Humoral hypercalcemia of malignancy due to bipartite squamous cell/small cell carcinoma of the esophagus immunoreactive for parathyroid hormone related protein

Abstract

We report the case of a 63-year-old man who presented with weakness, fatigue, dehydration, confusion, abdominal pain, congestive heart failure and hypercalcemia. He expired and autopsy revealed an exulcerating carcinoma of the esophagus, invading the esophageal wall and metastasizing to the lungs, skin and lymph nodes. Histology demonstrated an epithelial tumor consisting of two components with transition between the two. One component was a keratinizing squamous cell carcinoma, whereas the other component consisted of pleomorphic small cells. The hypercalcemia was assumed to be due to parathyroid hormone related protein (PHRP), which was demonstrated by immunohistochemistry only in the pleomorphic small cells and not in the squamous cells. PHRP induced humoral hypercalcemia of malignancy is most often associated with squamous cell carcinomas. The finding that in our case, the pleomorphic small cell component was PHRP immunopositive and the squamous cell component showed no immunoreactivity, is intriguing and remains unexplained.