Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): clinico-pathological study of three cases

Introduction We report three cases of sinus histiocytosis, a rare disease of unknown aetiology with massive lymphadenopathy (SHML), also known as Rosai-Dorfman (RD) disease, in a paediatric population. This proliferative histiocytic disorder is defined by histological and immunohistochemical (IHC) characteristics and can manifest as nodal involvement with variable enlargement of the lymph nodes (two cases) and extranodal manifestations involving skin and larynx involvement (one case). One patient had hypergammaglobulinemia. The morphological investigation revealed that all lymph nodes showed hyperplasia of sinuses with abundant histiocytic cell with intracytoplasmic lymphocytes. Skin and larynx biopsies showed a histiocyte and lymphocyte infiltrate with similar characteristics. An ultrastructural study was carried out on material from one patient. In the IHC study, SHML cells expressed phagocytic markers such as CD68 and S100, but markers for Langerhan’s (CD1a) or dendritic cells (DRC, CD23 and CNA42) were absent. Two patients had a complete remission after surgical excision and no other treatment, but the third patient was treated with radiotherapy after a relapse with obstruction of the upper airway.Conclusion This disorder must be considered in the differential diagnosis of young patients who exhibit massive or multiple lymphadenopathies, especially when involvement of the cervical area occurs. Due to the good outcome of the disease, a conservative approach is justified.     

Sinus histiocytosis with massive lymphoadenopathy (Rosai-Dorfman disease). Clinico-pathological analysis of a paediatric case

Histochemical and immunohistochemical studies performed in only a few cases of sinus histiocytosis with massive lymphoadenopathy (SHML) indicated that SHML cells belong to themacrophage — histiocyte system, though their exact origin is still uncertain. We analyzed the morphological, antigenic and enzymatic characteristics of the histiocyte-like cells in one paediatric case of SHML (also named Rosai-Dorfman disease). The SHML cells expressed the S-100 protein, lectins concanavalin A, peanut agglutinin andmonocyte-macrophage related antigens CD 11c, CD 14, CD 33, CD 68 and LN 5. Reactivity with other anti-macrophage antibodies (MAC 387, lysozyme, alpha-1 anti-chymotrypsin) was variable. The CD1a antigen was present only in scattered cells, whereas HLA-DR and the HLA-DR associated invariant chain were absent. Cytochemistry demonstrated an intense activity of acid phosphatase and non specific esterase of SHML cells. A large amount of medium sized mononuclear cells were located in the sinuses and intersinusoidal tissue. Our findings suggest that SHML cells have intermediate features between phagocytes and Langerhans cells/interdigitating reticulum cells. The heterogeneity of marker expression on SHML cells might be related to the local content of factors (e.g., cytokines), capable of modulating the phenotype of monocyted and derived cells.     

Sinus histiocytosis with massive lymphadenopathy: Complicated by autoimmune hemolytic anemia

Sinus histiocytosis with massive lymphadenopathy is a rare histiocytic disorder with very few case reports in Indian literature. Immunological abnormalities have been documented in few cases. We report one such case of a child presenting with generalized lymphadenopathy and complicated by autoimmune hemolytic anemia, suggestive of an associated immune dysfunction.     

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) treated with 2-chlorodeoxyadenosine

Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease (RDD) is a rare but well-defined histiocytic proliferative disorder of unknown etiology that usually presents with cervical lymphadenopathy, fever, leukocytosis, and hypergammaglobulinemia in an otherwise healthy child. Although many patients undergo spontaneous remission, a subset of patients with systemic disease has a more serious course. For those patients with a poor outcome, steroids and chemotherapeutic agents such as etoposide or 6-mercaptopurine plus low dose methotrexate have been used. We present a child with a massive cervical lymphadenopathy treated with 2-chlorodeoxyadenosine (2-CdA, cladribine) after other approaches failed.     

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

Summary Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a unique disease of unknown etiology with a childhood predilection. Reports have established the worldwide distribution of the disorder. Although peripheral lymphadenopathy is the most common mode of presentation, numerous studies and individual case reports have established the fact that 30–40% of affected individuals have extranodal manifestations particularly in the head and neck region where the adenopathy tends to be concentrated. As yet, the pathogenesis of SHML has not been established but speculation relates the disorder to an aberrant response to an unspecified antigen, possibly an infectious organism.Because of the clinical manifestations, the radiographic features of SHML are not pathognomonic but rather engender a differential diagnosis which includes lymphomatous, pseudolymphomatous and infectious conditions. Appropriate imaging of patients with SHML depends upon presenting symptoms and signs. Radionuclide bone scanning may be helpful in the evaluation of suspected skeletal lesions or joint symptoms. Gallium scanning is often positive in nodal disease and CT, MRI and sonography are helpful in the evaluation of extranodal sites of involvement such as the orbit, eyelid, upper aero-digestive tract and retroperitoneum.     

窦组织细胞增生伴巨大淋巴结病诊疗进展

窦组织细胞增生伴巨大淋巴结病（ sinus histiocytosis with massive lymphadenopathy, SHML）又称为Rosai-Dorfman病,是一种病因不明,罕见的良性淋巴组织增生性疾病,好发于儿童及青少年。因其累及部位不同而临床表现多样,无明确实验室指标支持该病,且属于儿科少见病,在儿科临床极易误诊和漏诊,本文对其诊断及治疗方法等进行归纳总结,以提高对该疾病的认识。     

Sinus histiocytosis with massive lymphadenopathy (SHML) prednisone resistant but dexamethasone sensitive

Sinus histiocytosis with massive lymphadenopathy (SHML) is a histiocytic disorder affecting children and adults. It usually presents as markedly enlarged lymph nodes that require surgical biopsy for confirmation. This lesion is usually self-limited but can present in areas that can cause significant morbidity or disfigurement. We report a case that required therapy due to the severe disfigurement but was resistant till treated with dexamethasone. This case illustrates that SHML may be resistant to prednisone but still be sensitive to dexamethasone.     

Sinushistiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Response to methotrexate and mercaptopurine

We report a 3-year-old girl presenting with bilateral cervical lymph node enlargement persisting for > 3 months. Leukocytosis, elevated erythrocyte sedimentation rate, a marked hypergammaglobulinemia, and a moderate hepatosplenomegaly were also found. The diagnosis of sinushistiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, was established histologically by the demonstration of characteristic sinushistiocytosis with lymphocytophagocytosis. Treatment was started with high dose steroids, and a decline of lymph node size and a normalization of laboratory parameters occurred. However, when steroids were tapered, lymph node size rapidly reincreased. Chemotherapeutic treatment was started using etoposide, which was completely ineffective. Therefore, treatment was changed to a combinatory low dose methotrexate therapy and 6-mercaptopurine for 4 months. Whereas a prompt and complete remission was reached, single 6-mercaptopurine therapy was maintained and treatment has been discontinued after a total of 2 years. The child has remained healthy for 7 years. This case would recommend the use of methotrexate and 6-mercaptopurine for treatment of complicated SHML. © 1996 Wiley-Liss, Inc.     

Biliary wall calcification in Langerhans cell histiocytosis: report of two cases

Langerhans cell histiocytosis (LCH) is a disorder of unknown pathogenesis affecting one or more organs (unifocal or disseminated form) due to clonal proliferation of Langerhans cells. Liver involvement is more frequent in the disseminated form and the radiological findings of end-stage liver disease due to LCH are similar to those of sclerosing cholangitis. We present the multidetector CT findings in two children with LCH liver involvement and the unique finding of calcification of the biliary wall.     

Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness

Rosai-Dorfman disease (RDD) is a rare, sporadic histiocytic disorder characterized by painless but protracted lymphadenopathy. Its etiology remains unclear. The observation of congenital disease and reports of familial cases with seven pairs of siblings including three sets of identical twins suggests a genetic predisposition in some patients with this condition. We now report two brothers of consanguineous Palestinian parents, whose lymphadenopathy, lymph node histology, and polyclonal hypergammaglobulinemia indicated RDD. The presence of intrauterine fractures, short stature, and sensorineural hearing impairment suggested a rare familial form of the disorder. Moynihan et al. recently described a Pakistani family with a familial histiocytic disorder highly reminiscent of the brothers reported here, whose lymph node morphology was apparently consistent with RDD as well. The presence of sensorineural deafness, short stature, and joint contractures, however, suggested a separate, rare autosomal recessive syndrome referred to as Faisalabad histiocytosis, after the family's place of origin. We believe that the brothers described here represent a second family with Faisalabad histiocytosis, which mimics RDD histologically.     

Mediastinal lymphadenopathy: a variant of incomplete Kawasaki disease

A 14-month-old girl presented with a 4-d history of fever and generalized exanthema. Four characteristic symptoms of incomplete Kawasaki disease (KD) were present on admission (fever, rash, non-purulent conjunctival injection, oropharyngeal changes) and then followed by oedema of the hands and feet and mild plantar desquamation. The typical laboratory features of KD, such as elevated erythrocyte sedimentation rate, leukocytosis, thrombocytosis, and positive C-reactive protein were also seen. Ultrasound examination of the mediastinum revealed the presence of a lymph node, 30 mm in diameter, below the tracheal carina. Thoracic CT scan confirmed the mediastinal lymph node. The patient was treated with aspirin and intravenous γ -globulin. Ultrasound study of the mediastinum, which was carried out 6 weeks after hospital discharge, showed that the lymph node had disappeared. This case illustrates that lymph nodes other than cervical lymphadenopathy should be sought when the diagnosis of classical or atypical KD is suspected.     

Gastrointestinal involvement in Langerhans' cell histiocytosis (Histiocytosis X): A clinical report of three cases

The gastrointestinal tract may be involved in Langerhans' cell histiocytosis, either as part of a generalized disease or as a separate primary entitiy. Three patients with gastrointestinal involvement are described. One patient presented with a history of prolonged vomiting and diarrhoea with blood and mucus. In this case the diagnosis was based on colonic biopsies. Gastrointestinal tract involvement and its investigation in the diagnosis of Langerhans' cell histiocytosis are discussed.     

Paediatric Kikuchi-Fujimoto disease: a benign cause of fever and lymphadenopathy

Kikuchi-Fujimoto disease (KFD) is a rare and benign disease that typically affects the cervical lymph nodes. Its aetiology is unknown and a role of the autoimmune system in the pathogenesis is hypothesized. This self-limiting disease is often confused with malignancies. No specific management is generally required but long-term follow-up should be planned despite the low risk of recurrence, as recurrences have been described many years after the first episode and there is a high risk of development of an autoimmune disease or even lymphoma. We review the clinical and histological features of KFD and report an unusual case presenting with cervical and supraclavicular lymphadenopathy, and persistent fever.     

儿童Erdheim-Chester病2例报告并文献复习

目的探讨儿童Erdheim-Chester病(ECD)的临床特点。方法回顾分析2例ECD患儿的临床表现、诊断及α干扰素治疗效果,并结合文献进行总结。结果 2例男性患儿,分别为4、5岁,均表现为多饮、多尿、骨痛、肝脏增大等,与郎格罕斯细胞组织细胞增生症相似,但病理表现为黄色类脂质肉芽肿,免疫组化中CD1a(-)、S-100(-)。与成人ECD相比,儿童骨骼系统同样最易受累,神经系统比成人更易受累,心脏、皮肤等受累少于成人。2例患儿α干扰素治疗效果尚可。结论 ECD是一种临床上罕见的非郎格罕斯细胞性组织细胞增生症,早期识别、早期诊断可改善预后。     

School-aged children with Kawasaki disease: high incidence of cervical lymphadenopathy and coronary artery involvement

OBJECTIVE: We describe 10 school-aged children with Kawasaki disease (KD) with a high incidence of cervical lymphadenopathy and coronary abnormality. METHODS: Based on a database of 1002 children with KD in Chang Gung Children's Hospital from January 1983 to March 2001, 10 (1%) school-aged patients (five boys, five girls) who met the diagnostic criteria of KD were included for analysis. RESULTS: Cervical lymphadenopathy was noted in all (100%) of these patients. Unilateral neck mass mimicking acute suppurative infections not responding to antibiotic therapy was the initial presentation in nine (90%) of the 10 patients. The mean interval between disease onset and diagnosis was 9.9 +/- 3.3 days (range, 6-15 days). Seven (70%) of these patients responded to one course of high-dose intravenous immunoglobulin (IVIG) therapy (2 g/kg) and oral aspirin (80-100 mg/kg per day), two (20%) required a second course of IVIG, and one (10%) responded to high-dose aspirin treatment only. Coronary artery abnormality (dilatation or aneurysm) was documented by echocardiography in seven (70%) patients (four boys, three girls). In six patients, the coronary artery abnormalities resolved in 1 year, while one patient had persistent right coronary artery aneurysm, which necessitated continued anticoagulant and low-dose aspirin therapy. CONCLUSION: The incidence of school-aged children among patients with KD is about 1% in our hospital. These patients are notable for the high incidence of initial manifestations of unilateral neck mass and coronary artery involvement. This disease should be listed as the differential diagnosis in school-aged children presenting with fever and neck mass that do not respond to antibiotic therapy.