The international dataset on the association between Langerhans Cell Histiocytosis and other malignancies.

This article presents the international dataset of cases in which the association of Langerhans cell Histiocytosis (LCH) with other malignancies (AM) was documented occurring at any age before, concurrently or after LCH. These data are mostly derived from previously published manuscripts or from completed case report forms (CRFs) by Histiocyte Society (HS) members or colleagues. In particular, for each case of LCH-AM, the database reports all the available data about clinical and biologic characteristics of the two tumors, as well about treatment and status at follow-up. The AM were categorized as: i) leukemias [acute lymphoblastic or myeloid leukemia (ALL and AML, respectively), other leukemias] and myeloproliferative disorders; ii) lymphomas [Hodgkin lymphoma (HL) and non-Hodgkin lymphomas (NHL)] and iii) solid tumors. A total of 270 LCH-AM cases were documented, of which 116 (43%) occurred among children. After stratification by age at LCH diagnosis, using 18 years as cut-off between children and adults, we here provide details on the clinical characteristics in terms of LCH system involvement and affected organs, as well on the temporal relationship between the LCH and AM diagnoses, including details on the AM malignancy types. In 19 cases the LCH and the corresponding AM occurred in a different age group. The data set is available for future studies in view of new insights of the genetic or environmental determinants of LCH and/or of treatment related subsequent neoplasms.

Langerhans cell histiocytosis and associated malignancies: A retrospective analysis of 270 patients.

PURPOSE: The frequency of Langerhans cell histiocytosis (LCH) and associated malignancies (AM) is greater than statistically expected. Here, we analyze LCH-AM co-occurrence in both children and adults. METHODS: Between 1991 and 2015, data were collected by regular questionnaires to members of the Histiocyte Society and searches in PubMed and Abstract Books. Patients were grouped by age at LCH diagnosis (≤ and >18 years), and types and timing of AM occurrence were plotted with respect to the LCH diagnosis. For the statistical analysis, only the first AM were considered. RESULTS: A total of 285 LCH-AM in 270 patients were identified, 116 (43%) ≤ 18 years, and 154 (57%) >18 years. In childhood LCH-AM pairs, leukemias and myeloproliferative disorders (n = 58; 50.0%) prevailed over solid tumors (n = 43; 37.1%) and lymphoma (n = 15; 12.9%). In adults, solid tumors were reported in 61 patients (39.6%), lymphoma, and leukemias and myeloproliferative disorders in 56 (36.4%) and 37 (24.0%) patients, respectively. In most children, AM followed LCH (n = 69, 59.5%), whereas in adults, LCH and AM occurred concurrently in 69 patients (44.8%). In children, T-lineage acute lymphoblastic leukemia (ALL) and promyelocytic acute myeloid leukemia (AML) and retinoblastoma were over-represented and thyroid carcinoma in adults. CONCLUSIONS: The largest collection of data on LCH-AM to date clearly indicates inherent relationships between specific types of AM and LCH, which may be due to therapy effects, clonal evolution, and germ-line predisposition, respectively. Prospective thorough genetic analysis is warranted and will hopefully shed light on the association of LCH and second neoplasms.

Long term morbidity and health related quality of life after multi-system Langerhans cell histiocytosis.

BACKGROUND: Langerhans' cell histiocytosis, a clonal multisystem disorder, can affect children or adults resulting in long term sequelae. However, the overall morbidity for survivors has not been formally determined. PATIENTS AND METHODS: We performed a cross-sectional study of 40 unselected long term survivors of childhood multisystem Langerhans cell histiocytosis, involving clinical examination, health-related quality of life assessment, brain imaging, neuropsychometry, endocrine assessment, respiratory function tests and audiometry. A specific 'morbidity score' was devised to measure outcome. RESULTS: Seventy-five percent of patients had detectable long term sequelae, hypothalamic-pituitary dysfunction (50%), cognitive dysfunction (20%) and cerebellar involvement (17.5%) being the most common. Half had moderate to severe morbidity, and the worst-affected patients were unable to lead an independent adult life. Health-related quality of life, which correlated well with the morbidity score (p<0.001), was adversely affected in >50% of patients. CONCLUSION: Organ damage from multisystem Langerhans cell histiocytosis causes long term morbidity extending into adult life. Carefully planned, multidisciplinary follow up is essential to ensure early recognition of problems with appropriate interventions to reduce the impact on patients' 'quality of life'.

Intraocular Langerhans cell histiocytosis in a neonate resulting in bilateral loss of vision.

Intraocular involvement in Langerhans cell histiocytosis (LCH) is rare. We describe the case of a neonate with congenital disseminated LCH involving skin, liver, spleen, and intraocular structures including uvea and retina. Early and aggressive treatment according to the LCH-II treatment protocol was administered and resulted in remission of the disease. However, despite close follow-up and additional local treatment, involvement of intraocular structures resulted in severe long-term ophthalmological sequelae including complete bilateral loss of vision.

Cognitive outcome of long-term survivors of multisystem langerhans cell histiocytosis: a single-institution, cross-sectional study.

PURPOSE: Damage to the CNS, including the cerebellum, and to the hypothalamopituitary axis, is documented in Langerhans cell histiocytosis (LCH). Neuropsychologic deficits have been recognized, but this is the first study in which cognitive function has been systematically assessed in a cohort of patients. PATIENTS AND METHODS: Twenty-eight long-term survivors of multisystem LCH (mean age, 15.1 years) were investigated for intelligence, memory and learning, language, and academic attainments. RESULTS: The mean intelligence quotient (IQ) of the entire group was not significantly different from the mean of the population (ie, mean +/- SD, 100 +/- 1), but there were wide ranges (Full-Scale IQ [FSIQ]: mean, 93.6; range, 61.7 to 134; Performance IQ [PIQ]: mean, 92.2; range, 46 to 136; and Verbal IQ [VIQ]: mean, 93.7; range, 64.2 to 126). CNS involvement was a significant risk factor for lower scores, but sex, diabetes insipidus, and cranial radiotherapy were not. The CNS group had lower VIQ, PIQ, and FSIQ than patients with no CNS involvement (no CNS group: mean +/- SD FSIQ, 102.3 +/- 15.6; CNS group: mean +/- SD FSIQ, 73.6 +/- 7.7; P <.001). A similar pattern of results was obtained for all other cognitive measures. Even when effects of reduction in FSIQ were taken into account, specific deficits were found in patients in the CNS group. CONCLUSION: Long-term survivors of multisystem LCH, particularly patients with CNS involvement, may develop significant cognitive deficits. All patients should have formal, repeated neuropsychologic assessment as part of long-term follow-up, which will enable abnormalities to be detected early so that appropriate supportive measures can be offered.