Langerhans cell histiocytosis in adults is associated with a high prevalence of hematologic and solid malignancies

Abstract

Background: Langerhans cell histiocytosis (LCH) is a rare disorder of histiocyte proliferation. Previous case studies suggest a higher prevalence of hematologic and solid malignancies among LCH patients, possibly due to treatment with tumorigenic agents such as etoposide. We report the first large, single-institution experience of adult LCH patients with additional malignancies to study the characteristics of these patients.

Methods: We identified 132 consecutive patients >18 years of age with histologically confirmed LCH at our center between 1990 and 2015. Demographics and detailed oncologic history were recorded to identify patients with additional malignancies.

Results: Of 132 adult LCH patients, 42 (32%) patients had an additional malignancy. There were 53 malignancies among the 42 patients, with 31 (58%) preceding LCH diagnosis, 11 concurrent (≤3 months; 21%) with LCH diagnosis, and 11 (21%) after. Median age was 54 years (range 28-89) with a median follow-up of 3.7 years (0.1-22.2) for this cohort. OS at 3 years was 98% in patients with LCH alone and 82% among patients with additional malignancies, with 30 (71%) alive at last follow-up. Solid tumors, lymphomas, and other hematologic malignancies were observed as follows: 39 (74%), 9 (17%), and 5 (9%).

Conclusion: Our cohort of adult LCH patients demonstrates an unusually high number of additional malignancies. Our study includes predominantly malignancies diagnosed preceding or concurrent with LCH, suggesting a cause of malignancy independent of LCH treatment. Further exploration of the biology of this rare disease may elucidate the mechanism of frequent additional malignancies.

Keywords: Langerhans; Langerhans cell histiocytosis; eosinophilic granuloma; histiocytosis; second malignancies.

Figure 1

Cohort selection and distribution of additional malignancies in adult Langerhans cell histiocytosis patients (LCH)

Figure 2

Kaplan‐Meier overall survival outcomes for the Langerhans cell histiocytosis‐only and additional malignancy cohorts

Figure 3

Cumulative number of additional malignancies over time, relative to date of Langerhans cell histiocytosis diagnosis

Figure 4

Distribution of additional malignancies by cancer type and histology