title: Detection of occult sentinel lymph node micrometastases by immunohistochemistry in breast cancer. An NSABP protocol B-32 quality assurance study.
abstract: BACKGROUND
  Occult metastases, by definition, are not detected on initial examination. They may be present on slides but missed during screening or may be present in paraffin embedded tissue blocks and undetected without additional levels. Anticytokeratin immunohistochemistry (CK IHC) enhances detection of occult metastases, particularly micrometastases (> 0.2 mm but not larger than 2.0 mm) or isolated tumor cell clusters (< or = 0.2 mm). This study defines the rate at which pathologists miss metastases on CK IHC of sentinel lymph nodes (SLN).
  
  
  METHODS
  CK IHC sections 0.5 and 1.0 mm from the original surface of SLN tissue blocks were screened by pathologists using standard bright field light microscopes (LM) and by supervised computer assisted cell detection (CACD). All blocks were from breast cancer patients, initially classified 'node negative' on review of routinely stained sections from the surface of each block. Cases missed by LM screening but detected by CACD defined false negative screens.
  
  
  RESULTS
  Of 236 cases screened, LM detected 34 (14.4%; 95% CI: 9.6-20.2) cases and, in the 202 cases negative by LM, CACD detected an additional 30 (14.9%; 95% CI: 9.6-21.2%) cases with occult metastases. Occult metastases missed by LM screening ranged from 0.01 to 0.1 mm in greatest dimension. The probability of missing an occult metastasis < or = 0.02 mm; < or = 0.05 mm, and < or = 0.10 mm was 75%, 69.2%, and 61.2%, respectively. No occult metastases larger than 0.10 mm were missed by LM screening.
  
  
  CONCLUSIONS
  Pathologists screening the CK IHC stained slides may frequently miss detecting metastases < 0.10 mm.
authors.affiliation: Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont 05405-0068, USA. donald.weaver@uvm.edu
authors.forename: Donald L
authors.initials: DL
authors.lastname: Weaver
authors.forename: David N
authors.initials: DN
authors.lastname: Krag
authors.forename: Edward A
authors.initials: EA
authors.lastname: Manna
authors.forename: Takamaru
authors.initials: T
authors.lastname: Ashikaga
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Waters
authors.forename: Seth P
authors.initials: SP
authors.lastname: Harlow
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bauer
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Julian
mesh_terms: D001365:Axilla; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D011379:Prognosis; D021701:Sentinel Lymph Node Biopsy
chemical_list: D007633:Keratins