Submitting Author: Yea, Steven, MD/PhD
Institution: UCLA Medical Center
Additional authors:Sheeja Pullarkat, MD
Session: AML with recurrent genetic mutations Part II

This is an 86 year old female who presented to the hospital in August 2012, for an elbow infection and was found to be neutropenic. On admission, her CBC was WBC 2.2, RBC 2.4, HGB 8.9, HCT 26.8, MCV 111.5, MCH 37.1, MCHC 33.2, RDW 14.4, MPV 6.9, and PLT 230. Her past medical history was significant for left breast cancer that was treated with lumpectomy and local radiation, and endometrial carcinoma in 2010 that was treated with abdominal hysterectomy & bilateral salpingo-oophorectomy. Her serum B12 level was low at 102 pg/ml.

The microscopic slides of the peripheral blood smear, right posterior iliac crest bone marrow biopsy and aspirate smears were received in consultation. Specimens were fixed with B5 and formalin fixative.

PERIPHERAL BLOOD SMEAR:

The peripheral smear showed macrocytic anemia. A few nucleated RBCs were noted. The platelet count was normal. The white cell count was decreased with a differential of 2 blasts, 39 neutrophils, 3 eosinophils, 0 basophils, 50 lymphocytes, and 6 monocytes. Scattered neutrophils showed pseudo-Pelger Huet abnormality. Myeloid precursors were present.

BONE MARROW SMEARS AND TOUCH PREPARATIONS:

Bone marrow smears and touch preparations revealed numerous immature cells that were large with open chromatin, smooth nuclear contours, prominent nucleoli, and scant-to-moderate amounts of deeply basophilic cytoplasm, with some cells containing numerous vacuoles. Normal multilineage maturation was markedly decreased with striking erythroid preponderance. The erythroid precursors were dysplastic and showed megaloblastoid changes, nuclear budding, and cytoplasmic vacuolization. Megakaryocytes were present in adequate numbers. Scattered lymphocytes and plasma cells were present. There was no evidence of eosinophilia or basophilia. Iron stores were decreased per the iron stain.

BONE MARROW BIOPSY AND CLOT SECTIONS:

The decalcified bone marrow biopsy sections and aspirate clot sections showed a hypercellular marrow with an approximate cellularity of 60-70%. The marrow was diffusely infiltrated by sheets of immature cells. Rare scattered normal hematopoietic elements were present in the background. Megakaryocytes were present in decreased numbers. Several small lymphoid aggregates consisting of small mature lymphocytes were present. Iron stores were decreased per the iron stain.

IMMUNOHISTOHEMISTRY:

Antibody/Probe: Result/Comment

CD34 positive in blasts

CD117 positive in blasts

CD3 positive in scattered T cells and lymphoid aggregates

CD20 positive in scattered B cells and lymphoid aggregates

CD4 positive in scattered T cells and scattered blasts

CD56 negative

GPA positive in erythroid precursors, negative in blasts

MPO rare positive cells

TdT positive in subset of blasts

CD42b positive in megakaryocytes, negative in blasts

CD123 negative in blasts

FLOW CYTOMETRY:

Flow cytometry report showed blasts were positive for CD38, CD34, HLA-DR, and CD117.

KARYOTYPE:

46,XX[2]

MDS FISH (5q, 7cen, 7q, 8cen, 20q) Normal

NPM1 Mutation Detection: Negative for insertion mutation in exon 12

CEBPA Mutation Detection: No mutation detected within coding regions

FLT3 Mutation Detection: Negative for internal tandem duplication (ITD) between exons 14 and 15; Negative for mutation affection codon 835

C-KIT Mutation Detection: Negative for D816V mutation

The underlying cause of the macrocytic anemia, megaloblastoid changes, and erythroid & myeloid dysplasia was difficult to deduce. These morphologic features could have been caused by the patient’s B12 deficiency or they could have been the result of an underlying clonal abnormality, such as a Myelodysplastic syndrome. The cytogenetic studies were not helpful in differentiating between these two causes, as the MDS FISH and karyotype results were completely normal. The patient was treated with intramuscular B12 injections and chemotherapy for AML. She continued her care at an outside hospital and no further follow-up information was available.

Acute undifferentiated leukemia

- Macrocytic anemia and megaloblastoid changes due to B12 deficiency.

Acute leukemia, further workup required

Case 227