Case report: Targeted treatment strategies for Erdheim-Chester disease

Abstract

Introduction: Erdheim-Chester disease (ECD) is a rare disease that belongs to the group of Dendritic and histiocytic neoplasms. Only 2000 cases have been reported worldwide. It can present with a wide range of symptoms, making a differential diagnosis especially difficult. The primary and most important diagnostic tool is a biopsy of the affected organ/tissue. Nowadays the analysis of different mutations affecting the BRAF and MAPK pathways makes it possible to use targeted treatments, such as vemurafenib, dabrafenib, or cobimetinib.

Objective: Our aim is to present the results of three male patients treated in our hematology department.

Results: Our BRAF mutation-positive patient presented with retroperitoneal tissue proliferation and diabetes insipidus. The initial therapy of choice was dabrafenib. After 3 months of treatment, ¹⁸F-fluoro-deoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) scans showed regression, and after 2 years of treatment, no disease activity was detected. In our second patient, a recurrent febrile state (not explained by other reasons) and diabetes insipidus suggested the diagnosis. A femoral bone biopsy confirmed BRAF-negative ECD. The first-line therapy was interferon-alpha. After 3 months of treatment, no response was observed on ¹⁸FDG-PET/CT, and treatment with cobimetinib was started. The control ¹⁸FDG-PET/CT imaging was negative. Our third patient was evaluated for dyspnea, and a CT scan showed fibrosis with hilar lymphadenomegaly. A lung biopsy confirmed BRAF-negative ECD. We started treatment with interferon-alpha, but unfortunately, no improvement was observed. Second-line treatment with cobimetinib resulted in a partial metabolic response (PMR) according to control ¹⁸FDG-PET/CT.

Conclusions: Our results demonstrate that an appropriately chosen treatment can lead to a good therapeutic response, but dose reduction may be necessary due to side effects. With advanced targeted therapeutic treatment options, survival and quality of life are significantly improved.

Keywords: BRAF inhibitors; Erdheim-Chester disease (ECD); PET/CT; cobimetinib; histiocytosis; interferon alpha; myeloid neoplasm.

Figure 1

Abnormal contrast uptake (arrows) on the ¹⁸FDG-PET/CT image in the lower extremities (SUVmax 3.0) (A). The control ¹⁸FDG-PET/CT image shows regression after 4 months of dabrafenib treatment (SUVmax 1.5) (B). Control ¹⁸FDG-PET/CT images show CMR after dabrafenib treatment (C–E). A perirenal tissue sample shows fibrosis, macrophages, and lymphoplasmocytic infiltration (arrow) (hematoxylin and eosin x100) (F). Reactive inflammatory cells and fibrosis are seen in the perirenal tissue biopsy (hematoxylin eosin x400) (G).

Figure 2

Abnormal contrast uptake (arrows) on the PET/CT image in the lower extremities (SUVmax 11.9-10.9) and at the pectoralis major (SUVmax 5.4) (A). The control ¹⁸FDG-PET/CT image after interferon-alpha therapy shows refractory disease (SUVmax 18.8-16.0, 5.6-5.4) (B). Control ¹⁸FDG-PET/CT after 3 months of cobimetinib therapy shows disease regression (C). Control ¹⁸FDG-PET/CT after 6 months of cobimetinib therapy confirms CMR (D). The femoral biopsy sample shows fibrosis in the intratrabecular space and foamy histiocytes (hematoxylin eosin x100) (E). Femur biopsy with Touton giant cells (arrow) and foamy histiocytes (arrow) (hematoxylin eosin) (F).

Figure 3

Abnormal contrast uptake (arrows) on ¹⁸FDG-PET/CT image in the lower extremities (SUVmax 4.4-7.2) (A). Control ¹⁸FDG-PET/CT image after interferon alpha administration shows refractory disease (SUVmax 7.4-9.4) (B). Control 18FDG-PET/CT image after 3 months of cobimetinib administration shows disease regression (SUVmax 3.2) (C). Pulmonary tissue sample shows fibrosis with foamy histiocytes and lymphoplasmocytic infiltration (arrow) (hematoxylin eosin x100) (D). Pulmonary tissue sample shows fibrosis with foamy histiocytes (arrow) and lymphoplasmocytic infiltration (hematoxylin eosin x400) (E).

Figure 4

A maculopapular rash appeared after less than two weeks of cobimetinib therapy.