Squamous cell carcinoma of mandibular gingiva producing both parathyroid hormone- related protein and granulocyte colony-stimulating factor: a case report

Background: Malignant tumours occasionally secrete hormonal factors that can cause tumour-associated symptoms. Here, 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). Case presentation: 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. The postoperative TMN classifications were pT4aN2bM0 and Stage IV. 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. CCRT was scheduled for 66 Gy of irradiation; however, irradiation was terminated at 50 Gy because CT performed 4 weeks after the start of CCRT showed rapid disease progression, including enlargement of the primary tumour and metastases to the vertebral bone, lungs, liver, and kidneys. Chemotherapy was initiated with pembrolizumab, fluorouracil, or cisplatin. However, four weeks after the start of chemotherapy, a CT scan showed increased metastases and pleural dissemination; therefore, chemotherapy was discontinued, and the patient was transferred to palliative care. One week after the chemotherapy was discontinued, the patient died of respiratory failure. Conclusions: In this case, G-CSF and PTHrP derived from mandibular gingival carcinoma were considered to have caused leukocytosis and hypercalcaemia.