Submitting Author: Salama, Mohamed E, MD
Institution: University of Utah
Additional authors:Weiss R, Toydemi R, Shami P, Kelley T, Hussong J, Perkins SL
Session: AML with recurrent genetic abnormalities Part I

61-year-old female presented with pancytopenia.

A complete blood count demonstrated a white blood cell count of 2.4 K/uL, hemoglobin 5.1 g/dL, hematocrit 15.1%, and platelets of 73 K/uL. A manual differential count showed 3.6% blasts, 2.7% bands, 50.4% segmented neutrophils, 7.2% monocytes, and 36% lymphocytes. A peripheral blood smear showed a mild granulocytic left shift. The neutrophils showed normal nuclear segmentation & cytoplasmic granulation without significant evidence of dysplasia.

The bone marrow aspirate was suboptimal, but touch preparations made from the core biopsy showed erythroid dyspoiesis and 9% myeloblasts. The bone marrow biopsy showed a normocellular marrow (30%). There was trilineage hematopoiesis with a mild increase in immature myeloid cells and a myeloid to erythroid ration of 2:1. Dysmegakaryopoiesis with many hypolobate megakaryocytes was noted. Focal myelofibrosis (MF-1) was noted on reticulin stain performed on the core biopsy.

Flow cytometric analysis of the bone marrow aspirate specimen demonstrates phenotypically normal left shifted myeloid cells with increased atypical CD34 positive myeloblasts (weak CD2+, absent CD33) representing 12% of the total leukocytes. Immunohistochemical stain for CD34, performed on the core biopsy, showed approximately 5-10% CD34 positive blasts.

Chromosomal analysis 46,XX,t(3;3)(q21;q26.2)[8]/46,XX[12].

Fluorescence in situ hybridization (FISH) analysis was performed with the MDS panel probes and showed evidence of deletion 5q31 and deletion 7q31 in 11% and 12.0% of 200 scored cells, respectively.

An attempt for single nucleotide polymorphism (SNP) array is pending.

The inv(3)(q21;q26.2)/t(3;3)(q21;q26.2) is an infrequently observed recurring cytogenetic abnormality described in myelodysplastic syndromes (MDS). In addition, acute myeloid leukemia (AML) with inv(3) (q21q26.2) or t(3;3)(q21;q26.2) is a distinct subtype of AML with recurrent cytogenetic abnormalities in the World Health Organization classification. As noted in this case, additional cytogenetic abnormalities, including –7q & –5q are common findings associated with AML and MDS with inv(3)/t(3;3). A recent study demonstrated that AML and MDS with inv(3)/t(3;3) is associated with comparable adverse outcome. In addition, 65% of MDS cases progressed to acute leukemia within 2-10 months. These findings raise the possibility that MDS and AML associated with t(3;3) may represent a continuum of the same entity. As suggested by Cui et al, it is intuitive to consider extending the rule of AML classification in these patients even when a blast count is less than 20% as in AML patients with t(8;21), inv(16), or t(15;17). This may allow for more intensive intervention in appropriate candidates. The current patient has just initiated therapy for MDS and is being evaluated for possible allogeneic bone marrow transplant. Further outcome data may be available at the time of conference.

Reference: Cui W, Sun J, Cotta CV, Medeiros LJ, Lin P. Myelodysplastic syndrome with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) has a high risk for progression to acute myeloid leukemia. Am J Clin Pathol. 2011; 136(2):282-8.

Myelodysplastic Syndrome: Refractory anemia with excess blasts (RAEB) with t(3;3)(q21;q26.2).

Refractory anemia with excess blasts (RAEB-1) with t(3;3)(q21;q26.2)

Case 342