Serous tubal intraepithelial neoplasia: the concept and its application

Abstract

In recent years it has become clear that many extra-uterine (pelvic) high-grade serous carcinomas (serous carcinomas) are preceded by a precursor lesion in the distal fallopian tube. Precursors range from small self-limited 'p53 signatures' to expansile serous tubal intraepithelial neoplasms that include both serous tubal epithelial proliferations (or lesions) of uncertain significance and serous tubal intraepithelial carcinomas. These precursors can be considered from three perspectives. The first is biologic underpinnings, which are multifactorial, and include the intersection of DNA damage with Tp53 mutations and disturbances in transcriptional regulation that increase with age. The second perspective is the morphologic discovery and classification of intraepithelial neoplasms that are intercepted early in their natural history, either incidentally or in risk-reduction surgeries for germline mutations. For the practicing pathologist, as well as the investigators, a distinction between a primary intraepithelial neoplasm and an intramucosal carcinoma must be made to avoid misinterpreting (or underestimating) the significance of these proliferations. The third perspective is the application of this information to intervention, devising strategies that will actually lower the ovarian cancer death rate by opportunistic salpingectomy, widespread comprehensive genetic screening and early detection. Central to this issue are the questions of (1) whether some STICs are metastatic, (2) whether lower-grade epithelial proliferations can invade prior to evolving into intraepithelial carcinoma, or (3) metastasize and become malignant elsewhere ('precursor escape'). An important caveat is the persistent and unsettling reality that many high-grade serous carcinomas are not associated with an obvious point of initiation in the fallopian tube. The pathologist sits squarely in the midst of all of these issues, and has a pivotal role in managing expectations for stemming the death rate from this lethal disease.

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer

“…Thus, more recent evidence supports the idea that most HGSC in both sporadic and hereditary ovarian cancer are of fallopian tubal origin (23,41,42). Despite the fact that an obvious precursor STIC was contiguous with invasive carcinoma, one third of these patients were not associated with STIC in the fallopian tube (41). Fallopian tube hosts progenitor to the majority of HGSC.…”

Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube

“…Larger studies will be required to test these hypotheses. Epithelial cell dynamics in the fallopian tube have not been extensively studied, but in the last two decades, interest in this organ has been piqued by strong evidence to support a fallopian tube origin for the majority of high-grade serous 'ovarian' carcinomas (Callahan et al, 2007;Chen et al, 2017;Lee et al, 2007;Medeiros et al, 2006;Meserve et al, 2017). The pseudostratified epithelium of the fallopian tube consists of two major cellular populations.…”

Ovarian cancer stem cells: still an elusive entity?

“…First, in contrast to the classical view that the different OC hystotypes derive from metaplastic changes of one single tissue, the ovarian surface epithelium (OSE) [13, 14], it has become increasingly clear that only a subset of epithelial OC actually develops within the OSE, while most OC variants originate in non-ovarian districts [15]. As outlined in greater detail below (see “The normal counterpart of OCSC”), this is best exemplified by HGSC, for which clinical, pathological, and experimental evidence supports the fallopian tube as a frequent site of origin [16–19]. …”