Humoral Hypercalcemia of Malignancy with a Parathyroid Hormone-Related Peptide-Secreting Intrahepatic Cholangiocarcinoma Accompanied by a Gastric Cancer

Abstract

Humoral hypercalcemia of malignancy (HHM) is caused by the oversecretion of parathyroid hormone-related peptide (PTHrP) from malignant tumors. Although any tumor may cause HHM, that induced by intrahepatic cholangiocarcinoma (ICC) or gastric cancer (GC) is rare. We report here a 74-year-old male who displayed HHM with both ICC and GC and showed an elevated serum PTHrP level. Treatment of the hypercalcemia with saline, furosemide, elcatonin, and zoledronic acid corrected his serum calcium level and improved symptoms. Because treatment of ICC should precede that of GC, we chose chemotherapy with cisplatin (CDDP) and gemcitabine (GEM). Chemotherapy reduced the size of the ICC and decreased the serum PTHrP level. One year after diagnosis, the patient was alive in the face of a poor prognosis for an ICC that produced PTHrP. Immunohistochemical staining for PTHrP was positive for the ICC and negative for the GC, leading us to believe that the cause of the HHM was a PTHrP-secreting ICC. In conclusion, immunohistochemical staining for PTHrP may be useful in discovering the cause of HHM in the case of two cancers accompanied by an elevated serum PHTrP level. Chemotherapy with CDDP and GEM may be the most appropriate treatment for a PTHrP-secreting ICC.

Combined Hepatocholangiocarcinoma Associated with Humoral Hypercalcemia of Malignancy and Chronic Inflammatory Demyelinating Polyneuropathy

“…As shown in studies investigating the prevalence and prognosis of different paraneoplastic syndromes in HCC, HHM can be found in 4-8% of HCC [4]. HHM has rarely been reported in patients with cholangiocarcinoma (CC) and represents a marker of poor prognosis of the disease [5–9]. CHCC is a rare tumor with poor prognosis, with incidence ranging from 1.0% to 4.7% of all primary hepatic tumors [10].…”

Recurrent distal cholangiocarcinoma and humoral hypercalcemia of malignancy: report of a rare case and literature review

“…Therefore, these patients were excluded from the assessment of PTHrP concentration. In addition, patients for whom survival times were not reported or who were still alive at the time of publication were excluded from the assessment [4,16,17,20,21,25,26].…”

Roles of Parathyroid Hormone-Related Protein (PTHrP) and Its Receptor (PTHR1) in Normal and Tumor Tissues: Focus on Their Roles in Osteosarcoma

“…Furthermore, Danilin et al ( 89 ) showed that the mRNA-binding protein HuR is involved in increased expression of PTHrP and in mRNA stabilization in CCRC. A number of case studies reported a strong expression of PTHrP in pancreatic adenocarcinoma ( 90 ), intrahepatic cholangiocarcinoma ( 91 ), pancreatic neuroendocrine cancer and that PTHrP levels were elevated in the patient serum ( 92 ).…”