Two human melanoma cell lines were transduced with the human interleukin (IL)-7 and IL-2 genes using retroviral-mediated gene transfer. Stable, high-level cytokine expression was achieved. The in vitro growth of transduced tumors was unaltered. Neither of the IL-2- transduced melanoma cell lines grew in athymic mice, whereas one IL-7- transduced melanoma line showed retarded in vivo growth. This is consistent with animal studies suggesting a predominantly T-cell response to IL-7-transduced tumors and a more nonspecific response to IL-2-transduced tumors. Both IL-7- and IL-2-transduced melanoma cell lines could induce cytotoxic lymphocytes in mixed lymphocyte-tumor cultures. The expression of putative melanoma antigens (MAGE)-1 and MAGE-3 was unaltered by cytokine transduction. In one cell line, IL-7 transduction resulted in a marked inhibition of the immunosuppressive peptide transforming growth factor (TGF)beta 1. The results allow a comparison of immunobiologic properties of IL-7- and IL-2-transduced human melanoma cell lines in consideration of their use in genetically engineered tumor vaccines. IL-7 transduction results in stable cytokine expression and phenotypic alterations that appear to be favorable for enhanced immunogenicity and it deserves clinical testing.
Introduction/Objective Sarcomatoid porocarcinoma of skin is an exceedingly rare and diagnostically challenging malignancy of the sweat gland. In this report, we describe a rare case of a sarcomatoid eccrine porocarcinoma initially diagnosed to be a squamous cell carcinoma (SCC) in a patient with metastatic urothelial carcinoma (UC). Methods/Case Report Our patient is a 60 year old male with stage IV, poorly differentiated UC status post TURBT with residual tumor, and a 4 x 3 x 1 cm, polypoid, ulcerating skin nodule on his right cheek presumptively diagnosed to be an SCC on biopsy at an outside hospital. Given the concern that this cutaneous lesion may be a metastatic UC with squamous differentiation, the skin nodule was re-biopsied at our hospital. On histology, the lesion consisted of sheets of squamoid, polygonal cells in the dermis with pleomorphic nuclei showing irregular contours, prominent nucleoli, coarse chromatin, and frequent mitoses. The tumor was focally connected to the epidermis, which established it as a primary skin neoplasm and not a metastatic lesion. The tumor cells stained diffusely positive for vimentin, AE1/AE3, CK5/6, HMW CK, CK7, p63, and p16, negative for CK20, GATA-3, BerEP4, and Sox10, and showed high Ki67 proliferation index. Within the tumor sheets were poorly formed, focal ductal elements that stained positive for CAM5.2, EMA, CEA, and CK19, and negative for p63. The tumor showed comedo necrosis, epidermal ulceration, and no keratinization. The tumor was diagnosed to be a porocarcinoma given its positive staining for CK7 and p16, presence of focal ductal elements, and epidermal connection, with sarcomatoid features indicated by strong vimentin expression. Results (if a Case Study enter NA) NA. Conclusion In this report, we described an exceedingly rare, diagnostically challenging case of a sarcomatoid porocarcinoma initially suspected to be a cutaneous SCC or metastatic UC with squamous differentiation. Although the tumor cells morphologically resembled SCC, its positive staining for CK7 and p16, presence of ductal elements, and lack of keratinization, favored a diagnosis of porocarcinoma rather than cutaneous SCC. Its focal connection to the epidermis and lack of GATA-3 expression favored a primary skin neoplasm rather than a metastatic UC. Its sarcomatoid nature was indicated by strong vimentin expression. Sarcomatoid porocarcinoma is diagnostically challenging given its rarity and potential to mimic other cutaneous malignancies such as SCC.
Introduction/Objective Neuroendocrine (carcinoid) tumors of the duodenum are extremely rare and account for only 2-4% of gastrointestinal tract neuroendocrine tumors. We report two cases of incidentally discovered duodenal neuroendocrine tumor which respectively occurred in a patient with invasive gastric adenocarcinoma and in a patient with pancreatic intraductal papillary mucinous neoplasm (IPMN). Methods/Case Report The first case involved a 60-year old male who presented with melena and symptomatic anemia and was found on EGD to have a large circumferential mass at the gastric antrum/pylorus, which was revealed to be an invasive gastric adenocarcinoma on biopsy. At the time of distal gastrectomy for this malignancy, a concurrent, 0.6 cm-sized, low grade neuroendocrine tumor was incidentally discovered at the duodenal margin. The duodenal tumor consisted of nests and trabeculae of monotonous cells with ovoid/round nuclei, finely speckled “salt and pepper” chromatin, and low mitotic rate (< 2 mitoses/2 mm2), and invaded only into submucosa. The tumor cells were strongly and diffusely positive for neuroendocrine markers chromogranin, synaptophysin, and CD56, positive for CK7 and CDX2, negative for CK20, and with low Ki67 proliferation index (< 3%). The second case involved a 69-year old female who presented with epigastric pain and was found on abdominal CT to have a 4 cm-sized cystic mass in the pancreatic head. While biopsy of the pancreatic mass revealed an IPMN, a separate biopsy of an incidentally discovered, 1 cm-deep ulcer in the duodenum bulb revealed a low-grade neuroendocrine tumor with similar morphologic features, mitotic rate, and immunohistochemical staining pattern as the prior case while also negative for IMP3 stain. The patient had normal serum gastrin and urine HIAA levels, but elevated serum chromogranin-A levels. Results (if a Case Study enter NA) NA. Conclusion Duodenal carcinoids are rare (1-3% of primary duodenal tumors) and are mostly non-functional and unifocal. The duodenum is also the least common site (2-4%) for GI tract neuroendocrine tumors. The pathophysiology of these tumors is still poorly understood, with the majority occurring sporadically and a minority in the setting of hereditary cancer syndromes. This report documents two very rare instances of duodenal neuroendocrine tumor incidentally discovered with invasive gastric adenocarcinoma and pancreatic IPMN.
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