title: Clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large-format histologic sections.
abstract: BACKGROUND
  Breast carcinoma is a heterogeneous group of diseases deviating from each other not only in their clinical manifestations and outcome but also in their histologic appearance. The submacroscopic morphology of breast carcinomas, the distribution of the lesions, and the extent of the disease are seldom studied. Even more infrequently are these parameters included in surgical pathology reports. Conversely, the routine use of large-format histologic sections in workup of operated breast specimens provides better insight into the significance of these parameters. The aim of the study was to identify breast carcinoma growth patterns indicating increased metastatic potential of the tumor and a need for more aggressive therapy.
  
  
  METHODS
  In all, 500 consecutive breast cancer cases, all of which were documented on large-format histologic sections, were retrospectively analyzed. The distribution of both in situ and invasive components of the tumors (unifocal/multifocal/diffuse) was defined, determined, and compared with the type of surgical intervention performed and the frequency of ipsilateral lymph node metastasis as endpoints. The extent of the disease, the size of the tumor, the presence or absence of lymphovascular invasion (LVI), and the proportion of invasive lobular carcinomas in the categories with different distributions were also analyzed.
  
  
  RESULTS
  Only 34% of the analyzed cases could be categorized as unifocal. This kind of tumor distribution was associated with lymph node metastasis in 28% of the cases, with LVI in 18%, with breast-conserving surgery in 67%, and with a proportion of 4% invasive lobular carcinomas. Tumors with a unifocal invasive component upgraded to multifocal or diffuse because of the distribution of the associated in situ component had similar characteristics. With their larger extent, tumors with a diffuse in situ component required mastectomy in 43% of cases. Multifocal distribution of the invasive component in the tumors was associated with higher frequency of LVI (42%) and lymph node metastases (48%), with a substantially lower number of cases undergoing breast-conserving surgery (33%) and with a higher proportion of lobular carcinomas (25%). If the multifocal invasive foci were associated with a diffuse in situ component, the proportion of invasive lobular carcinomas was only 5%. The extent of the lesions (defined as the area of breast tissue involved by in situ, invasive, and/or intravascular tumor foci) was >or=2 cm in >90% of multifocal cases and >or=4 cm in >70%. Diffusely growing invasive carcinomas were rare (only 20 cases), but were associated with lymph node metastasis in 60% of cases and resulted in mastectomy in 85% of the cases. Approximately two-thirds (65%) of these tumors belonged to invasive lobular carcinomas. The extent of diffusely growing invasive carcinomas was >or=4 cm in 75% of the cases. Although LVI was detected in only 10% of tumors with a diffusely growing invasive component, such tumors were found to have lymph node metastasis significantly more often (odds ratio of 2.33) and required mastectomy much more frequently (odds ratio of 2.58) compared with purely unifocal breast carcinomas.
  
  
  CONCLUSIONS
  These results indicate that the distribution of invasive and in situ tumor structures in breast carcinomas as defined in the current study, together with the extent of disease, are important morphologic parameters which determine the required surgical intervention and are related to biologic factors such as metastatic capacity. The method of large-section histology allows the examiner to properly document and demonstrate these important parameters, thus facilitating understanding of their clinical relevance.
authors.affiliation: Department of Pathology and Clinical Cytology, Central Hospital, Falun, Sweden. tibor.tot@ltdalarna.se
authors.forename: Tibor
authors.initials: T
authors.lastname: Tot
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology* / Q000601:surgery; D002277:Carcinoma / Q000473:pathology*; D002278:Carcinoma in Situ / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008408:Mastectomy; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies