Hypercalcemia Caused by PTH-rP Associated with Lung Metastasis from Urinary Bladder Carcinoma: An Autopsied Case.

Abstract

Weanalyzed the parathyroid-related protein (PTH-rP) content in tissue specimens obtained from a 61-year-old manwith hypercalcemia associated with lung metastasis from urinary bladder carcinoma using radioimmunoassay and immunohistochemistry. Radioimmunoassayshowed that the PTH-rP content was higher in metastatic lung tumor tissue than in non-tumorous lung tissue. Immunohistochemicalanalysis revealed the presence of PTH-rPin tumor cells. Furthermore, proliferation of osteoclasts was found in bone marrowat autopsy. The results suggest that PTHrP induced humoral hypercalcemia of malignancy in a patient with urinary bladder cancer. (Internal Medicine 33: 673-676, 1994) Key words: humoral hypercalcemia of malignancy, metastatic tumor IntroductionThe hypercalcemia of malignancy maybe classified as either humoral hypercalcemia of malignancy (HHM)or local osteolytic hypercalcemia, depending on the etiology. Since Albright first proposed the clinical criteria for diagnosis of HHM(1), a number offactors that contribute to HHM, including parathyroidrelated protein (PTH-rP), transforming growth factors, prostaglandin E2, interleukin-1 , tumor necrosis factor (TNF)-a and TNF-B have been identified (2-6).PTH-rP contributes to the hypercalcemia found in patients with lung cancer (7), breast cancer, renal cancer (8), myeloma, and adult T-cell leukemia (9). The NH2-terminal regions of PTH-rP and parathyroid hormone are homologous (8, 10, 1 1). Both proteins, which have 34-amino acid NH2-terminals, have similar effects on renal and osteoblast cell membranes in vitro and on calcium and inorganic phosphate flux in vivo (12)(13)(14).Weperformed an autopsy in a patient who died of lung metastasis from urinary bladder carcinoma associated with hypercalcemia and investigated the presence of PTH-rP in cancer cells using radioimmunoassay (RIA) (15) and immunohistochemical studies. Case ReportA 61 -year-old Japanese man developed macrohematuria in March 1989. A cytoscopy revealed a tumor in the urinary bladder, which was hsitologically diagnosed as transitional cell carcinoma. In January 1990, he underwent total cystectomy. In October 1990, he complained of coughing and exertional dyspnea. A chest roentgenogram showed multiple tumors in the right lung field. Abronchofibroscopic examination showed that the bronchus of the right upper lobe was completely obstructed. A biopsy confirmed the presence of a pulmonary metastasis of transitional cell carcinoma of the urinary bladder. He underwent radiation therapy in November 1990. Radiation therapy (total 60 Gray) was administered to the right upper lung field. Radiation therapy improved atelectasis of the right upper lobe and eliminated the obstruction of the right upper bronchus. The patient was referred to our hospital on November7, 1992 for evaluation of dyspnea on exertion and fever. Onadmission, his temperature was 37.5°C, pulse rate 90/min, respiratory rate 1 8/ min, and blood pressure 122/60 mmHg.His performance status was grade 3. Physical examination revealed no masses in the head or ...

Humoral hypercalcemia of malignancy caused by renal pelvic urothelial carcinoma with broad squamous differentiation: An autopsy case

“…To our knowledge, autopsy was performed in only one previously reported case with HHM-related urothelial carcinoma. 4 In their report, multiple metastatic calcifications in the lungs and kidneys were observed as seen in the present case, however, there is no detailed description on the findings of vertebral bone. 4 Humoral hypercalcemia is also known to be caused by several signaling substances, other than PTH-rP.…”

“…4 In their report, multiple metastatic calcifications in the lungs and kidneys were observed as seen in the present case, however, there is no detailed description on the findings of vertebral bone. 4 Humoral hypercalcemia is also known to be caused by several signaling substances, other than PTH-rP. Asao et al reported a case of urothelial carcinoma and treatment-refractory hypercalcemia, possibly due to a serum elevation in 1,25 dihydroxy vitamin D produced by the tumor.…”

Mechanisms and treatment of hypercalcemia of malignancy

“…Hypercalcemia attributed to elevated concentrations of humoral PTHrP has been estimated to occur in 33-84% of breast cancers [33][34][35][36][37][38], 46-76% of lung cancers [35,36,38], 21-63% of non-Hodgkin's lymphomas (NHLs) [38][39][40] and 92% of adult T-cell leukemia/ lymphomas due to the human T-lymphotropic virus type 1 (HTLV-1) infection [39]. Infrequently, PTHrPmediated hypercalcemia occurs in head and neck tumors [41,42], renal cell carcinoma [43,44], bladder cancer [45], pancreatic carcinoma [46], hepatocellular carcinoma [47], carcinoid tumors [48] and melanoma [49].…”

Malignancy-related Hypercalcemia Caused by Metameric Cutaneous Metastasis of Parathyroid Hormone-related Protein-producing Bladder Carcinoma with Squamous Cell Differentiation: An Autopsy Case of Cobb Syndrome

“…PTHrP: parathyroid hormone-related protein, WBC: white blood cell, G-CSF: granulocyte colony-stimulating factor, F: female, M: male, SCC: squamous cell carcinoma, TCC: transitional cell carcinoma, AC: adenocarcinoma, CD: cancer death bladder cancer has been reported in spinal cord injury patients with recurrent urinary tract infections (17), and we speculate that this patient was also in an environment in which squamous cell carcinoma of the bladder was more likely to develop than chronic cystitis due to prolonged balloon retention from the development of rectovesical disorders caused by Cobb syndrome. Although PTHrP production has been reported in bladder cancer, most cases are from transitional epithelial carcinoma, and this is the fifth case of PTHrP-producing hypercalcemia in squamous cell carcinoma that we found reported (Table 2) (16,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31).In bladder cancer, PTHrP production as well as G-CSF production characterized by hyperleukocytosis has been reported (32).…”