Paraneoplastic leukemoid reaction – poor prognostic marker in urothelial bladder carcinoma

Discussion

We report here on the rare occurrence of PLR in a urothelial bladder cancer. Several mechanisms have been proposed to explain the pathophysiology of PLR. The levels of IL-1[alpha and beta], IL-3, G-CSF, GM-CSF, IL-6, and TNF-[alpha] have all been reported to be elevated in various solid tumors and suggested to contribute to an elevated leukocyte count.³ With previous reports that receptors for G-CSF have been found on cell surfaces of several nonhematopoietic cell types, Tachibana and Murai have proposed the mechanism of a cancer cell’s simultaneous acquisition of the ligand promotion and its receptor expression conferring an autocrine growth advantage.⁴ They have also reported on the capability of bladder cancer cells to induce a leukemoid reaction in their host through the stimulation of leukocyte production, which has been associated with aggressive tumor cell growth and a poor clinical outcome. In addition, He and colleagues have also described the correlation between PLR and high degree of malignancy, high probability of metastasis, recurrence, and poor prognosis.⁵

We observed the leukocytosis of 70 x 10³ cells/mm³ on the day of resection with a slight drop postoperatively, peaking at 161.5 x 10³ cells/mm³ less than a month after resection of the tumor. There is no clear understanding of the cause of the persistent and rapid progression of leukocytosis seen in this patient postoperatively. There is also a dearth of literature describing similar occurrences, with even fewer attempting to explain the pathophysiology of this occurrence.

When faced with similar occurrences in patients, clinicians usually treat for occult infection. Once infections and myeloproliferative diseases have been ruled out, clinicians may consider obtaining a patient’s serum G-CSF level or performing an immunohistochemistry analysis of urothelial cells for overexpression of G-CSF, when available.⁵ However, despite any efforts to diagnose earlier, there is little clinicians currently have to offer these patients as treatment.

As presented in this report, PLR portends a worse prognosis for patients because of its ability to not only masquerade as an infection leading to a delay in the proper treatment, but also because of its association with a more aggressive tumor cell behavior and growth, making it critically important for clinicians to be able to identify these patients early on. With further investigation into immune regulation and G-CSF receptor signaling, there may be future discoveries of novel methods to diagnose this condition and also advancements in the treatment options made available to these patients.