| Session: Mast cell disease |
| Case number: 146 |
Submitter(s): Emily L. Howard, Lei Chen, Steven A. Schichman.
Clinical history
An 81 year old man presented to the VA hospital in June 2006 with fatigue, weight loss (30 lb over three years), and a three year history of monocytosis (1.4-3.4 K/uL) and thrombocytopenia (82-154 K/uL). His past medical history was noncontributory. His only medication was multivitamins. Physical examination was unremarkable. A CBC showed WBC 5.3 K/uL with 38% monocytes, Hgb 14.3 g/dL, Plt 106 K/uL.[figure1]A bone marrow biopsy demonstrated hypercellular marrow with myeloid hyperplasia and dysplastic megakaryocytes.[figure2]Cytogenetics were normal: 46,XY[20]. FISH examination was negative for the bcr/abl rearrangement, -5, 5q-, -7, 7q-, +8, +9, 13q- and 20q-.
Subsequently, he was referred to the University Myeloma Institute in October 2006. CBC showed WBC 4.3 K/uL, Hgb 12.1 g/dL, Hct 36.2%, MCV 93 fL, MCHC 33.4 g/dL, Platelet 82 K/uL, RDW 18.1% with an automated differential count of 22% Neutrophils, 32% Lymphocytes, 44% Monocytes, 2% Eosinophils. Serum tryptase was 148.0 ug/L [0.4-10.9]. An SPEP showed increased Gamma region 2.3 g/dL [0.7-1.6]. IFE showed: Kappa free light chain 7.9 mg/dL [0.3-1.9], Lambda free light chain 6.4 mg/dL [0.6-2.6], IgG 2130 mg/dL [714-1394], IgA 517 mg/dL [95-353], IgM 432 mg/dL [40-275].
Details of gross/microscopic pathology:
The peripheral smear shows giant platelets.[figure3]The bone marrow aspirate has moderately cellular particles. Megakaryocytes are frequent and include micromegakaryocytes with minimal cytoplasm and cells with increased numbers of nuclei.[figure4] Myeloid and erythroid precursors exhibit a complete sequence of maturation with no dysplasia.
The core biopsy shows hypercellular marrow (95%) with a multifocal, spindle cell infiltrate involving 30% marrow cellularity. The nodular lesions have paratrabecular, interstitial and perivascular locations. There is an admixed inflammatory infiltrate including numerous eosinophils and plasma cells.[figure5]A reticulin stain highlights marked fibrosis within the nodules.[figure6]
Immunophenotype (flow cytometry/immunohistochemistry):
Immunohistochemical stains showed strong positivity for CD117[figure7][figure8]and weak staining for mast cell tryptase.[figure9]The spindle cells are negative for SMA, cytokeratin, S-100 and CD34. A toluidine blue stain highlights granules in many spindle cells.[figure10]An immunostain for CD68 demonstrates staining of hematopoietic elements and spindle cells. A CD138 immunohistochemical stain highlights scattered plasma cells, comprising 5% of cellularity. In-situ hybridization studies for light chains shows no restriction.
Flow cytometry detected no aneuploidy by DNA index.
Cytogenetics:
46,XY[cp20]/45,XY,-13[1]. A FISH panel was negative for inv(3), -5, 5q-, -7, 7q-, +8, 13q-, 20q-.
Molecular analysis:
c-kit Asp816Val mutation.
Interesting feature(s) of submitted case:
1) 3 year history of monocytosis mimicking CMML.
2) Hypergammaglobulinemia.
Proposed diagnosis:
Systemic mast cell disease.
Panel diagnosis:
Differential diagnosis includes systemic mastocytosis and SM-AHNMD/CMML
Comments:
Studies performed by the panel: positive for D816V mutation, CD25+
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