Case Series Open Access
Volume 3 | Issue 2 | DOI: https://doi.org/10.33696/haematology.3.049

Multiple Myeloma with Neutrophilia: Two Etiologic Pathways for a Rare Presentation of a Common Diagnosis

  • 1University of South Carolina School of Medicine Greenville, Greenville SC, USA
  • 2Pathology Associates, Greenville SC, USA
+ Affiliations - Affiliations

*Corresponding Author

Jennifer Knight MD, Jenny.knight@prismahealth.org

Received Date: September 05, 2022

Accepted Date: September 15, 2022


Objectives: Multiple myeloma (MM), a neoplastic proliferation of plasma cells, is a common diagnosis among hematologic malignancies. Leukocytosis, specifically neutrophilia, is also very common, typically as a secondary abnormality. However, having both multiple myeloma and neutrophilia simultaneously is rare and could arise by two distinct pathways: either by separate, but concurrent, clonal neoplasm of neutrophils (e.g chronic neutrophilic leukemia) or by a paraneoplastic-type process thought to be secondary to plasma cell stimulation of granulocyte colony-stimulating factor (G-CSF). Distinguishing between the two determines treatment and prognosis.

Methods: A retrospective evaluation of two cases of MM with neutrophilia and comprehensive literature search for all MM with neutrophilia reported in the literature was completed. 

Results: We report two cases in which persistent neutrophilia was related to underlying multiple myeloma. One case showed trending of neutrophilia concordant to the varying response of his MM to multiple pharmacotherapies, and the other case had steadily elevated neutrophils without worsening symptoms in the setting of observation alone. 

Conclusions: After thorough evaluation of the literature and detailed comparison with our two new cases, a flow chart is presented to differentiate neutrophilia secondary to MM from other differential diagnoses, which could affect treatment options and potentially have prognostic implication.


Multiple myeloma, Neutrophilia, Leukocytosis, Gammopathy, Chronic neutrophilic leukemia


Multiple myeloma (MM) is a common hematologic malignancy, with 32,110 new cases diagnosed in the United States in 2019, resulting in 12,960 deaths [1]. While neutrophilia is also a common entity, it most often arises secondary to other etiologies, such as infection or inflammatory processes. Primary causes of neutrophilia, such as chronic myeloid leukemia (CML), are less common, with chronic neutrophilic leukemia (CNL) being an extremely rare cause of neutrophilia (~200 reported cases) [2-5].

While MM and neutrophilia are both common, it is uncommon for the two to present together. In a 2003 study of 1,027 patients newly diagnosed with MM, none reported a white blood cell count greater than 25 cells × 10L that was not attributable to another cause [6]. Interestingly, in most cases, neutrophilia resolves during typical MM treatment, indicative of secondary neutrophilia related to the plasma cell clone. There are, however, rare incidences when neutrophilia does not resolve, suggesting an alternate biology [7-10]. In these cases, CNL is typically the only remaining differential diagnostic consideration as other myeloid neoplasms can more easily be excluded based on morphologic features and/or genetic mutations. Definitive determination of the genesis of neutrophilia (discrete neoplasm or reactive) is essential as treatments for MM and CNL are different [11,12], portending different prognoses (MM 10+ years, MM with neutrophilia poorer prognosis and CNL 2 years) [12-14].

Here we report two cases of MM with neutrophilia and a comprehensive literature review to explore the origin, course of disease, treatments and outcomes.


Following IRB approval, a retrospective evaluation of two cases of MM with neutrophilia was completed. A complete evaluation of the datapoints associated with the course of the disease to include initial presentation, diagnosis, treatments and outcomes were collected. A comprehensive literature search was completed for all MM with neutrophilia reported to exclude cases that were not available in English or those which the institution could not obtain. Information from the cases reported here and from the literature was used to create a flow chart to assist in the diagnosis of MM with neutrophilia versus concurrent MM and CNL for consideration of treatment for optimal patient care and outcomes.

Case 1

A 70-year-old male with no significant past medical history presented for further hematologic evaluation after imaging and lab work for urolithiasis showed mild splenomegaly and leukocytosis (WBC, 46.3 cells × 10L; normal: 4.0-11.0 cells × 10L). Follow up a month later revealed worsening leukocytosis (WBC, 56.8 cells × 10L; absolute neutrophil count (ANC), 54.2 cells × 10L; normal: 1.4-7.0 cells × 10L), significant anemia (hemoglobin, 9.6 g/dL; normal: 13.5-17.5 g/dL), and mild thrombocytopenia (platelets, 120 cells × 10L; normal: 125-390 cells × 10L) with associated splenomegaly (spleen palpable 1-2 cm below the costal margin). The patient denied notable symptoms such as fever, chills, or weight loss, and no lymphadenopathy was detected. His creatinine was 1.2 mg/dL (normal: 0.4-1.7 mg/dL) with estimated GFR of 60 mL/min (normal: >59 mL/min) and calcium of 9.3 mg/dL (normal: 8.4-10.4 mg/dL). Dohle bodies and toxic granulation were noted on review of the smear, but there was no left shift or rouleaux (Figure 1). A myeloproliferative neoplasm was suspected. CML was excluded with negative BCR-ABL1 testing. A bone marrow biopsy demonstrated nearly 100% cellularity with prominent myeloid hyperplasia (myeloid:erythroid::12:1; normal 2-3:1), but there were no other morphologic features to suggest a myeloproliferative neoplasm and no dysplasia or increased blasts. However, a monoclonal lambda plasma cell population accounting for 20% of marrow cellularity was identified diagnostic of MM (Figures 2 and 3). Karyotype was normal, and a limited FISH panel revealed a gain of 1q, portending a poor prognosis [15,16]. Neutrophilia was speculated to be secondary to clonal plasma cell triggered production of granulocyte colony stimulating factor (G-CSF). Subsequent serum protein electrophoresis revealed a 3.6 g/dL IgA lambda monoclonal protein with serum immunoglobulin studies showing an elevated IgA level of 4068.10 mg/dL (normal; 84.50-499) but normal serum free light chain ratio of 0.80 (normal; 0.26-1.65). The patient was started on dexamethasone and bortezomib treatment with mild improvement of his leukocytosis. Lenalidomide was added with continued improvement. With less than one year of treatment, the patient had achieved complete remission of MM and resolution of the neutrophilia (IgA, 302.7 mg/dL; no detectable M spike; WBC, 8.2 cells × 10L). Laboratory evidence of the MM fluctuated correlatively with the neutrophilia for the following 20 months (Figure 5). Additional therapies have included carfilzomib and dexamethasone. Five years after initial presentation, there is continued correlative undulation of his blood cell counts, with his most recent results showing WBC of 14.4 cells × 10L, ANC of 12.0 cells × 10L, and M spike of 0.22. His IgA level has stabilized to normal. His last laboratory results showed an IgA of 366 mg/dL. His kidney function and calcium levels remain normal (Cr, 1.24 mg/dL; Ca, 8.9 mg/dL). He continues on carfilzomib and dexamethasone therapy.

Figure 1. Peripheral blood smear. Neutrophilia with toxic granulation. No left shift beyond occasional bands (WG; 1000x).

Figure 2. Hypercellular bone marrow. A. The bone marrow exhibits nearly 100% cellularity. Expected cellularity for this patient is approximately 30% (H&E; 40x). B. A predominance of myeloid maturation is visible (H&E; 200x).

Figure 3. . Plasma cells. A. CD138 immunohistochemistry highlights approximately 20% plasma cells in the bone marrow that are difficult to see by H&E because of the myeloid hyperplasia (x200). B. Kappa and, C. Lambda light chains by in situ hybridization show the plasmsa cells are lambda light chain restricted (x200).

Figure 4. Neutrophilia and M spike levels over time. Note the undulating levels of neutrophilia with corresponding changes in M-spike levels throughout the course of treatment (75 weeks).

Figure 5. Diagnostic and prognostic flow chart. Algorithm for the workup of a starting diagnosis of unexplained neutrophilia or MM.

Case 2

A 67 year-old Caucasian male with a history of Factor 5 Leiden presented to his primary physician with cellulitis for which he was treated with antibiotics. During these treatments leukocytosis was noted: WBC 21 cells × 10L and ANC 18 cells × 10L. After successful treatment of the cellulitis, WBC decreased to 14.9 cells × 10L. On a three-month follow-up, however, leukocytosis had worsened (WBC, 20.3 cells × 10L) without cellulitis or swelling of the left leg and no other apparent source of infection or inflammation. The patient was referred to a hematologist oncologist for further evaluation of persistent leukocytosis.

He denied B-symptoms, and no splenomegaly was reported. A leukemoid reaction was suspected, although a myeloproliferative neoplasm remained on the differential. While further evaluation was required, no documentation was noted for two years. Eventually, a bone marrow biopsy was performed and was found to be hypercellular with a myeloid:erythroid ratio of 10:1. Additionally, a monoclonal kappa plasma cell population was identified accounting for approximately 15% of cellularity. Peripheral blood at that time showed a WBC count of 34.4 cells × 10L with an ANC of 30.7 cells × 10L and no left shift. Hemoglobin and platelet count were normal. Karyotype and a MM FISH panel were normal. Mutation analysis for JAK2 and BCR-ABL1 had been performed on peripheral blood and were negative. He was diagnosed with smoldering MM with the neutrophilia favored to be related to the MM. The patient elected to refrain from treatment. Nine years after presenting, he continues to decline treatment. His M spike and leukocytosis remain stable (M spike, ~1.4 g/dL; WBC, ~30 cells × 10L; ANC, ~27 cells × 10L). He has complaints of fatigue and night sweats but renal function, hemoglobin, and calcium levels remain normal (Cr, 1.00 mg/dL; hgb, 14.0 g/dL; calcium, 8.8 mg/dL).


A comprehensive literature review found 35 cases of concurrent plasma cell neoplasms and neutrophilia, including the two cases listed above (Table 1). The first reported case was in 1978, with diagnoses of CNL and MM. The paper defined the CNL diagnosis using leukocytosis with predominant neutrophilia (WBC, 19 cells × 10L; 88% segmented neutrophils and bands), splenomegaly, granulocytic hyperplasia in the bone marrow, and negative Ph chromosome [17].

Table 1. Comprehensive Literature Reviewa [4,5,7-10,17,20-22,24-45]. A comprehensive literature search was completed for all MM with neutrophilia reported to exclude cases that were not available in English or those which the institution could not obtain. 
Author Age and sex WBC (cells*10^9L) Segs + bandsb Hypercell BM Genetics Splenomegaly Toxic granulation Monoclonal protein (mgd/L) BM PC percentage G-CSF evidence Diagnoses Treatment and response Outcome
Vorobiof et al. (1978) 70 YOM 19.0 88% yes (-) BCR-ABL yes - 1400 IgA kappa 15% - CNL with MM - 28 months; still alive
Watanabe et al. (1984) 71 YOF 86.4 89% yes (-) BCR-ABL yes yes 1447 IgG lambda, 453 IgA kappa - G-CSF elevated in plasma CNL with paraproteinemia pRBC transfusion with improvement of symptoms 38 months; death due to heart failure
Franchi et al. (1984) 64 YOF 35.0 80% yes - yes - 2200 IgG lambda 12% - CNL progressing to MM busulfan, steroids with development of neutropenia 228 months after CNL dx; 48 months after MM dx; death due to bronchopneumonia
Mehrotra et al. (1985) 65 YOF 57.0 88% yes (-) BCR-ABL yes yes 2300 IgG lambda - - CNL allopurinol with worsening splenomegaly 96 months; still alive
Lewis et al. (1986) 62 YOF 25.3 91% yes (-) BCR-ABL yes yes 750 IgA lambda 20% - MM prednisolone, melphalan, cyclophosphamide without improvement of neutrophilia; added busulfan with improvement of neutrophilia 96 months; death
Lewis et al. (1986) 72 YOF 36.3 91% yes (-) BCR-ABL yes - 2100 IgA lambda 30% - MM melphalan without improvement of leukocytosis 48 months; death due to AML
Zoumbos et al. (1987) 57 YOM 55.4 90% yes (-) BCR-ABL yes - kappa light chain 60% - CNL progressing to MM allopurinol and busulfan with improvement of neutrophilia -
Kubo et al. (1989) 62 YOF 20.1 82% yes (-) BCR-ABL  - - 330 IgA kappa 5.90% no G-CSF elevation in plasma CNL associated with MM - 96 months; still alive
Abe et al. (1989) 70 YOF - - - - - - IgG kappa - - Neutrophilia progressing to MM - 144 months; death due to AML
Standen et al. (1990) 65 YOF 13.7 86% yes (-) BCR-ABL no yes after initial txt 500 IgG lambda 15% no GSF elevation in plasma MM tumor removal, radiotherapy with worsening leukocytosis and MM -
Standen et al. (1990) 76 YOF 72.3 91% yes (-) BCR-ABL yes yes 5600 IgG lambda - no GSF elevation in plasma CNL with PCD melphalan and prednisone with improvement of neutrophilia -
Rovira et al. (1990) 31 YOF 23.9 82% yes (-) BCR-ABL no - kappa light chain 80% - CNL progressing to MM melphalan-prednisone 96 months; still alive
Dieguez et al. (1992) - - - yes - yes yes 5730 IgG lambda - - CNL associated with MM melphalan and prednisone with minimal response -
Florensa et al. (1993) 61 YOF 66.0 90% - (-) BCR-ABL no yes lambda light chain - - CNL no therapy -
Cehreli et al. (1994) 60 YOF 62.4 85% yes (-) BCR-ABL yes yes kappa light chain - - CNL with MM etoposide and hydroxyurea and doxorubicin without improvement 4.6 months; death
Mori et al. (1995) 57 YOF 33.4 95% yes (-) BCR-ABL yes yes 3628 IgA - - CNL associated with MM busulfan with minimal response 22 months; death due to pneumonia
Nagai et al. (1996) 73 YOM 28.08 85% yes (-) BCR-ABL  - - 3200 IgG kappa 7.60% G-CSF elevated in plasma Plasma cell dyscrasia associated with CNL melphalan then busulfan with transient improvement followed by relapse of neutrophilia -
Ito et al. (1996) 30 YOM 42.2 91% yes (-) BCR-ABL yes yes 1269 IgG kappa - - CNL with MGUS no therapy 144 months; still alive
Usada et al. (1997) 56 YOM 9.9 81% yes (-) BCR-ABL yes   1020 IgA lambda 14% G-CSF in BM, G-CSF elevated in plasma MM vincristine, doxorubicin, dexamethasone, melphalan and prednisolone and interferon with improvement of myeloma cells 120 months; death due to respiratory failure
Stevenson et al. (1998) 60 YOF 21.0 85% yes - yes - 2100 IgA lambda 6% - MM with reactive leukocytosis cortisone injection, dexamethasone, melphalan and autologous stem cell rescue with improvement of leukocytosis -
Dincol et al. (2002) 71 YOM 38.0 86% yes (-) BCR-ABL yes yes 3993 IgG kappa 4% - CNL associated with MM progressing to AML melphalan with improvement of MM and neutrophilia 17 months; death due to bronchopneumonia
Kohmura et al. (2004) 94 YOM 31.3 90.50% yes - no no IgG 35% Anti-G-CSF Ab, GCSF in BM, GCSF elevated in plasma, G-CSF mRNA MM melphalan, prednisolone, dexamethasone with improvement of neutrophilia -
Kusaba et al. (2004) 68 YOM 29.9 82% - (-) BCR-ABL  - yes lambda light chain - Anti-GCF Ab, G-CSF elevated in plasma CNL associated with MM melphalan and prednisone without response; ranimustine, vincristine, melphalan, dexamethasone with improvement of neutrophilia -
Fukuno et al. (2006) 74 YOM 25.7 71% yes (-) BCR-ABL yes yes lambda light chain - G-CSF in BM CNL progressing to MM no therapy 24 months; death due to renal failure
Gnerre et al. (2007) 40 YOF 21.0   yes - no yes 2128 IgM lambda 30% - MM associated with neutrophilia and nephrotic syndrome diuretics, albumin infusion, bisphosphonates, melphalan, prednisone with improvement of neutrophilia and MM -
Sebasky et al. (2008) 56 YOM 22.6 - - (-) BCR-ABL no yes (nov 2007) IgG kappa 46% G-CSF elevated in plasma MM vincristine, doxorubicin, dexamethasone with improvement of neutrophilia 9 months; death due to MM
Hartley et al. (2010) 60 YOF 44.11 79% yes (-) BCR-ABL, (-) Jak2-V617 no - 1305 IgA kappa 7% - MGUS with neutrophilia no therapy -
Nedeljkovic et al. (2014) 81 YOM 26.8   yes (-) BCR-ABL, (+) Jak2-V617 yes no 1600 IgG kappa 15-20% - CNL w/ smoldering PC myeloma - -
Taiwo et al. (2014) 63 YOF 65.59 91% yes (-) BCR-ABL no yes 276.9 lambda light chain 10% - smoldering MM hydroxyurea with worsening neutrophilia; bortezomib and dexamethasone with improvement of neutrophilia -
Blombery et al. (2014) 57 YOF 114.0 92% - (-) BCR-ABL, (-) Jak2-V617, (+) CSF3R no - 600 IgG kappa - - MGUS progressing to CNL - -
Shi et al. (2015) 78 YOM 47.5 86% yes (-) BCR-ABL yes - 434 lambda light chain 6.40% - CNL progressing to MM progressing to AML hydroxyurea without improvement; cyclophosphamide, prednisone, thalidomide 48 months; death due to AML
Milojkovic et al.  (2015) 52 YOM 22.5 84% - (-) CSF3R  - yes 8000 IgG lambda 10-15% - MM with neutrophilic leukemoid reaction hydroxycarbamide -
An et al. (2020) 48 YOF 57.1 84% - (-) BCR-ABL, (-) Jak2-V617, (-) CSF3R yes yes 4575 kappa light chain - - MM with neutrophilic leukemoid reaction bortezomib, lenalidomide, and dexamethasone with improvement of neutrophilia -
Hall et al. (2021) 70 YOM 46.3 86% yes (-) BCR-ABL yes yes 4068 IgA 20% - MM arising with leukemoid reaction Currently, carfilzomib and dexamethasone with stable IgA and variable neutrophilia 60 months; still alive
Hall et al. (2021) 67 YOM 20.3 84% yes (-) BCR-ABL, (-) Jak2 no no 1655.8 IgA 15% - Smoldering kappa MM with leukemoid reaction Currently, refrains from treatment w/ no worsening of symptoms 108 months; still alive
a) cases that were unavailable or not in English were excluded; immunoglobulins that were not quantified are mentioned without values but the diagnosis was multiple myeloma
b) Segs: Segmented neutrophils


The definition of CNL has evolved since the first reported case. Starting in 2008, WHO criteria for CNL specifically state that a plasma cell neoplasm must be excluded, suggesting a neutrophilic reactive process may have been underlying some of the previously diagnosed cases of CNL, cases which were likely MM with neutrophilia (Table 2) [18,19]. In fact, a 2016 literature review of 150 reported cases of CNL found that only 40 cases met the current WHO criteria for the diagnosis. This was primarily because previous guidelines did not rule out underlying inflammatory processes from abnormal production of G-CSF [12]. Some have suggested the mechanism underlying this abnormal G-CSF production is through monoclonal B-cell clones (plasma cells being terminally differentiated B cells) producing cytokines that induce production of interleukins and tumor necrosis factor (TNF) that then stimulate T-cell production of G-CSF [20,21]. This theory is not novel. Ectopic production of G-CSF causing neutrophilia is seen secondary to solid organ neoplasms including lung, thyroid, gastric, gallbladder, and urinary bladder, and in other hematologic neoplasms including Hodgkin lymphoma and anaplastic large cell lymphoma [22]. Thus, high levels of G-CSF could provide evidence of a secondary response of the neutrophils in contrast to a clonal proliferation.The limitation to its use is the inavailability of either G-CSF levels or G-CSF immunostains, particularly for smaller institutions.

More recently, studies have identified a mutation in the gene encoding granulocyte colony-stimulating factor receptor (CSF3R), which regulates JAK/STAT signaling. It has been reported to be present in 80% of patients with CNL [23]. The discovery of this mutation makes diagnosis less reliant on exclusion criteria. Since its discovery, only one reported case to date has demonstrated the presence of this mutation in a patient with MM and neutrophilia to support true concurrence of CNL and MM [24]. Thus, as the likelihood of concurrent CNL and MM is exceedingly low, extended genetic evaluation for neutrophilia in the setting of newly diagnosed MM is neither economical nor timely, particularly when constraints from payers or access to molecular testing may be insurmountable hurdles. Neither of the presented cases were tested for CSF3R even though each met almost all other criteria for CNL (Table 2). While genetic testing for CSF3R may be definitive in the cause of neutrophilia if actually detected, it is not necessary to test for this specifically in cases when a bone marrow is biopsy diagnostic of MM.


Table 2: WHO Guidelines of diagnostic criteria for CNL [18]. Criteria for a diagnosis of CNL that were fulfilled (yes) or not fulfilled (no) at the time of MM diagnosis by the herein reported patients.
  Case 1 Case 2
-Peripheral blood WBC ≥25 x 109/L,
-Segmented neutrophils plus banded neutrophils constitute ≥ 80% of the white blood cells
-Neutrophils precursors (promyelocytes, myelocytes, and metamyelocytes) <10% of the white blood cells
-Myeloblasts rarely observed
-Monocyte count <1 x 109 L
-No dysgranulopoiesis
-Hypercellular bone marrow
-Neutrophil granulocytes increased in percentage and number
-Neutrophil maturation appears normal
-Myeloblasts constitute <5% of the nucleated cells
-Not meeting WHO criteria for BCR-ABL1 positive CML, polycythemia vera, essential thrombocythemia, primary myelofibrosis Yes
(BCR-ABL1 negative in peripheral blood)
(BCR-ABL1 and JAK2 V617Fnegative in peripheral blood
-No rearrangement of PDGFRAPDGFRB, or FGFR1, and no PCM1-JAK2 fusion Not testedb  Not testedc
-CSF3R T618I or another activating CSF3R mutation
-Persistent neutrophilia ≥ 3months, splenomegaly, and no identifiable cause of reactive neutrophilia including absence of plasma cell neoplasm or, if a plasma cell neoplasm is present, demonstration of clonality of myeloid cells by cytogenetic or molecular studies.
Not tested
Mild splenomegaly but exclusionary diagnosis of MM
Not tested
Exclusionary diagnosis of MM
a) Relative monocyte count less than 10%
b) Marrow was inaspirable, and this testing was not performed on peripheral blood. There was no eosinophilia.
c) Specific FISH testing for these abnormalities was not performed. Karyotype was normal. There was no eosinophilia.

In the cases where a patient presents only with unexplained neutrophilia, it is important to point out the significance of considering MM as a potential cause (Figure 4). As a bone marrow biopsy would be part of a typical workup for unexplained neutrophilia, specific evaluation for monoclonal plasma cells is an easy and efficient step for determining if neutrophilia is just the presenting symptom of a case of MM, which was true in both of our reported cases. Further, the literature shows several cases where a diagnosis of “CNL” preceded an alternate diagnosis of MM/MGUS with neutrophilia [4,5,25-28]. As cases with neutrophilia secondary to MM can show marked granulocytic hyperplasia in the marrow, which would potentially make plasma cells inconspicuous, immunohistochemical stains and/or ISH to specifically identify the plasma cells should be performed.

This overlap in presentation of CNL and MM with neutrophilia historically has led to confusion in diagnosis and can still cause misdiagnosis or delay in diagnosis of MM. Recogonition of MM with this rare presentation, however, is paramount because of differing treatments and prognosis between the two entities. Many studies have focused on differentiation between CNL and MM with neutrophilia, but few have discussed therapies for these rare disorders. Cases of CNL have the potential to be treated with JAK/STAT pathway targeted therapies [23]. Treatment for MM with neutrophilia, however, is still ill-defined. From the literature, 10 cases did not have improvement of their neutrophilia with typical treatment of their MM; however, in 13 instances, neutrophilia did improve with treatment. It is important to note that cases in this literature review span decades and treatment of MM has, of course, progressed over that time with more efficacious therapies. Thus, lack of resolution of the neutrophilia in older reported cases should not be equated to evidence of concurrent CNL. Rather, the neutrophilia could be considered another indicator of MM disease status when it is a secondary paraneoplastic-type process as was evident in case 1 (Figure 5). Consequently, it should rise and fall with myeloma laboratory results according to the response to treatment. Thus, here we suggest an alternative to extensive and expensive workup to differentiate CNL from MM with neutrophilia in instances where that testing may be unattainable. These findings, while they may not exclude CNL based on WHO criteria, suggest more justifiable evidence for a paraneoplastic process of MM. However, should the patient have declining levels of serum immunoglobulins, M spike, and serum free light chains but sustained neutrophilia with treatment, this would suggest a concurrent primary neutrophilia. In that event, CSF3R mutation analysis would be indicated.

In regards to prognosis, from the 18 reported cases that did include outcome data, MM with reactive neutrophilia averaged a five-year survival representing a better prognosis than CNL, but a worse prognosis than MM alone [12-14]. This rasies the question of whether neutrophilia in MM patients, could be considered not only as an indicator of disease, but as a prognostic factor. In our presented cases, the first patient is still living after 5 years of diagnosis and the second, 9 years after diagnosis. While treatment has not resolved neutrophilia in either case, the otherwise normal kidney function and relatively asymptomatic disease correlates with better prognosis in patients with MM with neutrophilia compared to those with CNL as seen in our literature search. However, given the time span of the reviewed cases and the overall relatively low number of cases from which to draw conclusions, this is an area that could be further evaluated in future studies.


In bone marrow biopsies for neutrophilia, MM needs to be considered with specific immunohistochemical stains and/or ISH for plasma cells employed as they may be inconspicuous in a background of hyperplasia. Neutrophilia in the setting of MM appears to correlate with prognosis with differing reported survival rates for MM alone, MM with secondary neutrophilia, and MM with concurrent CNL. Neutrophilia can be considered an indicator of MM disease status when it is a secondary paraneoplastic-type process, presumably secondary to elevated G-CSF. Future studies may further assess the prognostic indications of this rare presentation of MM.

Conflicts of Interest

All authors declare there are no conflicts of interest to disclose.

Funding Sources

The authors received no financial support for the research, authorship, and/or publication of this article.


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