PTHrp is a normal gene product, which helps tooth eruption and mammary gland development. However, PTHrp production in an adult is mostly related to solid tumor malignancy. The homology of PTHrp to PTH from the 1st to 13th amino acids decided the similar mechanism of acting at PTH-1 receptor on increasing bone resorption and calcium reabsorption at the distal renal tubule. Lung cancer is known to secrete PTHrp and PTHrp secreting hepatic cellular carcinoma (HCC) is exceedingly rare. It’s only been documented in case reports. Two cases of PTHrp secreting atypical HCC are included in this case report.
67 year old with history of alcohol abuse with 17.8 x 8.8 cm mass in the left hepatic lobe presented with acute encephalopathy and calcium of 14.4 mg/dl. Patient was treated with zolendronic acid 4mg, IV fluid and calcitonin. Patient has a PTH level of 7 pg/ml and PTHrp level of 335 pg/ml. Bone turnover marker Beta crosslaps of 1595 pg/ml. 25-hydroxy vitD of 25 ng/ml and 1,25 dihydroxy vitD of 42 pg/ml. Liver biopsy demonstrated moderately differentiated hepatocellular carcinoma. The undifferentiated portion was positive with CD56, CAM 5.2 suggestive of neuroendocrine differentiation and epithelial lineage. Patient had negative metastatic bone scan and no pathologic fractures. Second case is a 63 year old male with NASH cirrhosis was admitted for hypercalcemia of 13.2 mg/dl. Patient was found to have metastatic atypical hepatocellular carcinoma and L4 vertebral lesion. PTHrp was 30 pg/ml and PTH 14 pg/ml. Bone turnover marker Beta crosslaps of 405 pg/ml. 25-hydroxy vitD of 48 ng/ml and 1,25 dihydroxy vitD of 9 pg/ml. Patient expired prior to biopsy.
4 cases of similar HCC were found in the literature. The treatment approach was resection of tumor, chemo or ablation. Hypercalcemia is controlled with reduction of the tumor burden and rarely by zolendronic acid alone. Both of presented cases were too advanced for surgery or chemo treatment. When tumor was not amendable for treatment, the hypercalcemia was not controllable long term. A small size study in japan administering 10mg alendronate via hepatic artery rather than IV route for patients with HCC showed enhancement of the apoptosis of HCC in addition to controlling hypercalcemia. An animal study on anti-PTHrp monoclonal murine antibody showed improved mortality of PTHrp producing pancreatic carcinoma (FA-6) in transplanted nude mice.
Most of the patients with PTHrp mediated hypercalcemia have advance cancer that is not amendable for surgery or chemotherapy. A non-invasive treatment approach other than alendronate should be investigated to control PTHrp mediated hypercalcemia.