BACKGROUND: Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders in the L (Langerhans) group diseases. They range from self-limited benign diseases to lethal disseminated forms.
METHODS: This retrospective study was conducted in 3 tertiary hospitals in Saudi Arabia and Brazil. Histopathological records were searched for all patients diagnosed with ocular and periocular histiocytic disorders from January 1993 to December 2018. Histopathological slides and medical files were reviewed for data collection and simple analysis of demographics, clinical manifestations, and management. The relevant literature is reviewed.
RESULTS: Twenty-two eyes of 18 patients with biopsy-proven histiocytic disorders in the L group were included. Female-to-male ratio was 1.25:1. Average age at presentation was 14 years (range, 1-54). LCH was diagnosed in 14 eyes, while eight eyes had ECD. All LCH cases were unilateral and confined to the bone as cases of eosinophilic granuloma (EG), while patients with ECD were bilateral. Commonest presentations in EG and ECD were eyelid swelling (85.7%) and periocular xanthomas (75%), respectively. Orbit was involved in 100% of EG cases, with bony erosion in 54.5%. Relevant systemic involvement was found in 100% of ECD and 21% of EG cases. Surgical intervention was needed in 16 of the 22 eyes (72.7%). All EG and 25% of patients with ECD required surgical excision.
CONCLUSIONS: Histiocytic disorders are a rare group of diseases, including the L group. Relevant systemic associations require specific and selective therapy. A high clinical index and multidisciplinary collaboration are essential for the proper evaluation and management of these patients.

OBJECTIVE: Ophthalmic histiocytic lesions comprise a heterogeneous rare group of disorders that are characterized by an abnormal proliferation of histiocytes and may affect all age groups of both sexes. The aim of this study was to highlight the basic demographic, clinical, and histopathological characteristics of this rare group of diseases in ophthalmic practice, which has not been previously studied in this area. Only individual cases have been previously reported.
METHODS: This was a retrospective study of all biopsied ocular and periocular histiocytic lesions from two centers, King Khaled Eye Specialist Hospital (KKESH) and King Abdulaziz University Hospital (KAUH) in Riyadh, Saudi Arabia, from January 1993 to December 2018. The histopathological diagnosis was confirmed, and the cases were re-classified by reviewing all histopathological slides. The corresponding demographic and clinical data were analyzed. A relevant literature review was also carried out for comparison of our collected analyzed data to published data and to draw our own conclusions.
RESULTS: A total of 34 ocular/periocular histiocytic lesions in 28 patients who were mostly Saudis (92.9%) were included. The male-to-female ratio was 4:3. The median age at presentation was 6.4 years (range: 2.8-35 years). Twenty-two patients had unilateral involvement, and six patients had bilateral lesions. In patients with Langerhans cell histiocytosis (LCH; L group), the most common presenting findings were eyelid swelling (75%), periocular tenderness (37.5%), proptosis/globe displacement (37.5%) eyelid erythema (25%), and orbital pain (12.5%). In patients with Rosai Dorfman disease (RDD; R group), proptosis/globe displacement occurred in all patients and 80% had decreased vision. Patients in the C group (Cutaneous non-LCH histiocytoses) had variable clinical features because of the different locations of the histiocytic lesions, with the majority involving the eyelids (66.7%). Diagnosis was accurately reached clinically in 38.8%, 33.7%, and 46.7% of patients in the L, C, and R groups, respectively. Overall, the clinical diagnosis was in concordance with the histopathologic diagnosis in 14 out of 34 lesions (41.2%).
CONCLUSIONS: Histiocytic disease is more likely to be overlooked clinically owing to its rarity. In the C group, juvenile xanthogranuloma (JXG) was the most commonly encountered histiocytic lesion and had a tendency to present at a later age with extremely rare intraocular involvement in contrast to previously published reports. The median age at presentation was higher in group R. All patients in group L had strictly unilateral disease, while RDD (group R) was most commonly bilateral. Future research on genetic aspects, management, and prognosis is necessary.

BACKGROUND: Acetabular roof lesions (ARLs) in children are uncommon and may involve a variety of diseases. The acetabular roof is the main weight-bearing area of the hip joint, and lesions affecting the acetabular roof lead to fluid accumulation in the hip joint, causing hip pain and claudication. Methods for diagnosing and treating ARLs and the prognosis after treatment are rarely reported. We present our experience in a group of children and teenagers with ARLs to retrospectively explore the clinical and imaging features and histopathological diagnosis and report the treatment methods and follow-up observations.
METHODS: Patients with ARLs admitted to the Children\'s Hospital of Chongqing Medical University from April 2011 to September 2018 were selected retrospectively. We collected the basic information of patients (name, sex, age), main symptoms and signs, results of various laboratory tests, treatment methods, and intraoperative observations through the hospital medical record system. We collected X-ray, computed tomography (CT), magnetic resonance imaging (MRI) and pathological examination data through the Picture Archiving and Communications System. Follow-up data were collected through an outpatient medical record system, telephone, and chat software (such as WeChat). We used descriptive methods to analyze the lesion structure and destruction mode based on the imaging findings and histopathological diagnosis.
RESULTS: There were 14 ARL patients, including 6 with eosinophilic granuloma (EG), 5 with chronic osteomyelitis, 2 with bone cyst, and 1 with tuberculosis. One patient underwent percutaneous needle biopsy, 2 underwent open biopsy, and 11 underwent curettage; among them, 5 patients also underwent bone grafting. These lesions had no characteristic imaging findings, and the diagnosis was mainly based on histopathological examination. Most patients showed complete symptom resolution and good hip function at the 1-year follow-up.
CONCLUSIONS: ARLs are not common in children. The types of lesions are diverse and mostly benign, with EG being most common. Malignant tumors may also occur, such as Ewing\'s sarcoma, non-Hodgkin\'s lymphoma, metastases and neuroblastoma. CT and MRI can be helpful in diagnosing certain cases, but incisional biopsy is required in most cases.

The European Eosinophilic Granulomatosis with Polyangiitis (EGPA) study group first gathered in Firenze in December 2018. The discussion was centred around the clinical and therapeutic needs in EGPA which still remain unmet. Indeed, EGPA is a puzzling and rare disease which shares clinical features with other anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) and hypereosinophilic syndromes (HESs). Some of the recommendations published in 2015 are based on data derived from EGPA-related diseases, rather than from EGPA itself, and therefore need to be updated. Thus, the aim of the meeting was to stimulate ongoing research, to promote collaborative European studies and to define the main issues on which future studies should be focused. Current fields of research on EGPA include potential serological biomarkers of disease activity and of specific organ involvement, possible links between different genetic variants and clinical phenotypes, and new therapeutic perspectives. Herein, we give an overview of the meeting with the goal to stimulate an international collaboration and new points of discussion.

BACKGROUND: The incidence and radiological patterns of eosinophilic granuloma (EG) in China is not clear. We described the incidence, presentation, and imaging characteristics of Chinese EG patients in a tertiary hospital.
METHODS: A retrospective chart review was performed from January 2004 to October 2017 at a single tertiary general hospital. Seventy-six patients were pathologically identified as EG. Besides, 60 patients with preoperative imaging diagnosis of \"EG\" were analyzed to reveal the radiological patterns and their diagnostic power.
RESULTS: Fifty-three male and 23 female EG patients with a mean age of 18.1 ± 16.7 years (range 1-58 years) were retrospectively included. Significant differences were observed in gender (male to female = 2.3:1) and age (the highest incidence at the age of 0~5 years) for EG. EG predominantly involved the skeletal system: flat bones (31.43%) > irregular bones (24.76%) > long bones (22.86%) > other organs (20.95%). No obvious relationships between season, biochemical markers, and EG incidence were observed. The common presenting symptoms were pain followed with local mass, and most patients underwent surgical resection. Among 60 imagingly diagnosed \"EG\" patients from April 2009 to October 2017, only 22 were with histological confirmation. The correct diagnosis rates were 37.1% (13 out of 35), 16.7% (5 out of 30), and 22.2% (8 out of 36) for plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI), respectively.
CONCLUSIONS: Chinese EG has a varied presentation, age distribution, and gender difference. EG diagnosis is still based on biopsy or histopathology instead of imaging techniques.

Eosinophilic granuloma (EG) is a rare bony disease deriving from abnormal proliferation of histiocytes, and is the most common form of presentation of Langerhans cell histiocytosis. EG predominantly affects the axial skeleton. However, when localised in the head and neck district, mandibular lesions account for the majority of cases. Mandibular lesions can mimic other pathological conditions, making biopsy fundamental for differential diagnosis. Treatment depends on the severity of the disease, ranging from pharmacological treatment to surgical approach. However, EG is also reported to possibly undergo spontaneous resolution. In this case report, we describe a rare case of EG with particularly aggressive behaviour in a young patient. Initially, local pharmacological treatment with intralesional administration of corticosteroids lead to worsening of the symptoms, increase in lesion\'s dimensions, and disruption of the cortical bone. A more invasive therapeutic approach involving radical surgery was then performed, with consequent resolution of the disease.

BACKGROUND: Langerhans cell histiocytosis (LCH) of the orbit is a rare clinical entity with a diagnostic and therapeutic dilemma.
METHODS: This was a retrospective study of eight patients with orbital LCH.
RESULTS: All eight patients in our series were male, and the mean age at presentation was 8 years (median 6 years; range, 7 months-23 years). All of them had unilateral disease, and the most common presenting complaint was upper eyelid swelling (n = 6). The mean duration of symptoms was 6 weeks (median, 3 weeks; range, 2-20 weeks). Visual acuity was unaffected in seven cases. Clinical diagnosis included rhabdomyosarcoma (n = 4), malignant lacrimal gland tumor (n = 2), orbital cysticercosis (n = 1), and orbital tuberculosis (n = 1). The diagnosis of orbital LCH was confirmed by incisional biopsy (n = 7) or fine-needle aspiration cytology (n = 1). Four cases underwent careful limited curettage and received intralesional steroid, and four cases were treated with intralesional steroid alone after incisional biopsy. Complete tumor resolution was achieved in seven cases after receiving a mean of one intralesional steroid injection (median, 1; range, 1-2), while one patient was advised systemic chemotherapy for residual tumor. No tumor recurrence was noted in any case at a mean follow-up duration of 30 months (median, 23 months; range, 7-96 months). None of the cases developed diabetes insipidus or multisystem disease during the follow-up period.
CONCLUSIONS: Minimal local intervention with intralesional steroids with/without careful curettage achieves complete tumor resolution in unifocal orbital LCH.

OBJECTIVE: To describe the clinical presentation, treatment, and outcome of patients with histiocytic lesions of the orbit.
METHODS: Retrospective study of 9 patients treated and followed up between October 2001 and January 2018.
RESULTS: Eight patients in our series were males and one patient was female. The mean age at presentation was 16.8 years (range, 1 to 42 years). All patients had unilateral disease. The most common presenting complaint was upper eyelid swelling in 8 of 9. All patients underwent preoperative computed tomography (CT) and magnetic resonance imaging (MRI). Eight of 9 patients demonstrated orbital bone erosion with adjacent soft tissue mass. Destruction of the orbital roof and contrast enhancement of dura were detected in 3 cases. All cases underwent orbitotomy and subtotal tumor excision with additional bone curettage (4 cases) and intraorbital steroid (40 mg triamcinolone acetonide) injection (3 cases). Adjuvant systemic chemotherapy consisting of vinblastine and prednisone was administered in 3 cases with dural involvement. External radiotherapy (1000 cGy) was applied in one case because of widespread disease. Histopathologic diagnoses were eosinophilic granuloma (7 cases), necrotic xanthogranuloma (1 case), and Langerhans cell sarcoma (1 case). The mean follow-up period after diagnosis was 19.7 months (range, 1-96 months). There was no systemic or multifocal bone involvement in eosinophilic granuloma cases at initial presentation and follow-up. None of these patients developed diabetes insipidus or neurologic symptoms. The patient with Langerhans cell sarcoma died from systemic disease 1 month after diagnosis of the orbital tumor. The patient with necrotic xanthogranuloma did not develop any malignancy at 9 months follow-up.
CONCLUSIONS: Eosinophilic granuloma was the most frequently encountered orbital histiocytic lesion in our series. Eosiophilic granuloma usually responded well to subtotal tumor excision, bone curettage, and intraorbital corticosteroid injections. Systemic chemotherapy was used in cases with full thickness bone destruction and adjacent dural enhancement in an effort to prevent the development of central nervous system disease.

BACKGROUND: Eosinophilic granuloma (EG) of bone refers to a generally benign form of Langerhans cell histiocytosis localized to the bone. Patients may present with a solitary lesion (monostotic) or multiple sites of involvement (polyostotic).
METHODS: This study was done to evaluate the clinicopathological pattern of 6 cases of EGs of the skull diagnosed at a tertiary care hospital. All patients of EG were included with the help of medical records over a 5-year period that is, November 2009 to November 2014. They all had been preoperatively evaluated by skull X-ray and computed tomography. To rule out a multifocal disease scintigraphy was performed in all cases preoperatively. Surgical excision was performed, and EG was diagnosed on histopathology and immunohistochemistry.
RESULTS: There was a male predominance. Parietal bone was the most common affected bone. Total excision of the lesion was performed in all cases. No patient received postoperative radiotherapy. The follow-up period ranged from 6 months to 3 years. No tumor recurrence was noted.
CONCLUSIONS: With an unknown etiology, nonspecific clinical and radiological findings with diagnosis possible only on histopathological examination, EG needs to be considered in the differential diagnosis as a skull mass, especially in children.

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.