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We report a case of humoral hypercalcemia associated with a rapidly growing gastric carcinoma. To our knowledge, this is the first such case of gastric carcinoma reported with raised plasma parathyroid hormone related peptide (PTHrP) and absent bone metastases.
A 69 year old woman presented with fatigue and intermittent sharp epigastric pain for one week. Upper gastrointestinal radiographs and endoscopy demonstrated a necrotic, friable mass in the mid stomach. Biopsy of the mass and a surrounding satellite polypoid lesion showed poorly differentiated adenocarcinoma and gastric adenoma with high grade dysplasia, respectively (fig 1). Four weeks after the first symptoms had arisen the liver edge was palpable 3 cm below the costal margin. Computed tomographic scan of the abdomen demonstrated several hypodense lesions in the liver and aortic adenopathy compatible with metastases. The following results were found: haematocrit, 0.24; white blood cell count, 12.7 × 109/litre; platelets, 460 × 109/litre; calcium, 2.54 mmol/litre; albumin, 31 g/litre; international normalised ratio, 1.2; alkaline phosphatase, 1075 units/litre, alanine amino transferase, 16 units/litre; total bilirubin, 10.26 μmol/litre; lactate dehydrogenase, 1765 units/litre; carcinoembryonic antigen, 327 μg/litre; ferritin, 302 μg/litre; Fe, < 2 μmol/litre; and total iron binding capacity, < 21 μmol/litre. Chest x ray was negative. Two weeks later the patient developed mental confusion and dehydration. Serum calcium was 2.8 mmol/litre, phosphorus 0.5 mmol/litre, and albumin 26 g/litre. With intravenous hydration and pamidronate (90 mg), serum calcium rapidly became normal and the patient's mental status returned to baseline. Neither radionuclide bone scan nor magnetic resonance scan of the brain suggested metastases. The intact PTH (IRMA; Nichol's Institute) was 6 ng/litre (normal, 10–65). However, PTHrP (1-40 IRMA; Nichols Institute) was 5.4 pmol/litre (normal < 1.3). The patient died of progressive liver failure three weeks later.
Hypercalcaemia is rarely associated with gastric cancer. In the literature, two cases of gastric adenocarcinoma with hypercalcaemia have been reported in which the tumour cells expressed PTHrP.1,2 In both cases, bone metastases were present and plasma PTHrP values were not reported. Alipov et al found that PTHrP was expressed on tumour cells in 71 of 92 patients with gastric adenocarcinoma, none of whom had humoral hypercalcaemia.3 PTHrP expression in the tumour tissue was strongly associated with poorly differentiated cancers (34 of 34) as opposed to well differentiated ones (10 of 23). Normal gastric mucosa and adenomas did not express PTHrP. Our case is consistent with the findings of Alipov et al because cancer cells expressed PTHrP, whereas adenoma did not (fig 1). Our case is notable for rapid clinical deterioration coupled with raised tissue and plasma PTHrP. These results suggest that PTHrP expression is associated with poor prognosis in gastric cancer. Whether PTHrP plays a direct role in cancer progression4 or is a byproduct of oncogene activation (for example, ras and src5) remains to be determined.