title: Periocular Breast Carcinoma Metastases: Predominant Origin From the Lobular Variant.
abstract: OBJECTIVE
  To further define the histopathologic features of breast carcinoma conducive to orbital metastasis.
  
  
  METHODS
  Ten new female patients with orbital or eyelid breast cancer metastases encountered between 2011 and 2016 had their medical records reviewed for determining their clinical characteristics. Microscopic glass slides from biopsies and immunohistochemical test results were also analyzed. Biomarkers studied included cytokeratin 7, nuclear estrogen and progesterone receptors, HER2, and E-cadherin.
  
  
  RESULTS
  All orbital metastatic lesions were lobular (nonductal) carcinomas that could arise as late as 24 years after the diagnosis of the primary breast tumors. The average age of patients at the time or orbital presentation was 64 years. Metastases were composed of small tumor cells with round, orthochromatic nuclei, and a small amount of cytoplasm. The cells were disposed in a variably fibrotic tumor-associated stroma. Two lesions were variants of lobular carcinoma-namely, alveolar and pleomorphic (the latter displaying cellular crowding, with some degree of nuclear atypia and less stroma). Three of the 9 orbital metastases presented with enophthalmos and 2 displayed euphthalmos despite variably sized orbital masses. In 2 cases, synchronous bilateral orbital metastases prevented any relative difference in globe position. Estrogen and progesterone receptors were usually detectable whereas E-cadherin could not be demonstrated.
  
  
  CONCLUSIONS
  Breast pathologists no longer refer to primary breast carcinomas and their orbital metastases as "scirrhous." It has been determined that the majority of orbital breast metastases are lobular carcinomas. This may be due to their lack of intercellular cohesiveness and the absence of E-cadherin which normally is expressed in many neoplastic cell types including ductal breast carcinomas, limiting their dispersion. In contrast, the majority of primary breast carcinomas are ductal. The ubiquitous collagenous matrix in breast metastases retracts, partially accounting for enophthalmos. The presence of euphthalmos despite an orbital mass additionally suggests some retraction of fibrous tissue (with or without fat atrophy) that suppresses relative proptosis. Metastatic lobular breast carcinoma is further implicated if there is a concomitant limitation in extraocular motility or vision decline.
authors.affiliation: *David G. Cogan Ophthalmic Pathology Laboratory, †Massachusetts Eye and Ear Infirmary, and ‡Harvard Medical School, Boston, MA, U.S.A.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Jakobiec
authors.forename: Anna M
authors.initials: AM
authors.lastname: Stagner
authors.forename: Natalie
authors.initials: N
authors.lastname: Homer
authors.forename: Michael K
authors.initials: MK
authors.lastname: Yoon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009918:Orbital Neoplasms / Q000175:diagnosis / Q000556:secondary*; D012189:Retrospective Studies