which has been shown to be effective for treating hairy cell leukemia and chronic myelogenous leukemia [10]. There are reports of response to imatinib therapy in ECD, and although the mechanism is unclear, it is well tolerated [10].

Other therapies that have been reported in the literature in case reports and small case series include immunosuppressants such as cyclophosphamide, methotrexate, azathioprine, cyclosporine, and various chemotherapeutic agents [21, 27]. Autologous bone marrow transplantation [10], radiation therapy and surgical intervention of brain or bone lesions [21, 27] have also been reported with variable results, and with mostly unsustained responses [21, 27]. Given the high prevalence of bony involvement, bisphosphonate therapies have been attempted with only partial success and their role remains unclear [10, 21, 27]. Glucocorticoids have been widely used for the treatment of ECD but have been shown to have little impact on disease [1, 10, 27] except in a few cases when used in high doses [10, 27, 32].

Prognosis

The prognosis of ECD is variable, with 5-year survival between 40 and 70% [1, 11, 21], depending on the degree of multisystem involvement [26]. While it is unclear if pulmonary­ involvement carries any prognostic weight [10, 27], CNS and cardiovascular involvement are well-estab- lished harbingers of a worse prognosis [4, 10, 21]. CNS involvement (especially with pituitary in ltration) accounts forapproximately30%ofalldeaths[1,26,32].Cardiovascular complications, including heart failure from pericardial, myocardial, or aortic in ltration [1, 4, 10, 21], or myocardial infarction related to in ltration of coronary arteries [27], are responsible for about 61% of deaths [27]. Cardiac involvement is a late complication of ECD [21].

Clinical Vignette

A 63-year-old female presented with 2 years of progressive wheezing and daily cough that were worse when lying fat. These symptoms were associated with shortness of breath with ascending 1 fight of stairs, sneezing, bilateral eye pain, fatigue, and left upper extremity discomfort. Her history was remarkable for gastro-esophageal refux disease controlled with daily proton pump inhibitor, and motor vehicle

collision complicated by cervical spine trauma and right-sided hemothorax 5 years prior to presentation. Initial CXR was abnormal, and subsequent CT of the chest demonstrated mass-like subpleural consolidation in the right lower lobe (RLL), bilateral lower lobe ground glass opaci cation, and pleural and subpleural interstitial thickening consistent with brosis (see Clinical Vignette gure). A PET-CT was obtained revealing increased FDG uptake in several distributions, including the RLL subpleural consolidation, thickened pleura, scattered airspace disease of the right lung, and mediastinal lymph nodes. Biopsy of the RLL subpleural consolidation revealed marked infammation and brosis but was nondiagnostic. She underwent a video-­assisted thoracic surgery lung biopsy of her left lung, which revealed a broinfammatory process with a lymphangitic distribution, and a focal chronic interstitial in ltrate with abundant macrophage aggregates and non-necrotizing granulomatous infammation of airspaces and interstitium. Immunohistochemistry was positive for CD34, which together with the histopathology was consistent with the diagnosis of ECD. A subsequent bone scan revealed pathognomonic changes of ECD with increased uptake within the distal diaphysis and metadiaphyseal regions of each femur. She completed initial evaluation with pulmonary function tests that showed a mild restrictive defect with reduced diffusion capacity, an MRI head which was negative, and a cardiac MRI which revealed cardiac involvement of her ECD.

During the course of the patient’s evaluation, she was also found to have chronic myelomonocytic leukemia (CMML). Ultimately, it was discovered that the patient harbored a BRAF V600 E mutation leading to her ECD, with NRAS and ASXL1 mutations causing chronic myelomonocytic leukemia (CMML). Treatment was initiated with dabrafenib/trametinib (BRAF + MEK inhibitor) which resulted in remarkable improvement in pulmonary function testing, radiographic changes, and symptoms of dyspnea, cough, and wheezing (Fig. 16.12). Unfortunately, the patient’s hematologic malignancy progressed and she passed away 4 years after her diagnosis of ECD due to complications of acute myeloid leukemia.