Osteosarcoma of the Humerus Developing as Second Malignancy in the Irradiation Field Outside the Primary Tumor: 11 Years after Ewing Sarcoma of the Scapula and 29 Years after Breast Cancer

Purpose: Development of sarcoma is a known late rare negative side effect of radiotherapy. We add two cases to emphasize the need for open-end follow-up and critical evaluation to avoid misinterpretation. Patients, Methods, and Results: Two patients developed osteosarcoma as a second malignancy in the humerus after adjuvant radiotherapy of a primary tumor not directly involving the later affected bone. The first patient had a Ewing sarcoma of the scapula at age 13 years. Though after neoadjuvant chemotherapy the resected specimen showed only fibrotic necrotic areas within clear resection margins, the study group indicated adjuvant radiotherapy in a field including the shoulder joint. At age 24 years she developed an osteosarcoma of the humeral head, which was resected and reconstructed with a proximal humerus endoprosthesis. She is alive without disease at age 32 years. The second patient presented with an osteosarcoma of the proximal humerus 29 years after irradiation for breast cancer including the shoulder joint. The sarcoma was misinterpreted as radiation-induced necrosis and the patient was treated with a reverse shoulder endoprosthesis. Pathologic examination of the resected humeral head then showed a typical osteosarcoma. Two years later the humeral reverse shoulder implant was resected and a proximal humerus tumor prosthesis implanted leaving the original glenosphere. Conclusions: In both cases radiation-induced osteosarcoma developed in bone not affected by the primary cancer. Protecting uninvolved structures must be warranted in the planning of radiotherapy. The long latency between the primary and second cancer mandates long-term—best indefinite—follow-up, as with appropriate treatment of a radiation-induced osteosarcoma good healing rates comparable to those of primary osteosarcoma can still be achieved.

Sporadic versus hereditary gastrinomas of the duodenum and pancreas: Distinct clinico-pathological and epidemiological features

Gastrinomas are defined as gastrin secreting tumors that are associated with Zollinger-Ellison syndrome （ZES）. ZES is characterized by elevated fasting gastrin serum levels, positive secretin stimulation test and clinical symptoms such as recurrent peptic ulcer disease, gastroesophageal reflux disease and occasional diarrhea. Genetically, nonhereditary （sporadic） gastrinomas are distinguished from hereditary gastrinomas, which are associated with multiple endocrine neoplasia type 1 （MEN1） syndrome. In general, duodenal gastrinomas are small and solitary if they are sporadic and multiple as well as hereditary. The sporadic gastrinomas occur in the duodenum or in the pancreas while the hereditary gastrinomas almost all occur in the duodenum. Our series of 77 sporadic duodenal neuroendocrine tumors （NETs） includes 18 patients （23.4%） with gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET archives of the departments of pathology in Zürich, Switzerland, and Kiel, Germany, 24 patients （4.5%） suffered from sporadic pancreatic gastrinomas and ZES. These NETs have to be distinguished from tumors with immunohistochemical positivity for gastrin but without evidence of ZES. An additional 19 patients suffered from MEN1 and ZES. These patients showed exclusively duodenal gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1- associated duodenal gastrinomas is better than that of pancreatic gastrinomas, since they progress slowly to liver metastasis. In summary, sporadic and MEN1- associated gastrinomas in the duodenum and pancreas show different clinico-pathological and genetic features. The incidence of sporadic duodenal gastrin-producing tumors is increasing, possibly due to optimized diagnostic procedures. In contrast, pancreatic MEN1- associated gastrinomas seem to be extremely rare. A considerable subset of tumors with immunohistochemical expression of gastrin but without evidence of ZES should be designated as functionally inactive NETs expressing gastrin, but not as gastrinomas.