Submitting Author: Klimkowska, Monika Anna, MD, PhD
Institution: Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, Sweden
Session: Therapy-related myeloid neoplasms

29-year-old man, overweight, previously healthy, presenting with cough and tiredness. History of alcohol overconsumption; no medication. On admission fever, signs of hemolytic anemia, coagulopathy, pneumonia possibly due Mycoplasma infection. Lab status: Hgb 62 g/L, MCV 114 fL, WBC 6.5x10(9)/L, PLT 40x10(9)/L, CRP 50 mg/L; fibrinogen 1.5 g/L, ferritin >3000 µg/L. Serology negative for HIV, EBV and CMV.

In spite of antibioticotherapy progression of cytopenias. Required intensive care and 5 weeks of respirator treatment, developed neurological complications. Treated for HLH according to HLH-2004 protocol (betaprednisone, etoposide 100 mg/m2 intermittent, cyclosporine A), even G-CSF administration; initially pancytopenic but slowly improving. After total of two months intensive therapy successfully recovered, initially small dose of betaprednisone under follow-up. Persistent ferritin increase though, initially thought to be due to alcohol-related liver injury.

Three and half months later readmitted due to dyspnea and mild fever. Lab status: Hgb 165 g/L, MCV 90 fL, WBC 23.5x10(9)/L, PLT 19x10(9)/L, CRP 56 mg/L; fibrinogen 3.1 g/L, ferritin 1771 µg/L, sCD25 4156 U/mL. Rapidly worsening, with coagulopathy and multiorgan failure developing under three days, with fatal outcome.

MC2048-11 (first admission): aspiration from crista iliaca, MGG-stained smears, buffered formalin fixation of BM tissue.

- BM: almost maximal cellularity, hemophagocytosis, erythropoietic hyperplasia and megaloblastic features but no complete ring sideroblasts; M/E ratio of 0.7; 1% blasts. Dysplastic megakaryocytes. Increased histiocytes and lymphocytes. PB: anemia with anisopoikilocytosis, leukoerythroblastosis.

MC2199-11 (three weeks after admission, under treatment, shortly after G-CSF administration): aspiration from crista iliaca, MGG-stained smears, buffered formalin fixation of BM tissue.

- BM: 80% cellularity on average, M/E ratio of 0.7, persistent dysplasia in erythropoiesis and thrombocytopoiesis, slightly aberrant myelopoiesis. Normal amount of blasts, no hemophagocytosis. PB: deep anemia with anisopoikilocytosis and megaloblastic picture, leukocytosis with dominance of neutrophiles, no blasts.

E181-12 (last admission, one day before decease): MGG-stained BM and PB smears. No tissue material, only several smears available.

- BM: hypercellular smears with proliferation of immature monocytoid cells (up till 52% blasts in BM), dysplastic erythropoiesis and hemophagocytosis (even by blasts). PB: 39% blasts, signs of hemophagocytosis, anemia with anisopoikilocytosis, dysplastic neutrophils.

MC2048-11:

- IHC: dominance of GPA+ erythropoiesis. CD34+ under 3%, dispersed cells; CD117+ 5%, groups of cells. Increased histiocyte population, no granulomas. Mild increase in plasma cells. Few EBER+ lymphocytes.

- FC (L2484-11): 46% cells in mononuclear gate; CD117+ 13% total in sample, of those 5% were also CD34+ HLA-DR+ CD36+ CD71+ CD33-. Myelopiesis with maturation but with small fractions of cells CD33+CD56+. CD14+ monocytes 0.8% total. T-cells 5% total, normal expression of CD2, CD5, CD7, CD4/CD8 ratio 0.7; NK-cells 1.6% total; B-cells 2%, mature phenotype, polyclonal, plasma cells 1.4%, polyclonal.

MC2199-11:

- L2668-11: 8% cells in mononuclear gate. 0.6% CD117 total of which 0.1% are also CD34+. CD14+ monocytes 0.7% total. T-cells 1.5% (CD4/CD8 ratio 2.8), NK-cells0.1%, B-cells 0.3%, plasma cells 0.5% total.

Not known

Not done

Initial presentation with clinical signs of HLH and cytological florid erythroid hyperplasia, though with multilineage dysplastic features, possibly related to substance abuse; no details of vit. B12 or folate deficiency known.

After successful HLH-treatment and a short period in a relatively good shape, the patient developed acute myeloproliferation cytologically consistent with acute myeloid leukemia of monocytic type, again with signs of hemophagocytosis, which can suggest translocation t(8;16). This analysis was unfortunately not available at our institution.

Cytological findings in the last BM sample can suggest a therapy-related AML. However, the administered dose of etoposide was moderately high but development of acute leukemia unusually rapid.

Multilineage dysplasia (true MDS?) with hemophagocytosis in first sample.

Acute myeloid leukemia, probably therapy-related, cytologically consistent with AML M5, with hemophagocytosis in last sample.

Therapy-related myeloid neoplasm, acute myeloid leukemia

Case 253