A WBC count exceeding 50,000/mm
3 associated with extramedullary causes is termed a LR. It results in a severe left shift with the presence of immature myeloid cells in the peripheral blood [
1]. Experts now agree that it is not essential the WBC count exceeds 50,000/mm
3 to be diagnose LR; counts beyond the normal upper limit (4000-10,000/mm
3) are sufficient [
1]. Some of these cases have been misdiagnosed as acute leukaemia due to the severe elevation in the WBC count. However, leukaemia commonly presents with anaemia and immature myeloid cells on a peripheral blood smear, and bone marrow biopsies typically show hypercellularity. [
2,
9] The evidence is available directly by bone marrow biopsy and by an inverse correlation between tumour response and leucocytosis, as well as an increased PLR [
10]. LR typically presents with elevated levels of mature polymorphonuclear cells and immature cells of granulocyte lineage on peripheral smears. Leucocyte alkaline phosphatase is typically normal or elevated in LR. Leucocytosis is a typical response to infections, drugs, chromosomal abnormalities, and paraneoplastic phenomen [
11]. LR can also be a paraneoplastic manifestation of several cancers [
3]. In solid tumours, LR can be caused by an increased granulocyte colony stimulating factor or other growth factors including granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6), which is thought to be produced by malignant cells of the cervix, pancreas, hepatocellular carcinoma, and lung cancer [
3]. In the normal physiologic state, GM-CSF can stimulate proliferation and differentiation of neutrophil colony-forming cells. GM-CSF can also alter several functions of mature neutrophils [
12]. During LR, over-expression of GM-CSF is associated with subsequent leucocytosis [
13]. Mari K et al. reported a patient with esophageal squamous cell carcinoma (ESCC) with remarkable leucocytosis and high G-CSF levels [
14]. ESCC is a disease with a poor prognosis, and the prognosis of ESCC with LR is considered even poorer [
14]. Shun et al. also reported a case of aggressive G-CSF producing ESCC with increased WBC, and neutrophil counts, and increased C-reactive protein(CRP) [
15]. The counts of WBC and neutrophils, and serum CRP levels may be markers of its progression. The neutrophil counts are especially important as a marker of progression [
15]. Antoine et al. reported that leucocytosis and neutrophilia were independent prognostic factors of poor overall survival (OS), progression free survival (PFS), and locoregional control (LRC) in patients with locally advanced ESCC undergoing exclusive chemoradiation [
16]. Animal experiments have demonstrated that IL-6 can sustain neutrophil/macrophage colonies in vivo, and IL-6 can act on other immune cells, which may induce the production of several CSFs by the bone marrow [
17]. Due to the rarity of PLR, studies on this disease have been very limited. HurtadoCordovi J et al. reported that only 77 (10%) among 758 patients who had solid tumours with hyperleukocytosis in their cohort had PLR [
18]. The prognosis of patients with PLR is poor. According to a review, 78% patients died within 12 weeks of the first detection of hyperleukocytosis; only 10% of patients were observed to survive more than 1 year after successful treatment of the malignancy. Owing to the poor prognosis of patients with PLR, it is essential to rule out life-threatening causes prior to making a diagnosis of PLR. In terms of early diagnosis and subsequent disease management, staining for GM-CSF early in the course of the disease may provide valuable information. Treatment strategies are limited in patients with PLR, and these are rarely reported in the literature. The effective treatment for leucocytosis is removal of the inciting tumour. Unfortunately, extirpation is not always definitive [
19]. In a retrospective, single-institution study, Granger and Kontoyiannis reported that patients with PLR who survived longer than 1 year had received effective antineoplastic therapy, chemotherapy, or surgery [
20]. Moreover, it has been reported that 78% of patients either died or were discharged to hospice within 12 weeks of their initial extreme leucocyte count findings [
21]. Here, we report a case of esophageal adenocarcinoma with an abnormal haematological picture dominated by LR. Our patient, underwent radical esophagectomy. Postoperatively, his WBC counts decreased to normal values, and he has been free of recurrence for 6 months.
In conclusion, an accurate and timely diagnosis of LR associated with esophageal adenocarcinoma and appropriate treatment strategies can improve the prognosis of patients with this rare condition.