BACKGROUND: Humoral hypercalcemia of malignancy (HHM) is a rare presentation of cholangiocarcinoma, with few reports in prior literature. HHM is due to the production of parathyroid hormone related peptide (PTHrP) from malignant tissues leading to hypercalcemia, often hard to control. Currently, HHM due to cholangiocarcinoma has been associated with poor prognosis and therapies utilized to manage HHM have not been shown to increase survival. Furthermore, biomarkers such as cytokeratin-7 (CK7) have been shown to correlate with worse prognosis in cholangiocarcinoma. While surgical treatment can be curative for cholangiocarcinoma, current nonsurgical treatment options for HHM due to cholangiocarcinoma have not been associated with improved prognosis. CASE DESCRIPTION: We present a rare case of HHM secondary to cholangiocarcinoma. This case presents a rare case of HHM due to cholangiocarcinoma with an atypical presentation in a 55-year-old female. This patient presented with abdominal swelling and severe hypercalcemia prompting evaluation for a possible gastrointestinal source and was found to have HHM due to cholangiocarcinoma. She was treated for her hypercalcemia medically, however due to the extent of her disease she was unable to undergo surgery. Chemotherapy was not considered during her initial presentation as she originally had a malignancy of unknown primary. Ultimately, shortly after her initial presentation, the patient passed at another hospitalization 36 days after her initial presentation. CONCLUSIONS: HHM rarely presents in cholangiocarcinoma, and of the reported cases, it is often associated with poor prognosis. Given the complexity of these cases, a multi-disciplinary approach is necessary for optimal management of these patients. The ability to risk-stratify patients with unique presentations such as this is crucial for accurate diagnosis and potential treatment. HHM in cholangiocarcinoma is poorly studied due to its rarity
however, given the prognosis of this syndrome, further research is essential for earlier detection and better treatments.