Intraepidermal cells of Paget's carcinoma of the breast can be genetically different from those of the underlying carcinoma

Hum Pathol. 2003 Dec;34(12):1321-30. doi: 10.1016/s0046-8177(03)00405-2.


Paget's carcinoma (PC) of the breast is characterized by neoplastic cells of "glandular" type located within the epidermis of the nipple-areolar complex, often associated with an underlying ductal carcinoma, either in situ or invasive. At present the origin of PC cells is controversial, although there is a widespread opinion that PC cells are "foreign" elements to the epidermis resulting from an epidermotropic migration of neoplastic elements from an underlying ductal carcinoma. An alternative view is that some cases result from neoplastic transformation of preexisting, innocent intraepidermal clear cells of the nipple-areolar complex (Toker cells) that migrate from nonneoplastic ducts. Consequently, 10 cases were studied using methods for clonality (ie, loss of heterozygosity and mitochondrial DNA displacement loop sequence analysis). Microdissection of intraepidermal neoplastic cells and of cells from underlying duct carcinomas and metastases was performed. In no fewer than 2 cases, PC cells were genetically different from underlying lesions, which showed consistent homology among themselves. Therefore, it is suggested that the rule of epidermotropism by neoplastic cells from an underlying carcinoma is not applicable to all cases, and that in some cases PC cells might be the result of neoplastic transformation of preexisting intraepidermal nonneoplastic cells. Consequently, the underlying tumors are coincidental neoplastic lesions (collision tumors).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma, Intraductal, Noninfiltrating / genetics*
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Cell Transformation, Neoplastic
  • DNA, Mitochondrial / genetics
  • DNA, Neoplasm
  • Female
  • Humans
  • Immunohistochemistry
  • Loss of Heterozygosity
  • Lymphatic Metastasis
  • Male
  • Microdissection
  • Middle Aged
  • Mutation
  • Paget's Disease, Mammary / genetics*
  • Paget's Disease, Mammary / pathology
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA


  • Biomarkers, Tumor
  • DNA, Mitochondrial
  • DNA, Neoplasm