LANGERHANS CELL HISTIOCYTOSIS IN ADULTS IS ASSOCIATED WITH INCREASED HEMATOLOGIC AND SOLID MALIGNANCIES

Abstract

Introduction: Langerhans cell histiocytosis (LCH) is a rare disorder of histiocyte proliferation occurring predominantly in children. Previous retrospective and small case studies have suggested higher rates of both hematologic and solid malignancies among LCH patients, possibly due to treatment with tumorigenic agents such as etoposide. Here, we report on our 25-year institutional experience of adult LCH patients with additional malignancies, in an era prior to the widespread use of etoposide. Methods: We identified 170 consecutive patients over 18 years of age who presented with histologically confirmed LCH (S100+, CD1a+) at our center between 1990 and 2015. Demographics and detailed oncologic history was recorded to identify patients with additional malignancies, excluding non-melanoma skin cancers. The Kaplan-Meier method was used to estimate overall survival. Results: Of 170 consecutive adult LCH patients, 62 (36.5%) patients had an additional malignancy. There were a total of 81 malignancies among the 62 patients, with 47 (58%) occurring before LCH diagnosis, 18 concurrent (≤3 months; 22%) with LCH diagnosis, and 16 (20%) after. Fifteen patients presented with 2 malignancies in addition to their LCH diagnosis, and 2 patients presented with ≥3 malignancies. Median age was 65 years (range 28–90) with a median follow-up of 3.5 years (0–22). Median overall survival (OS) was 11.2 years, with 45 (72.5%) alive at last follow-up. The following distribution among lymphomas, other hematologic malignancies, and solid tumors were observed: 10 (12%), 7 (9%), and 64 (79%). The most commonly observed lymphomas included follicular lymphoma (30%), classical Hodgkin's lymphoma (20%), and B-cell lymphoma (20%). Most common hematologic malignancies included acute myeloid leukemia and multiple myeloma (29% each). The most common solid tumor histologies were lung (24%), breast (15%), and colorectal cancer (11%). Conclusions: Our cohort of adult LCH patients demonstrates an exceptionally high number of malignancies. Although our retrospective study is open to referral bias, our findings are consistent with numerous published small retrospective studies and case reports. Other large retrospective studies were performed when etoposide was widely used, and etoposide was suggested as a possible cause for an observed increase in hematologic malignancies after LCH treatment. Yet our study shows an increased prevalence of other malignancies before or concurrent with LCH diagnosis and thus suggests a cause of malignancy independent of LCH treatment. Further exploration of the biology of this rare disease may elucidate the mechanism of increased second malignancies. Keywords: etoposide; histiocytes.