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Chapter 36: Inflammatory and Malignant Histiocytosis

INTRODUCTION

  • Histiocyte is an archaic term for macrophages. The histiocytoses include diseases arising from all cells of the mononuclear phagocytic system, with diseases characterized by presumed lineage and biology into dendritic cell (DC) disorders, macrophage-related disorders, and malignant histiocytic disorders (Table 36–1).

  • Historically, the histiocytic disorders have been characterized by the phenotype of disease-specific histiocytes (Table 36–2).

  • Now, recurrent mitogen-activated protein kinase (MAPK) pathway mutations in clonal myeloid cells in Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), juvenile xanthogranuloma (JXG), Rosai-Dorfman disease (RDD), and malignant histiocytic diseases clearly separate these neoplastic diseases of inflammatory cells from hemophagocytic lymphohistiocytosis (HLH), characterized by polyclonal reactive macrophages.

TABLE 36–1HISTORICAL CLASSIFICATION OF HISTIOCYTIC DISORDERS
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TABLE 36–1 HISTORICAL CLASSIFICATION OF HISTIOCYTIC DISORDERS
Dendritic Cell–Related
 Langerhans cell histiocytosis
 Juvenile xanthogranuloma/Erdheim-Chester disease
Macrophage-Related
 Hemophagocytic syndromes
 Primary hemophagocytic lymphohistiocytosis
 Secondary hemophagocytic syndromes
 Rosai-Dorfman disease
Malignant Diseases
 Monocyte-related leukemias
 Extramedullary monocytic tumor (myeloid sarcoma)
 Macrophage-related histiocytic sarcoma
 Dendritic cell malignancy (malignant histiocytosis)

Data from Weitzman S, Egeler RM: Histiocytic Disorders of Children and Adults. Basic Science Clinical Features, and Therapy. Cambridge University Press; 2005:14-39; Chikwava K, Jaffe R. Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders. Pediatr Dev Pathol. 2004;7(6):607-614; Lau SK, Chu PG, Weiss LM. Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders. Am J Surg Pathol. 2008;32:615-619

TABLE 36–2CHARACTERISTIC IMMUNOPHENOTYPE OF PATHOLOGIC CELLS IN HISTIOCYTIC DISORDERS
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TABLE 36–2 CHARACTERISTIC IMMUNOPHENOTYPE OF PATHOLOGIC CELLS IN HISTIOCYTIC DISORDERS
  LCH Malignant Histiocytosis ECD/JXG HLH RDD
HLA-DR ++ + – + +
CD1A ++ +/– – – –
CD14 +/– – ++ ++ ++
CD68 +/– +/– ++ ++ ++
CD163 – – ++ ++ ++
CD207 (Langerin) +++ +/– – – –
Factor XIIIa – – ++ – –
Fascin – +/– ++ +/– –
Birbeck granules + +/– – – –
Hemophagocytosis +/– +/– – +/– –
Emperipolesis – – – – +

+, faint staining of a few cells; ++, easily visualized (moderate) staining on many cells; +++, strong staining on many cells. ECD, Erdheim-Chester disease; HLA-DR, human leukocyte antigen-D related; HLH, hemophagocytic lymphohistiocytosis; JXG, juvenile xanthogranuloma; LCH, Langerhans cell histiocytosis; RDD, Rosai-Dorfman-Destombes disease.

CLONAL HISTIOCYTOSES

Langerhans Cell Histiocytosis

Definition

  • The term Langerhans cell histiocytosis includes disorders previously called histiocytosis X (eosinophilic granuloma, Letterer-Siwe disease, Hand-Schüller-Christian disease), self-healing histiocytosis, and Langerhans cell granulomatosis.

  • The hallmark LCH DC has abundant eosinophilic to amphophilic cytoplasm and a nucleus that is kidney-shaped, deeply indented, or grooved.

Epidemiology

  • In pediatric patients, the incidence of LCH has been estimated to be 2 to 10 cases per 1 million.

  • The male-to-female ratio is close to 1.

  • Median age ...

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