Philadelphia Chromosome-Negative Myeloproliferative Neoplasm With a Novel Platelet-Derived Growth Factor Receptor-β Rearrangement Responsive to Imatinib
Authors: Dennis Cornfield, Usman Shah, Nicholas Cross, Courtney Bennett, Guoxian Sun
Journal: Journal of Clinical Oncology (2012)

A 48-year-old man was transferred to our institution with fever, generalized pain, and weakness.In the year before his hospitalization, he had experienced recurring oral ulcers, necrotizing scrotal ulcers that required multiple debridements and antibiotics, and an intestinal perforation that required ileal resection, temporary ileostomy formation, and multiple subsequent surgical procedures to deal with anastomotic leaks, abdominal abscesses, and intestinal adhesions.Tissue pathology of the small bowel consistently demonstrated intestinal necrosis with neutrophilic infiltrates, of unclear cause.Scrotal pathology also showed neutrophilic infiltrate associated with epidermal necrosis.Vasculitis was not present in intestinal or scrotal specimens.The peripheral blood was negative for BCR-ABL gene rearrangement and JAK2 mutation.HIV serology was negative.Other problems before this admission included a single episode of noninfectious synovitis of the left knee and deep venous thrombosis of the right upper arm that was related to an indwelling venous catheter.Behcet's disease was suspected, and the patient began receiving treatment with corticosteroids before transfer to our hospital.Physical examination on admission showed a thin, chronically ill-appearing man in no acute distress.Abnormalities included a small ulcer on the right buccal mucosa, a larger ulcer with minimal purulent discharge on the scrotum, and partial superficial wound dehiscence of a surgical incision on the lower abdomen.No hepatosplenomegaly was detected.Laboratory studies showed no overt evidence of an autoimmune disorder.Mesenteric arteriogram showed no evidence of vasculitis.CBC showed a significant leukocytosis with a prominent left shift to the myelocyte stage and with numerous forms that seemed dysplastic (WBC of 27.6 ϫ 10 9 with 44% neutrophils, 31% bands, 9% metamyelocytes, 6% myelocytes, and 1% nucleated RBC), mild anemia (hemoglobin of 10.4 g/dL, mean corpuscular volume 95 fL), and normal platelet count.Notably, there was no eosinophilia or monocytosis.Peripheral blood smear revealed numerous dysplastic granulocytes, often with prominent, retained primary cytoplasmic granules (Fig 1).Bone marrow aspirate smears showed hypercellular particles with granulocytic hyperplasia.Granulopoiesis was mildly left shifted and exhibited numerous dysplastic forms, including retained primary granules and Pelger-Huet cells (Fig 2).Bone marrow biopsy was 100% cellular, with adequate but inconspicuous megakaryocytes and erythroid precursors, marked granulocytic hyperplasia with maturation to the mature polymorphonuclear stage but left shifted to predominantly the myelocyte/ metamyelocyte stage (Fig 3), and moderate, extensive reticulin fibrosis.Multiple cytogenetic abnormalities were present in 10 metaphase cells: 53,XY,ϩi(X)(p10),ϩY,t(5;12)(q33;q24.1)(blue arrows),ϩ8,ϩ8,ϩ18,ϩ19,ϩ22 (yellow arrows); 10 metaphase cells