Squamous cell carcinoma (SCC) of the lung is the type of lung cancer most commonly associated with hypercalcemia through the paraneoplastic production of parathyroid hormone-related peptide (PTHrP).
Pathophysiology
- PTHrP mimics the action of parathyroid hormone (PTH), leading to increased bone resorption and renal tubular reabsorption of calcium, resulting in hypercalcemia.
- This paraneoplastic syndrome is more frequently observed in SCC compared to other types of lung cancer, such as adenocarcinoma or small cell lung carcinoma (SCLC).
Diagnostic evaluation
- Diagnostic evaluation of hypercalcemia in the context of suspected lung cancer should include serum calcium levels, PTH levels, and PTHrP levels.
- Elevated serum calcium with low or normal PTH and elevated PTHrP levels support the diagnosis of PTHrP-mediated hypercalcemia.
- Imaging studies such as chest X-ray and computed tomography (CT) scans are essential for identifying the primary lung tumor and assessing its extent.
- Biopsy of the lung lesion, followed by histopathological examination, is necessary to confirm the diagnosis of SCC.
Management
- The mainstays of treatment for hypercalcemia of malignancy are IV hydration, bisphosphonates, calcitonin, denosumab, and in some patients, prednisone and cinacalcet
- Patients with underlying advanced kidney disease and refractory severe hypercalcemia should be evaluated for hemodialysis
In conclusion, SCC of the lung is the type of lung cancer most commonly associated with hypercalcemia through the paraneoplastic production of PTHrP. The diagnosis is supported by elevated serum calcium with low or normal PTH and elevated PTHrP levels. Management includes hydration, bisphosphonates, calcitonin, denosumab, prednisone, cinacalcet, and potentially hemodialysis in severe cases.