Hypercalcemia associated with parathyroid hormone-related protein produced by B-cell type primary malignant lymphoma of the kidney

Abstract

A patient with primary non-Hodgkin's (B-cell type) lymphoma of the kidney developed hypercalcemia at the terminal stage of the disease. Although the plasma parathyroid hormone level was low, urinary cyclic AMP excretion was elevated. Serum osteocalcin (BGP) was suppressed and the plasma level of 1,25(OH)2D was within the normal range. Serum concentrations of PTH-related protein (PTHrP)-like immunoreactivity (PRP-LI) were elevated, and the tissue concentration of PRP-LI in the postmortem lymph node showed high level along with elevated serum PRP-LI, furthermore the production of PTHrP by the tumor was demonstrated by immunohistochemistry and Northern blotting analysis. These findings indicate that the hypercalcemia of the patient was caused by the PTHrP-producing B-cell lymphoma. Hypercalcemia was restored to normocalcemia by bisphosphonate treatment. Our case will add further information on humoral hypercalcemia in B-cell lymphoma, which rarely has been demonstrated to produce PTHrP.

Hypercalcemia and huge splenomegaly presenting in an elderly patient with B-cell non-Hodgkin's lymphoma: a case report

“…They also demonstrated the presence of immunoreactive PTHrP in the tumor extract and proved the bioactivity of the tumor extract producing C-AMP in osteoblasts. Since that time, a limited number of patients with hypercalcemic B-cell NHL secondary to PTHrP have been reported [6,8-15]. Table 2 shows the clinical and laboratory data of 10 such patients, including ours.…”

“…Uncontrolled synthesis of 1-25(OH) 2 D 3 as the etiology of hypercalcemia has also been described in patients with B-cell NHL [6,16-18]. …”

Vitamin D-Mediated Hypercalcemia in Lymphoma: Evidence for Hormone Production by Tumor-Adjacent Macrophages

“…The hypercalemia that is frequently associated with both Hodgkin's and non‐Hodgkin's lymphomas has been well documented in previous studies. ( 1–4 , 12–21 ) However, to date, studies have failed to fully define the precise basis for this abnormality. On the one hand, a significant number of reports have described an association with raised circulating levels of 1,25(OH) 2 D 3 , ( 4 , 12–18 ) similar to that observed with granulomatous diseases such as sarcoidosis.…”

“…( 3 ) On the other hand, several reports have highlighted a role for PTHrP as a lymphoma product that may or may not be linked to the vitamin D status of the host. ( 2 , 19–21 ) Despite this wealth of case reports, the key questions remain as to whether lymphoma‐associated hypercalcemia is caused by extrarenal 1α‐hydroxylase, and if so, what is the cellular source of this ectopic 1,25(OH) 2 D 3 . After the cloning of the gene for human 1α‐hydroxylase, ( 5–8 ) we have developed a polyclonal antiserum to the enzyme that has allowed us to define the immunlocalization of this enzyme in renal and extrarenal tissues.…”

Hypercalcemia in the Intensive Care Unit

“…In addition, lymphomas may occasionally secrete 1,25-dihydroxy vitamin D or PTH-related protein (PTHrP) resulting in hypercalcemia. [37][38][39][40] Cases of tumors producing PTH are only rarely reported in the medical literature.…”