A Rare Case of Bladder Cancer With Squamous Differentiation Causing Hypercalcemia and Leukocytosis

The most common cause of humoral hypercalcemia of malignancy is excessive secretion of parathyroid hormone-related peptide (PTHrP), which can include solid tumors, most commonly squamous cell carcinoma (SCC). It is unusual to see hypercalcemia associated with bladder cancer and local tumor-related secretion of PTHrP from SCC of the bladder. In addition to hypercalcemia, leukocytosis can be a concomitant neoplastic syndrome resulting from cytokine production of granulocyte colony-stimulating factor (G-CSF) from poorly differentiated cells. We discuss a case of a 62-year-old male who came to medical attention after a workup for weight loss, fatigue, and urinary retention revealed a new bladder mass, sepsis from a urinary source, and hypercalcemia. His hypercalcemia was initially managed with calcitonin, bisphosphonates, and intravenous (IV) fluids until surgery, after which the serum calcium briefly normalized and his leukocytosis reached its nadir. Pathology identified poorly differentiated SCC. However, due to the locally invasive nature of the tumor, he had an incomplete resection and experienced rebound hypercalcemia and worsening leukocytosis. This report highlights a rare case of poorly differentiated SCC of the bladder associated with the paraneoplastic syndrome of hypercalcemia and leukocytosis, both of which corresponded to poor prognosis. Managing PTHrP-mediated hypercalcemia requires both the correction of the immediate metabolic disturbance and treatment of the underlying malignancy; lastly, the persistent leukocytosis in this case was not associated with sepsis or infection and likely correlated with the incomplete eradication of the malignancy.