My elderly patient has a WBC count of 60,000 without obvious hematologic malignancy.  How likely is it that his leukocytosis is related to an infection?

Although extremely high WBC count in the absence of myeloproliferative disease may be associated with solid tumors and other causes, infections are often the most common cause of leukemoid reaction (LR), including tuberculosis, Clostridiodes difficile colitis, shigellosis, salmonellosis, pneumonia, abscesses, as well as  parasitic infections (eg, malaria), fungal infections (mucormycosis), and viral diseases (eg, HIV, EBV, Chickungunya fever).1-4   

In a study of 173 hospitalized patients (mean age 69 y) with leukemoid reaction (defined in this study as WBC ≥30,000/µl), infection was the most common cause of LR (48%), followed by tissue ischemia/stress (28%), inflammation (eg, pancreatitis, diverticulitis without perforation) and obstetric diagnoses (7% each) and malignant tumor (5%).1 

In the same study, the most common infections were “sepsis”, pneumonia and urinary tract infections.  Bacteremia was documented in 13%, while Clostridiodes difficile toxin assay was positive in 7% of patients.  The highest WBC counts were observed in patients with either a positive blood culture or positive C. difficile toxin.  In-hospital mortality rate was very high at 62%.

Similarly, in a study involving 105 hospitalized patients, the most common cause was infection, followed by malignancy and other causes. 2 In a smaller study of 25 patients with “extreme” leukocytosis (defined as WBC ≥50,000/µl) infection was considered the cause in 52% and malignancy in 44% of patients; about one-third were bacteremic (eg, Pseudomonas sp, Streptococcus pneumoniae, E. coli).3

Bonus Pearl: Did you know that besides infections and malignancy, drugs (eg, corticosteroids, epinephrine) and ingestion of ethylene glycol have also been associated with LR? 1,3,4

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References

  1. Potasman I, Grupper M. Leukemoid reaction:Spectrum and prognosis of 173 adult patients. Clin Infect Dis 2013;57:e177-81. https://pubmed.ncbi.nlm.nih.gov/23994818/
  2. Portich JP, Faulhaber GAM. Leudemoid reaction: A 21st-century study. https://pubmed.ncbi.nlm.nih.gov/31765058/
  3. Halkes CJM, Dijstelbloem HM, Eelman Rooda SJ, et al. Extreme leucocytosis: not always leukaemia. The Netherlands J Med 2007;65:248-51. https://pubmed.ncbi.nlm.nih.gov/17656811/
  4. Kumar P, Charaniya R, Sahoo R, et al. Leukemoid reaction in Chickungunya fever. J Clin Diagn Res 2016;10:OD05-OD06. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948452/

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My elderly patient has a WBC count of 60,000 without obvious hematologic malignancy.  How likely is it that his leukocytosis is related to an infection?

My patient with metastatic lung cancer has a WBC count >20,000 without an obvious cause. Can it be related to the cancer?

Absolutely! Although tumor necrosis may be associated with mild to moderate leukocytosis, another explanation for a rise in WBC count (particularly when “leukemoid” like) in patients with cancer may be related to granulocyte colony-stimulating factor (G-CSF) production by the neoplasm itself.  

In vivo production of G-CSF by bladder cancer was reported over 25 years ago in a patient with marked leukocytosis (>100,000)1.  Subsequently, numerous G-CSF-producing tumors have been reported, including those associated with the genitourinary  tract (eg, bladder, ureter, prostate), lung, gynecological organs, gallbladder, stomach, esophagus, small intestine, pancreas, mesothelioma, thyroid, and myeloma2.

 In most cases, G-CSF-producing tumors are advanced with very poor prognosis 2.  Although the mechanism underlying a link between G-CSF production and tumor progression is unclear, a direct action on GCSF receptors of tumor cells, formation of more aggressive cancer cells,  and changes in  the function of T-cells and endothelial cells that may enhance tumor growth have been postulated2.

 

References

  1. Ito N, Matsuda T, Kakehi Y, et al. Bladder cancer producing granulocyte colony-stimulating factor. N Engl J Med 1990;323:1709-10. http://www.nejm.org/doi/pdf/10.1056/NEJM199012133232418
  2. Yamano T, Moril E, Ikeda J-I, Aozasa K. Granulocyte colony-stimulating factor production and rapid progression of gastric cancer after histological change in the tumor. Jpn J Clin Oncol 2007;37:793-796. https://academic.oup.com/jjco/article/37/10/793/831502
My patient with metastatic lung cancer has a WBC count >20,000 without an obvious cause. Can it be related to the cancer?