Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature

Abstract

Blast phase in chronic myelogenous leukemia (CML) has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia), and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66-year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117). Fluorescence in situ hybridization (FISH) of vitreous fluid detected BCR-ABL1 gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation.

Figure 1

Gross photomicrograph depicting pupil-optic nerve (PO) section of enucleated eye which reveals diffuse thickening of the iris and part of the choroid layer.

Figure 2

Blasts cells infiltrating the iris (H&E, magnification ×20).

Figure 3

Sheets of monotonous mononuclear blast cells (H&E, magnification ×400).

Figure 4

Flow cytometric immunophenotypic analysis of vitreous fluid: blast gate (P4 gate in the top line) represents the dim CD45+ cells with low side light scatter (SSC). Blast gate (P3 gate in the bottom line) represents the same population of blasts analyzed for cytoplasmic markers in a separate tube. The distinct cluster of blasts (red color population) exhibit the following immunophenotypic characteristics: positive for CD34, CD117, CD7, CD11b, CD13 (dim), and CD33; negative for CD19, CD10, CD20, CD3, CD5, CD15, CD16, CD61, CD235a, HLA-DR, CD14, cytoplasmic CD3, cytoplasmic CD79a, cytoplasmic MPO, and cytoplasmic TdT.

Figure 5

CD34 immunohistochemistry: sheets of monotonous CD34 positive blast cells (magnification ×400).

Figure 6

CD117 immunohistochemistry: focal and variable intensity of CD117 expression is seen in the blasts (magnification ×400).

Figure 7

TdT immunohistochemistry: sheets of blasts showing nuclear expression of TdT (magnification ×400).

Figure 8

Fluorescence in situ hybridization assay on vitreous humor smear shows two BCR-ABL1 fusion signals, one BCR probe signal, and two ABL1 probe signals; thus a t(9;22) BCR-ABL1 gene rearrangement with gains of 9 and 22 [orange = 9q34 ABL1 probe; green = 22q11.2 BCR probe].

Figure 9

Fluorescent in situ hybridization on original diagnostic bone marrow aspirate shows one BCR-ABL1 fusion signal, two BCR probe signals, and three ABL1 probe signals in 90.5% of interphase cells.