Frequency of Systemic Mastocytosis in Chronic Myelomonocytic Leukemia – A Single Institutional Study
Ryan C Johnson, Brock A Martin, Jason R Gotlib, Daniel A Arber, Tracy I George. Stanford University Medical Center, Stanford, CA
Background: Systemic mastocytosis (SM) may arise de novo or may be associated with a clonal hematological non-mast cell lineage disease (AHNMD). AHNMDs are typically myeloid malignancies including acute myeloid leukemia, myelodysplastic syndrome, and myelodysplastic/ myeloproliferative neoplasms including chronic myelomonocytic leukemia (CMML). CMML has been reported to be among the most frequent of the AHNMDs. What is not known is the incidence of SM in patients with CMML. We retrospectively assessed a large series of patients with CMML to estimate our frequency of SM via morphology, immunophenotyping, KIT mutation analysis, and appropriate clinical history.
Design: 66 patients (age range 33-86 yrs, average 69 yrs) with either CMML-1 or CMML-2 were identified from our institutional database from 1997-2012 and had diagnostic bone marrow specimens available for review. Mast cell morphology was assessed via Wright-Giemsa stained blood and aspirate smears, and biopsies were stained with H&E. Immunohistochemical staining was performed via an automated platform (Ventana Benchmark, Tucson, AZ) and antibodies to tryptase, CD117, and CD25 were performed on bone marrow biopsy samples. Polymerase chain reaction (PCR) amplification and sequencing of KIT was performed on fresh tissue with probes directed at exon 17 of the KIT gene and directly sequenced.
Results: All patients were confirmed as having CMML after review of clinical findings, peripheral blood and aspirate smears, bone marrow biopsy, immunophenotyping and cytogenetic/molecular genetic studies. After immunohistochemistry, morphology, and KIT mutational analysis, 2/66 (3%) cases met criteria for SM; 1 patient had CMML-1, and 1 patient had CMML-2. One case was made at the initial diagnosis, and in one case the patient developed SM twelve years after the diagnosis of CMML. 11/66 (16.7%) cases met criteria for mast cell hyperplasia, a benign finding.
Conclusions: No large retrospective series to date has been performed assessing the frequency and temporality of SM in patients with CMML. Mastocytosis associated with CMML is an infrequent occurrence and may occur either at presentation or later in the course of the disease. Although infrequent, we recommend that all cases of CMML be examined for the presence of SM by assessing mast cell morphology, performing immunohistochemistry and conducting KIT mutation testing if suspicion for systemic mastocytosis exists.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 215, Monday Morning