A 57-year-old man presented with a rapidly growing tumor of the right eye caruncle. Thirteen years ago, he was diagnosed with essential thrombocythemia. No therapy had been given until 11 years thereafter, when he developed anemia (hemoglobin 99 g/L), leukocytosis (39.9 × 10⁹/L), and symptomatic splenomegaly (24 cm) resulting from biopsy-proven postthrombocythemic myelofibrosis. These conditions were successfully treated with ruxolitinib, leading to leukocyte and spleen size decrease (17.8 × 10⁹/L and 11 cm, respectively). At that time, a CALR type 1 mutation (52-bp deletion; c.1092_1143del) could be detected. Two years later, the patient complained of a caruncular tumor, and 6% blasts appeared in his peripheral blood. Microscopic examination of the ocular tumor showed a nested neoplasm embedded in an elasto-fibrotic loco-typical collagen stroma and consisting of scattered large, atypical megakaryocytes, focally maturating myelopoiesis, and collections of immature-appearing cells reminiscent of monoblasts/promonocytes, with most cells staining characteristically granularly positive with the mutational-specific anti-calreticulin antibody CAL2 in their endoplasmic reticula, yet with the covering squamous epithelium remaining negative (panels A-C; 40× objective and 400× total magnification [A-B],  10× objective and 100× total magnification [C]; hematoxylin and eosin stain [A,C], immunoperoxidase stain [B]).

Both the 6% peripheral blasts and the extramedullary myeloid tumor of the eye were considered indicative of imminent accelerated phase, and the patient underwent allogeneic hematopoietic cell transplantation. He is until now in complete clinical, morphologic, and molecular remission.