In the case of the 69-year-old male patient, the karyotype came back positive for t(9;22), signifying the presence of the Philadelphia chromosome diagnostic of chronic myeloid leukemia. There were no pathogenic somatic mutations. “Taken together, these genetic findings allowed us to make a diagnosis of CML, BCR-ABL1 positive, chronic phase. So this is likely a case of CML with p230 or neutrophilic CML,” Dr. Pozdnyakova said. The patient was likely to have carried the diagnosis since the elevated WBC count was detected a year earlier. The patient responded well to TKIs.
“p230 is very rare and low yield and that is the main reason why we do not test for it,” she told CAP TODAY. “In addition, regardless of the fusion, t(9;22) is readily picked up by conventional karyotype and/or FISH. If p210 and p190 are negative and t(9;22) is present, we assume p230.” While p190 is rare in CML, she added, it is common in B lymphoblastic leukemia, which is why their assay includes p190.
“We need to always perform BCR-ABL1 testing by different modalities to exclude CML in cases presenting with persistent neutrophilia,” she emphasized. “And next-generation sequencing analysis can help exclude a clonal process or confirm the presence of another myeloproliferative neoplasm, or MDS/MPN overlap.”
Dr. Pozdnyakova offers the following algorithm for workup of a CBC presenting with neutrophilia:
- Confirm the neutrophilia. Exclude spurious cases, such as platelet clumping.
- If true neutrophilia is present, review the clinical presentation (symptomatic neutrophilia that could be explained by ongoing infection, recent surgery, G-CSF, etc.? or unexplained neutrophilia? duration of neutrophilia?) and remainder of the CBC for other abnormalities (other cytoses or cytopenia?) and ask the laboratory to prepare a well-made peripheral smear for assessment of red cell, white cell, and platelet morphology (reactive/toxic/dysplastic morphologic changes? inclusions—initiate microbiology workup?).
- In an asymptomatic patient with mild neutrophilia and no associated CBC or peripheral smear abnormalities, the laboratory evaluation could end at this point with a plan to repeat testing if symptoms develop and/or in several weeks to determine if the neutrophilia is persistent.
- If there is suspicion for neoplastic neutrophilia (differential diagnosis: CML, CNL, Ph- MPN, atypical CML, other MDS/MPN), then: BCR-ABL1 (PCR or karyotype); cytogenetics (could be normal, unless CML); NGS-based molecular testing to look for somatic mutations associated with myeloid malignancies; bone marrow biopsy.
Karen Lusky is a writer in Brentwood, Tenn.