Practical guidance for assessing and reporting lymphovascular space invasion (LVSI) in endometrial carcinoma

Abstract

Lymphovascular space invasion (LVSI) is an important prognostic parameter in endometrial carcinoma (EC) and has gained increasing interest in recent years due to an expanding body of evidence of its independent prognostic value, especially when the presence of LVSI is quantified. A key strength of LVSI as a prognostic factor is that it can be detected on routine microscopic examination, without ancillary tests, and thus can be used in low-resource settings. A weakness, however, is the lack of uniformly applied criteria for assessment and quantification of LVSI, resulting in interobserver variation in diagnosis. This is confounded by artefacts and other morphological features that may mimic LVSI (commonly referred to as pseudo-LVSI). Despite these issues, multiple studies have shown that LVSI is strongly associated with lymph node (LN) metastasis and is an independent risk factor for LN recurrence and distant metastasis. Consequently, the presence of substantial/extensive LVSI has become an important consideration in formulating adjuvant treatment recommendations in patients with EC, and this has been incorporated in the recent International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system. Herein, we review the current literature on LVSI in EC and discuss its role as a prognostic marker, the reproducibility of LVSI assessment and distinction between LVSI and its mimics. We provide illustrations of key diagnostic features and discuss the two-tiered (none/focal versus substantial) system of LVSI classification. This work is intended to provide guidance to practising pathologists and unify the approach towards LVSI assessment in EC.

Keywords: endometrial carcinoma; lymphovascular space invasion (LVSI); mimics; prognosis; reproducibility.

Figure 1

Examples of true lymphovascular space invasion (LVSI) in endometrial carcinoma (EC). The vessels involved in these photomicrographs are situated in the myometrium beyond the invasive tumour border. Note the presence of ‘soft clues’ for true LVSI such as the presence of perivascular lymphoid aggregates, close proximity to arterial and/or venous vessels, the rounded nature of the tumour emboli and the lack of stromal elements in the tumour emboli. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Lymphovascular space invasion (LVSI) in endometrial carcinoma (EC). LVSI should be diagnosed in the myometrium beyond the advancing tumour front. These examples display how an area with substantial LVSI can be appreciated at low power, displaying a spray‐like distribution. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Examples of pseudo‐lymphovascular space invasion (LVSI). A, Autolysed tumour fragments often become displaced along cut surfaces during grossing and may also be displaced into vascular spaces. B, Tumour fragments pushed into vessels and into myometrial cleft‐like spaces. C, Example of a case with retraction artefact. Note the presence of fine strands of cytoplasm between the embolus and the vessel wall, which is a strong clue for retraction. D, MELF (microcystic, elongated and fragmented)‐type invasion with partially flattened epithelial lining simulating endothelial cells. Note the presence of stromal elements in some of these examples of pseudo‐LVSI as a useful clue to distinguish from true LVSI tumour emboli. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

MELF (microcystic, elongated and fragmented) pattern of myometrial invasion in endometrial carcinoma, mimicking lymphovascular space invasion (LVSI). Note the focally cuboidal epithelial cells lining the space (A, haematoxylin and eosin). The lining cells stain for cytokeratin, confirming their epithelial nature (B). [Color figure can be viewed at wileyonlinelibrary.com]

Figure 5

Immunohistochemistry for D240 and CD31 highlights that tumour emboli are within vascular space. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 6

Enumeration of vessels. In both photomicrographs, multiple tumour emboli are present within a vascular space. While it is difficult to know whether this represents involvement of a single or multiple vessels, we interpret both these photomicrographs as showing involvement of a single vessel. When this is seen in isolation, these cases would be diagnosed with focal lymphovascular space invasion (LVSI). [Color figure can be viewed at wileyonlinelibrary.com]

Figure 7

The number of endometrial carcinomas plotted against the number of involved lymphovascular space invasion (LVSI)‐positive vessels. Note the small number of cases that fall within the borderline range of three to five vessels. [Color figure can be viewed at wileyonlinelibrary.com]