Rapid progression of a granulocyte colony-stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: A case report and literature review

Abstract

Abstract. The current study presents the case of a 72-year-old woman with a rapidly enlarged liver metastasis from esophagogastric junction (EGJ) cancer, accompanied by progressive leukocytosis (47,680/µl) and elevated serum granulocyte colony-stimulating factor (G-CSF; 779 pg/ml). The patient underwent right hemihepatectomy 26 months after a total gastrectomy. On the seventh post-operative day the patient's leukocyte count and serum G-CSF level decreased to 4,280/µl and ≤19.5 pg/ml, respectively. Histologically, the lesion was a well to moderately differentiated adenocarcinoma similar to the primary lesion. Therefore, this tumor was clinically diagnosed as a G-CSF-producing liver metastasis from EGJ cancer, although immunohistochemical staining for G-CSF was negative. A right pulmonary nodule detected simultaneously with the hepatic mass was resected four months following the hepatectomy and was diagnosed as a pulmonary metastasis. The patient's leukocyte count was normal at the time of her initial surgery for EGJ cancer, and her clinical course varied for different metastatic sites. The liver metastasis was accompanied by progressive leukocytosis and elevated serum G-CSF and demonstrated rapid tumor growth during a six-month period, whereas the non-G-CSF-producing pulmonary metastasis grew slowly during the same period. In addition 21 reported cases of G-CSF-producing upper gastrointestinal tract cancer were reviewed to elucidate the clinicopathological features of this disease.

Paraneoplastic leukemoid reactions induced by cytokine-secreting tumours

“…Also, in tumours with multiple metastatic sites, CSF-secreting ability can be found in some metastatic sites while not found in the others. CSF-producing metastatic foci grow more rapidly than the non-CSF-producing metastatic foci of the same primary tumour 21. This can be explained by the phenomenon that CSF-secreting tumour cells can express CSF receptors on their cell membranes, which bind the same ligand that they secrete 11.…”

“…If the underlying malignancy is not clinically apparent, tumour-induced leukocytosis could easily be mistaken for infection or myeloproliferative neoplasm (MPN) 23. This, in turn, can lead to unnecessary diagnostic procedures, such as bone marrow aspiration and biopsy with extensive molecular and ancillary testing 4 15 21. The presence of fever can distract the treating clinician’s attention to pursue a diagnosis of infection instead of PLR as the cause of unexplained leukocytosis.…”

“…Tubal gut endoscopy and radiologic imaging are minimally invasive techniques that can be used 15. Also, since CSTs are metabolically active, they tend to have a high uptake on F-fluorodeoxyglucose positron emission tomography (FDG-PET), which is reported to be effective in localising the underlying malignancy and shortening the diagnostic delay 15–17 21. Due to CSF-induced myeloproliferation, FDG-PET can also show a high and diffuse avidity in the bone marrow, particularly in the axial skeleton 15 17…”

“…Some diagnostic criteria have been proposed to help establishing a diagnosis of PLR 14 15 21. These are1 a marked unexplained leukocytosis,2 increased plasma CSF level,3 a decrease in WBC count following therapy causing tumour burden reduction,4 confirmation of G-CSF production in the tumour by immunohistochemistry or immunofluorescence staining, and5 an increase in WBC count or CSF levels if subsequent tumour recurrence/relapse occurs.…”

“…Left shifted myelopoiesis with toxic granulation can be also seen (figures 3 and 4). 18 21 Erythroid precursors and megakaryocytes are usually unremarkable. The characteristic ‘dwarf’ megacaryocytes of CML are not seen.…”