[1294] Myelodysplasia and Bone Marrow Failure in an Autosomal Dominant Monocytopenia Immunodeficiency Syndrome

KR Calvo, DC Vinh, I Maric, P Noel, M Stetler-Stevenson, D Arthur, S Pittaluga, SM Holland. NIH Clinical Center, Bethesda, MD; NIAID, NIH, Bethesda, MD; NCI, NIH, Bethesda, MD

Background: Recently a group of patients was described with autosomal dominant and sporadic monocytopenia, B and NK lymphopenia with susceptibility to opportunistic infections (mycobacteria, fungi and papillomaviruses) and myelodysplasia (Vinh et. al. Blood 2009 in press).
Design: We performed detailed bone marrow analysis on a subset of these patients (N=15; 8 females and 7 males) with peripheral cytopenias and available marrows. All patients had monocytopenia, B and NK lymphopenia and at least one additional cytopenia.
Results: Bone marrows showed multilineage myelodysplasia (MDS) with distinctive diagnostic features. In contrast to typical MDS, the majority of patients were young (median age of 36 years) and the bone marrows were hypocellular (13/15; 87%) with increased reticulin fibrosis (9/10; 90%). Virtually all patients had megakaryocytic dysplasia with characteristic markedly atypical large megakaryocytes showing separation of nuclear lobes in a background of monolobated megakaryocytes and micromegakaryocytes. Seven out of 15 patients had discordance between the platelet count (over 150 k/uL) and the level of megakaryocytic dysplasia. Aberrant expression of CD34 in megakaryocytes was common. Dysplasia of the myeloid series (10/14; 71%) often showed markedly abnormal granulation patterns, hyposegmentation, and binucleation in granulocytes. Increased blasts (over 5%) were noted in 2 patients. Dyserythropoiesis was seen in 11 of 15 (73%). Despite peripheral monocytopenia and B-cell lymphopenia, abundant histiocytes and plasma cells were present in the marrow. Atypical plasma cells with increased binucleation and aberrant expression of CD56 were seen in 4 out of 8 patients studied (50%). Clonal cytogenetic abnormalities were identified in 7 of 15 patients, including three monosomy 7, one trisomy 8, and one 7q deletion.
Conclusions: The majority of patients were defined as MDS-unclassifiable, with two cases of refractory anemia with excess blasts. These findings suggest a distinctive form of MDS associated with an autosomal dominant and sporatic immunodeficiency syndrome. The combination of these characteristic morphological features in conjunction with the relative early age of onset of MDS, monocytopenia, and history of opportunist infections may aid in the early recognition of this syndrome.
Category: Hematopathology

Tuesday, March 23, 2010 9:00 AM

Platform Session: Section B, Tuesday Morning

 

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