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.     

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.     

Tissue localization of human eosinophil cationic proteins in allergic diseases

Mouse monoclonal antibodies were raised to the storage and secreted forms of eosinophil cationic protein (ECP), and were used to study the presence of activated eosinophils and secreted ECP in the tissues of patients with a variety of allergic diseases. Immunocytochemical localization was shown with alkaline phosphatase-linked second antibodies, and fast-red substrate. Deposition of a red reaction product indicated sites in tissues where eosinophils had become activated, and where secreted ECP was present. Activated eosinophils and secreted ECP were found together in (1) skin lesions of patients with chronic urticaria, (2) gut lesions of patients with eosinophilic gastroenteritis and ulcerative colitis, and (3) tissues containing granulomas in patients with allergic granulomatosis and vasculitis - the Churg and Strauss syndrome. These results show the value of these techniques for determining the sites of eosinophil activation and secretion in allergic diseases. They support the suggestion that ECP may be involved in the development of these tissue lesions.     

Granulomatous prostatitis: distinction among allergic, nonspecific, and post-transurethral resection lesions

A variety of granulomatous lesions of the prostate, with and without extensive infiltration by eosinophils, have been described. Differing concepts of their pathogenesis, and especially of their relation to allergic states, have produced confusion and controversy. In a review of 62 patients in whom granulomatous lesions in the prostate were diagnosed from 1950 to 1982 at The Johns Hopkins Hospital, the authors identified four major categories. In nine cases specific granulomatous prostatitis was caused by tuberculosis and had typical caseous foci. Nonspecific granulomatous prostatitis was present in 31 cases. These lesions were densely cellular, granulomatous reactions extending throughout entire lobules; three were also characterized by extensive infiltration by eosinophils. Post-transurethral resection granulomas were found in 13 patients who had recently undergone prostatic surgery. These granulomas closely resembled rheumatoid nodules, and four were surrounded by numerous eosinophils. In nine patients the causes of granulomatous prostatitis were varied: two patients had malacoplakia, one had sarcoid, and six had foreign body-type granulomatous. No cases of allergic granulomatous prostatitis were identified. Nonspecific and post-transurethral resection granulomatous prostatitis may both show abundant infiltration by eosinophils and appear histologically identical to the condition that has been described as allergic granulomatous prostatitis; however, in this series both occurred in the absence of asthma or other allergies. The distinction between the rare allergic granulomatous prostatitis, as a reflection of a more generalized allergic reaction, and both post-transurethral resection granulomas and nonspecific granulomatous prostatitis is important, given the differences in clinical outcome and treatment.     

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.     

Histopathologic and histobacteriologic studies of chronic periapical changes of the permanent teeth

Chronic periapical lesions were recognized clinically and radiologically in 109 patients aged from 10 to 79, twice as frequent in the maxilla as in the mandible. Histopathological analysis revealed periapical granulomas and cysts. Forty-eight periapical granulomas were studied histobacteriologically. Detailed microscopic analysis of these cases in order to find bacteria was negative. Histopathological analysis of 72 periapical granulomas and 13 cysts (including four follicular cysts) revealed mixed forms apart from homogenous granulomas. In addition changes in the composition of infiltrate cells are rather qualitative than quantitative, therefore classification of periapical lesions into periapical granulomas and cysts seems justified and sufficient for diagnostic and clinical needs. Detailed analysis of cellular composition of periapical granulomas and cysts shows that immunologic agents may play a role in the pathomechanism of these lesions.     

Carcinoma of type II pneumocytes: immunodiagnosis of a subtype of "bronchioloalveolar carcinomas"

Formalin-fixed paraffin-embedded tumor tissues from North American (N = 12) and Japanese (N = 11) patients with lung carcinomas were stained by the immunoperoxidase method for surfactant-specific apoprotein. Cytoplasmic and focal nuclear staining was seen in three "bronchioloalveolar carcinomas" occurring in Japanese patients. We refer to these three tumors as carcinomas of Type II pneumocytes. These neoplasms formed discrete masses with minimal growth along the alveolar septa at margins of the tumors. Papillary growth with lymphocytic infiltrates in the stalks of the papillary processes was the usual growth pattern. Focal noncaseating granulomas were seen in the stroma of 2 cases, and similar granulomas in the draining lymph nodes were noted in 1. The abundant cytoplasm was foamy, and the nuclei were generally vacuolated with frequent eosinophilic inclusions in the vacuoles. By electron microscopy, osmiophilic lamellar bodies or whorled lamellas were seen in the cytoplasm of the 3 tumors staining for surfactant apoprotein. The nuclei in 2 of the 3 cases contained tubular inclusions; the tubules had a diameter of 60 nm and a 20-nm core.     

Sarcoid-like lesions associated with the immune restoration inflammatory syndrome in AIDS: absence of polymerase chain reaction detection of Mycobacterium tuberculosis in granulomas isolated by laser capture microdissection

Highly active antiretroviral therapy (HAART)-treated human immunodeficiency virus (HIV)-positive patients can develop granulomatous lesions within the first few weeks of initiating therapy. This immune syndrome, called immune restoration inflammatory syndrome (IRIS), can induce sarcoid-like lesions in tissues. The pathogenesis of these granulomas is currently unknown because no pathogen has been identified to date in the lesions using morphological and/or microbiological approaches. However, the role of certain microbes, such as Mycobacterium tuberculosis, is still debated. The aim of this study was to look for the presence of M. tuberculosis in sarcoid-like lesions occurring in 14 AIDS patients treated with HAART. We used the PCR DNA amplification method in granulomas microdissected from sections stained by hematoxylin–eosin from formalin-fixed, paraffin-embedded specimens. Results were compared to those obtained from microdissected tuberculosis (TB) granulomas (15 patients) and from microdissected sarcoidosis granulomas (12 patients). M. tuberculosis DNA was undetectable from the microdissected sarcoid-like granulomas, whereas DNA from M. tuberculosis was isolated in all the microdissected TB granulomas and was absent in the microdissected sarcoidosis granulomas. Taken together, these data showed that M. tuberculosis DNA is not associated with the presence of sarcoid-like lesions occurring in HIV-positive patients treated with HAART.     

Bronchocentric granulomatosis

The clinical and morphologic features in 15 patients with bronchocentric granulomatosis were reviewed. Patients were divided into two groups on the basis of the morphologic findings. Group I consisted of five patients with necrotizing granulomas containing abundant eosinophils in the areas of necrosis. Three of these patients were asthmatic, two had elevated blood eosinophil counts, and in one there were fungal hyphae within necrotizing granulomas. In another case a sputum culture was positive for Aspergillus. The findings in these cases support the contention that some bronchocentric granulomas associated with tissue eosinophilia may represent a hypersensitivity reaction to inhaled Aspergillus. Group II included 10 patients with bronchocentric granulomas showing many polymorphonuclear cells but few eosinophils. None of these 10 had asthma, and blood eosinophilia was found in only one patient. The etiology and pathogenesis of these bronchocentric granulomas is unclear. The differences in morphology and clinical symptomatology between the two groups suggest that these lesions may arise from more than one etiologic agent and pathogenetic mechanism.Follow-up information was available for 11 individuals. Corticosteroids were given to four patients and lesions were resected from five patients. Neither recurrence of bronchocentric granulomas nor death due to them was reported.     

FOCAL PALISADING GRANULOMA IN THE PROSTATE AND BLADDER: A Clinicopathologic Study of 88 Total Cystectomy Specimens

In close inspection of 88 total cystectomy specimens, 20 were found to have rheumatoid nodule-like lesions known as "focal palisading granulomas". Nineteen of these nodules were from patients with a history of previous transurethral resection (TUR). Such granulomas were identified in the prostate in 3, in the bladder in 13, and in both prostate and bladder in another 3. The remaining one patient had undergone a cold cup biopsy followed by electric coagulation. The granulomas were characterized microscopically by the presence of central necrosis surrounded by palisading histiocytes and fibroblasts, and were situated in areas of the previous TUR. There were no granulomas in 20 other patients with no history of previous TUR and other surgical procedures. The lesions were commonly seen in the superficial zone of the bladder wall and in the prostate and, as proved by serial sections, opened onto the mucosal surface of the bladder and urethra, respectively. The observation confirmed that the focal palisading granulomas occurred not only in the prostate but also in the bladder, and seemed to be closely related to surgical procedures, especially to the electrocauterizing process, in both the bladder and prostate.     

Focal palisading granuloma in the prostate and bladder. A clinicopathologic study of 88 total cystectomy specimens

In close inspection of 88 total cystectomy specimens, 20 were found to have rheumatoid nodule-like lesions known as "focal palisading granulomas". Nineteen of these nodules were from patients with a history of previous transurethral resection (TUR). Such granulomas were identified in the prostate in 3, in the bladder in 13, and in both prostate and bladder in another 3. The remaining one patient had undergone a cold cup biopsy followed by electric coagulation. The granulomas were characterized microscopically by the presence of central necrosis surrounded by palisading histiocytes and fibroblasts, and were situated in areas of the previous TUR. There were no granulomas in 20 other patients with no history of previous TUR and other surgical procedures. The lesions were commonly seen in the superficial zone of the bladder wall and in the prostate and, as proved by serial sections, opened onto the mucosal surface of the bladder and urethra, respectively. The observation confirmed that the focal palisading granulomas occurred not only in the prostate but also in the bladder, and seemed to be closely related to surgical procedures, especially to the electrocauterizing process, in both the bladder and prostate.     

A comparative study of the histopathology and immunohistochemistry of pythiosis in horses, dogs and cattle

Twenty-one cases of pythiosis in horses (n = 10), dogs (n = 9) and cattle (n = 2) were investigated. The aetiology in all cases was confirmed by immunohistochemistry. Data related to the clinical course and outcome and localization of the lesions were obtained from pathology reports. The equine lesions consisted of fibrotic tissue with multiple, often coalescing, areas of immature granulation tissue encircling eosinophilic cores. Affected dogs had gastrointestinal and/or cutaneous lesions with either or both of a granulomatous/pyogranulomatous or necrotizing eosinophilic inflammatory reaction. In cattle, cutaneous lesions were characterized by multifocal to coalescing granulomas with surrounding fibrosis. The number of intralesional hyphae, the distribution of hyphae, the presence of angioinvasion and the nature of the local inflammatory reactions were associated with the different types of lesions observed.     

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.     

Flame figures associated with eosinophilic dermatosis of hematologic malignancy: is it possible to distinguish the condition from eosinophilic cellulitis in patients with hematoproliferative disease?

Eosinophilic dermatosis of hematologic malignancy is a multifaceted dermatosis with a wide morphological spectrum, presenting as pruritic, erythematous, papular and occasionally vesicular, urticarial, nodular eruptions. Histopathologically eosinophil infiltration in the super and deep dermis was found. We reported a case of eosinophilic dermatosis of hematologic malignancy presented as urticarial and vesicular lesions in a patient with chronic lymphocytic leukemia. A skin biopsy revealed a prominent subepidermal blister and a diffuse infiltrate of eosinophils with flame figures in the dermis and subcutaneous tissue. Although flame figures associated with eosinophilic dermatosis of hematologic malignancy is rarely reported, we believe that it would not seem unusual to find them in this skin disease. Eosinophilic cellulitis, which share clinical and histological features with eosinophilic dermatosis of hematologic malignancy, has also been described as showing an association with hematoproliferative diseases. In order to clearly describe eosinophilic dermatosis in patients with hematologic malignancies, the terminology eosinophilic dermatosis of hematologic malignancy, instead of eosinophilic cellulitis, would be a more suitable term in patients with eosinophilic dermatosis.     

The local immune response in ulcerative lesions of Buruli disease

Buruli disease (BU) is a progressive necrotic and ulcerative disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU is considered the third most common mycobacterial disease after tuberculosis and leprosy. Three clinical stages of the cutaneous lesions have been described in BU: pre-ulcerative, ulcerative and healed lesions. In this study we used immunohistochemistry and automated morphometry to determine the percentage of macrophages and of CD4/CD8 lymphocytes and their expression of interferon (IFN)-gamma, interleukin (IL)-10, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta. Expression of these cytokines was correlated with the inflammatory response evaluated by histopathology. All the studied BU ulcerative cases showed extensive necrosis and chronic inflammation. The most important feature was the presence or absence of granulomas co-existing with a mixed pro-inflammatory/anti-inflammatory cytokine balance. When granulomas were present significantly higher expression of IFN-gamma was seen, whereas in ulcerative lesions without granulomas there was increased expression of IL-10 and significantly higher bacillary counts. These features correlated with the chronicity of the lesions; longer-lasting lesions showed granulomas. Thus, granulomas were absent from relatively early ulcerative lesions, which contained more bacilli and little IFN-gamma, suggesting that at this stage of the disease strong suppression of the protective cellular immune response facilitates proliferation of bacilli.     

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.     

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.     

Renal cholesterol granulomas: identification and morphological pattern of development

Cholesterol granulomas are infrequent and rarely described renal lesions occurring usually in the interstitium, characterized by clusters of foreign body giant cells containing ingested cholesterol crystals. Over a seven-year period, we observed them in 5 of 789 (0.6%) renal biopsies from patients with nephrotic syndrome of varying glomerulopathies. Four patients had renal insufficiency at the time of biopsy, while the fifth developed it within three months. To define the lesions we studied the morphogenesis of cholesterol granulomas by light and electron microscopy. Initially small cholesterol crystals formed in tubular epithelium; the crystals enlarged and were released into tubular lumina where they elongated or were passed in the urine. Further luminal growth caused the crystals to become lodged at some point in the nephron, distort and destroy tubule cells, and pierce through basement membranes with subsequent exposure to interstitial monocytes and formation of granulomas. It is likely these morphological abnormalities evolve from lipid disturbances in the nephrotic syndrome.     

Recent advances in the diagnosis of Churg-Strauss syndrome.

Most pathologists assume that a diagnosis of Churg-Strauss syndrome (CSS) requires the finding of necrotizing vasculitis accompanied by granulomas with eosinophilic necrosis in the setting of asthma and eosinophilia. However, recent data indicate that this definition is too narrow and that adherence to it leads to cases of CSS being missed. CSS has an early, prevasculitic phase that is characterized by tissue infiltration by eosinophils without overt vasculitis. Tissue infiltration may take the form of a simple eosinophilia in any organ, and a fine-needle aspirate showing only eosinophils may suffice for the diagnosis in this situation. The prevasculitic phase appears to respond particularly well to steroids. Even in the vasculitic phase of CSS, many cases do not show a necrotizing vasculitis but often only an apparently nondestructive infiltration of vessel walls by eosinophils. In modern biopsy materials, granulomas frequently cannot be found. In the postvasculitic phase of CSS, healed vascular lesions resemble organized thrombi but typically show very extensive destruction of elastica and, often, an absence of eosinophils. The widespread use of steroids as therapy for asthma has led to the peculiar and confusing situation in which the steroid therapy accidentally suppresses CSS and changes in steroid treatment uncover the disease; this type of "formes frustes" CSS is now well recognized with leukotriene receptor antagonist treatment and will be seen with increasing frequency as other steroid-sparing therapies for asthma are introduced.     

The eosinophilic fibrohistiocytic lesion of the bone marrow

Summary Seven patients are described, six with severe osteoporosis and the seventh with osteogenesis imperfecta with moderate osteoporosis. The iliac bone marrow trephine biopsy specimens of all seven showed peculiar infiltrates consisting of elongated mast cells, eosinophils, plasma cells, and varying numbers of lymphocytes. Only one patient exhibited signs of allergy with urticaria pigmentosa; the other six patients had no abnormalities that could be related to a known mast cell disease. The lesions described here are the same as those described in five patients by Rywlin as eosinophilic fibrohistiocytic lesion in the bone marrow. However, in our methacrylate sections the fibrohistiocytes are shown to be mast cells. Although a relationship with drug hypersensitivity is disputed, the presence of the mast cells and eosinophils suggests an allergic condition.