Granulocyte-colony stimulating factor producing cervical cancer with elevated levels of parathyroid hormone-related protein: a case report and literature review

Abstract

Systemic effects associated with hormones and cytokines secreted by tumor cells can cause paraneoplastic syndrome. Leukemoid reactions and hypercalcemia are relatively common manifestations of paraneoplastic syndrome. Here, we describe the case of a 90-year-old woman who presented with leukocytosis and hypercalcemia and was diagnosed with granulocyte-colony stimulating factor (G-CSF)-producing cervical cancer with elevated levels of parathyroid hormone-related protein (PTHrP). The patient visited our hospital complaining of general fatigue and anorexia. On admission, she presented with marked leukocytosis, hypercalcemia, and an increase in C-reactive protein level. On the basis of abdominal magnetic resonance imaging and histopathological examination, the patient was diagnosed with cervical cancer. Additional tests confirmed elevated plasma levels of G-CSF, PTHrP, and serum interleukin-6. Immunostaining of pathological specimens of the uterine cervix showed expression of G-CSF in tumor cells. The patient was diagnosed with G-CSF-producing cervical cancer accompanied by elevation of PTHrP levels. As a treatment for hypercalcemia, discontinuation of oral vitamin D derivative and administration of saline and elcatonin were ineffective, and therapeutic intervention with zoledronic acid hydrate was required. Considering the patient's advanced age, surgical resection of cervical cancer was not performed. She died from congestive heart failure approximately 3 months after hospitalization. This case was indicated to be a paraneoplastic syndrome in which G-CSF and PTHrP-induced leukocytosis and hypercalcemia. To the best of our knowledge, there have been no reports of G-CSF-producing cervical cancer with elevated PTHrP levels, and our case is the first report.

Keywords: Cervical cancer; Granulocyte-colony stimulating factor; Hypercalcemia; Paraneoplastic syndrome; Parathyroid hormone-related protein.

Fig. 1

Magnetic resonance imaging of the uterus. a T2-weighted fat-suppressed image showed diffuse thickening of the uterus. Arrows indicate the uterus. b The diffusion-weighted image revealed a diffuse high signal of the uterus

Fig. 2

Histopathological findings of the cervix. a Necrotic findings are observed in cervical tissue. Hematoxylin and eosin (HE) staining, original magnification 100 × . Scale bar = 200 μm. b Arrow heads indicate squamous cell carcinoma of the cervix, showing multinucleated cell morphology. HE staining, original magnification 400 × . Scale bar = 50 μm

Fig. 3

Immunostaining of the cervix with antigranulocyte colony stimulating factor (G-CSF) antibody [CSF3/3166R] (Abcam, United Kingdom). a The expression of G-CSF (dark brown area) is observed in the cervical specimen. Original magnification 100 × , Scale bar = 200 μm. b Cervical tumor cells are strongly stained. Original magnification 200 × , Scale bar = 100 μm

Fig. 4

Clinical course in this case. The antibacterial drug was ineffective and leukocytosis persisted. Hypercalcemia was refractory to the withdrawal of vitamin D derivative and administration of saline and elcatonin. Bisphosphonate (zoledronic acid hydrate) was effective and normalized the corrected calcium level