The Usefulness of Elastin Staining to Detect Vascular Invasion in Cancer

Abstract

Tumor prognosis hinges on accurate cancer staging, a pivotal process influenced by the identification of lymphovascular invasion (LVI), i.e., blood vessel and lymphatic vessel invasion. Protocols by the College of American Pathologists (CAP) and the World Health Organization (WHO) have been established to assess LVI in various tumor types, including, but not limited to, breast cancer, colorectal cancer (CRC), pancreatic exocrine tumors, and thyroid carcinomas. The CAP refers to blood vessel invasion as "angioinvasion" (vascular invasion) to differentiate it from lymphatic vessel invasion (lymphatic invasion). For clarity, the latter terms will be used throughout this review. The presence of lymphatic and/or vascular invasion has emerged as a pivotal prognostic factor; therefore, its accurate identification is crucial not only for staging but also for providing the patient with an honest understanding of his/her prognosis. Given the prognostic importance of the correct identification of LVI, specific staining techniques are employed to distinguish lymphatic vessel invasion from angioinvasion and to differentiate true LVI from artifact. These encompass hematoxylin and eosin (H&E) staining, elastic staining, Factor VIII staining, Ulex europaeus I agglutinin staining, CD31, CD34, D2-40, ERG, and D2-40 (podoplanin) immunohistochemical (IHC) stains among others. Based on a review of numerous publications regarding the efficacy of various methods for LVI detection, elastin staining demonstrated superior accuracy and prognostic value, allowing for more targeted treatment strategies. The clinical significance of accurately detecting LVI cannot be overstated, as it is strongly linked to higher cancer-related mortality and an increased risk of tumor recurrence. This review aims to examine the existing literature on the use of elastin stains in the detection of vascular invasion among different types of tumors and its prognostic value.

Keywords: College of American Pathologists; TNM classification; World Health Organization; angioinvasion; elastin stain; immunohistochemistry; lymphovascular invasion; staging; venous invasion.

Figure 1

Schematic diagram for the interpretation of the presence of vascular invasion. The diagram illustrates a neoplasm (green) surrounded by a fibrous pseudocapsule (tan). For vascular invasion to be considered true invasion, the neoplastic cells should either penetrate through the vessel wall or should instigate a reaction to the vascular deposit via thrombus formation. Left to right: tumor deposit juxtaposed to the vessel wall (technically, although some pathologists may not count this as significant vascular invasion; this scenario is considered a “judgmental call”); tumor deposit juxtaposed to the vessel wall and associated with a thrombus; tumor cells directly penetrating the vessel wall and demonstrating thrombus formation. Above: tumor deposits within an organized thrombus, adherent to the vessel wall, external to the fibrous pseudocapsule of the tumor.

Figure 2

Schematic diagram depicting the benefit of using elastic staining to visualize vascular invasion in tumor tissue samples.

Figure 3

Schematic diagram for the interpretation of pitfalls in assessing vascular invasion. The diagram illustrates a neoplasm (green) surrounded by a fibrous pseudocapsule (tan). Three scenarios are presented from left to right where tumor in/abutting the vessel should not be counted as true vascular invasion: free-floating tumor fragments within the vessel lumen (likely a result of artifactual displacement); tumor bulging and compressing/abutting the vessel wall externally; endothelialized tumor cells floating withing the vessel (may be a result of the tangential sectioning of a tumor bulging into a vessel) which prompt taking deeper sections to exclude or include definitive vascular invasion.