Codon 172 in the IDH2 gene is a mutational hotspot in tall cell carcinoma with reversed polarity of the breast

We read with interest the case report by Zhang et al. (1) in a previous issue of Gland Surgery (February 2021) that described a case of tall cell carcinoma with reversed polarity of the breast (TCCRP) with a genetic analysis using targeted next-generation sequencing (1). Histologically, the tumor presented by Zhang et al. (1) appeared to show typical histologic features of TCCRP characterized by tall columnar cells with reversed nuclear polarity, arranged in solid and solid papillary patterns (2). In addition, an IDH2 mutation was detected in the breast tumor, genetically supporting a diagnosis of TCCRP. TCCRP is a distinct breast cancer subtype characterized by frequent IDH2 mutations (in 80–90% of cases), while IDH2 mutations are extremely rare in unselected breast cancer cases (3,4). In the paper by Zhang et al. (1), the results of IDH2 mutation detection were shown in Figure 4A. The authors interpreted the genetic result as IDH2 p.R120G, a novel mutation, rather than IDH2 R172 and described the need to consider the presence of an IDH2 mutation at other sites than codon 172 in the discussion section. © Gland Surgery. All rights reserved.