case_images: PMC10972997_01
case_images: 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).
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case_images: f1
case_images: In 2020, a perirenal tissue biopsy was performed, supporting the diagnosis of ECD ( Figures 1F, G ). In April 2020, mutational analysis confirmed the BRAF V600E mutation. 18FDG-PET/CT was performed and showed typical osteosclerotic lesions in the distal bones ( Figure 1A ). In July 2020, the control 18FDG-PET/CT scan showed disease regression ( Figure 1B ), and subsequent control 18FDG-PET/CT scans indicated complete metabolic remission (CMR) ( Figures 1C-E ).
case_images: PMC10972997_02
case_images: 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).
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case_images: f2
case_images: The unusual association of these rare symptoms has been attributed to a possible histiocytic disease and an 18FDG-PET/CT scan supported the diagnosis with sclerotic lesions in the metaphysis of the long bones and cutaneous/skeletal involvement was also described ( Figure 2A ). A biopsy of the right femur had been performed, which confirmed BRAF-negative ECD ( Figures 2E, F ). In March 2021, treatment with pegylated interferon alpha was started at a dose of 180 ug once a week but was ineffective based on response assessment with 18FDG-PET/CT in June 2021 ( Figure 2B ). December 2021, 18FDG-PET/CT showed CMR ( Figure 2C ). During cobimetinib therapy, the patient developed skin symptoms in the form of a maculopapular rash, and dose reduction was required after the first month. The skin symptoms resolved on the modified dose (40 mg once daily), and the patient is still in CMR ( Figure 2D ).
case_images: PMC10972997_03
case_images: 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).
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case_images: Figure 3A ). Femoral bone biopsy supported the diagnosis of ECD in 2017 ( Figures 3C-E ). In the first line, we administered interferon-alpha therapy, but no significant improvement was detected on the control 18FDG-PET/CT scan in February 2023 ( Figure 3B ).
case_images: A maculopapular rash appeared after less than two weeks of cobimetinib therapy.
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case_images: f4
case_images: As an adverse event, maculopapular rash occurred during the first two weeks of treatment ( Figure 4 ), and a dose reduction (40 mg once daily) was necessary.