Chronic neutrophilic leukaemia and plasma cell‐related neutrophilic leukaemoid reactions

Abstract

SummaryMany cases reported as 'chronic neutrophilic leukaemia' have had an associated plasma cell neoplasm. Recent evidence suggests that the great majority of such cases represent a neutrophilic leukaemoid reaction to the underlying multiple myeloma or monoclonal gammopathy of undetermined significance. We have analysed all accessible reported cases to clarify the likely diagnosis and to ascertain whether toxic granulation, D€ ohle bodies and an increased neutrophil alkaline phosphatase score were useful in making a distinction between chronic neutrophilic leukaemia and a neutrophilic leukaemoid reaction. We established that all these changes occur in both conditions. Toxic granulation and D€ ohle bodies are more consistently present in leukaemoid reactions but also occur quite frequently in chronic neutrophilic leukaemia. The neutrophil alkaline phosphatase score is increased in both conditions and is of no value in making a distinction.Keywords: monoclonal gammopathy of undetermined significance, multiple myeloma, chronic leukaemia, chronic neutrophilic leukaemia.As defined in the 2008 World Health Organization (WHO) classification (Bain et al, 2008), chronic neutrophilic leukaemia (CNL) is a Philadelphia-negative myeloproliferative neoplasm (MPN) characterized by a white cell count (WBC) of at least 25 9 10 9 /l with segmented neutrophils and band forms comprising more than 80% of leucocytes, circulating blast cells less than 1%, immature granulocytes (promyelocytes, myelocytes and metamyelocytes) less than 10% and monocytes less than 1Á0 9 10 9 /l. There is no evidence of another MPN or a myelodysplastic syndrome (MDS), no dysplasia in any lineage and no evidence of a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). There should be no identifiable cause of physiological neutrophilia or, if such is present, there should be evidence of clonality. From the early 1900s onwards, more than 200 cases of CNL have been described but many of these would not meet current diagnostic criteria. The first known case meeting current criteria is that described by Tuohy in 1920 as 'A case of splenomegaly with polymorphonuclear neutrophil hyperleukocytosis' (Tuohy, 1920). However four other early cases had atypical features and appear more likely to have been primary myelofibrosis (Rathery, 1902;Hirschfeld, 1904;Emile-Weil & S ee, 1932). It is important to distinguish CNL from the neutrophilic leukaemoid reaction that can occur with multiple myeloma (plasma cell myeloma) and monoclonal gammopathy of undetermined significance (MGUS), which is attributable to cytokine release by neoplastic plasma cells. We were interested in reports of toxic granulation and D€ ohle bodies in patients considered to have CNL and we have also observed these phenomena in neutrophilic leukaemoid reactions. As toxic granulation is uncommon in myeloid neoplasms, this caused us to question whether some cases diagnosed as CNL might in fact have had a leukaemoid reaction to a plasma cell neoplasm. An increased neutrophil alkaline phosphatase (NAP) ...

Chronic neutrophilic leukemia 2016: Update on diagnosis, molecular genetics, prognosis, and management

“…A favorable prognosis of MG-associated CNL has been previously noted by other investigators, and contrasts with that expected from true CNL [11]. This is consistent with the mounting evidence that CNL with a MG represents a plasma cell driven reactive process rather than a MPN [12]. This evidence includes spontaneous remissions of apparent CNL during treatment of the associated plasma cell proliferative disorder, the aberrant production of CSF3 by clonal plasma cells and the demonstration of polyclonal neutrophils in these cases [11,[13][14][15][16][17].…”

“…This evidence includes spontaneous remissions of apparent CNL during treatment of the associated plasma cell proliferative disorder, the aberrant production of CSF3 by clonal plasma cells and the demonstration of polyclonal neutrophils in these cases [11,[13][14][15][16][17]. It is recommended that evidence of a plasma cell dyscrasia be sought during the initial evaluation of suspected CNL, and if found, clonality of the neutrophil lineage should be confirmed before making this diagnosis [2,3,12,18]. Confirmation of CSF3R mutational status provides a new specific tool for this.…”

“…In view of the reported frequency of CNL and monoclonal gammopathy of undetermined significance and multiple myeloma, the WHO recommends that the BM of all possible cases of CNL be examined for evidence of a plasma cell dyscrasia [3,14]. If a plasma cell dyscrasia is present, clonality of the neutrophil lineage should be supported by cytogenetic or molecular techniques before making the diagnosis of CNL [3,12,18].…”

Neutrophilic Leukemoid Reaction Associated with Malignancy Initially Suspected as Chronic Neutrophilic Leukemia

“…Furthermore, NLR can be present years before the diagnosis of carcinoma [5]. A few studies have reported that CNL or NLR can occur in plasma cell neoplasms [6,7].…”

“…In addition, in CNL patients without the CSF3R T618I mutation, mutations in other genes such as ASXL1, TET2, SRSF2, JAK2, and SETBP1 have also been reported [3,7]. It would be helpful to examine the mutations mentioned above as well as the CSF3R T618I mutation to determine clonality, but we could not perform them.…”