Submitting Author: Shao, Haipeng, MD, PhD
Institution: H. Lee Moffitt Cancer Center
Session: AML with myelodysplasia-related changes

The patient is a 72-year-old man presented with fatigue. He was found to have pancytopenia (hemoglobin of 92 g/L, white blood cell count of 0.98 x109/L, and platelet count of 62 x 109/L). He had constitutional symptoms and was transfusion dependent. The patient had a bone marrow biopsy which showed myelodysplastic syndrome with fibrosis. The patient was treated with Revlimid and prednisone followed by Vidaza. He had little response and later developed splenomegaly. Repeat bone marrow biopsy showed transformation to acute myeloid leukemia. He received induction chemotherapy with no response and died of sepsis one month later.

Biopsy: posterior iliac crest

Fixation: 10% neutral buffered formalin

In the first bone marrow biopsy performed at our institute, the aspirate smears were hemodilute with no spicules. Blasts were not increased on the aspirate smears. The core biopsy showed a markedly hypercellular marrow with over 95% cellularity (Figure 1). There was trilineal hyperplasia (panmyeloisis). Megakaryocytes were markedly increased in numbers and dysplastic with a predominance of small hypolobated forms (Figure 2). Erythroid precursors showed progressive maturation. Myelopoiesis was left-shifted. Reticulin stain showed marked reticulin fibrosis (3+, Figure 3).

In the second bone marrow biopsy, the aspirate smears were hemodilute with no spicules, but showed predominance of blasts (63%). The blasts were medium to large with high N/C ratio, round nuclei, fine chromatin, and scant cytoplasm (Figure 6). The bone marrow core biopsy was markedly hypercellular with average 95% cellularity (Figure 7). Megakaryocytes are moderately increased in number and dysplastic with many small hypolobulated forms (Figure 8). The marrow is extensively infiltrated by immature mononuclear cells/blasts, accounting for approximately 60% of the cells (Figure 9). Erythroid precursors and maturing myeloid cells are markedly decreased. Reticulin stain shows marked reticulin fibrosis (3+, Figure 10).

Immunohistochemistry/Flow cytometry In the first bone marrow biopsy, CD61 showed markedly increased dysplastic megakaryocytes (Figure 4). CD34 showed <5% scattered blasts (Figure 5)

Flow cytometry on the second bone marrow aspirate detected approximately 63% blasts with monocytic differentiation. They showed expression of HLA-DR, CD34, CD117, CD13, CD33, CD11b, weak CD11c and CD4 (Figure 11). The blasts showed aberrant expression of CD56, and were negative for MPO.

Cytogenetic study showed 44,X, Y,der(11;17)(q10;q10)[17]/46,XY[3] in the first biopsy, and 44,X,-Y,der(11;17)(q10;q10)[cp3]/44,idem,inv(3)(q21q26),t(8;14)(p21;q11.2),del(20)(q11.2)[cp15]/45,X,-Y[2] in the second biopsy.

FISH study showed 91% nuclei positive for 20q deletion.

JAK2 mutations were not detected in the initial biopsy.

This is an interesting case of acute myeloid leukemia with inv(3)(q21q26), evolving from previous myelodysplastic syndrome with fibrosis. Both the first and second bone marrow biopsies showed marked dysmegakaryocytic hyperplasia associated with marked reticulin fibrosis. However, the first marrow had no increase of blasts, while 6 months later, the marrow showed approximately 60% blasts and appearance of inv(3)(q21q26), which was not present in the initial marrow. Both biopsies had the same clonal change of der(11;17)(q10;q10), which supports clonal evolution from MDS to AML with inv(3)(q21q26). This case suggests that EVI1 over-expression functions as a “second-hit” in the leukemogenesis of AML with inv(3)(q21q26).

Acute myeloid leukemia with inv(3)(q21q26); RPN1-EVI1

Acute myeloid leukemia with inv(3)(q21q26); RPN1-EVI1, arising from myelodysplastic syndrome

Case 277