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.

Non-metastatic squamous cell carcinoma in two Hermann’s tortoises (Testudo hermanni)

“…Squamous cell carcinomas (SCC) are rarely reported to occur in the order testudines. Two reports identified this neoplasm in testudinidae (tortoises): A Brazilian giant tortoise (Geochelone denticulata) 12 and a Hermann's tortoise (Testudo hermanni) [13][14][15] whereas eight cases of squamous cell carcinomas were described in turtle species others than testudinidae: An Indian black turtle (Melanochelys trijuga), 11 an European pond turtle (Emys orbicularis), 7 an Eastern box turtle (Terrapene carolina), 8 a Red-eared slider (Trachemys scripta elegans), 12 a Common snake-necked turtle (Chelodina longicollis), a Spiny soft shell turtle (Apalone spinifera spinifera) 10 and two Loggerhead sea turtles (Caretta caretta). 9 The neoplasm appeared at different locations, mostly the skin 10,11 but also included the oral cavity 12 and the coelom.…”

“…HHM is caused by de novo secretion of parathyroid hormone-related protein (PTHrP) by the tumor cells or thought to be associated with tumor induced osteolysis. 14 The present case report describes two cases of SSC in Hermann's tortoises without metastatic spread but in one case with clinical and pathologic lesions similar to HHM in mammals.…”

Esophageal carcinoma with humoral hypercalcemia and leukocytosis successfully treated by a two-stage operation: report of a case

“…Another possible reason for the successful outcome in this case was the fact that the patient was almost completely free from any typical symptoms of hypercalcemia. Because impaired general condition in patients with esophageal carcinoma with hypercalcemia and leukocytosis has been reported to be mainly caused by hypercalcemia [3][4][5][6][7][8], the absence of such symptoms of hypercalcemia in our case is thus considered to have played a major role in the patient's relatively good preoperative condition. Even though such a patient suffers from esophageal carcinoma with humoral hypercalcemia and leukocytosis but without a giant metastatic lesion, it might be better to consider a two-stage operation, consisting of a curative resection in the first stage and a subsequent reconstruction procedure in the second stage, to reduce the risk of postoperative complications.…”

“…Esophageal carcinoma complicated with both hypercalcemia and leukocytosis is very rare, and to our knowledge, there have been only six such reported cases to date (Table 1) [3][4][5][6][7][8], five of whom were Japanese patients. The majority of such patients tend to demonstrate an advanced stage of cancer, impaired general condition, and a poor prognosis.…”

“…The simultaneous production of PTHrP and G-CSF in esophageal carcinoma is very rare, and only six such cases have been reported to date [3][4][5][6][7][8]. Most cases of esophageal carcinoma with hypercalcemia and leukocytosis show severe inflammatory response, rapid tumor growth, poor general condition, and resistance to chemotherapeutic drugs.…”