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

Abstract

BackgroundLangerhans 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.MethodsWe 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.ResultsOf 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%).ConclusionOur 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.

Spectrum of histiocytic neoplasms associated with diverse haematological malignancies bearing the same oncogenic mutation

“…Conversely, transformation of antecedent haematological malignancies to secondary histiocytic neoplasms may also occur [17,18]. In the 1990s, the LCH‐Malignancy Study Group of the Histiocyte Society already reported recurrent associations between LCH and leukaemia or lymphoma [19,20], which were confirmed in later studies [21,22]. Likewise, a high prevalence of haematological malignancies was also observed in adults with ECD [23] or HS [24].…”

Concomitant Langerhans cell histiocytosis of cervical lymph nodes in adult patients with papillary thyroid carcinoma: A report of two cases and review of the literature

“…However, it was typically associated with concomitant metastasis in the same lymph node. 33,34,36 In fact, this will make the diagnosis more challenging, as cells seen in LCH can mimic those seen in PTC and malignant melanoma; moreover, both malignant melanoma and LCH show S100 protein-positive reaction. In both of our cases, there was no evidence of metastases in lymph nodes.…”

“…Additionally, several studies have shown a higher prevalence of hematological and solid malignancies among LCH patients. 35,36 A study by Jennifer Ma et al 36 of adult LCH patients found an exceptionally high number of additional malignancies. The identified malignancies were diagnosed either earlier or at the same time as a diagnosis of LCH, indicating that the cause of malignancies is not secondary to LCH treatment.…”

Successful Outcome of a Case of Acute Myeloid Leukemia With t(8;21)/AML-ETO Following Langerhans Cell Histiocytosis

“…The chemotherapy for LCH and genetic predisposition may be explanations. Previously, 27 such cases have been reported [1], and lymphomas, solid tumors, and other hematologic malignancies have been associated with chemotherapy for LCH [2]. Most patients develop AML at least 2 years (mean: 5.5 years) after LCH treatment [3].…”

“…A safe dose of etoposide does not truly exist; between 2 and 20 years after exposure to etoposide, 1%-5% of patients may develop t-AML [5]. Etoposide-associated AML has been described after its usage for a wide spectrum of diseases, including non-Hodgkin lymphoma [6], acute lymphoblastic leukemia [7], solid tumors [2], and hemophagocytic lymphohistiocytosis [5]. The cytogenetic abnormalities of t-AML reported in patients with LCH include t(15;17), 11q23, +16, and +21 [8,9,10].…”