From the Guidelines
CD117 positive cells on a bone marrow biopsy are highly suggestive of systemic mastocytosis or other mast cell disorders, and their significance should be interpreted in the context of clinical presentation, other laboratory findings, and overall bone marrow morphology. The presence of CD117 positive cells is a key diagnostic criterion for systemic mastocytosis, a condition characterized by the accumulation of abnormal mast cells in various tissues, including bone marrow 1. CD117 positivity is also seen in other conditions, such as acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. To distinguish between these conditions, additional testing is typically needed, including:
- Genetic analysis for mutations like KIT D816V, which is common in mastocytosis
- Flow cytometry to characterize the abnormal cell population
- Immunohistochemistry for other markers like tryptase, CD25, and CD2 The pattern and intensity of CD117 staining, along with other markers, help distinguish between these conditions. It is essential to interpret the significance of CD117 positive cells in the context of the patient's clinical presentation, other laboratory findings, and overall bone marrow morphology, as isolated CD117 positivity is not diagnostic of any specific condition. The European Competence Network on Mastocytosis recommends detecting KIT mutations at position 816 using techniques like ASO-qPCR, which has a high sensitivity of ± 0.01% 1.
Some key points to consider when evaluating CD117 positive cells on a bone marrow biopsy include:
- The clinical presentation of the patient, including symptoms like skin lesions, hepatomegaly, splenomegaly, and lymphadenopathy
- Other laboratory findings, such as serum tryptase levels, complete blood count, and differential
- The overall bone marrow morphology, including the presence of other abnormal cell populations
- The results of additional testing, such as genetic analysis and flow cytometry.
In contrast, the evidence from the 2009 study on gastrointestinal stromal tumors (GIST) is not directly relevant to the interpretation of CD117 positive cells on a bone marrow biopsy, as GIST is a distinct clinical entity that typically presents with abdominal masses or gastrointestinal symptoms 2.
From the Research
Significance of CD117 Positive Cells on Bone Marrow Biopsy
- CD117 is a transmembrane protein receptor encoded by the c-kit proto-oncogene, and its expression is present on approximately 4% of normal bone marrow mononuclear cells 3.
- The presence of CD117 positive cells on bone marrow biopsy can be indicative of various conditions, including: + Acute myelogenous leukemia (AML) and chronic myelogenous leukemia in myeloid blast crisis 3. + Systemic mastocytosis, a disorder characterized by an abnormal increase in tissue mast cells 4, 5, 6. + Mast cell leukemia, a highly aggressive neoplasm 6.
- CD117 expression can also be seen in other conditions, such as myelodysplastic syndromes (MDS) and myeloproliferative disorders in blast crisis (MPD-BC) 3.
- The diagnostic criteria for systemic mastocytosis include the presence of one major criterion and one minor criterion or three minor criteria, with CD117 expression being a key marker for the diagnosis of this condition 5, 6.
- Immunohistochemical analysis of bone marrow mast cells in systemic mastocytosis has shown expression of CD2, CD117/Kit, and bcl-x(L), which can be useful diagnostic markers 7.
Diagnostic Implications
- The presence of CD117 positive cells on bone marrow biopsy should be interpreted in the context of other clinical and laboratory findings, including morphologic analysis and immunophenotyping 3, 4, 6.
- High-sensitivity flow cytometric analysis can be used to evaluate systemic mastocytosis, including the identification of a discrete CD117-positive mast cell population 4.
- The use of antibodies against tryptase, CD117 (KIT), and CD25 is recommended in every suspected case of mastocytosis 6.