Head and Neck Pathol (2009) 3:69–77 cytomorphologic and architectural, and may also include perineural and angiolymphatic invasion. Both the AFIP and Brandwein system are point based, assigning point values to each adverse histologic parameters and with ascending point scores equating to a higher grade. The modiﬁed Healey system can be considered a ‘best ﬁt’ type system: certain histologic parameters characterize a particular grade, and a tumor is graded based on its predominant morphologic features. Grading of mucoepidermoid carcinoma is not without ﬂaws. One clear deﬁciency in all systems, particularly the point based schemes, the difﬁculty in application. Grad- ing under these systems is a cumbersome and time consuming activity, and many of the criteria are not at all well-deﬁned. In fact, based on personal experience, if asked, most pathologists tend not to use a formal system because of the time commitment and lack of ‘user friendliness.’ However, evidence suggests that the repro- ducibility of an informal or personal grading scheme is lower than when a standard grading scheme is used [23, 24] (Fig. 4). Given an adequate sample size, all systems appear to be prognostically useful even independent of stage. However, the way in which each system correlates with outcome varies. The AFIP system appears to ‘down grade’ tumors while the Brandwein system appears to ‘upgrade’ tumors [24]. While these differences appear minor prognostically, therapeutically they have signiﬁcant implications. The clinical expectation of a low grade mucoepidermoid car- cinoma is that it is a ‘low risk’ tumor that is almost always cured by surgery alone and has a negligible lymph node metastatic rate. Here the danger of the AFIP system is potentially placing biologically more aggressive tumors into this low grade category increasing the failure rate of low grade tumors. Conversely, high grade mucoepidermoid carcinomas are aggressive tumors requiring adjuvant 75 treatment and neck dissection. The concern with the Brandwein system is that it may place some indolent tumors in this high risk category, in which case some patients may receive unnecessary radiation or additional surgery. The differences in grading schemes are ampliﬁed par- ticularly with respect to intermediate grade tumors. There does not appear to be a clear cut answer on the manage- ment of patients in this category, but the few studies addressing this question on a single institution yield vary- ing results. Aro et al. [17] using the AFIP system suggest that intermediate grade mucoepidermoid carcinoma cluster with high grade mucoepidermoid carcinoma, and should be treated in a similar fashion. However, Nance et al. [18] showed that intermediate grade mucoepidermoid carci- noma cluster with low grade mucoepidermoid carcinoma using the Brandwein system. Based on limited experience, the Healey system does not seem to have either of these limitations, but since intermediate grade tumors using this system literally behave in a fashion that is ‘intermediate’ to low and high grade, management may be even more ambiguous than with the other systems. Finally, variants of mucoepidermoid carcinoma such as oncocytic or sclerosing variants may not be amenable to conventional grading schemes. Limited evidence to date suggests that even oncocytic mucoepidermoid carcinomas that are considered high grade (Fig. 5) by a conventional grading scheme may behave indolently, with only one recurrence noted [25]. However, evidence is still insufﬁ- cient to make a ﬁrm recommendation to discard grading for these variants. Thus current recommendations for grading mucoepi- dermoid carcinomas are: • Utilize a standard scheme, rather than an ‘intuitive’ approach. (As a more streamlined well deﬁned system Fig. 4 Grading of mucoepidermoid carcinoma. a A low grade tumor demonstrating a well demarcated border, macrocystic spaces and a bland cyst lining. b An intermediate grade tumor demonstrating a more solid growth with only few microcysts, and focal inﬁltration. It is important to note that the Brandwein system may potentially classify this tumor as high grade (inﬁltration if these nests are considered ‘small enough’, and intracystic component \25% equates to 4 points), while the AFIP grading system still categorizes this tumor as low grade (score is only 2/14). c High grade mucoepider- moid carcinoma with no cystic spaces and a highly inﬁltrative growth pattern. Inset: showing anaplasia or pronounced nuclear atypia