ReviewAggressive histiocytic disorders that can involve the skin
Section snippets
Class I: Langerhans cell disease
The LC is now well accepted to be a cutaneous antigen presenting cell and not a tissue histiocyte. It is a bone marrow-derived cell that migrates into the epidermis and hair follicle epithelium.1 LCs stain positive for S-100 protein, CD1a, CD45, and CD101; CD1a staining is considered specific for LCs. When visualized with electron microscopy, LCs contain unique organelles, called Birbeck granules, which arise from the cytoplasmic membrane by receptor-specific endocytosis.8 An antigen called
Class II: Non-Langerhans cell histiocytic diseases
NLCDs are disorders in which histiocytes accumulate in tissues. Many of the diseases in this class are rare and poorly understood. The cell of origin for the NLCD is the monocyte/macrophage, a cell of diverse differentiation potential. Much less is known about the different pathways of differentiation in monocyte/macrophages than in other hematopoietic cells, such as lymphocytes and neutrophils. The monocyte/macrophage can become any of the following types of cell, explaining in part the
Class III: Malignant histiocytic disorders
Malignant histiocytoses are caused by malignant transformation of monocyte/macrophage stem cells. The prognosis of malignant histiocytosis is similar to leukemia or lymphoma.
Clinical
LCD encompasses a spectrum of overlapping diseases that were previously known as Letterer–Siwe disease, Hand-Schuller-Christian disease, eosinophilic granuloma, and Hashimoto–Pritzker disease.11 The clinical presentations of each subtype can vary greatly, however, and the above diseases were all recently reclassified as LCD, based on common immunologic and ultrastructural features.12 Although they are now classified together, it is still useful to review the clinical presentations of
Non-Langerhans cell histiocytoses/non-Langerhans cell histiocytic disease
NLCDs are diseases caused by infiltration of mononuclear phagocytes/histiocytes and include juvenile xanthogranuloma (JXG), multicentric reticulohistiocytosis (MRH), sea-blue histiocyte syndrome (SBHS), sinus histiocytosis with massive lymphadenopathy (SHML, also known as Rosai–Dorfman syndrome), necrobiotic xanthogranuloma (NXG), xanthoma disseminatum (XD), and hemophagocytic lymphohistiocytosis (HLH), which can all show aggressive behavior.
Summary
Clinical and histologic characteristics of LCD and seven different potentially aggressive histiocytic disorders, including JXG, MRH, SBHS, SHML, NXG, XD, HLH, and MH were reviewed in this article. Their unique histologic features are summarized in Table I. Except for LCD and MH, most are generally considered to be benign and self-limited. However, when histiocytes infiltrate vital organs, these “benign” histiocytoses may lead to a fatal outcome, hence the term “aggressive histiocytoses.” It is
References (131)
- et al.
Origin and differentiation of dendritic cells
Trends Immunol
(2001) - et al.
Langerhans' cell histiocytosis
Hematol Oncol Clin North Am
(1987) - et al.
Histiocytic syndromes: a review
J Am Acad Dermatol
(1985) - et al.
Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis
Lancet
(1994) - et al.
Differentiation of Langerhans cells in Langerhans cell histiocytosis
Blood
(2001) - et al.
Juvenile xanthogranuloma: forms of systemic disease and their clinical implications
J Pediatr
(1996) - et al.
The risk intraocular juvenile xanthogranuloma: survey of current practices and assessment of risk
J Am Acad Dermatol
(1996) - et al.
Juvenile xanthogranuloma with central nervous system lesions
J Am Acad Dermatol
(1986) - et al.
Juvenile xanthogranuloma
J Am Acad Dermatol
(1997) - et al.
Xanthogranulomatosis in an adult: lipid analysis of xanthomas and plasma
J Am Acad Dermatol
(1987)
Juvenile xanthogranuloma associated with cytomegalovirus infection
Am J Med
Loss of the nf1 tumor suppressor gene decreases fas antigen expression in myeloid cells
Am J Pathol
Multicentric reticulohistiocytosis
Oral Surg Oral Med Oral Pathol
Multicentric reticulohistiocytosis: systemic macrophage disorder
Baillieres Clin Rheumatol
Unexpected splenic nodules in leukemic patients
Hum Pathol
Cutaneous sinus histiocytosis (Rosai–Dorfman disease) presenting clinically as vasculitis
J Am Acad Dermatol
Sinus histiocytosis with massive lymphadenopathy. Case report and review of a multisystemic disease with cutaneous infiltrates
J Am Acad Dermatol
Clinical and histopathologic spectrum of cutaneous Rosai–Dorfman disease in Taiwan
J Am Acad Dermatol
Necrobiotic xanthogranuloma with paraproteinemia
J Am Acad Dermatol
Asteroid bodies and other cytoplasmic inclusions in necrobiotic xanthogranuloma with paraproteinemia
J Am Acad Dermatol
Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging
J Am Acad Dermatol
Activation of monocytes in vivo causes intracellular accumulation of lipoprotein-derived lipids and marked hypocholesterolemia—a possible pathogenesis of necrobiotic xanthogranuloma
Atherosclerosis
Epidermal Langerhans cells are derived from cells originating in bone marrow
Nature
Embryonic beginnings of definitive hematopoietic stem cells
Ann N Y Acad Sci
Hematopoiesis and stem cells: plasticity versus developmental heterogeneity
Nat Immunol
Monocytes and macrophages in human skin
The epidermis: an immunologic microenvironment
CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha
J Exp Med
Expression and function of B7 on human epidermal Langerhans cells
J Immunol
Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders
Pediatr Dev Pathol
Langerhans cells—dendritic cells of the epidermis
Apmis
Histiocytosis syndromes in children
Lancet
Histiocytosis X: a seven-year experience at a children's hospital
J Am Acad Dermatol
Hand-Schuller-Christian disease with secondary cutaneous involvement
Clin Exp Dermatol
Langerhans cell (eosinophilic) granulomatosis. A clinicopathologic study encompassing 50 years
Am J Surg Pathol
Congenital self-healing histiocytosis
Am J Dermatopathol
Long-term sequelae of histiocytosis X
Am J Pediatr Hematol Oncol
Langerhans'-cell histiocytosis in 58 adults
Eur J Med Res
The pathology of adult type Letterer-Siwe disease
Clin Exp Dermatol
Xanthomatous cutaneous lesions of histiocytosis X
Arch Dermatol
Histiocytosis X (Langerhans' cell histiocytosis). Prognostic role of histopathology
Arch Pathol Lab Med
Cutaneous histiocytosis X. The presence of S-100 protein and its use in diagnosis
Arch Dermatol
Langerhans' cell histiocytosis. Definitive diagnosis with the use of monoclonal antibody O10 on routinely paraffin-embedded samples
Am J Surg Pathol
Immunohistochemical comparison of cutaneous histiocytoses and related skin disorders: diagnostic and histogenetic relevance of MS-1 high molecular weight protein expression
J Pathol
Langerhans cell histiocytosis: a pathologic combination of oncogenesis and immune dysregulation
Pediatr Blood Cancer
Langerhans cell histiocytosis
Curr Opin Hematol
Increased blood myeloid dendritic cells and dendritic cell-poietins in Langerhans cell histiocytosis
J Immunol
The role of vascular endothelial growth factor in Langerhans cell histiocytosis
J Pediatr Hematol Oncol
Langerhans cell histiocytosis: the case for conservative treatment
Arch Dis Child
Fatal congenital systemic juvenile xanthogranuloma with liver failure
Pediatr Dev Pathol
Cited by (0)
Supported by a National Institutes of Health NIAMS Skin Diseases Research Center grant to Dr Gilliam (grant no. PO30-AR39750-13) and NIAMS R01 AR49284-03.
Conflicts of interest: None identified.