[dropcap]H[/dropcap]aving reviewed the possible causes of neutrophilia and their related morphologic changes, most of which were reactive, Dr. Pozdnyakova introduced a key case: a 69-year-old male who presented with chronic leukocytosis and neutrophilia (Fig. 8). “The CBC showed a WBC count close to 30,000, with an absolute neutrophil count of over 24,000. There was no significant left shift.” The myelocyte count was one percent. The CBC was notable for four percent basophilia, a concerning fact in this case, along with the persistent neutrophilia (elevated with a steady increase over 10,000 for about one year).
The neutrophils provided “unremarkable morphology with proper nucleus segmentation and cytoplasmic granulation,” Dr. Pozdnyakova said, noting none of the changes she had reviewed could be seen in this smear.
Dr. Pozdnyakova provided a differential diagnosis for persistent non-congenital neutrophilia, which is almost invariably associated with a myeloid neoplasm. Chronic myeloid leukemia, BCR-ABL1 positive, is the most common cause, she said. Other diagnoses associated with persistent neutrophilia are chronic neutrophilic leukemia, Philadelphia-negative myeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis (pre-fibrotic stage).
“Another one is atypical chronic myeloid leukemia, which is an MDS/MPN overlap syndrome. Or chronic myelomonocytic leukemia proliferative type also can present with neutrophilia,” she said. “Acute myeloid leukemia, especially with NPM1 and FLT3 mutations, in addition to blasts, can also present as neutrophilia.”
CML is the most common myeloproliferative neoplasm presenting with neutrophilia, and it has unique treatment, and thus all cases presenting with persistent neutrophilia should undergo testing to look for the presence of BCR-ABL1 translocation, Dr. Pozdnyakova said. Karyotype, FISH, and RT-PCR each have benefits and limitations, and all three may be needed to diagnose CML, she said.
“Karyotype allows us to look for additional abnormalities, in addition to BCR-ABL1 translocation (9;22). And RT-PCR is performed to look for the BCR-ABL1 fusion length, which could be different, and to quantify the levels of the fusion at baseline and for monitoring response to therapy.” FISH is seldom required, she said, though it can detect cryptic BCR-ABL1 rearrangements, observed in about one percent of cases.
Depending on the breakpoints in the BCR or ABL1 genes, three primary types of BCR-ABL1 genes can be formed, which result in fusion proteins of dissimilar lengths: p210, p190, and p230, she said, adding, “It’s important to know the type of BCR-ABL1 fusion for prognostic and diagnostic purposes.”
The most common fusion is p210, seen in more than 95 percent of cases and associated with typical CBC findings of significant leukocytosis with granulocytes in all stages of maturation, and with increased eosinophils and basophilia. “Those patients demonstrate an excellent response to tyrosine kinase inhibitors,” Dr. Pozdnyakova said.