Figure 8.
Histopathologic features of ALK-positive histiocytosis. (A) Photomicrograph of the hematoxylin and eosin (HE)-stained slide of a frontal bone tumor (Case 7; original magnification ×200) with classic xanthogranuloma morphology including many Touton giant cells. (B) HE image of a spinal nerve root tumor (Case 15; original magnification ×200) showing abundant lipidized (“foamy”) histiocytes. (C) HE image (Case 31; original magnification ×400) showing a more monomorphic histiocytic infiltrate in the skin dissecting through the dermal collagen bundles. (D) HE image of a liver biopsy (Case 4; original magnification ×400) showing sinusoidal infiltration by large histiocytes (indicated by black arrows) with ALK immunoreactivity (inlet). (E) HE image of a CNS tumor (Case 18; original magnification ×400) with a monomorphic, dense infiltrate of histiocytes that demonstrate separated red and green signals on ALK break-apart FISH analysis (inlet). (F) HE image of a CNS lesion (Case 20; ×100) showing marked infiltration of the perivascular (“Virchow-Robin”) spaces by histiocytes with clear CD163 immunoreactivity (inlet). (G) CD163 immunostain of a CNS tumor (Case 18; original magnification ×200) showing diffuse strong expression by the monomorphic histiocytic infiltrate. (H) ALK immunostain (Case 7; original magnification ×200) showing strong cytoplasmic and membranous staining of lesional histiocytes and Touton giant cells. (I) ALK immunostain of a breast tumor (Case 12; original magnification ×400) showing focal, exclusive dot-like immunoreactivity that could be misinterpreted as negative. (J) S100 immunostain of a liver biopsy (Case 4; ×200) showing immunoreactivity by the large sinusoidal histiocytes. (K) P-ERK immunostain (Case 15; original magnification ×400) showing diffuse positive staining by the lesional cells, as well as clear emperipolesis (intact intracytoplasmic leukocytes). (L) Cyclin D1 immunostain of an oculomotor nerve tumor (Case 21; original magnification ×200) showing cytoplasmic and strong nuclear staining in histiocytes with frequent nuclear indentations.

Histopathologic features of ALK-positive histiocytosis. (A) Photomicrograph of the hematoxylin and eosin (HE)-stained slide of a frontal bone tumor (Case 7; original magnification ×200) with classic xanthogranuloma morphology including many Touton giant cells. (B) HE image of a spinal nerve root tumor (Case 15; original magnification ×200) showing abundant lipidized (“foamy”) histiocytes. (C) HE image (Case 31; original magnification ×400) showing a more monomorphic histiocytic infiltrate in the skin dissecting through the dermal collagen bundles. (D) HE image of a liver biopsy (Case 4; original magnification ×400) showing sinusoidal infiltration by large histiocytes (indicated by black arrows) with ALK immunoreactivity (inlet). (E) HE image of a CNS tumor (Case 18; original magnification ×400) with a monomorphic, dense infiltrate of histiocytes that demonstrate separated red and green signals on ALK break-apart FISH analysis (inlet). (F) HE image of a CNS lesion (Case 20; ×100) showing marked infiltration of the perivascular (“Virchow-Robin”) spaces by histiocytes with clear CD163 immunoreactivity (inlet). (G) CD163 immunostain of a CNS tumor (Case 18; original magnification ×200) showing diffuse strong expression by the monomorphic histiocytic infiltrate. (H) ALK immunostain (Case 7; original magnification ×200) showing strong cytoplasmic and membranous staining of lesional histiocytes and Touton giant cells. (I) ALK immunostain of a breast tumor (Case 12; original magnification ×400) showing focal, exclusive dot-like immunoreactivity that could be misinterpreted as negative. (J) S100 immunostain of a liver biopsy (Case 4; ×200) showing immunoreactivity by the large sinusoidal histiocytes. (K) P-ERK immunostain (Case 15; original magnification ×400) showing diffuse positive staining by the lesional cells, as well as clear emperipolesis (intact intracytoplasmic leukocytes). (L) Cyclin D1 immunostain of an oculomotor nerve tumor (Case 21; original magnification ×200) showing cytoplasmic and strong nuclear staining in histiocytes with frequent nuclear indentations.

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