Introduction

Langerhans cell (LC) disease covers a wide range of clinical presentations with peaks of incidence in early and later life. What ties these disparate conditions together is their histopathology, which has as its bedrock the identification, in the tissues or fluids, of a population of abnormal Langerhans cell histiocytosis cells (LCH cells). Like all other laboratory tests, biopsy pathology must be subjected to the rules of sensitivity and specificity. Sensitivity relates to the incidence of false negative samples. Sampling is always an issue in biopsy pathology, but considerations of sensitivity relate to those features that are essential to the diagnosis so that ideally, all patients with LCH will be identified. Specificity in a diagnostic biopsy is concerned with false positive results, and deals with the differential diagnosis of those conditions most likely to be mistaken for LCH. Since LCH involves a multitude of different anatomical sites, each of which has unique issues of access, intrinsic anatomy and cell populations, as well as the other lesions characteristic to that site, the sensitivity and specificity of LCH diagnosis must be considered for each site.

The diagnostic criteria for LCH have been a moving target. Birbeck and colleagues first described intracytoplasmic inclusions in dermal LCs (Birbeck et al., 1961). Soon after Birbeck granules were found in histiocytosis X (Basset and Nezelof, 1966), tying histiocytosis X and dermal LCs together (Nezelof et al., 1973). Later CD1a was identified as a useful diagnostic marker for LCs and later for histiocytosis X (Murphy et al., 1983).