Institution: Department of Pathology and Laboratory Medicine, University of California, Davis
Additional authors:Elham Vali Khojeini, MD
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN
HISTORY
The patient is a 71 year-old African American male with a history of a myeloproliferative neoplasm (BCR-ABL negative by cytogenetics and FISH) who now presents with unintentional weight loss and abdominal pain due to enlarged spleen.
DETAILS
Bone marrow, left and right posterior iliac crest, aspirate smear, touch prep, core biopsy (fixed in formalin), and peripheral blood smear.
Gross description: Two tan cores of roughened tissue measuring 2.5 and 1.0 cm in length x 0.2 cm in maximum diameter. Dry tap and only touch prep smears were made.Peripheral blood smear: Increased blasts (50%) that are medium in size with scant agranular basophilic cytoplasm, round nuclear contours, fine chromatin, and prominent nucleoli.Touch prep: Dry tap. Touch preps showed increased blasts with the same morphology as the peripheral blood smear. There is erythroid hypoplasia.Core biopsy: Hypercellular marrow (>90%) with clusters of blasts (30%) and increased megakaryocytes with atypical morphology (hypolobated, small, and hyperchromatic nuclei).IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Immunohistochemical stains: (CD3, CD34, CD56, CD79a, CD117, PAX5, TdT, CD61, CD123, CD19, CD2, and CD7) were examined. The neoplastic cells are positive for CD34, CD56, CD117, TdT, CD19, and CD7.
By flow cytometry, the blasts population is positive for cCD3, CD33/CD13 (dim), CD7 (subset), CD19, CD117 (partial), TdT (partial), and negative for monocytic markers.CYTOGENETIC FINDINGS
46,XY,t(3;21)(q26.2;q22)[16]
46,XY,del(20)(q11.2)[4]MOLECULAR FINDINGS
Nucleophosmin Mutation Analysis:
Negative for NPM1 mutation.FLT3 Internal Tandem Duplication: Negative.FLT3 D835 Variant: Negative.INTERESTING FEATURES
The morphologic features are most consistent with an acute myeloid leukemia and some of the immunophenotypic findings (CD13, partial MPO) suggest this; however the cytoplasmic CD3 would imply that there is T-cell lineage expression. There have been reports of T lymphoblastic leukemia/lymphomas (T-LBL) that aberrantly express myeloid markers (CD13/CD33) and have found to be associated with FLT3 mutation. In this case molecular studies for FLT3 were negative. Interestingly, there was also a t(3;21) detected in this case, which has been implicated with therapy related MDS and AML and not associated with T-LBL. Overall, we feel that this case best fits acute leukemia with ambiguous lineage (T/myeloid).
Reference:Hoehn D, Medeiros LJ, Chen SS, et al. CD117 expression is a sensitive but nonspecific predictor of FLT3 mutation in T acute lymphoblastic leukemia and T/myeloid acute leukemia. Am J Clin Pathol. 2012;137(2):213-219.Li S, Yin CC, Medeiros LJ, Bueso-Ramos C, Lu G, Lin P. Myelodysplastic syndrome/acute myeloid leukemia with t(3;21)(q26.2;q22) is commonly a therapy-related disease associated with poor outcome. Am J Clin Pathol. 2012;138(1):146-152.PROPOSED DIAGNOSIS
Acute leukemia with ambiguous lineage (T/myeloid).
CONSENSUS DIAGNOSIS
Acute myeloid leukemia with t(3;21)(q26.2;q22) in patient with history of myeloid disorder, possibly a myeloproliferative neoplasm