Serous tubal intra‐epithelial carcinoma: what do we really know at this point?

Abstract

Serous tubal intra‐epithelial carcinoma (STIC) is the earliest morphologically recognisable step in the development of invasive high‐grade serous carcinoma of the fallopian tube. Lesions occurring prior to STIC within the carcinogenic sequence for the pathogenesis of invasive high‐grade serous carcinoma include the p53 signature and secretory cell outgrowth (SCOUT). Variable histological criteria have been used for diagnosing STIC, but a combination of morphology and immunohistochemistry for p53/Ki‐67 improves interobserver agreement. Half of all carcinomas identified in risk‐reducing salpingo‐oophorectomy specimens are in the form of STIC; however, STIC also may be incidentally found on occasion in specimens from women at low or average risk of ovarian/tubal/peritoneal carcinoma. TP53 mutation is the earliest known DNA sequence alteration in STIC and almost all invasive high‐grade serous carcinomas of the ovary and peritoneum. Data on the clinical behaviour of STIC are limited. While the short‐term follow‐up in the prior literature suggests a low risk of malignant progression, a more recent meta‐analysis indicates a 10‐year risk of 28%. STIC probably should be best regarded as a lesion with uncertain malignant potential at present, and future molecular analysis will help to classify those with higher risk of dissemination. This review provides an update on the current knowledge of STIC and related issues.

Morphologic and Molecular Heterogeneity of High-grade Serous Carcinoma Precursor Lesions

“…STIL is the lesion with nuclear atypia but to a lesser degree as compared with STIC and with Ki-67 proliferation index <10%. p53 signature represents a stretch of tubal epithelial cells showing a p53-missense–type immunostaining pattern but without any recognizable atypia 17 . The study design is schematically summarized in Figure 1A.…”

“…Cases with a diagnosis of STIC or STIL were identified in the pathology archives at the Johns Hopkins Medical Institutions in Baltimore, MD, and the Inova Fairfax Hospital in Fairfax, VA. The diagnoses of those lesions were finalized in consensus pathology meetings at the local hospitals using the criteria defined in a previous study 17 . Formalin-fixed and paraffin-embedded tissue blocks as well as the original hematoxylin and eosin staining slides were obtained.…”

“…The group of tubal lesions without morphologic atypia but showing a p53-missense–type immunostaining pattern are termed p53 signature. In clinical practice, p53 signatures cannot be identified on a basis of routine hematoxylin and eosin staining unless p53 immunohistochemistry is applied 17 …”

“…In clinical practice, p53 signatures cannot be identified on a basis of routine hematoxylin and eosin staining unless p53 immunohistochemistry is applied. 17 Recent studies have shed light on the molecular landscape of STIC and STIL, revealing key molecular alterations involved in their development. 1,13,[18][19][20] However, the heterogeneity of tubal precursor lesions has not been well characterized.…”

“…In clinical practice, p53 signatures cannot be identified on a basis of routine hematoxylin and eosin staining unless p53 immunohistochemistry is applied. 17 …”