Figure 1.
Imaging and histologic features of patient responses to dabrafenib. (A) Representative fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography of patients 3 and 4 demonstrating responses to dabrafenib. Pretherapy imaging in patient 3 (leftmost panel) demonstrates significant thymic, cervical, periportal FDG avidity as well as diffuse bone marrow uptake, with near-complete resolution at 7 weeks after start of dabrafenib. Similarly, patient 4 exhibited diffuse, extensive FDG avidity of the marrow space, lymph nodes, liver, and spleen. Repeat imaging obtained after 6 weeks of dabrafenib (right) showed dramatic improvement of hypermetabolic areas. Bone marrow examination of patient 2 at diagnosis revealed an increased number of histiocytes (B; original magnification ×400, hematoxylin and eosin stain), which was confirmed by CD163 immunohistochemistry (C; original magnification ×400). The histiocytes are BRAF positive (red reaction product) as assessed by BRAF V600E–specific immunohistochemistry (D; original magnification ×400). The histiocytic hyperplasia persisted following dabrafenib therapy (E; original magnification ×400, hematoxylin and eosin stain), as confirmed by CD163 immunohistochemistry (F; original magnification ×400). BRAF immunohistochemistry (brown reaction product) labels some histiocytes but also smaller cells with myeloid morphology (G; original magnification ×400). In patient 1, despite dabrafenib therapy, hemophagocytic histiocytes remained evident in the bone marrow aspirate (H; original magnification ×1000). Bone marrow histiocytic hyperplasia was confirmed by CD163 immunohistochemistry (I, original magnification ×400; J, original magnification ×1000), which highlights scattered hemophagocytic forms (arrow). Numerous BRAF-positive cells were present, as assessed using BRAF V600E–specific immunohistochemistry (K, original magnification ×400; L, original magnification ×1000, brown reaction product), including histiocytes (L, black arrows) as well as cells with myeloid morphology (L, cross-hatched arrows).

Imaging and histologic features of patient responses to dabrafenib. (A) Representative fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography of patients 3 and 4 demonstrating responses to dabrafenib. Pretherapy imaging in patient 3 (leftmost panel) demonstrates significant thymic, cervical, periportal FDG avidity as well as diffuse bone marrow uptake, with near-complete resolution at 7 weeks after start of dabrafenib. Similarly, patient 4 exhibited diffuse, extensive FDG avidity of the marrow space, lymph nodes, liver, and spleen. Repeat imaging obtained after 6 weeks of dabrafenib (right) showed dramatic improvement of hypermetabolic areas. Bone marrow examination of patient 2 at diagnosis revealed an increased number of histiocytes (B; original magnification ×400, hematoxylin and eosin stain), which was confirmed by CD163 immunohistochemistry (C; original magnification ×400). The histiocytes are BRAF positive (red reaction product) as assessed by BRAF V600E–specific immunohistochemistry (D; original magnification ×400). The histiocytic hyperplasia persisted following dabrafenib therapy (E; original magnification ×400, hematoxylin and eosin stain), as confirmed by CD163 immunohistochemistry (F; original magnification ×400). BRAF immunohistochemistry (brown reaction product) labels some histiocytes but also smaller cells with myeloid morphology (G; original magnification ×400). In patient 1, despite dabrafenib therapy, hemophagocytic histiocytes remained evident in the bone marrow aspirate (H; original magnification ×1000). Bone marrow histiocytic hyperplasia was confirmed by CD163 immunohistochemistry (I, original magnification ×400; J, original magnification ×1000), which highlights scattered hemophagocytic forms (arrow). Numerous BRAF-positive cells were present, as assessed using BRAF V600E–specific immunohistochemistry (K, original magnification ×400; L, original magnification ×1000, brown reaction product), including histiocytes (L, black arrows) as well as cells with myeloid morphology (L, cross-hatched arrows).

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