Clinical Research Of Langerhans Cell Histiocytosis In Children

Objective: To raise awareness of langerhans cell histiocytosis (LCH), improve the level of diagnosis and treatment of, and investigate the mothod to improve the cure rate and the quality of life, by retrospecting the clinical characteristics and therapeutic process of LCH.Methods: Clinical data of 62 cases of LCH hospitalized during Jan 2002 to Dec 2010 in Children's Hospital of Chongqing Medical University. The age of onset, gender, region, season of on set, clinical manisfestations, laboratory examination, imaging examination, pathology, process of diagnosis and treatment, and prognosis.Results:1. 62 cases were diagnosed according to《The efficacy standard and diagnostic criteria of hematopathy》by Zhangzhinan. 40 cases were diagnosed presumptively, 3 cases diagnosed provisionally, and 19 cases diagnosed definitely. 31 cases of Letterer-Siwe disease (L-S), 10 cases of Hand-Schuller-Christian disease (H-S-C), and 21 cases of eosinophilic granuloma were reported. 2. The age of patients ranged from 1 month to 15 year and 3 month's old, 14 month on average. 40.7% patientd were less than 1 month, 27.4% were between 1 to 2 years'old, and 8.1% were between 2 to 3 years'old. Patients less than 3 years'old were 74.2%. There were 34 male, 28 female, and the ratio male to female was 1.21:1. There were no gender difference between the group of less than 1 month and more than 4 years'old.3. The season of onset were different : 15 cases in spring, 23 cases in summer, 14 cases in autumn, and 10 in winter. There were more patient in summer than other seasons.4. The region distribution were different: 41 cases were from Chongqing, 16 from Sichuan, 2 from Guizhou, 1 from Henan, and 1 from Fujian. 40 were from countryside, 22 from the city. The ratio of countryside and city was 1.86:1.5. There were 6 cases with Mediterranean anemia, 1 case with autoimmunehemolyticanaemia, and 2 cases with Rathk's cystis.6. 23 cases ever had misdiagnosis history, and the misdiagnosis rate was 37.1%. The main reasons of misdiagnosis were skin diseases, otitis media, lymphadenitis, and other hematonosis.7. 32 cases had fever. 34 cases had tetters (mainly were hemorrhagic, seborrheic, and eczematid tetters. 5 cases had hemorrhagic spot, 1 case had similar spot of papular urticaria, 1 had scabies-like spot, and 1 case had sudamina-like spot), 31 cases had enlargement of the lymph nodes, liver, and spleen. 43 cases had anemia, 13 had respiratory symptoms, 17 had otorrhea, 3 had eye-tubercle, 8 had diabetes insipidus, 34 had manifestations of bone. 3 cases had swollen gum, 2 had loss of teeth, 9 had diarrhea (including 3 hematochezia), 6 had edema, and 1 had jaundice.8. 43 cases had anemia by hemanalysis (29 were moderate or severe anemia), PLT of 19 cases were less than 100×10~9/L, and WBC of 2 cases were less than 4×10~9/L.9. 58 cases received test of liver and kidney function. 27 cases had low albumin, and 11 had high bilirubin (mainly conjugated bilirubin). Kidney function of 58 cases were normal. 3 cases received urine protein test, and 1 got high urine protein. 1 case received urine protein test for 24 hours, and quantity of protein was high. Addis count was applied to 1 case, and RBC was high.10. 13 cases received test of immunoglobulin. 10 had high IgA, 6 had high IgG, 6had high IgM, 2 had high IgE. 1 case had low IgG, IgA and IgM. 6 cases received classification of lymphocyte. 6 had high CD19+, 3 had low CD4+, 1 had high CD8+ and 1 had low CD8+. 2 cases had low ratio of CD4+/CD8+. 2 cases received autoantibody test, and 1 case had antinuclear antibody and ss-DNA antibody. 8 cases received antihuman globulin test, and 1 cases had positive result of both direct and indirect test.11. 23 cases had antibody test of CMV and EBV. 23 cases had positive results. 17 cases had positive CMV, and 6 cases had positive EBV. 12. 61 cases received bone marrow cytomorphologic examination. All had Stimulating or hypertrophic bone marrow image, except one had found some histiocytes. Chromosome examination was applied to 33 cases. 1 had chromosome translocation, and 1 had chromosome deletion.13. 57 cases received imaging examination. Interstitial changes were found in 24 cases. Patchy and nodule were found in 1 case.14. A total of 59 patients have taken bone X-ray examinations. 52 were of skull, 51 of trunk skeleton, 52 of extremities and 49 of pelvic. Among them 40 showed bone destructions. The number was 52, 51, 52 and 49 respectively according to the previous categorized examination site. Multiple bone destruction was more common than bone destruction of a single site and often involved skull, femur, vertebrae, ribs, ilium and humerus. There were 4 reported destruction of sella, of which 2 had diabetes insipidus.15. 26 patients have cranial CT or MRI done. Among them 2 showed space-occupying lesion with 1 in the trigone of left lateral ventricle and the other on the joints of grey and white matter in parietal occipital area. The former was testified to be the metastastic tumor, the latter did not take the biopsy. There were 9 reported an abnormal manifestation of pituitary, of which 4 had diabetes insipidus.16. 62 patients have done biopsy. Among them there were 29 eruption prints, 5 skin biopsies, 26 bone biopsies, 5 lymphnode biopsies, 5 superficial mass biopsies, 5 ear discharge smears. A mass of histiocytes were shown in every case (some by repeated examinations). 22 have done immunohistochemical examinations, among which 22 were positive for S100 only and 19 positive for S100 and CD1α. Birbeck particle was found in 1 of 19 cases positive for CD1αby electron microscopy.17. Totally 33 patients have undergone surgery and chemotherapy. Among them 27 were assigned to combined chemotherapy, 6 who have bone destruction of a single site and 5 who have eosinophilic granuloma were treated with surgery. The chemotherapies involved were LCH-Ⅲ, mordified DAL-HX83/90 and mordified LCH-Ⅰ. There were 26 out of 33 responded to our investigation with follow-up ranged from 6-46 months (average 18.1 months). Among them 6 were completely recovered ( 1 L-S and 5 EGB ), 18 showed improvement (5 L-S, 4 H-S-C and 9 EGB), 2 showed signs of deterioration ( 1 H-S-C and 1 EGB).Conclusion:1. LCH can seen in all age groups of children, of which different types have different comman onset age. Our data showed that all L-S occurred in 2 years old below, all H-S-C occurred in the 1-4 years of age, EGB was more common in the older children, but also can occur as early as 5 months old.2. Our data showed that the incidence ratio of male and female of 1.21:1 in children with LCH, the male incidence was slightly higher than female, but there was no difference of incidence ratio(0.92:1) between male and female under the age of 1, consistent with those reported, the incidence ratio between male and female children more than 4 years old had no difference(0.8:1), inconsistent with the reported, probably relating to the fewer data sample of children less than 4 years old.3. The geographical distribution of LCH was wide, the incidence ratio between urban and rural children was 1.86:1, a higher incidence in rural children.4. The most common involved system were bone, skin, liver, spleen, lymph nodes, blood system and lung. Skin rashes, bone damage, pulmonary lesions, liver&spleen&lymph node enlargement, anemia were the clinical features of the disease5. The typical rash was meaningful for diagnosis, especially in L-S, as to atypical rash, dermatopathological biospy also should be done for searching diagnosis evidences.6. 64.5% patients had bone destruction, which could also be seen in L-S, moreover, poly-bone destruction was more comman than single-bone destruction. So general bone X-ray inspect should be done for patients who were suspected LCH.7. Nearly 40% patients had abnormal lung imaging (mainly were interstitial changes), So chest X-ray inspect should be done for patients who were suspected LCH. 8. For patients with abnormal pituitary imaging and without urine collapse disorder, we should concern closely whether urine collapse disorder would happen, patients with intracranial space-occupying lesions should be wary about the probability of the central nervous system involvement.9. By pathological examination such as multifocal rash tabletting and (or) lymph node biopsy, bone biopsy, we could find mass histiocytes for pathological diagnosis evidences. Immunohistochemical check such as S - 100, CD1αand electron microscopy for Birbeck granule should be done for diagnosis and definitely diagnosis if condition permits.10. Our study suggested that LCH compromised humoral immunity and cell-mediated immunity.Meanwhile, infection with CMV and EBV was as high as 88.5%. Therefore, screening of immune function and viral antibodies would help a lot in diagnosis of etiology.11. Chemotherapy definitely improved outcome. With early diagnosis and correct classification, even L-S would be cured. The outcome of EGB would be improved with surgery and chemotherapy for bone lesions. Patients with diabetes insipidus had a poor outcome.