2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis.

OBJECTIVE: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1×109/L (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3-ANCA positivity (-3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1) and haematuria (-1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% CI 77% to 91%) and the specificity was 99% (95% CI 98% to 100%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis demonstrate strong performance characteristics and are validated for use in research.

Histological Classification and Differential Diagnosis of Nonepisodic Angioedema With Eosinophilia: A Clinicopathologic Study of 12 Cases With Literature Review.

Nonepisodic angioedema with eosinophilia (NEAE) is a rare condition characterized with monoepisodic angioedema, a nonfebrile state, eosinophilia, normal serum IgM levels, and lack of internal organ involvement. The histology of this disease is not yet well known. The purpose of this study was to characterize the histopathologic features of NEAE. Twelve cases of clinically confirmed NEAE were retrieved from 6 institutions, and these cases were reviewed regarding the clinical data and histopathology, particularly regarding granulomatous lesions. The authors demonstrated that the histology of NEAE can be classified into 3 patterns that of eosinophilic granulomatous panniculitis (7/12 cases), eosinophilic dermatitis without granuloma formation (3/12 cases), and invisible dermatosis (2/12 cases). Six of the 7 granulomatous cases showed the characteristic eosinophilic granulomatous lesions containing individual necrotic adipocytes with membranous fat changes, which could be a differential clue to the diagnosis of NEAE. Review of the previously reported cases (n = 37) revealed that the histological classification could be adaptable to these reported cases. The authors should recognize the histological variation of NEAE and distinguish it from the histological mimickers, including eosinophilic granulomatosis with polyangiitis, erythema nodosum, hypereosinophilic syndrome, and episodic angioedema with eosinophilia.

Traumatic ulcerative granuloma with stromal eosinophilia of the oral mucosa: histological and immunohistochemical analysis of three cases.

Traumatic ulcerative granuloma with stromal eosinophilia is an ulcerated oral lesion which pathogenesis is still unclear. Clinically, this disease is characterized by the presence of chronic ulcerative lesions with elevated and indurated borders in the oral mucosa. It usually develops rapidly and persists for several weeks or months, it presents mainly on the tongue but other areas such as gingival, cheek and vestibular mucosa may also be involved. We report three cases showing their clinical, histological and immunohistochemical analysis. In this study the authors underline the importance of a correct differential diagnosis and monitoring of these patients in order to prevent the development of possible serious complications.

Eosinophilic granuloma of the jaws: an analysis of clinical and radiographic presentation.

Eosinophilic granuloma (EG) is the localized and mildest form of histiocytosis-X group of diseases. In this study, 22 patients of pathologically proven EG involving the jaws were retrospectively studied concerning the clinical and radiographic presentation. The clinical and radiographic presentation of the 22 cases was quite varied, and the accuracy of clinical and radiographic diagnosis was low. However, the clinical and radiographic presentation correlated with the lesion site, and accordingly all the jaw lesions could be divided into three types (Alveolar Type, Intraosseous Type, and Mixed Type). Our classification based on the lesion sites reveals the correlation between the clinical and radiographic presentation of EG and the lesion sites, and may be useful in the identification of lesions of EG in the jaws.

Histopathological study of feline eosinophilic dermatoses.

A retrospective study was conducted on skin specimens from 24 cats with eosinophilic granuloma complex. The specimens were stained with haematoxylin and eosin and Gallego's trichrome stain. In all specimens, flame figures and/or large foci of so-called "collagen degeneration" were detected and histopathological features were not predictive of the clinical picture. Use of the term eosinophilic dermatosis was advocated in diagnostic dermatopathology. On trichrome-stained sections, normally stained collagen fibres were identified in the middle of both flame figures and large foci of "collagen degeneration" and the debris surrounding collagen bundles showed the same tinctorial properties as eosinophil granules. Eosinophil degranulation around collagen bundles seemed to represent the major pathogenetic event in these lesions, analogous with human flame figures. The term flame figures might therefore be more accurately used to designate those foci of eosinophilic to partly basophilic debris commonly referred to as "collagen degeneration".

Traumatic eosinophilic granuloma of the oral mucosa: a CD30+(Ki-1) lymphoproliferative disorder?

Traumatic eosinophilic granuloma of the oral mucosa, also known as eosinophilic ulcer, is considered to be a reactive lesion of unknown aetiology. It usually presents as a tongue ulcer and injury has been considered to play a role in its cause. We present a 72-year-old man who had suffered multiple episodes of recurrent eosinophilic ulcers of the oral mucosa which underwent self-healing. Biopsy specimens (including fresh tissue) were studied with a combination of histology, electron microscopy and immunohistochemistry. A dense cell infiltrate composed of eosinophilis, lymphocytes and large mononuclear cells was constantly shown. Immunostains showed that the infiltrate was mainly composed of CD3+,CD4+,CD8-T-cells and CD1a + dendritic cells. Approximately 70% of the T-cells expressed CD30 (Ki-1) antigen. On the basis of the clinical behaviour, histology and antigenic features, it seems reasonable to suggest that traumatic eosinophilic granuloma of the oral mucosa may represent the oral countpart of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders. This group of cutaneous lymphomas are indeed characterised by non-aggressive clinical behaviour (sequential evolution in ulceration, necrosis and self-regression) and expression of CD30 antigen by the infiltrating large T-cells.

Langerhans cell (eosinophilic) granulomatosis. A clinicopathologic study encompassing 50 years.

We summarize our experience with 238 cases of Langerhans cell granulomatosis (LCG), 198 of whom were followed for a median period of 10.5 years. Our patients did well unless overtreated, and no deaths were attributed to the disorder itself. The disease may appear in unifocal or multifocal form, and treatment is based on this fact. Virtually all patients recovered completely except for occasional residual orthopedic problems or residual diabetes insipidus. Several of the patients underwent subsequent pregnancies without difficulty. The granulomas primarily occur in bone, but lung, skin, and lymph nodal involvement is not uncommon. Involvement of thyroid, thymus, and other sites is rare. The hallmark of the disease is the accumulation of Langerhans cells (LCs). We review the pathology of LCG by histology, electron microscopy, and immunolabeling. LCs originally were identified in squamous epithelium, but these cells are part of the widespread system of dendritic cells. The latter cells, which arise from CD34+ progenitors, are specialized and efficient antigen-presenting cells for T-cell-mediated immunity. In LCG, however, the major associated cells are not T cells, but mature eosinophils: hence the original name eosinophilic granuloma. Confusion about terminology has been based upon the scanty and rather crude pathology reports in the original literature. The term histiocytosis X was meant to cover a spectrum of three diseases--eosinophilic granuloma, Hand-Schüller-Christian disease (HSC), and Letterer-Siwe disease (LS)--but HSC and LS have no basis in pathology and hence the terms are meaningless. The term HSC has become a synonym for multifocal eosinophilic granuloma (LCG). The term LS has been used in reporting a number of benign, malignant, or unknown conditions. We prefer the term LCG to avoid confusion with the term histiocytosis X because there is evidence that the LC is not a member of the mononuclear phagocyte system and hence not a tissue macrophage, and because the use of the term "histiocyte" has become a convenience in much of the literature when reporting incompletely understood diseases.

[Uni- and multifocal eosinophilic granulomas in adults. Diagnostic and therapeutic approaches. Apropos of 3 cases]. / Granulomes éosinophiles uni- et multifocaux de l'adulte. Approaches diagnostiques et thérapeutiques. A propos de trios observations. multifocal eosinophilic granulomas in adults. Diagnostic and therapeutic approaches. Apropos of 3 cases]

Unifocal and multifocal eosinophilic granuloma are Langerhans cell histiocytosis of unknown cause. Over the last 10 years, recent insights in pathogenesis and characterization of this pathology have been made. The authors report three cases of adult unifocal and multifocal eosinophilic granuloma. A review of literature underlines diagnostic features and therapeutic aspects of this disease.

Histiocitosis X pulmonar primaria (granuloma eosinofílico pulmonar)

La histiocitosis X pulmonar primaria es una patología infrecuente que afecta predominantemente a personas entre los 20 y los 40 años, usualmente con historia de tabaquismo. Presentamos un grupo de tres pacientes con esta entidad que se estudiaron en el Hospital Santa Clara en los últimos 20 años. Los síntomas más frecuentes fueron tos con expectoración mucosa y disnea. En todos se documentó historia de tabaquismo. La radiografía de tórax mostró infiltrado intersticial reticulonodular difuso, con volumen pulmonar normal y signos de hipertensión pulmonar precapilar. Todos se presentaron con hipoxemia severa y cor pulmonale. La histopatología confirmó el diagnóstico de histiocitosis X pulmonar primaria.

[Eosinophilic granuloma of the maxilla]. / Ziarniniak kwasochlonny szczeki.

The author, on the basis of 72 cases of eosinophilic granuloma of the viscerocranium treated in the past 41 years suggested his own terminology. He distinguishes several forms depending on their localization: 1) formae simplices granulomatosis eosinophilici: gingivae, interosseum, tunicae mucosae sinus maxillaris. 2) formae mixtae granulomatosis eosinophilici: gingivo- osseum, gingivo-osseo-sinusale, osseo-vestibulare, osseo-sinusale, sinu-osseo-vestibulare. The first part of the mixed form points the initial place of the focus of eosinophilic granuloma, the latter suggests the direction of expansion of the lesions. The author discussed the methods and results of applied by him therapy.

[Classification of benign tumors and cysts of the jaws]. / Classification des tumeurs bénignes et kystes des maxillaires.

On the basis of 324 cases of maxillary tumours, the authors review the classification of these neoplasms. The most frequent tumours are benign epithelial odontogenic tumours, which represent 55% of all tumours. The most common of these tumours is the ameloblastoma, followed by the odontomas. Most of the tumours of non-dental origin are benign (72% of this group). Amongst the malignant tumours, osteosarcomas are much more common than chondrosarcomas. The authors also discuss the various types of cyst and their respective relative frequency.

[Cytological classification of bone tumors]. / Tsitologicheskaia klassifikatsiia opukholei kostei.

The creation of a classification is a first need for the improvement of the cytological diagnosis. The cytologic classification of bone tumours is worked out on the basis of the International Histological Classification. The possibilities and limitations of the cytologic method are taken into consideration. A brief description of all nosological entities mentioned in the classification is given.

Histiocytosis X: diagnosis by electron microscopy.

The three histiocytosis X diseases are often initially misdiagnosed because of their frequently slow and insidious onset. Cutaneous lesions are commonly seen and are often the initial manifestation. The atypical histiocytes in all clinical types of histiocytosis X contain characteristic intracytoplasmic granules that can be seen with the electron microscope. Skin biopsy is thus a simple and rapid method for confirming the diagnosis of histiocytosis X.

The histiocytic disorders: a pathophysiologic analysis.

The histiocytoses are a diverse group of disorders involving cells of the mononuclear phagocyte series. These diseases are usually characterized by proliferation and activation of macrophages caused either by external stimuli or by an intrinsic cellular abnormality. We propose that these conditions be classified as reactive histiocytosis (inciting agent known or unknown), lipid storage disorder, and mononuclear phagocyte neoplasia based on apparent cause and natural history. Recent knowledge of monocyte-macrophage development and function allows for construction of pathophysiologic models of diseases formerly approached in a descriptive fashion. Macrophage activation appears to mediate many clinical features of th histiocytic disorders, such as hemophagocytosis, fever, and osteolysis. Further understanding of the pathogenesis of the histiocytic disorders should lead to improved therapy.

[Malignant hypereosinophilic syndrome. Report of an exceptional case (author's transl)]. / Síndrome hipereosinofílico maligno: presentación de un caso excepcional.

The case of a 43-year-old man with a highly malignant hypereosinophilic syndrome is reported. The condition is classified as such according to Hardy and Anderson's criteria, accepted by many other authors. Other diseases of known etiology which may present high levels of eosinophils in the peripheral blood, such as parasitosis, allergies, neoplasias, collagenosis, etc., were discounted beforehand. The difficulties in distinguishing between these diseases are discussed; they are often accompanied by clinical manifestations which also arise in very different conditions including eosinophilic leukemia, Engfeldt and Zetterström's eosinophilic collagenosis, Löffler's fibroplastic endocarditis, etc. A particularly striking feature of this condition is the formation of large tumor masses of mature eosinophils. They begin in various bones, which they destroy almost completely, and invade the surrounding tissues, destroying them as well. These tumors act similarly to malignant eosinophilic myelocytomas, a fact which has not been reported previously in the literature as far as we know. Although the eosinophils act as though they were neoplastic, they maintain the characteristics of mature cells, both cytomorphologically and ultrastructurally as well as cytochemically (consistently chloroacetate esterase negative). The tendency to diagnose eosinophilic leukemia solely on the basis of the malignancy of the condition and a tissue infiltration of eosinophils without determining the existence of cytologic and/or cytochemical anomalies of the cells showing them to be leukemic is discussed. The authors were unable to find any reports in the literature in which the eosinophils were presented with unmistakeably blastic cellular characteristics. Various nosologic considerations are offered.