NOSOLOGY AND PATHOLOGY OF LANGERHANS CELL HISTIOCYTOSIS

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INTRODUCTION AND NOSOLOGY

Langerhans cell histiocytosis (LCH) is a rare disorder in which lesions contain cells with features similar to the Langerhans cell (LC) of the epidermis. Synonyms of Langerhans cell histiocytosis include the following:

  • Histiocytosis X

  • Eosinophilic granuloma

  • Hand-Schuller-Christian disease

  • Letterer-Siwe disease

  • Langerhans cell granulomatosis

  • Langerhans cell (eosinophilic) granulomatosis

  • Type II histiocytosis

  • Hashimoto-Pritzker disease

  • Self-healing histiocytosis

  • Pure cutaneous histiocytosis

  • Non-lipid

THE EPIDERMAL LANGERHANS CELL

Normal Langerhans cells reside primarily in the epidermis, in the orobuccal and vaginal epithelia, and in the lungs. They represent 1% to 2% of all epidermal cells and play a critical role in cutaneous immunosurveillance. After antigen contact, the Langerhans cells migrate through the dermal lymphatics to regional lymph nodes, most likely to present antigen to paracortical T cells, after which they presumably become interdigitating dendritic cells. Indeterminate cells, believed to be precursors

HISTOPATHOLOGY OF THE BASIC LESION

The histopathology of LCH is generally uniform regardless of the clinical severity, but it is influenced to some degree by the site of the lesion and more so by the age of the lesion.10, 15, 23, 33, 84, 108 The basic lesion of LCH is formed by collections of pathologic Langerhans cells (PLC), indeterminate cells, interdigitating cells, and macrophages accompanied by T lymphocytes with variable numbers of multinucleated giant histiocytes and eosinophils. Granulocytes and plasma cells, when

SECONDARY DENDRITIC CELL PROCESSES

It has become apparent that not all lesions that feature dendritic cells, including Langerhans cells, fit into the spectrum of LCH. Aggregates of dendritic cells, most often Langerhans cells, are encountered in association with Hodgkin's disease and less often with other lymphomas and tumors of the lung and thyroid.3, 9, 26, 34, 83 When the lesional cells feature the Langerhans cell phenotype, distinction from LCH requires clinical correlation. In lesions associated with lung tumors, it appears

HISTOPATHOLOGY OF THE SPECIFIC ORGANS

The basic lesion described previously is seen in various sites involved in LCH, although lesions of brain and lymph node may show different patterns and cellular phenotypes. Only special features related to location are noted subsequently.

FINE-NEEDLE ASPIRATION (FNA) OF LANGERHANS CELL HISTIOCYTOSIS

Several studies have demonstrated the feasibility of diagnosing LCH by FNA.2, 28, 63, 66, 106 Cytologic specimens are cellular and composed of large numbers of benign-appearing CD1a-positive histiocytes that only occasionally cluster. The PLCs are polygonal, with abundant clear blue (Diff-Quick and Geimsa stained) or eosinophilic (H&E stained) cytoplasm with irregular borders, surrounding oval or indented nuclei with fine homogeneous chromatin, and indistinct nucleoli. A nuclear groove or

ELECTRON MICROSCOPY OF LCH

LCs and PLCs have general features of histiocytes by electron microscopy, including abundant cytoplasm and irregular plasma membranes, but with nuclei that tend to be irregularly shaped or lobated. The one distinctive feature is the presence of the Langerhans cell or Birbeck granule.27, 45, 76, 98 The granules are rod- or racquet-shaped cytoplasmic structures 200 to 400 nanometers in length with a constant width of 33 nanometers. They have a zipper-like appearance with a central striated line

DNA Ploidy Profiles

DNA ploidy studies performed on archival paraffin-embedded tissue from LCH patients with localized and disseminated forms of the disease generally show a diploid population.34, 74, 87, 93 S-phase fractions have not been studied in detail. Only four cases of LCH with aneuploid cell populations been reported, too few to judge prognostic relevance.34, 87 The case of a 76-year-old man with a generalized nodular eruption, constitutional symptoms, and no signs of internal involvement appears to have

PATHOPHYSIOLOGY

Aberrations of cellular immunity have been postulated as underlying the pathogenesis of LCH. Immune abnormalities resulting in unchecked proliferation of PLCs after exposure to a virus or some other stimulus have been suggested. Findings suggestive of immune dysfunction, including abnormal immunoglobulin levels, mitogen responses, and T-suppressor cell levels, have been noted inconsistently.24 That LCH might be a pathologic response to virus(es) with or without an immunologic abnormality

SUMMARY

The pathology of LCH is continuing to be defined and diagnostic features clarified as unprecedented research is done. Although the etiology of LCH remains unknown, new information on cytokines, viruses, immunologic dysfunction, cell surface antigen expression, and clonality in the disease are providing essential pieces of the puzzle.

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    Address reprint requests to Laura Schmitz, MD, North Pathology Associates, North Memorial Medical Center, 3300 Oakdale North, Robbinsdale, MN 55422

    This work was funded, in part, by the Histiocytosis Association of America.

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