Hypercalcemia is uncommon in lymphoma, it is generally a feature of histologically high grade disease with other aggressive clinical features, such as the presence of B symptoms and an elevated lactate dehydrogenase (LDH). The mechanism of hypercalcaemia is unknown but there is strong evidence for humoral factors that may or may not be related to parathyroid hormone (PTH).
Case: A 92-year-old lady who was found to have incidental hypercalcaemia (calcium 2.603.50 mmol/l) on routine testing and was relatively asymptomatic at presentation. Imaging revealed the presence of widespread lymphadenopathy and histology confirmed a low grade B-cell non-Hodgkins lymphoma. She had no B symptoms and her LDH was not elevated. Calcium levels failed to come down on initial hydration and repeated bisphosphanate therapy. Further investigations were carried out to exclude other causes and these came as negative except raised PTH levels of 34 pl/l (918 pl/l). This was further investigated with sestamibi and parathyroid USS showed no evidence of parathyroid pathology. Chemotherapy was not immediately initiated, as this was a histologically low-grade disease with no B-symptoms, but was later initiated due to the refractory hypercalcaemia. The patient was treated with ritxuimab and oral chlorambucil. She was also given calcimimetics (cinacalcet) until further evaluation with PTH-related protein (PTHrP) levels. Cinacalcet was discontinued soon due to lack of response on maximum dose. Afterwards patient was commenced on steroids and chemotherapy was continued to complete 6 full cycles. Subsequently, calcium came down to normal levels and repeat imaging with PET/CT confirmed a complete metabolic remission.
This is a very rare case of refractory hypercalcaemia secondary to malignancy, which failed to respond to initial and more advanced treatment with calcimimetics but responded to steroids/chemotherapy. PTHrP levels are provisionally reported as undetectable but concomitant administration of cinacalcet affects the PTHrP levels that can give false negative results.