Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade

被引:134
作者
Davison, Jon M. [1 ]
Choudry, Haroon A. [2 ]
Pingpank, James F. [2 ]
Ahrendt, Steven A. [2 ]
Holtzman, Matthew P. [2 ]
Zureikat, Amer H. [2 ]
Zeh, Herbert J. [2 ]
Ramalingam, Lekshmi [2 ]
Zhu, Benjamin [1 ]
Nikiforova, Marina [1 ]
Bartlett, David L. [2 ]
Pai, Reetesh K. [1 ,2 ]
机构
[1] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Med Ctr, Div Surg Oncol, Dept Surg, Pittsburgh, PA 15213 USA
关键词
appendix; disseminated peritoneal adenomucinosis; low-grade mucinous neoplasm; mucinous adenocarcinoma; peritoneal mucinous carcinomatosis; pseudomyxoma peritonei; DISSEMINATED PERITONEAL ADENOMUCINOSIS; GOBLET CELL CARCINOIDS; PSEUDOMYXOMA PERITONEI; CYTOREDUCTIVE SURGERY; INTRAPERITONEAL CHEMOTHERAPY; SINGLE-INSTITUTION; ORIGIN; PROGNOSIS; CARCINOMATOSIS; MUTATIONS;
D O I
10.1038/modpathol.2014.37
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Previous studies have demonstrated that the prognosis of disseminated mucinous appendiceal neoplasms is highly dependent upon tumor grade. Reflecting this, the 7th edition of the American Joint Committee on Cancer (AJCC) staging system now incorporates a three-tier grading system for prognostic staging of mucinous appendiceal tumors. However, the grading criteria are not well described. In order to address this issue, we evaluated clinicopathologic and molecular features of 219 cases from 151 patients with widely disseminated appendiceal mucinous neoplasia treated at our institution between 2004 and 2012. We identified histologic features that were associated with worse overall survival on univariate analysis: destructive invasion, high cytologic grade, high tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cell component (all with P<0.0001). We used these morphologic characteristics to classify neoplasms into three grades: AJCC grade G1 lacked all adverse histologic features; AJCC grade G2 had at least one adverse histologic feature (except a signet ring cell component); and AJCC grade G3 were defined by the presence of a signet ring cell component. Patients with AJCC grade G2 and grade G3 adenocarcinomas had a significantly worse prognosis compared with AJCC grade G1 (P<0.0001 for each). A trend toward worse overall survival was identified for patients with AJCC grade G3 adenocarcinomas compared with AJCC grade G2 adenocarcinomas (P = 0.07). Our multivariate analysis found that this three-tier grading system was a significant predictor of outcome (P = 0.008), independent of other prognostic variables. After controlling for other prognostic variables, AJCC grade G2 was associated with a 2.7-fold increased risk of death (95% confidence interval (CI), 1.2-6.2) and AJCC grade G3 was associated with a 5.1-fold increased risk of death (95% CI, 1.7-14) relative to grade G1 tumors. Our results indicate that evaluation of a limited set of adverse histologic features allows for the separation of disseminated mucinous neoplasms of appendiceal origin into three morphologically defined and prognostically relevant grades as advocated by the AJCC.
引用
收藏
页码:1521 / 1539
页数:19
相关论文
共 33 条
[21]   Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women [J].
Ronnett, BM ;
Shmookler, B ;
DienerWest, M ;
Sugarbaker, PH ;
Kurman, RJ .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, 1997, 16 (01) :1-9
[22]   DISSEMINATED PERITONEAL ADENOMUCINOSIS AND PERITONEAL MUCINOUS CARCINOMATOSIS - A CLINICOPATHOLOGICAL ANALYSIS OF 109 CASES WITH EMPHASIS ON DISTINGUISHING PATHOLOGICAL FEATURES, SITE OF ORIGIN, PROGNOSIS, AND RELATIONSHIP TO PSEUDOMYXOMA-PERITONEI [J].
RONNETT, BM ;
ZAHN, CM ;
KURMAN, RJ ;
KASS, ME ;
SUGARBAKER, PH ;
SHMOOKLER, BM .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1995, 19 (12) :1390-1408
[23]  
Ronnett BM, 2001, CANCER, V92, P85, DOI 10.1002/1097-0142(20010701)92:1<85::AID-CNCR1295>3.0.CO
[24]  
2-R
[25]   Modern Systemic Chemotherapy in Surgically Unresectable Neoplasms of Appendiceal Origin A Single-Institution Experience [J].
Shapiro, Jamie F. ;
Chase, Judy L. ;
Wolff, Robert A. ;
Lambert, Laura A. ;
Mansfield, Paul F. ;
Overman, Michael J. ;
Ohinata, Aki ;
Liu, Jun ;
Wang, Xuemei ;
Eng, Cathy .
CANCER, 2010, 116 (02) :316-322
[26]   Genetic alterations in goblet cell carcinoids of the vermiform appendix and comparison with gastrointestinal carcinoid tumors [J].
Stancu, M ;
Wu, TT ;
Wallace, C ;
Houlihan, PS ;
Hamilton, SR ;
Rashid, A .
MODERN PATHOLOGY, 2003, 16 (12) :1189-1198
[27]   Neoadjuvant FOLFOX Chemotherapy in 34 Consecutive Patients With Mucinous Peritoneal Carcinomatosis of Appendiceal Origin [J].
Sugarbaker, Paul H. ;
Bijelic, Lana ;
Chang, David ;
Yoo, Dal .
JOURNAL OF SURGICAL ONCOLOGY, 2010, 102 (06) :576-581
[28]   Molecular genetic evidence supporting the clonality and appendiceal origin of pseudomyxoma peritonei in women [J].
Szych, C ;
Staebler, A ;
Connolly, DC ;
Wu, R ;
Cho, KR ;
Ronnett, BM .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (06) :1849-1855
[29]   Cytogenetic analysis of several pseudomyxoma peritonei lesions originating from a mucinous cystadenoma of the appendix [J].
Teixeira, MR ;
Qvist, H ;
Giercksky, KE ;
Bohler, PJ ;
Heim, S .
CANCER GENETICS AND CYTOGENETICS, 1997, 93 (02) :157-159
[30]   A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei [J].
Yan, Tristan D. ;
Black, Deborah ;
Savady, Renaldo ;
Sugarbaker, Paul H. .
ANNALS OF SURGICAL ONCOLOGY, 2007, 14 (02) :484-492