CENTRAL NERVOUS SYSTEM DISEASE IN LANGERHANS CELL HISTIOCYTOSIS
Section snippets
LCH-CNS STUDY
Information provided in this article is based on both a comprehensive review of the literature and on data from the LCH-CNS Study. The latter was a retrospective collection of clinical data and information on imaging and histopathology of LCH in patients who presented with signs and symptoms of CNS involvement. The goal was to gather information on the variety of clinical and morphologic patterns of this disease.
Between 1991 and 1996, material on 38 patients was compiled from 27 institutions in
MAGNETIC RESONANCE IMAGING CHANGES AND DIFFERENTIAL DIAGNOSES (Table 2)
The increased availability of MR imaging has improved the diagnosis of CNS abnormalities. Most LCH patients now undergo MR imaging for the evaluation of DI. In one exceptional case in the LCH-CNS Study, profound abnormalities in the cerebellum and pons were found on such an occasion in the absence of any CNS symptoms apart from DI, which was associated with skull and temporal bone lesions. This case underscores the sensitivity of MR imaging and provides evidence for the importance of evaluating
HISTOPATHOLOGY
Four stages of LCH-CNS were described by Norman61: a hyperplastic-proliferative stage, a granulomatous stage, a xanthomatous stage, and a stage of fibrosis. Based on hematoxylin and eosin morphology of autopsy material, Kepes45 provided a comprehensive overview of the disorder in 1979. He proposed that the LCH cells arose from adventitial cells of blood vessels, causing perivascular histiocytic aggregates that evolved into larger granulomatous masses that contained variable portions of foamy
HYPOTHALAMIC-PITUITARY INVOLVEMENT
There is an outstanding but unexplained predilection of LCH for the hypothalamic-pituitary system, occurring mostly in the setting of systemic disease. It is also observed as an isolated entity described as Ayala's disease or Gagel's granuloma in early reports.4, 25
The signs and symptoms range from disturbances in social behavior, appetite, and temperature regulation or sleep pattern in case of hypothalamic involvement; to polyuria and polydipsia as manifestations of posterior pituitary
SPACE-OCCUPYING CNS LESIONS
Lesions exerting a mass effect may arise from neighboring bone lesions, from the meninges, or from the choroid plexus. The symptoms depend on the size and site of the lesions, and they are related largely to raised intracranial pressure or focal damage. They include headaches, vomiting, papilledema and optic atrophy, seizures, and other focal symptoms. These lesions may occur with or without other evidence of LCH.12, 59 They appear localized or multifocal,27 with some tendency to symmetry in
CEREBELLAR SYNDROME/NEUROLOGIC DEGENERATION
The second most common site of LCH-CNS involvement after the hypothalamus-hypophyseal axis is the cerebellum.1, 5, 13, 22, 37, 39, 46, 77, 86 The incidence of this finding is unknown. In the LCH-CNS Study, 23 of 38 patients (60%) presented with changes in the cerebellum. The frequency of signs of cerebellar dysfunction in recent studies varies from 1% to 12%, presumably depending on the different duration of the observation periods, which ranged from 13 to 25 years.24, 78, 85 Neurologic
COMBINATION OF DIFFERENT CNS MANIFESTATIONS
As already mentioned, the majority of patients display more than one type of lesion. Often DI with structural changes in the hypothalamic-pituitary region heralds the involvement of other parts of the brain, sometimes by years. In the infratentorial space, the bilateral symmetric changes in the cerebellar dentate nuclei and white matter are the most common finding. Supratentorially, extraparenchymal lesions deriving from the meninges and the choroid plexus are frequently seen. They range from
SPECULATIONS ON PATHOGENESIS
The etiology of LCH-CNS remains poorly understood. The crucial questions are the following: Where do LCH-CNS lesions come from, and what factors influence the development of the various types of lesions? Why are the hypothalamus-pituitary and the cerebellar-pontine regions preferential sites? Are any special local factors encouraging the development of infiltrates? Are there any specific host factors influencing the development of more tumorous infiltrates in some patients and of degenerative
GUIDELINES FOR THE MANAGEMENT OF
LCH-CNS PATIENTS
ACKNOWLEDGMENT
The authors are grateful to V. Broadbent, G. D'Angio, and A. J. Barkovich for their expert advice and also wish to thank E. Thiem, B. Holzinger, and M. Minkow for their help in the evaluation of the patient data and preparation of the manuscript.
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2022, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Estimates of CNS involvement in LCH patients vary widely and are reported to range from 3.4% to 57% (Yeh et al., 2018). CNS LCH most commonly affects the HPIT region (Grois et al., 1998; Fahrner et al., 2012). While a confirmatory biopsy is required to make a definitive diagnosis of LCH, tumor location may make performing a biopsy difficult and/or clinically contraindicated in some patients.
Histiocytic disorders
2021, Lanzkowsky's Manual of Pediatric Hematology and OncologyEndocrine and metabolic assessment in adults with Langerhans cell histiocytosis
2018, European Journal of Internal MedicineCitation Excerpt :In more than a half of cases oncogenic mutations could be found, more frequently BRAFV600E [6,9,10] or rarely KRAS and TP53 but probably LCH is not a classical neoplastic disease but a neoplastic process with inflammatory manifestations [11]. About pituitary gland, autoptic series showed infiltrative Langerhans cells in about 5–50% of the LCH population [12–15] but really few studies have examined the real prevalence of endocrine diseases among adult LCH patients prospectively [16,17]. Diabetes Insipidus (DI) is the most frequent endocrine alteration described, its prevalence being among 15% and 50% of LCH patients [18,19], in particular about 40% considering only LCH MS-RO− patients, and at present it is considered the most common LCH permanent complication [15,20].
Histiocytosis Syndromes
2016, Lanzkowsky's Manual of Pediatric Hematology and OncologyStrategies for the Prevention of Central Nervous System Complications in Patients with Langerhans Cell Histiocytosis: The Problem of Neurodegenerative Syndrome
2015, Hematology/Oncology Clinics of North AmericaNeurological Manifestations of Histiocytic Disorders
2023, Current Neurology and Neuroscience Reports
Address reprint requests to Nicole G. Grois, MD, St. Anna Children's Hospital, Kinderspitalgasse 6, A-1090 Vienna, Austria