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Published on: March 26, 2018
Bone marrow staging of patients with non-Hodgkin lymphoma by flow cytometry: correlation with morphology
P R Duggan1, D Easton, J Luider
1Division of Hematology, Department of Medicine, University of Calgary, Alberta, Canada.
Insights
Flow cytometry (FC) detects minimal bone marrow involvement in non-Hodgkin lymphoma (NHL) missed by morphology. Combining both methods improves detection, but minimal disease significance requires further study.
Area of Science:
- Hematology
- Oncology
- Diagnostic Pathology
Background:
- Immunophenotypic analysis is crucial for hematolymphoid disorder diagnosis.
- The utility of flow cytometry (FC) in staging non-Hodgkin lymphoma (NHL) bone marrow involvement remains undefined.
Purpose of the Study:
- To evaluate the role and sensitivity of FC in detecting bone marrow involvement in NHL patients.
- To compare FC findings with traditional morphologic examination of bone marrow biopsies.
Main Methods:
- Retrospective analysis of 157 staging and 70 restaging bone marrow biopsies from 195 NHL patients.
- Independent review of morphologic and FC analyses, with discrepancies resolved by a third reviewer.
- FC analysis using a panel of monoclonal antibodies to classify bone marrow involvement as positive (>5%), minimal (<5%), negative, or nondiagnostic.
Main Results:
- FC and morphology agreed in 78% of cases; discrepancies occurred in 22%.
- FC identified minimal disease (12%) missed by morphology, while morphology detected disease (7%) missed by FC.
- FC revealed bone marrow involvement in 17% of morphologically negative/suspicious biopsies, primarily minimal disease.
Conclusions:
- Neither morphology nor FC alone is sufficient for detecting all NHL bone marrow involvement.
- FC excels at identifying minimal bone marrow lymphoma, while morphology is better for >5% involvement.
- FC results may lead to restaging early-stage NHL as Stage IV; clinical significance of minimal involvement needs further research.
Background:
Immunophenotypic analysis is an established tool in the diagnosis and classification of many hematolymphoid disorders; however, the role of flow cytometry (FC) in detecting bone marrow involvement during the staging of non-Hodgkin lymphoma (NHL) has yet to be defined.
Methods:
The authors retrospectively analyzed 157 staging and 70 restaging bone marrow biopsies on which morphologic and FC analyses were performed; these biopsies were taken from 195 consecutive patients. Bone marrow biopsies were blindly and independently reviewed and determined to be positive, negative, or suspicious for morphologic involvement by NHL, with disagreements settled by a third reviewer. A selected panel of monoclonal antibodies was used to determine whether bone marrow involvement was immunophenotypically positive (>5%), minimal (<5%), negative, or nondiagnostic.
Results:
FC and morphology agreed in 78% of cases (178 of 227: 129 both negative, 49 both positive) and were discrepant in 22% (49 of 227). Seven percent (16 of 227) were morphologically positive but showed no evidence of disease on FC, whereas 12% (27 of 227) were positive by FC but had no morphologic involvement. Of the 162 morphologically negative or suspicious bone marrows, 27 were shown to be involved by FC, resulting in a false-negative detection rate of 17%. Most of these (22 of 27, 81%) had minimal detectable disease. Seven percent of Stage I and 26% of Stage II NHL cases with negative staging bone marrow morphologically were found to be involved by FC.
Conclusions:
Neither morphologic examination of bone marrow biopsy specimens nor FC alone is adequate to detect all cases of NHL with bone marrow involvement. FC is most sensitive for detecting minimal bone marrow lymphoma, whereas morphology will detect most cases in which involvement is >5%. Cases of early stage NHL with morphologically negative bone marrow could potentially be restaged as Stage IV on the basis of FC results. The clinical importance of minimal bone marrow involvement by NHL needs further evaluation.

