Case 332

Submitting Author: Orazi, Attilio, MD
Institution: Weill Cornell Medical College, New York, NY
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN

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HISTORY

81 year old man with ten year history of polycythemia vera (PV) managed over the years with phlebotomies and hydrea until the end of 2005 when he developed mild splenomegaly followed by leukoerythroblastic anemia (end of 2006). Bone marrow biopsy performed in January 2007 showed changes consistent with early post-PV myelofibrosis. Patient became transfusion dependent.

In 2008, a repeated bone marrow examination (case material submitted) confirmed the diagnosis of post-PV myelofibrosis. Thalidomide was attempted to ameliorate cytopenia but it was discontinued because of pneumonitis associated with fatigue, edema and rapidly increasing splenomegaly. Splenectomy (case material submitted) was performed at the end of 2009. After the diagnosis of extramedullary myeloblastic transformation (in spleen) the patient was treated with azacitidine with no significant improvement. Patient died in May 2010.

DETAILS

1. Bone marrow biopsy (2008) measuring 2.0 cm x 0.2 cm x 0.2 cm submitted in Bouin’s fixative was processed. The bone marrow biopsy showed a markedly osteomyelosclerotic bone marrow with severely decreased hematopoiesis. A variably increased number of granulocytes and megakaryocytes were noted. The reticulin and trichrome stains showed 4+ fibrosis (MF-3). Corresponding CBC results: Hb 11.5 g/dl; WBC 7.4 x10/9/L (N, 79%; Band, 6%; Meta, 2%; Myelo, 2%; Lymph, 7%; Mono, 4%; Blasts, 0%). NRBC: 1% of the WBC. The aspirate was a dry tap. No flow cytometry or cytogenetics could be performed.

2. Spleen, splenectomy (2009) fixed in formalin of 2700 grams that measured 25x22x8. The spleen showed marked expanded red pulp due to a diffuse proliferation of immature myeloid cells displaying blastic features. Maturing myeloid precursors and terminally differentiated neutrophils an eosinophils were also noted.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

1. Bone marrow biopsy (1998) immunohistochemical stains: CD34 was only detected in marrow endothelial cells. No blast identified. CD117 was positive only in rare scattered round shaped mast cells. The bone marrow aspirate was a dry tap. No flow cytometry or cytogenetics could be performed.

2. Spleen immunhistology: The immature myeloid cells are positive for MPO, CD117, lysozyme but negative for CD34.

Flow cytometry analysis on the specimen revealed 4% of dim CD45-positive cells corresponding to blasts. These were HLA-Dr, CD117, CD13, CD33, MPO positive. CD34, CD14 and CD11b only weakly/focally pos. Opening the gate (70% of the analyzed cells) 53% of the cells expressed MPO.

CYTOGENETIC FINDINGS

Peripheral blood (dry tap bone marrow) and spleen karyotype showed a 46,XY[20].

MOLECULAR FINDINGS

JAK2 V617F positively demonstrated both in peripheral blood and spleen.

INTERESTING FEATURES

The first bone marrow biopsy (2007) showed a hypercellular (80%) bone marrow morphologically consistent with a diagnosis of PV with focal evidence of myelofibrotic progression (reticulin, 2-3/4; MF-1 to MF-2). The second marrow confirmed a diagnosis of post-PV MF. In conjuction with the clinical findings, the bone marrow fulfilled the WHO 2008 criteria for suhc a diagnosis. Interstingly in this case, the spleen was the first clear evidence of acute (blastic) transformation of the PV to AML. Extramedullary AML was confirmed by the presence of a large proportion immature myeloid cells in red pulp. Coexistent evidence of trilineage myeloid metaplasia was also noted. Flow cytometry of the spleen further confirmed the presence of both an increased number of blasts among a large number of maturing myeloid cells. Post-PV myelofibrosis represents the most common type of disease progression of PV. In PV patients who have not received P32 or alkylating agent therapy, acute transformation occurs mostly after the onset of post-PV MF. It remains to be seen if anti JAK2 therapy by preventing/slowing splenomegalic progression in PV might be effective in reducing the incidence of acute transformation in these patients.

PROPOSED DIAGNOSIS

Bone marrow: Post-PV myelofibrosis. Spleen: Acute myeloblastic transformation, extramedullary (in spleen) of Post-PV MF.

CONSENSUS DIAGNOSIS

Bone marrow: Post polycythemic myelofibrosis

Spleen: Acute myeloblastic transformation, extramedullary (in spleen) of post polycythemic myelofibrosis