Malignant Transformation and Stromal Invasion from Normal or Hyperplastic Tissues: True or False?

Abstract

Carcinogenesis is believed to be a multi-step process, progressing sequentially from normal to hyperplastic, to in situ, and to invasive stages. A number of studies, however, have detected malignancy-associated alterations in normal or hyperplastic tissues. As the molecular profile and clinical features of these tissues have not been defined, the authors invited several well-recognized pathologist, oncologists, biologist, surgeons, and molecular biologist to offer their opinion on: (1) whether these tissues belong to a previously unrevealed malignant entity or focal alterations with no significant consequence? (2) whether these alterations are linked to early onset of cancer or cancer of unknown primary site, and (3) how to further define these lesions?

Untitled

“…Check for updates cently been done for these lesions in humans [11,[19][20][21]. Moreover, in this study, changes in canine myoepithelial cells similar to those in human IELs were found, and new IELs not reported in the veterinary literature are described.…”

“…A recent, predominantly epidemiologic report that included clinical and histopathologic data from 90 female canines with 296 tumors hypothesized those malignant mammary tumors could develop from pre-existing low-risk IELs and that the malignant tumors would be the final stage [77]. Although the authors of the report described the very beginning, as also reported for women by Man, et al [20]. For example, it is not plausible that highly prevalent lesions (such as CIS, which exhibit a variable morphology) can derive from a monomorphic atypical IEL (such as ADH, which had a very low prevalence in this study) and are not spatially related to high-risk lesions (CIS, ICA and Complex carcinoma).…”

“…Such changes were common in malignant epithelial cells in this study. These findings suggest that the linear model of tumor progression cannot be applied in every case [79] and that these spontaneous lesions are malignant from the beginning [19,20].…”

“…This characteristic would make the lobe/lobule more susceptible to endo-or exogenous oncogenic stimuli than lobes or lobules of the same mamma that do not bear or have a lower number of potentially malignant cells [11,20]. One of the most important findings in the sick lobe is that these cells are malignant from the outset [11].…”

Histologic Evidence of the "Sick Lobe" Carcinogenesis Theory and the Frequency of Intraepithelial Lesions in the Mammary Glands of Female Canines with no Clinical Signs of Neoplasia

“…3) The use of 'intraepithelial' means that these pathologies are independent of their immediate environment; however, as recent research demonstrates, the stroma has a more significant role in the evolution of these lesions than previously acknowledged [20,[46][47][48][49][50][51][52][53][54]. Our own research in canines clearly shows that these pathologies are accompanied by significant (and to some extent are dependent on) changes starting in early development not only of myoepithelial cells but also their surrounding microenvironment, which includes the basal membrane, the amount of connective tissue and the infiltration of leukocytes [19,[55][56][57][58][59][60][61][62][63][64][65][66][67].…”