Langerhans cell histiocytosis of bone in children: a clinicopathologic study of 108 cases.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that is characterized by abnormal proliferation of pathological Langerhans cells (LCs). In this study, a total of 108 pediatric patients with LCH of bone were evaluated retrospectively for illustrating the clinicopathologic features of this disease, with a goal of improving the diagnosis, treatment, and prognosis. METHODS: A retrospective study was based on the clinical records and pathological data of 108 patients (13 days to 12 years of age) with LCH of bone from a single hospital. Hematoxylin-eosin stain and immunohistochemical stain were applied. The follow-up was conducted to June 2008. RESULTS: The peak age of the patients ranged between 3 years and 6 years (80.6%, 87/108), and male gender predominated. The most common clinical presentation was local pain, and the imaging findings commonly showed an isolated lytic lesion in the bone. Of the 108 patients, 79 (73.1%) had single bone involvement, 27 (25.0%) had multi-bone involvement (with or without related skin involvement), and 2 (1.8%) had multisystem involvement. Histologically, all the lesions revealed abnormal proliferation of pathological Langerhans cells along with an admixture of eosinophils, lymphocytes, and other inflammatory cells. The LCs have similar shape and are positive for cluster of differentiation 1a (CD1a) (100.0%, 60/60), S100 (90.0%, 54/60), CD68 (41.7%, 25/60), lysozyme (Lys) (40.0%, 24/60), and macrophage antigen compound (MAC) 387 (30.0%, 18/60); cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. The overall survival rate was 98.0% at a median follow-up of 5 years. CONCLUSIONS: LCH of bone in children is predominant in males and usually shows as an isolated lytic lesion. Histologically, the lesions reveal abnormal proliferation of pathological Langerhans cells, admixed with various types of inflammatory cells. The patients have a good prognosis, except those with multi-system involvement.

[Unusual expression and molecular mechanisms of E-cadherin, beta-catenin in correlation with clinicopathologic parameters in neuroblastoma].

OBJECTIVE: To study the expression of E-cadherin and beta-catenin in neuroblastomas of various degrees of differentiation, and to investigate their molecular mechanisms in correlation with clinicopathologic parameters. METHODS: Immunohistochemistry EnVision method was used to detect E-cadherin and beta-catenin expression in 90 paraffin-embedded tissue samples of neuroblastomas. The methylation status of CpG islands of E-cadherin promoter was investigated by MSP in 7 fresh tissue and 24 paraffin-embedded tissue samples. The mutation status of exon 3 of beta-catenin gene was studied by PCR in 7 fresh tissue samples. Statistical analysis of the data was performed by SPSS software. RESULTS: E-cadherin and beta-catenin were abnormally expressed in neuroblastomas in general. The expression of beta-catenin in well-differentiated neuroblastoms was markedly higher (47/70, 67.1%) than that of the poorly differentiated tumors (8/20, 40.0%). There was a markedly decreased expression of both genes in tumors with lymph node metastasis than those without. Demethylation was seen in some regions of the promoter of E-cadherin in 31 cases of nuroblatomas. PCR of the exon 3 of beta-catenin followed by DNA sequencing demonstrated rearrangements and mutations in 7 cases, including 2 cases harboring identical point mutation at gene position 27184, leading to a T-->A alteration. CONCLUSIONS: The abnormal over-expression of E-cadherin in neuroblastomas is independent of the methylation status of their promoter sequences. The abnormal expression of beta-catenin may be related to mutational changes at exon 3 of the gene.