Westra W H, Sturm P, Drillenburg P, Choti M A, Klimstra D S, Albores-Saavedra J, Montag A, Offerhaus G J, Hruban R H
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Am J Surg Pathol. 1998 Oct;22(10):1247-54. doi: 10.1097/00000478-199810000-00010.
Osteoclast-like giant cell tumors (OCGTs) of the pancreas and liver are enigmatic tumors. Despite their striking morphologic resemblance to certain mesenchymal tumors of bone and tendon sheath, it has been suggested that these tumors may, in fact, arise from epithelial precursors. It is also unclear whether the osteoclast-like giant cells in OCGTs are neoplastic or nonneoplastic. We identified OCGTs of the pancreas and liver that were associated with atypical intraductal epithelial proliferations or mucinous cystic neoplasms. To determine the relationship between the noninvasive epithelial proliferations and the infiltrating OCGTs, each individual component was analyzed for mutations at codon 12 of the K-ras oncogene. Four of the five-duct epithelial lesions harbored activating mutations of the K-ras oncogene. In each case, the same K-ras mutation was also present in the mononuclear cells from the paired OCGT. Moreover, these same mutations were detected when the osteoclast-like giant cells were individually microdissected and analyzed. A panel of immunohistochemical stains was performed, and the osteoclast-like giant cells demonstrated macrophage differentiation. These cells were consistently reactive for the monocyte/macrophage marker KP1, but showed absent staining for a panel of epithelial markers. The infiltrating mononuclear cells lacked strong staining for epithelial markers and monocyte/macrophage markers. These findings suggest that OCGTs of the pancreas and liver are undifferentiated carcinomas that arise directly from intraductal epithelial precursors. The finding of K-ras mutations in the osteoclast-like giant cells may reflect their propensity to phagocytize tumor cells.
胰腺和肝脏的破骨细胞样巨细胞瘤（OCGTs）是一种神秘的肿瘤。尽管它们在形态上与某些骨和腱鞘的间充质肿瘤极为相似，但有观点认为，这些肿瘤实际上可能起源于上皮前体细胞。此外，OCGTs中的破骨细胞样巨细胞是肿瘤性的还是非肿瘤性的，目前也尚不清楚。我们发现胰腺和肝脏的OCGTs与非典型导管内上皮增生或黏液性囊性肿瘤有关。为了确定非侵袭性上皮增生与浸润性OCGTs之间的关系，我们对每个单独的成分进行了K-ras癌基因第12密码子的突变分析。在五个导管上皮病变中，有四个存在K-ras癌基因的激活突变。在每种情况下，配对的OCGTs中的单核细胞也存在相同的K-ras突变。此外，当对破骨细胞样巨细胞进行单独显微切割和分析时，也检测到了相同的突变。我们进行了一组免疫组织化学染色，结果显示破骨细胞样巨细胞呈现巨噬细胞分化。这些细胞对单核细胞/巨噬细胞标志物KP1始终呈阳性反应，但对一组上皮标志物均无染色。浸润的单核细胞对上皮标志物和单核细胞/巨噬细胞标志物均缺乏强染色。这些发现表明，胰腺和肝脏的OCGTs是直接起源于导管内上皮前体细胞的未分化癌。在破骨细胞样巨细胞中发现K-ras突变可能反映了它们吞噬肿瘤细胞的倾向。
