Squamous Cell Carcinoma of Mandibular Gingiva Producing Both Parathyroid Hormone-related Protein and Granulocyte Colony-stimulating Factor: a Case Report

We describe a case of mandibular gingival carcinoma with hypercalcaemia and leukocytosis caused by tumour-derived parathyroid hormone-related protein (PTHrP) and granulocyte colony-stimulating factor (G-CSF). A 54-year-old man presented to our Department of Oral and Maxillofacial Surgery with a chief complaint of a left-sided mandibular gingival ulcer. A 42 mm × 20 mm sized ulcer was found on the left lower molar gingiva. Squamous cell carcinoma was pathologically diagnosed. The patient underwent a hemimandibulectomy, left-sided radical neck dissection, plate reconstruction, pectoralis major musculocutaneous flap reconstruction, and tracheostomy under general anaesthesia. Pathologically, two metastatic lymph nodes were identified. Residual tumour was suspected at the resection margins. Eight weeks after surgery, the patient started postoperative concurrent chemoradiotherapy (CCRT). Two weeks after CCRT, the patient developed hypercalcaemia. Serum levels of PTHrP and G-CSF increased in parallel with the progression of hypercalcaemia and leukocytosis. Immunohistochemical analysis of the surgical specimen showed positivity for G-CSF. Based on these clinical and pathological findings, the patient was diagnosed with hypercalcaemia and leukocytosis associated with malignancy and was treated with denosumab. Irradiation was terminated at 50 Gy because CT showed rapid disease progression. Chemotherapy was initiated, however, four weeks after the start of chemotherapy, a CT scan showed increased metastases and pleural dissemination. Therefore, chemotherapy was discontinued. One week after the chemotherapy was discontinued, the patient died of respiratory failure.