Familial Nasopharyngeal Carcinoma 6

120 J-C. Linpatients of three nonkeratinizing carcinomas (SP, RC,and Mix) into two subgroups each, according to thedegree of anaplasia and/or pleomorphism: Type A(with marked anaplasia and/or pleomorphism), andType B (with moderate or little anaplasia). They foundthat Type B had significant better survival than thoseof Type A in each three nonkeratinizing carcinomas(60.5% vs. 35% for SP, p < 0.005; 71.8% vs. 33.3% forRC, p < 0.0005; and 60% vs. 38.6% for Mix, p < 0.02).Based on these results, the authors proposed that thehistology of NPC could be divided into three grades ofmalignancy: high-grade malignancy (KSCC, 5-yearsurvival rate of 20%), intermediate malignancy (TypeA carcinomas, 5-year survival rates of 30%–40%), andlow-grade malignancy (Type B carcinomas, 5-yearsurvival rates of 60%–72%).Cheng et al. (2006a) proposed a prognostic scoringsystem for locoregional control in NPC followingconformal radiation therapy with or without chemotherapy.Histology was found to be one of the fourimportant factors in their model. Among 630 patientsincluded in that study, 17, 131, and 482 patients werejustified as WHO Types 1, 2, and 3, respectively. The5-year locoregional control rates for patients withWHO Type 1, 2, and 3 were 81%, 81%, and 91%,respectively. Multivariate analysis confirmed WHOType 3 as a favorable independent factor (hazardratio = 2.3, 95% CI = 1.4–3.8, p = 0.002).In summary, histological type is a significantprognostic factor for NPC patients in nonendemicregions with worse results in keratinizing sqaumouscell carcinoma. Due to the small number of patientswith keratinizing squamous cell carcinoma histologyin endemic areas, the histological impact on survivalis still unknown and deserves to be studied furtherwith multicenter cooperation. In addition, consensusbetween different pathologists should be reached toset uniform criteria for histological classification.9.5.3Factors Associated with Diagnostic Procedures9.5.3.1Parapharyngeal Space Invasionor Retropharyngeal LymphadenopathyParapharyngeal space (PPS) invasion and/or retropharyngeallymph nodes (RPLN) metastasis are twocommon routes of NPC spreading. Precise definitionof the extent of PPS and/or RPLN invasion is not possibleuntil the utilization of CT scan. The use of MRIfurther improves the discrimination between PPSinvasion and RPLN metastasis. Studies exploring theprognostic impact of PPS invasion and RPLN metastasissuggest that both conditions are significant factorsaffecting various survival endpoints, besidesTNM staging.Sham and Choy (1991) performed a thoroughinvestigation regarding PPS invasion on local controland short-term survival in 262 NPC patients who hadpretreatment CT scan. Three reference lines to gradethe extent of PPS invasion were proposed: The firstline was defined from the free edge of the medialpterygoid plate posterolaterally to the lateral borderof the carotid artery, the second line extending fromthe scaphoid fossa at the base of the medial pterygoidplate posterolaterally to the styloid process, and thethird line extending from the free edge of the lateralpterygoid plate posterolaterally to the posterior borderof the ascending ramus of the mandible. Thetumor is considered confined to the nasopharynx,with no PPS invasion, if the tumor is confined medialto the first line. Tumor on each side extending into theretrostyloid space, prestyloid space, and anterior partof the masticator space, by reaching or extendingbeyond the first, second, and third lines, respectively,were designated Grade 1, 2, and 3 PPS invasion,respectively. In this study, 84.4% (221/262) patientshad PPS invasion and 40.2% (105/262) of patients hadbilateral involvement. PPS invasion was shown as oneof the significant factors affecting local control andsurvival by both univariate (p = 0.0001 and p = 0.0001)and multivariate (p = 0.0001 and p = 0.0335) analyses.In a subsequent study of another group of 364NPC patients by the same research team and definitionof PPS invasion with a longer follow-up time,PPS invasion was confirmed to be a significantlyindependent prognostic factor for relapse-free survival,local failure-free survival, and metastasis-freesurvival by both univariate and multivariate analyses(Chua et al. 1996). The 5-year relapse-free, local failure-free,and metastasis-free survival rates for Grade0/1 and Grade 2/3 PPSI were 72% vs. 45% (p < 0.0001),86% vs. 72% (p < 0.0001), and 87% vs. 68% (p =0.0002), respectively.Three other studies used the same definition ofSham and Chua grading system to evaluate the prognosticimpact of PPS invasion (Heng et al. 1999; Maet al. 2001a; Kalogera-Fountzila et al. 2006).Kalogera-Fountzila et al. (2006) studied 162 NPCpatients with Stage II–IV disease from Greece andobserved the same results. PPS invasion has significanteffect on overall survival by both univariate