Submitting Author: Ewalt, Mark David, MD
Institution: New York Presbyterian Hospital - Columbia Univeristy Medical Center, Department of Pathology and Cell Biology
Additional authors:Daniela Hoehn, Bachir Alobeid, Govind Bhagat
Session: AML with myelodysplasia-related changes

The patient is a 49 year old woman with a past medical history of Type II diabetes mellitus, hypertension, hyperlipidemia, and bipolar disorder who initially presented to our institution’s emergency department with decreased vision of her left eye. An opthalmology consult led to the diagnosis of central retinal vein occlusion with neovascularization and diabetic retinopathy. At this presentation, the patient was also noted to be thrombocytopenic (82x10^9 platelets/L) compared to her most recent prior study two years ago, which showed a normal complete blood count and normal platelet count (238x10^9 platelets/L).

The patient was treated and discharged, but returned to the emergency department one week later with fever and dyspnea. At this point she was admitted. An abdominal ultrasound showed cholecystitis, hepatomegaly with steatosis, but no splenomegaly.

Laboratory work-up revealed normocytocytic anemia and thrombocytopenia (RBC 2.98 x 10^2/L, Hgb 8.1 g/dl, Hct 24.5%, MCV 82.2 fl, Plt count 51 x 10^9/L) with normal folate (10.3 ng/ml), vitamin B12 (831 pg/ml) and TSH (3.12 uIU/ml) levels and normal total bilirubin (0.5 mg/dl).

Review of a peripheral blood smear showed dysplastic and immature myeloid forms, including blasts (see image) and a sample was sent for flow cytometry that confirmed the presence of 2.6% myeloblasts. Cytogenetic analysis from a peripheral blood sample showed a complex karyotype including deletion 5q, monosomy 7, and deletion 20q, all of which were confirmed by FISH.

A bone marrow biopsy was performed (see representative images of H&E stained sections and immunohistochemical stains).

Following the initial presentation, the patient was treated with red blood cell and platelet transfusions for persistent anemia and thrombocytopenia and progressively developed leukocytosis with WBC counts in the 40-50 x10^9 WBC/L range, over the following four months. During this time, she was treated with lenalinomide. However, shortly after initiation of therapy (and four months after initial presentation), the patient presented to another institution with fever and altered mental status, and a bone marrow biopsy reportedly showed 30% myeloblasts. Treatment with decitabine was started and her peripheral WBC and bone marrow blast counts normalized with therapy. The patient, however, had persistent transfusion-dependent anemia and thrombocytopenia with 5-10% circulating myeloblasts. In the following months, she had frequent episodes of neutropenic fever and developed multiple infections. On her final admission, she presented to an outside hospital with fever, rigors, confusion, and diarrhea and was placed on supportive comfort care where she died (15 months following initial detection of an abnormal CBC with thrombocytopenia).

Bone marrow biopsy (left posterior iliac crest), fixed in (Bouin’s) fixative.

Bone marrow revealed panmyelosis with increased atypical/dysplastic megakaryocytes, elevated myeloblasts, and severe myelofibrosis (see representative image). Moderate to severe (2-3+) reticulin fibrosis, negative (0+) trichrome+ fibrosis.

No marrow aspirate obtained (dry tap).

IHC:

Mildly elevated (<5%) myeloblasts as seen by stain for CD34

Numerous bizarre megakaryocytes accentuated with a stain for CD61

Flow cytometry:

Flow cytometry of a peripheral blood sample (CD45dim, low to intermediate side scatter) detected a population of myeloblasts (CD34+, CD117+, CD33+, CD11c+, CD64-, CD5+, CD14-) accounting for 2.6% of all nucleated cells.

Complex karyotype (44~45,XX,del(5)(?q22),-7,t(12;15)(p12;q21),del(13)(q13q14),-20, -21,+mar1[cp18]/46,XX[2])

FISH:

90.9% cells show deletion 5q (EGR1/D5S23 probe)

66.9% cells show deletion 7q

24.3% cells show monosomy 7 (D7S486/CEP7 probe)

15.3% cells show deletion 20q (D20S108 probe)

0% cells show trisomy 8 (CEP8 probe)

0% cells show TP53 or ATM deletion (LSI TP53/ATM probe)

JAK2 V617F mutation was negative

Young woman with rapid development of panmyelosis, myelofibrosis and elevated blast count with MDS-associated cytogenetic changes in the absence of splenomegaly and JAK2 V617F mutation.

Acute panmyelosis with myelofibrosis (APMF)

Refractory anemia with excess blasts - 1 (RAEB-1), with fibrosis

Case 105