A Head and Neck Sarcoma Registry was established by the Society of Head and Neck Surgeons to review treatment results of a rare tumor by surgeons with special interest in this anatomic site. Two hundred fourteen patients were analyzed. There were 194 adult tumors and 20 pediatric tumors. The major sites included parotid and neck, 20%; face and forehead, 18%; maxilla and palate, 13%; scalp, 12%; mandible, 11%; paranasal sinuses, 7%; larynx, 2%; and oral cavity, 5%. Eighty-four percent were resectable. The disease-free survival was 56%; overall survival was 70% at 5 years. Major determinants of survival were adequacy of resection (margins free of tumor) and tumor type. Survival differed according to tumor cell type (tumor grade was not available). Patients with chondrosarcoma and dermatofibrosarcoma had survival approaching 100%. Patients with malignant fibrous histiocytoma (MFH) and fibrosarcoma (FSA) had intermediate survival of 60% to 70%. The worst survival, less than 50% at 5 years, occurred in patients with osteosarcoma, angiosarcoma, and rhabdomyosarcoma in decreasing order. This suggests a rationale for identifying high-risk patients for prospective adjuvant protocols. This study emphasizes the value of recording uncommon tumors to provide relevant information for future study and possibly therapy.

We have previously shown that Wnt5A and ROR2, an orphan tyrosine kinase receptor, interact to mediate melanoma cell motility. In other cell types, this can occur through the interaction of ROR2 with the cytoskeletal protein filamin A. Here, we found that filamin A protein levels correlated with Wnt5A levels in melanoma cells. Small interfering RNA (siRNA) knockdown of WNT5A decreased filamin A expression. Knockdown of filamin A also corresponded to a decrease in melanoma cell motility. In metastatic cells, filamin A expression was predominant in the cytoplasm, which western analysis indicated was due to the cleavage of filamin A in these cells. Treatment of nonmetastatic melanoma cells with recombinant Wnt5A increased filamin A cleavage, and this could be prevented by the knockdown of ROR2 expression. Further, BAPTA-AM chelation of intracellular calcium also inhibited filamin A cleavage, leading to the hypothesis that Wnt5A/ROR2 signaling could cleave filamin A through activation of calcium-activated proteases, such as calpains. Indeed, WNT5A knockdown decreased calpain 1 expression, and by inhibiting calpain 1 either pharmacologically or using siRNA, it decreased cell motility. Our results indicate that Wnt5A activates calpain-1, leading to the cleavage of filamin A, which results in a remodeling of the cytoskeleton and an increase in melanoma cell motility.

To study the biologic behavior and natural history of this rare but challenging tumor faced by oncologists, a clinicopathologic study of 42 patients with histologically proven adrenal cortical carcinoma from Roswell Park Memorial Institute (1929--1977) was done. These constituted .04% of all cancer cases and 0.2% of all autopsy cases. Age range was 3--74 years with median of 53 years; female to male ratio was 1.5 to 1. Clinical manifestations were: abdominal mass (36%), metastatic disease (30%), hormonal excess (17%) and weakness with lethargy (17%). Nine of ten functioning tumors were seen in female patients. Tumors arose in left adrenal in 26 patients, right adrenal in 12, and in four the site could not be determined because of bilateral presence of cancer. Median duration of symptoms was six months. At diagnosis, 52% had distant metastases, 41% had locally advanced tumor and 7% had tumor confined to adrenal. Sixteen patients underwent "curative" resection. Tumor diameter ranged from 1--30 cm with median of 10 cm. Of 28 patients who received different chemotherapeutic regimens, three (11%) had objective response; four of ten patients had objective response to radiation therapy. Overall median and five-year survival rates were 14 months and 24%. Prolonged survival (P less than .05) was noted in women, patients who had "curative" resection, a disease-free interval of more than 12 months, and tumor size greater than 10 cm diameter. Patients with functional tumors had longer median survival than those with non-functional ones (28 vs. 12), but P value was greater than .05. A second primary cancer was noted in 22.4% of cases, breast and lymphoma being the most common. At autopsy in 31 patients, the most common metastatic sites were retroperitoneal lymph nodes 68%, lung 71%, liver 42%, and bone 26%. To improve survival, an aggressive surgical approach is recommended to extirpate the tumor with involved organs and retroperitoneal lymph nodes. Adrenal carcinoma should be suspected in patients with metastatic cancer with an occult primary.

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From 1950 to 1973, 254 patients with metastatic cancers from occult primary tumors, comprising 0.5% of all the referred cancer patients were seen. The average age was 59 years. Clinical presentation was commonly in the form of metastatic lesions in lung, cervical lymph node, bone or liver. Radiological and radioisotopic investigations proved helpful in determining the extent of disease rather than the origin of primary tumor. Adenocarcinoma was the commonest type, followed by undifferentiated and squamous cell carcinomas. The origin of the primary tumor was established in 77 (30%) patients, mostly at autopsy. It was in the lung in 40% of the cases, followed by stomach, pancreas, kidney, ovary and colon. Some correlation was found between clinical presentation and the origin of the primary tumor. Histologically different second cancers were detected in 28 (11%) patients. Overall median and five-year survival rates were nine months and nine per cent respectively. Longer survival was seen in patients with squamous cell carcinoma metastases, middle and upper neck lymph node lesions, and those who had "curative" surgery. In localized metastatic lesions, surgical extirpation should be done. Depending on the histological type of the metastatic lesions, chemotherapy and/or radiation therapy have definite roles in the management of these patients. Periodic follow-up examinations also prove valuable.