Tyr–Ras transgenics developed multiple primary cutaneous and ocular melanomas. (A) Photomicrograph depicting founder TR59; note focal hyperpigmentation evident on paws and pinnae (arrows). (B) Photomicrograph of eroded cutaneous tumor (arrow) developing on pinna, early stage, line TR60. (C) Photomicrograph of late stage cutaneous tumors of pinnae with destruction of local structure. Also note hemorrhagic exophthalmus (arrow) representing an ocular melanoma, line TR39. (D) Photomicrograph of an early lesion on the abdomen, line TR60. Note the well-circumscribed pink dermal nodule with superficial telangiectasia (arrow). (E–H) Photomicrographs of histological sections of the cutaneous tumor in B. (E) Hematoxylin and eosin (H&E) 100×. Dermal proliferation of spindle-shape cells with varying degrees of pigmentation. (e) epidermis; (d) dermis. (F) H&E, 400×. Note the prominent cellular atypia at higher magnification. (G) S100 immunoperoxidase reaction, 400×. Nuclear as well as cytoplasmic immunoreactivity is present. (H) TRP1 immunoperoxidase reaction, 400×. Strong cytoplasmic immunoreactivity is detected. (I–L) Photomicrographs of histologic sections of the ocular tumor in C. (I) H&E, 50×. At this power, note the remnant of the sensory retina (r) destroyed by adjacent proliferating spindle cell mass. Distinct transition from melanotic (T1) to amelanotic (T2) tumors clearly visible at this power. (J) H&E, 400×. At higher power, heavy melanization present in T1 region of I. (K) S100 immunoperoxidase, 400×. Positive S100 immunoreactivity detected in T1 region of I. (L) S100 immunoperoxidase, 400×. S100 immunoreactivity is lost as tumor progresses beyond the transition zone to the amelanotic portion, T2 region of I.