LANGERHANS CELL HISTIOCYTOSIS IN ADULTS

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Langerhans cell histiocytosis (LCH) is a rare condition in adults. Its cause is uncertain, but with the recent demonstration of clonality32, 34 and its association with malignant disease,7 there has been a renewal of interest. There is a need for epidemiologic studies and a review of the clinical manifestations of LCH in adults and of its clinical course, because although it is rare, it forms an important differential diagnosis in lymphoma, myeloma, endocrinopathies, and skin disease.

Earlier series from large institutions2, 8, 21 and even multi-institutional reports26 have tended to combine childhood and adult data, which has obscured the adult picture. These series are retrospective; accrual to some of them has had a bias because of either institutional special interests or a deliberate concentration on LCH as seen in a particular organ9 or system.15 All these features emphasize the need for caution in the interpretation of the relatively small amount of clinical information available.

One of the earliest large series of LCH that included adults was from Johns Hopkins in Baltimore.2 This series included the whole spectrum of LCH; there were three patients over the age of 15 with eosinophilic granuloma (out of a total of nine), seven patients with disease affecting more than one system, and no adults with Letterer-Siwe disease. Of the total of 40 patients, 24 were male and 16 female, but if adults only are considered, the gender ratio is reversed, with more female than male patients. In adults, nearly all the bone presentations were in the skull, and half of these patients developed diabetes insipidus (DI). None of the adults died of LCH.

The next large series from a single institution that included a significant number of adults21 reported that more than half of the 17 patients with bone presentations had lesions in the head and neck. None of the adults in this group (range, 16 to 68 years of age) died. In patients with bone and soft-tissue involvements, 2 of 17 were older than 15 years, and both developed DI. They were alive at 8 and 21 years of follow-up. Only one patient had disseminated disease, with skin and mucous membrane involvement.

Enriquez et al8 reported on 117 patients from the Mayo Clinic, of whom 36 were adults ranging in age from 17 to 61 years, but gender was not commented on. All 19 of those with single-site disease were alive, but one death occurred out of the 14 patients with bone and soft-tissue involvement, giving an overall adult mortality of 3%, compared with 15% in the children.

The ratio of adults to children is shown in Table 1, from which it can be seen that about 30% of LCH occurs in adults.

From these large studies it would seem that adult LCH is less common than in childhood; male gender preponderance seen in children becomes less obvious with increasing age; bone presentation is frequent, and the skull and upper skeleton are most often involved. In general, those adults presenting with a local bone lesion run a benign course, but there is an obvious need for prospective studies.

Section snippets

INCIDENCE

The rarity of adult LCH makes assessment of its incidence difficult. Some of the best studies on incidence have been done in children. Carstensen and Ornvold4 contacted every department in Denmark that would have been likely to see LCH. The case histories of LCH were reviewed and the histology re-examined. Denmark has a population of 5.1 million, with 1.09 million children at risk throughout the study period (1975–1989). Ninety children were diagnosed (62 male, 28 female), giving an incidence

PRESENTING FEATURES

In considering presenting features and systemic involvement, emphasis is placed on aspects that predominate in adults. Adult LCH most commonly affects the skin, lungs, and bone,17 although DI is fairly common. Involvement of liver, spleen, lymph nodes, and bone marrow is much less frequent.

One of the largest early surveys of clinical presentations5 noted that more than three quarters of patients presented with skin involvement. A quarter had pulmonary lesions, whereas other presentations were

Bone

Skeletal involvement is one of the most common presenting features in adult LCH.2, 8, 21, 26 Between 1907 and 1967, 24 of 46 (66%) adults presenting in the Mayo Clinic had bone involvement. Another hospital series17 records 12 of 47 (23%) with bone pain. When bone lesions were the criterion for inclusion in the series,15 a clinicopathologic analysis showed differences between adults and children. Multiple sites of bone involvement were most frequently seen in children. The skull was the most

DIFFERENTIAL DIAGNOSIS

Because LCH frequently involves the skeleton in adults, it may be included in the differential diagnosis with multiple myeloma (MM)—lytic lesions with clear-cut margins on a radiographic survey are similar, and in both LCH and MM these lesions in the spine and long bones may be painful. Skull lesions in MM are usually painless, but this is not the case in LCH, and this may be helpful clinically. The presence of paraproteinemia and urinary light chain and plasma cell infiltration of the bone

ASSOCIATED DISEASE

The association of LCH with malignancy is well established and occurs more frequently than would be expected by chance. Many tumors are breast or lung cancers, and these often occur in young patients. A number of reviews have shown acute leukemia, Hodgkin's and non-Hodgkin's lymphoma, myeloma, and solid tumors can occur before, after, or concurrently with the diagnosis of LCH.7, 17, 19, 25, 33 Egeler et al7 were able to report 91 cases in the literature. Nearly half were lymphomas; solid tumors

TREATMENT

The treatment of LCH is covered comprehensively elsewhere in this issue, so an adult perspective is briefly included here. Treatment in adults has followed very closely the modalities used in children, with the exception that radiotherapy has probably been used more frequently. With growth inhibition no longer a constraint, radiotherapy is a rapid and effective treatment. Local curettage of bone has been used and, more recently, intralesional methylprednisolone.

The assessment of therapy in

ACKNOWLEDGMENTS

The author thanks Mrs Jo Barton for her invaluable help with the preparation of this manuscript.

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    Copyright © 1998 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.