title: High prevalence of neuroendocrine carcinoma in breast lesions detected by the clinical symptom of bloody nipple discharge.
abstract: OBJECTIVE
  Bloody nipple discharge (BND) is an important clinical symptom in breast disorders, especially cancers. However, the association between this symptom and breast neuroendocrine carcinomas (NECs) has not been sufficiently investigated or well understood.
  
  
  METHODS
  We clinicopathologically studied 89 cases using biopsy and/or resection in 144 patients who came to the hospital for a thorough examination of symptomatic BND.
  
  
  RESULTS
  Of these 89 cases examined histologically, 24 (27%) were neuroendocrine carcinomas (NECs) in which >50% of cells immuno-expressed chromogranin A and/or synaptophysin. Moreover, NECs made up 44% (24/55) of the mammary cancers found because of the BND. The frequency of diagnosing malignancy preoperatively in 24 NECs was 4% by nipple discharge cytology, 40% by fine needle aspiration cytology, 62% by core needle biopsy and 67% by mammotome biopsy. There were neither postoperative recurrences nor metastases in the NEC cases during a mean follow-up of 83.7 months. The 24 NECs were subclassified into neuroendocrine ductal carcinoma in situ (NE-DCIS) (9 cases) and microinvasive (7 cases) and invasive (8 cases) NECs with extensive NE-DCIS components. Most NECs had early-stage and low-grade pathological parameters: pTis or pT1 (96%), pN0 (96%), low nuclear grade (83%), absence of necrosis (88%), immuno-positivity of estrogen and progesterone receptors (100%) and absence of HER2 protein overexpression (100%).
  
  
  CONCLUSIONS
  NECs predominantly with NE-DCIS lesions, often under-diagnosed preoperatively, accounted for an important share of breast conditions associated with BND. It is, therefore, worth keeping this type of breast cancer in mind when performing medical examinations on patients with BND.
authors.affiliation: Department of Pathology, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi 409-3898, Japan. tomonori@yamanashi.ac.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Kunio
authors.initials: K
authors.lastname: Mochizuki
authors.forename: Hideko
authors.initials: H
authors.lastname: Yamauchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagata
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kondo
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsunoda
authors.forename: Seigo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Oishi
authors.forename: Tadao
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yamane
authors.forename: Ayako
authors.initials: A
authors.lastname: Inoue
authors.forename: Takanori
authors.initials: T
authors.lastname: Maruyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inoue
authors.forename: Shingo
authors.initials: S
authors.lastname: Inoue
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Ryohei
authors.initials: R
authors.lastname: Katoh
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism; D005122:Exudates and Transudates / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D009558:Nipples / Q000378:metabolism*; D015995:Prevalence
chemical_list: D014408:Biomarkers, Tumor