Lien Huang-Chun, Huang Chiun-Sheng, Yang Ya-Wen, Jeng Yung-Ming
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan.
APMIS. 2016 May;124(5):356-64. doi: 10.1111/apm.12516. Epub 2016 Feb 10.
Spindle neoplasms of the breast (SNB) primarily include metaplastic breast carcinoma (MBC), phyllodes tumour (PT), fibromatosis and primary nonspecific sarcoma (PNS). Mutations in MED12 exon 2 have been reported in PTs. Because spindle tumour components are shared by SNB, we assessed the diagnostic use of MED12 exon 2 mutation in SNB. We investigated MED12 exon 2 mutations in a total of 91 samples of SNB, including 49 PT cases that have been previously analysed. Mutations were identified using direct sequencing. MED12 exon 2 mutation was absent in all cases of MBC, fibromatosis and PNS, in contrast to the 71.4% positivity in PTs. MED12 mutations were identified in four of six previously diagnosed monophasic sarcomatous MCB cases, however, these four cases were revised as malignant PT based on additional bcl-2 staining, albeit very focal. Consistence in the MED12 mutational status between a paired core biopsy and a surgical specimen was observed in all 20 tested PT cases. In conclusion, we demonstrated the restriction of MED12 exon 2 mutation to PTs (73.6%, 39/53) and its absence in other SNB. MED12 exon 2 mutational analysis can be included in the differential diagnosis between PT and other SNB, especially with limited specimen where diagnostic clues are not evident.
乳腺梭形肿瘤（SNB）主要包括化生性乳腺癌（MBC）、叶状肿瘤（PT）、纤维瘤病和原发性非特异性肉瘤（PNS）。已报道PTs中存在MED12外显子2突变。由于SNB存在共同的梭形肿瘤成分，我们评估了MED12外显子2突变在SNB诊断中的应用。我们调查了总共91例SNB样本中的MED12外显子2突变，其中包括49例先前已分析的PT病例。采用直接测序法鉴定突变。所有MBC、纤维瘤病和PNS病例均未检测到MED12外显子2突变，而PTs的阳性率为71.4%。在6例先前诊断为单相肉瘤样MCB病例中，有4例检测到MED12突变，然而，基于额外的bcl-2染色（尽管非常局限），这4例病例被重新诊断为恶性PT。在所有20例检测的PT病例中，配对的粗针活检标本和手术标本之间的MED12突变状态一致。总之，我们证实MED12外显子2突变仅限于PTs（73.6%，39/53），而在其他SNB中不存在。MED12外显子2突变分析可纳入PT与其他SNB的鉴别诊断，尤其是在标本有限且诊断线索不明显的情况下。
