Hypercalcemia, Staghorn Calculus and Xanthogranulomatous Pyelonephritis: A Diagnostic Challenge Unmasking Metastatic Urothelial Carcinoma

Xanthogranulomatous pyelonephritis (XGP) is a rare, chronic inflammatory renal condition often associated with urinary tract obstruction, nephrolithiasis, and recurrent infection. Diagnostically, it can mimic malignancy on both clinical presentation and imaging. A 65-year-old woman presented with a three-week history of abdominal pain, fever, and giddiness. Cross-sectional imaging demonstrated a left staghorn calculus with hydronephrosis and features consistent with XGP and pyonephrosis. She underwent urgent percutaneous nephrostomy (PCN) with drainage of purulent material. During admission, she developed acute confusion and was found to have severe hypercalcemia (albumin-corrected calcium 3.7 mmol/L) with suppressed parathyroid hormone (PTH) and elevated parathyroid hormone-related protein (PTHrP). Positron emission tomography (PET)-CT imaging revealed widespread fluorodeoxyglucose (FDG)-avid lesions involving the left kidney, para-aortic lymph nodes, lungs, myocardium, and rectum. These findings were collectively worrisome for either disseminated infection or underlying malignancy. Tissue biopsy of a para-aortic lymph node demonstrated poorly differentiated metastatic carcinoma with squamous differentiation, ultimately establishing the presence of metastatic urothelial carcinoma, with involvement of the left kidney, lymph nodes, and lungs. The patient was referred for palliative systemic chemotherapy. This case illustrates the complex interplay of multiple pathologies: Staghorn calculi not only leads to complications such as XGP and obstructive pyonephrosis, but is also associated with urothelial carcinoma. Through production of PTHrP, humoral hypercalcemia of malignancy further propagates nephrolithiasis. The case highlights the diagnostic challenge of distinguishing XGP and its infective complications from urological malignancy, and underscores the critical role of PTHrP in prompting evaluation for occult malignancy. Maintaining diagnostic vigilance is crucial, given the possible co-existence of multiple pathologies.