Primary Pulmonary Squamous Cell Carcinoma Associated with Elevated IL-6, Leukocytosis, Hypercalcemia, Phagocytosis, Reactive Lymphadenopathy and Glomerular Mesangial Cell Proliferation via the Production of PTH-rP and G-CSF

Abstract

We report an autopsied case of a 74-year-old man with primary pulmonary squamous cell carcinoma (SCC) associated with leukocytosis, hypercalcemia, phagocytosis in the bone marrow, reactive lymphadenopathy and mesangial cell proliferation in the glomerulus. Laboratory examination revealed increased serum levels of parathyroid hormone-related peptide (PTH-rP), granulocyte colony stimulating factor (G-CSF), interleukin-6 (IL-6) and soluble interleukin 2 receptor (s-IL2R). An autopsy showed moderately differentiated SCC at the left lower lobe of the lung, of which tumor cells distinctly showed cytoplasmic immunoreactivity to anti-G-CSF and anti-PTH-rP antibodies. Thus, pulmonary SCC seemed to produce both G-CSF and PTHrP, causing leukocytosis, hypercalcemia, and IL-6 production from the bone. IL-6 also might have stimulated the proliferation of SCC and glomerular mesangial cells, and induced phagocytosis, reactive lymphadenopathy and hepatosplenomegaly by interacting with the mononuclear phagocytic system.

Primary squamous cell carcinoma of the stomach with paraneoplastic leukocytosis: a case report and review of literature

“…In some patients, the leukocytosis has an identifiable nonparaneoplastic etiology, most commonly infection, tumor necrosis, or glucocorticoid administration; none of these causes were identified in our patient. Leukocytosis with apparent expression of granulocytecolony stimulating factor (G-CSF) has been previously reported in SCC of the uterine cervix [10], urinary bladder [11], ureter [12], head and neck [13], and lung [14]. Although serum studies for elevated G-CSF were not performed in this case, it is likely that the gastric SCC was in some way associated with the patient's persistent leukocytosis given the rapid resolution after surgical removal of the neoplasm.…”

Systemic Leukocyte Alterations Are Associated With Invasive Uterine Cervical Cancer

“…Numerous reports demonstrate an association between high leukocyte counts and increased G-CSF expression and/or G-CSF serum levels in gastric, 27 pancreatic, 28 pulmonary, 29 renal, 30 and cervical carcinoma. In the latter, leukocyte counts and serum G-CSF levels returned to normal after radiotherapy.…”

A paraplegic patient with fever and leucocytosis: not always what it seems

“…This is caused by cancer cells producing PTH-rP with an almost identical structure to PTH, which is therefore able to bind bone and renal PTH-1 receptors. This enhances renal reabsorption and osseous release of calcium [10,11]. Besides the hypercalcaemia, PTH-rP might also be responsible for the leukocytosis and thrombocytosis.…”