Precancer versus Intraepithelial neoplasia

During carcinogenesis, morphologically identifiable lesions occur that precede the development of invasive cancer. These lesions are called precancers, premalignancies, preneoplastic lesions, incipient cancers, intraepithelial neoplasias, and preinvasive cancers. The plethora of terms reflects the difficulty of choosing a "best" canonical class term for the precancerous lesions. Currently, the term "intraepithelial neoplasia" seems to enjoy wide usage among the community of pathologists, but this term has limitations, as discussed in two prior papers:

   Berman JJ, Henson DE.
   Classifying the precancers: a metadata approach.
   BMC Med Inform Decis Mak. 2003 Jun 20;3:8. 
   Epub 2003 Jun 20.

   Seidman JD, Berman JJ.
   Premalignant nonepithelial lesions: 
   a biological classification.
   Mod Pathol. 1993 Sep;6(5):544-54.

1. Not all epithelial precancers are intraepithelial. Most of the mucosal dysplasias have a well-defined territory bounded by the junction between the epithelium and the underlying stroma. But not all premalignant epithelial lesions can be identified by the presence of atypical cell populations delimited by a basement membrane. Dysplastic lesions of the liver, kidney, thyroid and adrenal are not delimited by a basement membrane.

2.Not all precancers are epithelial. Intratubular germ cell neoplasms of testis, myelodysplasias, and non-autonomous lymphomas are examples of non-epithelial precancers.

3. Not all intraepithelial neoplasms are precancers. Neoplasms that are intraepithelial but that are not precancers include: seborrheic keratoses, intraepidermal nevi, common warts and most so-called benign epithelial tumors.

Likewise, the term pre-invasive cancer raises an existential question. Use of the term "pre-invasive cancer" implies that precancers have attained the biological properties of a cancer. This assumption may not be true. Precancers may lack constitutive properties of cancer or may have certain attributes that are absent in cancers. At this point, there is insufficient knowledge to conclude that precancers are types of cancer.

I like the term "precancers". It conveys only the defining features of the lesions: occurrence prior to cancers, and existence as an identifiable lesion.

- Jules Berman

key words: precancer, pre-cancer, premalignant, neoplasm classification, tumors, carcinogenesis