Yamaguchi Hiroshi, Shimizu Michio, Ban Shinichi, Koyama Isamu, Hatori Takashi, Fujita Izumi, Yamamoto Masakazu, Kawamura Shunji, Kobayashi Makio, Ishida Kazuyuki, Morikawa Takanori, Motoi Fuyuhiko, Unno Michiaki, Kanno Atsushi, Satoh Kennichi, Shimosegawa Tooru, Orikasa Hideki, Watanabe Tomoo, Nishimura Kazuhiko, Ebihara Yoshiro, Koike Naoto, Furukawa Toru
Department of Pathology, Saitama International Medical Center, Saitama Medical University, Hidaka, Japan.
Am J Surg Pathol. 2009 Aug;33(8):1164-72. doi: 10.1097/PAS.0b013e3181a162e5.
We have encountered cases of unusual intraductal pancreatic neoplasms with predominant tubulopapillary growth. We collected data on 10 similar cases of "intraductal tubulopapillary neoplasms (ITPNs)" and analyzed their clinicopathologic and molecular features. Tumor specimens were obtained from 5 men and 5 women with a mean age of 58 years. ITPNs were solid and nodular tumors obstructing dilated pancreatic ducts and did not contain any visible mucin. The tumor cells formed tubulopapillae and contained little cytoplasmic mucin. The tumors exhibited uniform high-grade atypia. Necrotic foci were frequently observed, and invasion was observed in some cases. The ITPNs were immunohistochemically positive for cytokeratin 7 and/or cytokeratin 19 and negative for trypsin, MUC2, MUC5AC, and fascin. Molecular studies revealed abnormal expressions of TP53 and SMAD4 in 1 case, but aberrant expression of beta-catenin was not observed. No mutations in KRAS and BRAF were observed in the 8 cases that were examined. Eight patients are alive without recurrence, 1 patient died of liver metastases, and 1 patient is alive but had a recurrence and underwent additional pancreatectomy. The mitotic count and Ki-67 labeling index were significantly associated with invasion. All the features of ITPN were distinct from those of other known intraductal pancreatic neoplasms, including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and the intraductal variant of acinar cell carcinoma. Intraductal tubular carcinomas showed several features that were similar to those of ITPN, except for the tubulopapillary growth pattern. In conclusion, ITPNs can be considered to represent a new disease entity encompassing intraductal tubular carcinoma as a morphologic variant.
我们遇到了一些以管状乳头样生长为主的不寻常的胰腺导管内肿瘤病例。我们收集了10例类似的“导管内管状乳头肿瘤（ITPNs）”病例的数据，并分析了它们的临床病理和分子特征。肿瘤标本取自5名男性和5名女性，平均年龄为58岁。ITPNs为实性结节状肿瘤，阻塞扩张的胰腺导管，且不含任何可见黏液。肿瘤细胞形成管状乳头，胞质内黏液很少。肿瘤表现为一致的高级别异型性。经常观察到坏死灶，部分病例可见浸润。ITPNs免疫组化显示细胞角蛋白7和/或细胞角蛋白19阳性，而胰蛋白酶、MUC2、MUC5AC和肌动蛋白呈阴性。分子研究显示1例TP53和SMAD4表达异常，但未观察到β-连环蛋白的异常表达。在检测的8例病例中未观察到KRAS和BRAF突变。8例患者存活且无复发，1例患者死于肝转移，1例患者存活但复发并接受了再次胰腺切除术。有丝分裂计数和Ki-67标记指数与浸润显著相关。ITPN的所有特征均与其他已知的胰腺导管内肿瘤不同，包括胰腺上皮内瘤变、导管内乳头状黏液性肿瘤和腺泡细胞癌的导管内变体。导管内管状癌显示出一些与ITPN相似的特征，除了管状乳头样生长模式。总之，ITPNs可被认为代表一种新的疾病实体，包括导管内管状癌作为一种形态学变体。
