“Time Shall Unfold…”: The Clinical Value of Grading Mammary Angiosarcoma

Abstract

The following maxims apply to all soft tissue tumors: (a) correct diagnosis and categorization into benign or malignant are imperative for appropriate management, (b) it is a rare benign tumor that recurs or metastasizes, (c) malignant tumors (ie, sarcomas) have potential to metastasize, and this capacity decrees mortality, and (d) grade of a sarcoma is predictive of metastasis (less so of local recurrence) and, thus, foretells mortality. The last axiom underscores the value of grading sarcomas.Albeit rare, angiosarcoma is the most common mammary sarcoma. At this site, angiosarcoma can either be primary (idiopathic) or secondary (ie, treatment-related, archetypally to radiation). The relentless progression of most cases of primary and secondary angiosarcomas has been well documented-although the clinical value of grading in this tumor remains contentious, more so for the primary ones.Two significant case series of primary mammary angiosarcomas stand out. In the classic series of 40 patients by Donnell et al, 1 published in 1981, which established the Rosen 3-grade system, survival probability among all grades was essentially similar at 1 year, but tumors of the highest grade fared worse at 5 and 10 years. More than a quarter of a century later, in 2008, Nascimento et al 2 in a rather contrarian series of 48 patients, utilizing the Rosen grading system, did not identify any statistically significant differences among the 3 grades-although of 14 patients with grade 1 tumors: 6 were dead of disease, 2 were alive with disease, and 6 had no evidence of disease-in a median follow-up of 23 months. The series of 48 patients by Kuba et al, 3 which appears in this issue of the Journal, found the 5-year survival for high-grade (combined grade 2 and 3) mammary angiosarcoma to be 38%, and that for low-grade ones to be 74%.These 3 series, published over a span of 4 decades, are understandably not comparable in every clinicopathologic respect (particularly in terms of management). Nonetheless, the combined data support the view that an effort should be made to grade primary mammary angiosarcomas, with the caveat that grading is not always predictive of outcome. One could also reasonably conclude that all angiosarcomas should be considered high-grade from the perspective of management. Such "managerial grading" 4 may be a pragmatic clinical solution given the inherent problems in the interpretation of criteria, interobserver variation and sampling.Notwithstanding the merits of "managerial grading", and the possible therapeutic implications of emerging genomic findings (ie, PIK3CA and KDR mutations, among others), and the increasing use of nomograms, etc.; at this time histologic grading (along with size and margin assessment) ought to be reported to provide conventional parameters for prognostication. Of course, the diagnosis of low-grade primary mammary angiosarcoma may be perilous in needle core biopsy material (given its notorious heterogeneity) and is a largely futile exercise in post-neoadjuvant chemotherapy specimens (sinc...