Case 231

Submitting Author: Gomez-Gelvez, Juan Camilo, MD
Institution: Henry Ford Health System
Additional authors:Javier Arias-Stella, MD Kristin Hunt-Karner, MD Koichi Maeda, MD Kedar Inamdar, MD
Session: AML with myelodysplasia-related changes

HISTORY

An 83-year-old male patient with previous medical history of myeloproliferative neoplasia (MPN) over the last two years. At that time of his diagnosis, he had been presenting occasional bleedings and chronic thrombocytosis (ranging from 498 to 1219 K/uL). MPN was diagnosed based on a positive JAK2 V617F mutation identified by molecular studies in peripheral blood on 07/2008. Bone marrow biopsy was not performed at that time. Due to the clinical and laboratory features the patient was managed as essential thrombocythemia (ET) and received therapy with anagrelide.

Two years after his initial diagnosis, the patient presented with leukocytosis (18.0 K/uL) due to neutrophilia (14.04 K/uL) with left shift and mild anemia (11.0 g/dL) in follow-up studies. For this reason he underwent bone marrow biopsy (see below).

The patient is still receiving anagrelide and continues to present with chronic leukocytosis (ranging from 18.3 to 33.2 K/uL), thrombocytosis (ranging from to 461 to 692 K/uL) and anemia (raging from 8.6 to 11.1 g/dL) without major complications.

DETAILS

Bone marrow biopsy from the right posterior-superior iliac spine, fixed in Bouin’s and decalcified with hydrogen chloride solution.

The biopsy core is hypercellular (80-90%) with features of myeloproliferative neoplasm. Cellular elements comprise of trilineage hematopoietic cells with markedly increased and atypical small-to-large megakaryocytes. They show frequent clustering and abnormal paratrabecular localization. Their nuclei are hyperchromatic and occasionally hyperlobulated. Reticulin stain reveals increased bone marrow reticulin fibrosis (MF-1 by WHO semiquantitative grading).

Bone marrow aspirate smears show atypically large megakaryocytes with abnormally lobulated nuclei and hyperchromasia. Mild dysmegakaryopoiesis is also seen in addition to mild dyserythropoiesis. Blast cells are not increased. Differential count is unremarkable with M:E ratio of 2.6:1. Prussian blue stain shows decreased particulate iron and 15% ring sideroblasts.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

CD34 immunostain does not reveal significant increase in CD34+ blasts. Flow cytometry not performed.

CYTOGENETIC FINDINGS

Normal male karyotype 46, XY.

Fluorescent in situ hybridization (FISH) was within normal limits.

MOLECULAR FINDINGS

Activating JAK2 V617F mutation was detected.

M-bcr/abl [t(9;22), p210] fusion gene transcript was not detected.

INTERESTING FEATURES

The clinical presentation with CBC data, presence of JAK2 V617F mutation and the bone marrow features of atypical megakaryocytic proliferation are all consistent with myeloproliferative neoplasm. Interestingly however, the case also demonstrates morphologic features of dysplasia in megakaryocytic and erythroid lineages including presence of up to 15% ring sideroblasts thus making this a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). More specifically, these findings support the diagnosis of a refractory anemia with ring sideroblasts (RARS) associated with marked thrombocytosis (RARS-T), which is an uncommon and currently listed as a provisional diagnostic entity in the 2008 WHO classification of Tumors of Hematopoietic and Lymphoid Tissues. This entity has refractory anemia with ring sideroblasts associated with thrombocytosis, abnormal megakaryocytes and commonly detected JAK2 V617F mutation, features that are all present in our case.

PROPOSED DIAGNOSIS

Refractory anemia with ring sideroblasts (RARS) and associated with marked thrombocytosis (RARS-T)

CONSENSUS DIAGNOSIS

Refractory anemia with ring sideroblasts and marked thrombocytosis (RARS-T), with JAK2 V617F mutation