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Neuroendocrine cells associated with neuroendocrine carcinoma of the breast: nature and significance
  1. Tomonori Kawasaki1,
  2. Kunio Mochizuki1,
  3. Hideko Yamauchi2,
  4. Shingo Inoue3,
  5. Tetsuo Kondo1,
  6. Naoki Oishi1,
  7. Tadao Nakazawa1,
  8. Tetsu Yamane1,
  9. Yoshihito Koshimizu1,
  10. Hiroko Tsunoda2,
  11. Hiroshi Yagata2,
  12. Masayuki Inoue3,
  13. Ayako Inoue3,
  14. Takanori Maruyama3,
  15. Hideki Fujii3,
  16. Ryohei Katoh1
  1. 1Department of Pathology, University of Yamanashi, Yamanashi, Japan
  2. 2Breast Center, St Luke's International Hospital, Tokyo, Japan
  3. 3First Department of Surgery, University of Yamanashi, Yamanashi, Japan
  1. Correspondence to Dr Tomonori Kawasaki, Department of Pathology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan; tomonori{at}


Background The developmental mechanisms of breast neuroendocrine carcinoma (B-NEC) have not been sufficiently analysed and are not well understood.

Aims To investigate NE cells in the background tissues surrounding B-NECs.

Methods Three cases (four breasts) having many NE cells in the background tissues of multifocal B-NECs were identified at the University of Yamanashi Hospital and St Luke's International Hospital, Japan. These patients were, respectively, 28-, 31- and 38-year-old women with no familial history of NE tumour. The totally-resected breasts were serially studied by immunohistochemistry for specific NE markers (chromogranin A/synaptophysin) and the morphologies and/or localisation of NE cells were investigated.

Results Immunohistochemical examination showed extensively-distributed NE cells in the background mammary ducts/lobules of the NECs in all breasts. These NE cells were classifiable into three emerging patterns: isolated/scattered, clustered and circumferential. Their distributions were intermingled and were not clearly related to B-NEC foci. NE cells were morphologically polygonal, oval or columnar with sometimes eosinophilic and/or fine-granular cytoplasm and round-to-ovoid nuclei lacking atypia. Some cells were located between epithelial and myoepithelial cells. Apical snouts were occasionally observed in NE cells forming luminal structures.

Conclusions Benign-appearing NE cells in the parenchyma of a breast with NEC could be regarded as hyperplastic from their emerging patterns and distribution; this NE cell hyperplasia may be associated with the histogenesis of B-NEC as a precancerous condition. These observations might raise questions about the treatment for B-NEC.

  • Breast
  • neuroendocrine cells
  • neuroendocrine cell hyperplasia
  • neuroendocrine carcinoma (NEC)
  • neuroendocrine ductal carcinoma in situ (NE-DCIS)
  • breast cancer
  • neuroendocrine tumours
  • breast pathology

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  • Funding This work was supported by a Grant-in-Aid for Young Scientists (B) (No. 21790347 and 23790394) from the Japanese Ministry of Education, Culture, Sports, Science and Technology and the Yamanashi University Characteristic Prior Research Fund 2008, 2009 and 2010.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Ethics Committee, University of Yamanashi and St Luke's International Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.