Institution: University of California, Los Angeles
Additional authors:Sheeja T. Pullarkat
Session: Extramedullary manifestations of myeloid neoplasms
HISTORY
The patient is 64-year-old female who was diagnosed with chronic myeloid leukemia in chronic phase in 2006. She was initially treated with imatinib and achieved an unknown response. Subsequently she was found to harbor the T315I mutation, and she underwent treatment with dasatinib, nilotinib, and then ponatinib. Due to the refractory nature of her disease, she underwent a matched related allogeneic stem cell transplant. She had been doing well until she presented again with fatigue. She subsequently underwent bone marrow biopsy which showed increased blasts in the marrow (12%), consistent with CML in the accelerated phase. She was treated with decitabine, however, remained persistently PCR positive for BCR-ABL. At the end of cycle four she presented with a skin rash over the lower back, suprapubic area, neck, and extremities. The rash was characterized by clusters of well-circumscribed, purplish, raised lesions.
DETAILS
The biopsy consisted of a 4 mm skin punch biopsy from the lower back. Grossly, the skin surface was tan and smooth. The biopsy material was fixed in formalin.
Histologic examination of this skin punch biopsy shows an atypical cellular infiltrate which consisted of large cells which spared the epidermis, but infiltratde through the dermal collagen and tracked along the deep dermal adnexal structures. These cells were characterized by enlarged nuclei, high N:C ratios, irregular nuclear contours, vesicular chromatin, and prominent nucleoli. The cytoplasm was moderately abundant and eosinophilic. Numerous eosinophils were present in the background.IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Immunohistochemical staining demonstrated that the atypical cells were positive for CD43, MPO, and a subset were positive for CD45, CD34, CD117. They were negative for TdT.
CYTOGENETIC FINDINGS
Original chronic phase CML:
46,XX,t(9;22)(q34;q11.2)[20]Accelerated phase: 46,XX,t(9;22)(q34;q11.2)[6]/45,idem,-16[8]/46,idem,t(3;3)(q21;q26.2)[6] Chromosomal analysis revealed an abnormal female karyotype with all cells exhibiting a reciprocal translocation between chromosomes 9 and 22 (Philadelphia positive). In addition, 6 cells exhibited a translocation between the two chromosomes 3q, suggestive of clonal evolution. A new third clone of 8 cells showed a loss of 16 along with the Ph' chromosome. No cytogenetically normal cell was observed. Both t(3;3) and -16 are secondary anomalies and consistent with CML-BP.MOLECULAR FINDINGS
FISH studies for Recipient/Donor/EVI1/BCR-ABL/chromosome 8/RARA: Signal pattern consistent with female (recipient) cells, EVI1 gene rearrangement and ABL1-BCR (9;22) fusions.
INTERESTING FEATURES
This case demonstrates an unusual presentation of chronic myelogenous leukemia transforming from accelerated phase to blast phase.
PROPOSED DIAGNOSIS
Blast transformation of chronic myelogenous leukemia presenting as myeloid sarcoma of the skin
CONSENSUS DIAGNOSIS
Blast phase of chronic myelogenous leukemia, BCR-ABL1, with t(3;3)(q21;q26.2);EVI1; involving skin (myeloid sarcoma), status post stem cell transplantation