Increased interleukin-27 production by antigen-presenting cells promotes regulatory T cell differentiation and contributes to inducing a remission in patients with eosinophilic granulomatosis with polyangiitis.

BACKGROUND: We investigated the cytokine production profiles of antigen-presenting cells (APCs) and the status of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in order to identify the cytokine profile that contributes to inducing differentiation of CD4(+) effector Th cells and regulatory T cells. METHODS: We counted the number of CD4(+)FOXP3(+) T cells, CD4(+)CD25(+)CTLA-4(+) T cells, CD4(+) T cells that predominantly produce IL-10 (Tr1 cells) and IL-17 (Th17 cells) and monocytes and monocyte-derived dendritic cells (mDCs) expressing Toll-like receptor (TLR)2 and TLR4 in the peripheral blood of 47 EGPA patients and 40 bronchial asthma patients (who did not have EGPA) and calculated the percentages of monocytes and mDCs that produced IL-23p19 and IL-27 in response to lipopolysaccharide (LPS) stimulation. RESULTS: Lower TLR4 expression was observed on the monocytes of relapsed EGPA patients and lower expression of both TLR2 and TLR4 on their mDCs than on the cells from EGPA patients in remission or non-EGPA patients. The percentages of monocytes expressing TLR4 were positively correlated with the percentages of regulatory T cells in peripheral blood. In addition, the percentages of monocytes and the percentages of mDCs that produced IL-27 and IL-23p19 in response to LPS stimulation were positively correlated with the percentages of Tr1 cells and Th17 cells in peripheral blood. A positive correlation was also found between the percentages of mDCs that produced IL-27 and the percentages of Tr1 cells. CONCLUSION: Increased dominancy of IL-23p19 and IL-27 production by the APCs of EGPA patients may be linked to differentiation of Th17 cells and Tr1 cells.

Operative case of Langerhans'cell histiocytosis of the skull with dural invasion. An immunohystochemical study of ki-67 expression of eosinophilic granuloma: case report and review of the literature.

Eosinophilic granuloma (EG), Letterer-Siwe disease and Hand-Schuller-Christian disease are collectively called Langherans-cell histiocytosis (LCH). While the latter two are systemic diseases, the former is a localized form of histiocytosis. Solitary EG of the skull are rare lesions characterized by a natural history not well defined yet. In this context, we report a case of a 23-year-old male suffering for a recurrent and progressive right parietal headache. On computed tomography (CT) it was observed an ostelytic lesion which on magnetic resonance imaging (MRI) appeared as an hyperintense soft mass on both T1 and T2 weighted images. The lesion showed a marked and heterogeneous enhancement after gadolinium administration. The surgical excision was complete and the severe headache disappeared. Immunohistochemical analysis of the specimen indicated an eosinophilic granuloma characterized by Ki-67 nuclear antigen expression with a labeling index of 20%. In the pertinent literature we have found two aggressive cases of EG showing the Ki-67 expression with a respectively 6.2% (occipital bone granuloma) and 10% (parietal bone granuloma) labeling index. That high proliferative activity suggests a local Langherans' cell proliferation along with an exuberant inflammatory response and also explains the aggressive clinical course and the rapid expansion of the lesion observed in some rare cases of solitary EG. This is the third case-report of calvarial EG characterized by Ki-67 nuclear antigen expression.

Vanek's polyp or inflammatory fibroid polyp. Case report and review of the literature.

BACKGROUND: Intussusception in an adult must make us suspect the presence of a tumor (benign or potentially dangerous) as the most frequent cause. Accurate diagnosis is of great importance in order to provide appropriate treatment and improve patient prognosis. CLINICAL CASE: We report the case of a 42-year-old male with abdominal pain. We performed a CT and found a small bowel intussusception. Definitive diagnosis according to the surgical specimen was inflammatory fibroid polyp (Vanek's polyp). CONCLUSIONS: Vanek's polyp is a benign lesion that occurs most frequently in the stomach and secondarily in the small bowel. Generally, it is uncommon, and its etiology is not completely known. Accurate diagnosis is done with immunohistochemistry. Because of the consequences that depend on the size and location of the lesion, it may be considered a malignant lesion. Treatment is resection.

Expression of matrix metalloproteinase-9 and significance of a macrophage assay in eosinophilic granuloma.

Although most cases of eosinophilic granuloma (an immune-mediated lesion) do not behave in an aggressive manner, occasionally, recurrence after treatment has been observed. This study aims to investigate the significance and relationship of matrix metalloproteinase-9 (MMP-9) and infiltration of macrophages in eosinophilic granulomas (EGs). The immunohistochemical strept avidin-biotin complex method was used to detect the expression of MMP-9 and CD-68 (for labeling macrophages) in 13 cases of EG. Three of whom showed local recurrence. The results showed that many of the Langerhans histiocytic cells, which reacted positively with MMP-9 protein antibody, were immunolabeled with CD-68 antibody. The results showed that there is a highly significant relationship between the expression of MMP-9 and macrophage count in EGs (P < .001), with recurrent lesions showing a higher mean expression of both MMP-9 and CD-68. In conclusion, there may be a cooperation between macrophages and MMP-9 in EGs, which correlates well with local recurrence. Their expression may therefore provide some prognostic indication of the possible aggressive and recurrence behavior of this lesion.

Eosinophilic granuloma manifesting as painless cervical lymphadenopathy in a patient positive for human immunodeficiency virus 1.

Eosinophilic granuloma is rarely reported within lymph nodes. Furthermore, it is even more rarely reported in the setting of human immunodeficiency virus (HIV) infection. No definitive etiologic association exists between Langerhans cell histiocytosis (LCH) and HIV. However, their potential relationship underscores the significance of cytokines and their influence on biological niches required for Langerhans development and homeostasis.

Aggressive eosinophilic granuloma of the parietal bone. An immunohystochemical study of Ki-67 expression.

Solitary eosinophilic granuloma (EG) of the skull is a rare lesion, the natural history of which is still to be defined. We report a case of a 26-year-old female who presented with progressive headache and nausea accompanied by a painful firm mass in her left parietal region, which grew very rapidly during the last two weeks before admission. Computed tomography scan showed an osteolytic lesion, which on magnetic resonance imaging appeared hyperintense on both T1- and T2-weighted images, with marked and heterogeneous enhancement after gadolinium administration. Total surgical excision of the lesion was performed and histopathological diagnosis was compatible with eosinophilic granuloma. Immuno-histochemical study of Ki-67 antigen expression was also performed with a labelling index of 10%. In a review of the pertinent literature, we found one case report showing a Ki-67 labelling index of 6.2% in a patient harboring EG of the occipital bone. These two relatively high percentages of proliferative activity suggest a role of local Langerhans'cell proliferation, along with that of inflammatory response, in the aggressive clinical course and rapid expansion observed in some rare cases of solitary eosinophilic granuloma.

Traumatic ulcerative granuloma with stromal eosinophilia: a reactive lesion of the oral mucosa.

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a benign lesion of the oral mucosa of an unclear pathogenesis. We analyzed the profile of the inflammatory infiltrate in 12 cases of TUGSE by using immunohistochemical analysis and polymerase chain reaction-based repertoire analysis to detect T- and B-cell receptor gene rearrangements. The inflammatory infiltrate consisted in most cases of B and T lymphocytes, macrophages, abundant eosinophils, and large atypical cells. In 5 cases, CD30+ cells were found. Spectratyping analysis displayed a polyclonal rearrangement of the T-cell receptor g gene in 6 cases and oligoclonality in 5 cases. Monoclonality was observed in 1 case that also fulfilled histologic criteria for lymphoma. Healing was uneventful in all cases, including the one suspected of being lymphoma, with no recurrences in more than 2 years'follow-up. TUGSE can be regarded reactive. Some cases, however, may harbor a dominant clonal T-cell population; in these cases, long-term follow-up is mandatory.

Splendore-Hoeppli phenomenon in the conjunctiva: immunohistochemical analysis.

PURPOSE: To present two cases of conjunctival lesions exhibiting the Splendore-Hoeppli phenomenon, each with different immunohistochemical findings. DESIGN: Interventional case reports. METHODS: Two young males with conjunctival lesions underwent biopsy. Demographic data and timing of biopsy were extracted from the charts. The biopsy specimens were formalin fixed and paraffin embedded for light microscopy. Immunohistochemical staining using the peroxidase method was carried out on each for IgG, IgM, IgA, the C3 component of complement, and eosinophilic major basic protein. MAIN OUTCOME MEASURES: Presence of positive or negative staining for the various antigens. RESULTS: Both biopsy specimens exhibited the Splendore-Hoeppli phenomenon, a morphologically unique process consisting of an amorphous, eosinophilic material surrounded by epithelioid histiocytes, multinucleated giant cells, lymphocytes, and eosinophils. Two staining patterns were seen. One revealed predominately immunoglobulin deposition, whereas the other revealed primarily eosinophilic major basic protein. This is the first instance we are aware of in which eosinophilic major basic protein was the predominate finding in an ocular specimen. CONCLUSION: The composition of Splendore-Hoeppli phenomenon material varies and may be related to various factors, including timing of biopsy and prior treatment.

Unusual recurrence in ureters and maxillary sinus of Langerhans cell histiocytosis involving mastoid bone.

We present a case of Langerhans cell histiocytosis (LCH) diagnosed in the mastoid bone. The tumor recurred in the ureter and maxillary sinus mucosa two years later. The diagnosis of LCH was based on morphology and immunohistochemistry. Involvement of the ureter and the maxillary sinus in LCH is extremely rare. To the best of our knowledge, this is the first case of LCH affecting the mastoid bone in a 16-year-old boy and recurring later in the ureter and maxillary sinus mucosa.

Eosinophil-rich CD30+ lymphoproliferative disorder of the oral mucosa. A form of "traumatic eosinophilic granuloma".

We describe 3 patients who had oral mucosal lesions with features of traumatic eosinophilic granuloma (TEG) and containing CD30+ atypical cells. In 1 patient, the oral lesion was followed by skin nodules. All lesions were evaluated histologically, by immunohistochemical analysis, and by polymerase chain reaction (PCR) analysis of the T-cell receptor (TCR) gamma chain gene. All oral lesions were characterized by a dense and deeply infiltrative lymphoproliferation, showing epitheliotropism and massive eosinophilia. They contained atypical large lymphoid cells, which expressed T-cell markers and CD30. PCR analysis showed a monoclonal rearrangement of the TCR gamma chain gene in all lesions and, in 1 patient, the same rearrangement in the oral and cutaneous specimens. The lesions in these patients seem to be the oral counterpart of the spectrum of primary cutaneous CD30+ lymphoproliferative disorders and should be recognized as such to avoid a diagnosis of large T-cell lymphoma and possible consequent overtreatment. However, they represent only a subset among several others within the complex and heterogeneous category of disorders referred to as TEG.

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.

Evaluation of Felis domesticus allergen I as a possible autoallergen in cats with eosinophilic granuloma complex.

OBJECTIVE: To investigate the role of Felis domesticus allergen I (Feld I) in the pathogenesis of eosinophilic granuloma complex (EGC) in cats. ANIMALS: 7 healthy cats and 6 cats with EGC. PROCEDURE: Epidermis was removed from 4 areas. Rubber stoppers filled with Feld I, saline (0.9% NaCl) solution, and PBS solution were glued to the skin lesions and removed 48 hours later. Fluid within each stopper was collected. Biopsy specimens were obtained at each site, snap frozen, and stored at -70 C. Total and differential numbers of cells in fluid were counted. Biopsy specimens were stained by use of monoclonal antibodies against feline CD4, CD8 and CD3. Data were analyzed by use of multivariate repeated-measures analysis. RESULTS: Healthy cats had a significant increase in number of CD3+ cells, compared with number of CD4+ and CD8+ cells, and Feld I caused a significant increase in number of CD3+ cells, compared with PBS or saline solutions. Cats with EGC had a significant increase in number of CD3+ cells, compared with number of CD4+ and CD8+ cells, and Feld I caused a significant increase in number of CD3+ and CD4+ cells, compared with PBS or saline solutions. Cats with EGC had an increased CD4+ response, a significantly decreased CD8+ response, and a significantly increased CD4-to-CD8 ratio compared with healthy cats. CONCLUSIONS AND CLINICAL RELEVANCE: The increased CD4+ response, significantly decreased CD8+ response, and significantly increased CD4-to-CD8 ratio are comparable to results in atopic people and allergic cats. Therefore, Feld I could be an autoallergen responsible for chronic inflammatory reactions in cats with EGC.

Eosinophilic granuloma of the temporal bone.

Histiocytosis X or Langerhans cell histiocytosis (LCH) is a disease that possesses three less distinctive and overlapping states called eosinophilic granuloma (EG), Hand-Schuller-Christian (HSC) disease and Letterer-Siwe (LS) disease. EG is the least severe and localized form of all LCHs and possesses the best prognostic result. A high index of suspicion is required to diagnose the EG, especially when an ear disease is refractory to medical treatment. Early detection is important to manage the EG properly and to minimize the complications or sequels of treatment. Definitive diagnosis of histiocytosis is made by histopathological means and immunohistochemical detection of S-100 and CD1 antigens in the tissue samples. And differential diagnosis of the subgroups is made according to the clinical manifestations such as visceral organ or bone involvement. Surgical excision, radiotherapy and chemotherapy, either alone or in combination, are the main treatment options.

Activated eosinophils are the major source of Th2-associated cytokines in the schistosome granuloma.

Eosinophils are a numerically dominant cell population within the schistosome granuloma. These granuloma eosinophils can produce a variety of cytokines, including IL-2, IL-4, IL-5, and IFN-gamma. Therefore, eosinophils may play a key role in the determination of the unique cytokine microenvironment within the granuloma milieu. These studies investigated the potential role of eosinophils in the regulation of granuloma immunopathology. We have characterized spleen- and granuloma-derived eosinophils based on cellular activation and cytokine production during the development of murine schistosomiasis. Based on the criteria of hypodensity and CD69 expression, granuloma eosinophils were highly activated and very homogeneous at 7 and 11 wk postinfection. Splenic eosinophils were also activated at 7 wk postinfection, but were much more heterogeneous than their granuloma counterparts. By 11 wk postinfection, few hypodense splenic eosinophils were observed. Eosinophils represented the majority of cytokine-producing cells in the granuloma and were a dominant source of IL-4. Eosinophils also produced IL-2, IL-5, and IFN-gamma, using the criteria of mRNA in situ hybridization and intracellular cytokine staining by FACS. Granuloma eosinophil activation and cytokine production were greatest at the time of maximum granuloma formation, i.e., 10-12 wk after initial cercarial exposure. Therefore, locally activated eosinophils, not Th2 lymphocytes, produce the majority of Th2 cytokines in the granuloma milieu and may be important determinators of immunopathology in schistosomiasis.

Tissue localization of transforming growth factor-beta1 in pulmonary eosinophilic granuloma.

Pulmonary eosinophilic granuloma is characterized by infiltration of the lungs with fibronodular lesions containing specialized Langerhans' cells. In some patients, progressive pulmonary fibrosis leads to significant respiratory impairment. Transforming growth factor-beta1 (TGF-beta1) promotes fibrosis by enhancing the synthesis of extracellular matrix components. The role of TGF-beta1 in promoting fibrosis in the setting of pulmonary eosinophilic granuloma is currently unknown. We used immunohistochemistry to evaluate the extent and distribution of TGF-beta1 and the extracellular matrix components type I collagen and decorin, a TGF-beta1-binding proteoglycan. Lung biopsies from 11 patients with pulmonary eosinophilic granuloma were evaluated. In biopsies with active inflammatory lesions containing Langerhans' cells, hyperplastic type 2 pneumocytes and alveolar macrophages within and surrounding the fibronodular lesions contained abundant TGF-beta1. Langerhans' cells were consistently devoid of immunoreactive TGF-beta1. Active inflammatory lesions also exhibited staining for decorin, in a loosely organized distribution. Advanced fibrotic lesions of eosinophilic granuloma, containing minimal inflammatory cells and few or no Langerhans' cells, exhibited weak or absent staining for TGF-beta1 within either hyperplastic type 2 pneumocytes or alveolar macrophages. The fibroconnective tissues of these advanced fibrotic lesions consistently revealed dense staining for decorin. Through their actions on extracellular matrix protein accumulation, TGF-beta1 and the TGF-beta1-binding proteoglycan decorin may modulate fibrotic repair accompanying pulmonary eosinophilic granuloma.

Intraoperative diagnosis of osseous eosinophilic granuloma by touch preparation: report of two cases with immunohistochemistry and electron microscopy.

We report two cases of eosinophilic granuloma (Langerhans cell histiocytosis) of bone, the diagnosis of which was made by intraoperative cytological evaluation of touch preparation. The clinical, cytologic, histologic, immunohistochemical, and electron microscopic findings are presented. Our cases demonstrate and further support that intraoperative cytologic analysis by touch preparation is a very useful method of diagnosis during intraoperative consultation on a bony specimen.

Eosinophilic cationic protein in chronic eosinophilic pneumonia and eosinophilic granuloma.

We measured eosinophilic cationic protein (ECP) concentrations in the circulation and bronchoalveolar lavage (BAL) fluids from patients with chronic eosinophilic pneumonia, patients with eosinophilic granuloma, and normal control subjects. Significantly increased ECP concentrations were found in the circulation of patients with chronic eosinophilic pneumonia and with eosinophilic granuloma compared with those found in control subjects. The ECP concentrations were well correlated to eosinophil counts in the circulation of patients with chronic eosinophilic pneumonia, while they were not in patients with eosinophilic granuloma. Chronic eosinophilic pneumonia patients had prominently increased ECP concentrations in BAL fluids compared with those found in control subjects, while eosinophilic granuloma patients did not. Those concentrations in chronic eosinophilic pneumonia patients were well correlated to eosinophil counts in the BAL fluid. Corticosteroid therapy remarkably decreased circulating ECP concentrations in three patients with chronic eosinophilic pneumonia, but it had no significant effects in two patients with eosinophilic granuloma. Measurement of ECP concentrations seems to be useful to evaluate the disease activity of chronic eosinophilic pneumonia.

Immunohistochemical phenotypes of histioeosinophilic granulomas of thymus and reactive eosinophilic pleuritis.

Immunohistochemical phenotyping of 7 cases of histioeosinophilic granulomas of thymus and 4 cases of reactive eosinophilic pleuritis was performed. All 11 cases of these 2 entities reacted identically. This supports the view that these 2 lesions are similar in nature. Both lesions are reactions to the presence of insufflated gas and its resorption.

Immunohistochemical and ultrastructural examination of histiocytosis X cells in pulmonary eosinophilic granuloma.

We describe histological, immunohistochemical, and ultrastructural findings in pulmonary eosinophilic granuloma (PEG) from three patients. The specimens were taken by open-lung biopsy. The lesions of the lung were composed of histiocytic cells, macrophages and eosinophils. The histiocytic cells reacted positively with anti-S-100 protein antibody. The histiocytic cells had various types of Birbeck granules in the cytoplasm. The histiocytic cells were histiocytosis X (HX) cells considered to be derived from Langerhans cells. Sporadic mitosis of HX cells was observed. Some HX cells had migrated from the lesions into the alveolar spaces through the alveolar cell layers. In the lesions of PEG, HX cells have self-reproduction and migration capability.