Available online 20 May 2023

Author links open overlay panel, ABSTRACT

Histiocytic neoplasms in the children are very rare, and histiocytoses can occur in the perinatal period. The presumed origins and presentation of specific histiocytoses in the pediatric age group are described. Common and newly described histiocytoses are presented including Langerhans cell histiocytosis, Rosai-Dorfman disease, histiocytic sarcoma, ALK positive histiocytosis, and hemophagocytic lymphohistiocytosis. Molecular findings common to pediatric histiocytoses are also discussed.

Section snippetsINTRODUCTION

The histiocytoses are rare neoplastic disorders of macrophages, dendritic cells or monocytic cells, which infiltrate tissues and organs and occur in both children and adults. The first attempt at an organized categorization of these lesions in 1987 1 was based on dividing them into 3 histiocytic classes (Class I to III disease). 21 However, increased understanding of the molecular etiology and behavior of the histiocytoses has changed our understanding of them. A revised classification of

EPIDEMIOLOGY

The exact incidence of histiocytoses is unknown due to uncertainty in the classification of many of these entities, but they were estimated to involve 0.142/100,000 persons younger than 20 years in the United States annually from 1973 to 2010.2 This number includes a heterogeneous group of dendritic and malignant histiocytic disorders, including acute monocytic leukemias. Children of Asian and/or Pacific Islander or indigenous American descent had the highest incidence rate, followed by

ETIOLOGY AND PRENATAL ORIGIN

Macrophages and dendritic cells, including Langerhans cells, are thought to be derived either from early yolk sac progenitors (Langerhans cells) or from bone marrow progenitors (subset of macrophages and dendritic cells).7 Although definitive evidence for the derivation of histiocytic neoplasms from precursor stem cells has been lacking, recent studies show at least a subgroup of patients with Langerhans cell histiocytoses and Erdheim-Chester disease have circulating peripheral blood cells

FETAL AND NEONATAL HISTIOCYTOSES

The incidence of histiocytosis in the neonatal period has been derived from rare studies of fetuses and neonates. In neonates, the most common types of histiocytoses are LCH, hemophagocytic lymphohistiocytosis (HLH), and JXG, which occurred in that order in one study.22 LCH is by far the most common histiocytosis in the neonatal period and is reported to cause fetal pleural effusion23, intrauterine fetal demise24, and hydrops fetalis.23, 24, 25 Neonatal systemic JXG with hydrops has also been

Langerhans Cell Histiocytosis (LCH)

LCH is the most common childhood histiocytosis and it is the most well understood histiocytosis. LCH has a defined morphology with an established phenotype, known molecular mutations, and well-characterized clinical presentations. LCH is included in the 5th edition of the WHO classification of hematolymphoid tumors and is defined as a clonal neoplasm of myeloid dendritic cells expressing a Langerhans cell phenotype with CD1a and CD207 expression.32 Langerhans cells are antigen presenting cells

Rosai-Dorfman Disease (RDD)

Among the histiocytoses that occur in the pediatric population, Rosai-Dorfman disease (RDD) is one of the most often overlooked and difficult to identify and can be easily misdiagnosed. RDD was initially described as “adenitis with lipid excess” by Pierre-Paul Destombes in 1965 and then was more thoroughly explored by Juan Rosai and Ronald Dorfman, in 1969, who called the lesion sinus histiocytosis with massive lymphadenopathy.69,70 Identical to RDD in adults, RDD in children consists of

MONOCYTIC HISTOCYTOSES

Monocyte-related histiocytoses are largely leukemias and tissue infiltration of leukemia, which include monocytic leukemia, myelomonocytic leukemia, and myeloid sarcoma. Myeloid leukemia is very rare in the pediatric age group, but when it occurs, tissue infiltration is more common than in adults.

MOLECULAR FINDINGS COMMON TO HISTIOCYTSES—A UNIFYING CONCEPT

The classification of histiocytic lesions have been confusing and recent genetic findings add to the complexity. Prior systems have focused on differences in the morphology and phenotype of the entities. For example, the morphology and phenotype of LCH (characterized by grooved nuclei and CD1a positivity, respectively) are different than the morphology and phenotype of JXG (often multinucleated giant cells and CDa1-); however many of the findings can overlap. On a molecular level, there are

SUMMARY

Histiocytoses in children are more common than in adults. Histiocytoses may develop in utero, causing fetal demise or symptoms in the neonatal period with poor outcomes if not quickly treated. Molecular findings in children are similar to those in adults, but more studies designed to detect differences are needed.

Disclaimer

The views expressed in this paper are those of the author and do not necessarily reflect the official policy of the Department of Defense or the U.S government.

Declaration of Competing Interest

The authors have no financial/personal interest or belief that could affect their objectivity. No potential competing interests exist.

View full text

© 2023 Elsevier Inc. All rights reserved.