweating, shivering, hepatomegaly and/or splenomegaly, abnormalities in serum liver tests (aminotransferase, alkaline phosphatase). Liver biopsy provides diagnostic information in approximately 15-30% of cases, identifying directly the microbial agent with special microbial stains and polymerase chain reaction or finding distinctive microscopic features, suggestive of specific microorganisms. In such cases appropriate therapy is possible. Unfortunately in one third of cases is impossible to reach aetiological diagnosis on histological criteria alone. In these cases a therapeutic attempt with steroids, effective in the idiopathic granulomatous hepatitis, may be useful.