Submitting Author: Gomez-Gelvez, Juan Camilo, MD
Institution: Henry Ford Health System
Additional authors:Javier Arias-Stella, MD, Koichi Maeda, MD, Kedar Inamdar, MD, PhD
Session: Erythroleukemia and megakaryoblastic AML and mimics

A 55-year-old male patient presented to the emergency department complaining of abdominal pain and diarrhea for approximately one month. On initial investigation, he was found to be pancytopenic with white cell count of 1.1 K/uL, hemoglobin of 7.0 g/dL, platelet count 43 K/uL, serum ferritin 306 ng/mL, vitamin B12 202 pg/mL, lactate dehydrogenase 111 IU/mL, and creatinine 0.8 mg/dL. PT, PTT, and INR were within normal limits. The patient underwent a bone marrow biopsy (see below) on admission. A diagnosis of AML was established for which the patient received modified induction chemotherapy (cytarabine + daunorubicin). After achieving complete remission, he underwent allogeneic non-related peripheral stem cell transplantation. The patient remained disease-free for 2 years until recently when he presented again to the emergency department with pneumonia. A laboratory work up at the time of presentation revealed a white cell count of 5.0 K/uL, hemoglobin of 8.0 g/dL and platelets of 58 K/uL. No circulating blasts were seen on peripheral blood examination. He died shortly after admission thus precluding any possibility to perform a bone marrow examination to evaluate for possible relapse.

Right posterior iliac bone marrow biopsy fixed in Bouin’s and decalcified with hydrogen chloride solution.

The myeloid series is markedly left shifted with an increase in the number of blasts. These are small-to-medium with high N/C ratio, rounded nuclei with finely dispersed chromatin and 1-3 prominent nucleoli. A few blasts have cytoplasmic extensions. Maturing myeloid cells are markedly reduced in number with dysgranulopoiesis. The erythroid precursors are markedly increased with left shifted macronormoblastic maturation and dyserythropoiesis. Megakaryocytes show unremarkable morphology. Differential count reveals 52% erythroid precursors and 30% myeloblasts (including erythroid cell population). The M:E ratio is 0.7:1.

The core biopsy shows a cellularity of 5-10% in average. The cellular infiltrates are patchy with major portions of the marrow space having very sparse cellular elements. Clot contains slightly more cellular marrow particles, approximately 25-30% in average cellularity. The cells comprise of increased immature mononuclear cells admixed with mainly erythroid clusters and polymorphous mix of plasma cells, small lymphocytes and eosinophils. Myeloid maturation appears to be arrested. Rare unremarkable megakaryocytes are present.

Sudan black B stain is positive in approximately 70% of the blasts cells. Non-specific esterase stain is negative. Prussian blue stain shows increase particulate iron 3+ to 4+ (on a 0-4 grading scale) with 72% sideroblasts and 2% ring sideroblasts.

Subsequent bone marrow examinations were reported as follows: on day 14 bone marrow biopsy showed minimal residual disease with <5% cellularity and 14% myeloblasts; on day 30 showed regenerative bone marrow with 50% cellularity and 2% myeloblasts: on day 90 showed no residual disease with 60-65% cellularity and 2.5% myeloblasts. Remaining follow-up bone marrow examinations showed findings similar to day 90.

By flow cytometric analysis, the blast population show a composite antigen profile of: CD10 Neg., CD19 Neg., HLA-DR+, CD13+, CD5 Neg., CD7 Neg., CD33+, CD11b Neg., CD15 Neg., CD34+, CD117+, CD56+ (partial), CD235a Neg., CD61 Neg., CD14 neg., cyMPO-/+ (significant minority), cytoCD3 Neg., cytoCD79a Neg., and cytoTdT Neg.

Normal male karyotype 46, XY.

Fluorescent in situ hybridization (FISH) analyses were all within normal limits.

There was no mutation of the FLT3 receptor by either internal tandem duplication (ITD) or D835 activating point mutation.

The bone marrow cellularity in this case is 5-10% thus making a case for diagnosis of acute myeloid leukemia in a hypocellular bone marrow (hypocellular AML/H-AML). The presence of dysplasia in this setting also raised the possibility of previously undiagnosed MDS in the background. Interesting features in this case include:

1. The low cellularity of the marrow is important to recognize as an important factor in this case which would have an impact in the management decision since patients with hypocellular bone marrows may not tolerate standard induction chemotherapy. Such patients need tailored induction regimens (as was provided to our patient) thus allowing the bone marrow a chance at regeneration. Since these patients are at increased risk of marrow failure following cytotoxic therapy, immediate stem cell transplant is a plausible consideration due to their increased risk of marrow failure.

2. The erythroid lineage by differential counts was more than 50% of nucleated cells and myeloblasts were 30% which raised the differential diagnosis of erythroleukemia (erythroid/myeloid) or AML, M6. The consideration of this subtype is more prevalent in the setting of hypocellular AML as discussed by Tuzuner et al (Hypocellular acute myeloid leukemia: the Rochester (New York) experience. Hematol Pathol. 1995;9(3-4):195-203). The author reports AML, M6 as the third most common subtype in his cohort of fourteen patients. This diagnostic entity was a challenge in our case given that the bone marrow biopsy in typical cases of AML, M6 is generally hypercellular. The criteria for AML, M6 need to be used with caution entertained in the context of appropriate clinical presentation and morphologic findings.

1. Hypocellular AML most likely arising from previously undiagnosed MDS.

2. Acute erythroleukemia (erythroid/myeloid) (AML, M6).

Acute myeloid leukemia with myelodyplasia-related changes and erythroid predominance

Case 234