Lymphovascular Invasion in Micropapillary Urothelial Carcinoma: A Study of 22 Cases

Abstract

is a known aggressive variant of urothelial carcinoma. However, the reasons for its aggressiveness remain unclear.Objective.-To investigate the frequency of lymphovascular invasion in 22 cases of MPUC.Design.-Consecutive tissue sections were stained with D2-40 and CD34 to highlight lymphovascular channels associated with MPUC. Spaces containing tumor cells were scored as positive for lymphovascular invasion if the staining pattern on immunohistochemistry was distinct and circumferential.Results.-Of 22 cases, 21 (95%) had lymphovascular invasion on immunohistochemical staining, with 91% lymphatic invasion and 4% vascular invasion. Interestingly, 8 cases were originally signed out as negative for lymphovascular invasion on the basis of hematoxylineosin-stained sections; of these, 7 (88%) had focal lymphovascular invasion evident on immunohistochemical staining.Conclusions.-Our results confirm that micropapillary lacunae are not lymphovascular channels. However, nearly all MPUC tumors (95% in this series) have evidence of lymphovascular invasion by immunohistochemical analysis. Our data support the use of micropapillary features as a morphologic marker for lymphovascular invasion and MPUC as an adverse histologic type of urothelial carcinoma.(Arch Pathol Lab Med. 2012;136:635-639; doi: 10.5858/ arpa.2011-0463-OA) M icropapillary urothelial carcinoma (MPUC) is a rare, clinically aggressive histologic variant of urothelial carcinoma (UC). It was first described by Amin et al 1 in 1994 and is characterized by small, infiltrating clusters of neoplastic cells that appear to float within clear lacunar spaces and that lack a fibrovascular core (Figure 1). Micropapillary urothelial carcinoma occurs almost exclusively in the setting of conventional UC, 2,3 and the proportion of MPUC predicts high pathologic stage and lymph node metastasis. 4,5 The overall prognosis is poor; the 5-year and 10-year survival in the largest study were 51% and 24%, respectively. 6Multiple investigators have examined vascular invasion in MPUC by using immunohistochemistry for factor VIII, Ulex europaeus, CD31, and CD34, 1,7-10 as summarized in Table 1. Together, these studies demonstrate vascular invasion in 23 of 33 cases (70%). But these studies are hampered by exclusive use of vascular endothelial markers, and the rate of lymphovascular invasion in MPUC may be even higher.

Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer

“…Particularly when this morphology is extensive, lymphovascular invasion is almost invariably present, showing a similar pattern of clustered micropapillae present within vascular spaces. 71 Proceeding from data that variants of urothelial carcinoma, including micropapillary, may be under 44 or over-recognized in the practice of surgical pathology and a desire to better characterize its diagnostic features, Sangoi et al 72 performed an interobserver reproducibility study of micropapillary urothelial carcinomas, sharing cases among a number of experts of the field. Although a number of features were identified as sensitive markers of micropapillary carcinoma, especially prominent retraction artifact, which may be seen in conventional urothelial carcinomas that do not meet criteria for the micropapillary variant (Figure 9b), the features that were identified as most specific to consensus micropapillary cases studied were the features of ‘multiple nests in the same lacuna’ (Figure 9c), ‘intracytoplasmic vacuolization,’ and related ‘epithelial ring forms’ (Figure 9d).…”

Is Immediate Radical Cystectomy Necessary for All Patients with Non-Muscle-Invasive Micropapillary Bladder Cancer?

“…Neither pattern of MP (sMP or iMP) nor extent of MP differentiation influenced OS, overall stage or lymph node involvement in the group as a whole; however, iMP differentiation was associated with LVI, indicating that iMP is essentially a morphological marker for LVI [5]. …”

“…Most are muscle invasive at presentation and show a propensity for associated carcinoma in situ (CIS) [3] and occult lymph node metastases [4]. Invasive MP (iMP) differentiation is associated with lymphovascular invasion (LVI) [5], and the recording of both LVI and the presence of variant histology such as MPUC is an important part of pathological assessment [6]. …”

Variants of Gastric Carcinoma: Morphologic and Theranostic Importance

“…Morphologically, when a distinction of IMPC within lacunar spaces from lymphovascular tumor emboli may be difficult, immunohistochemical studies including factor VIII, Ulex europaeus, CD31, CD34, and D2-40 as well as FLI1 and Erg nuclear stains would be useful to rule out lymphovascular tumor emboli from other types of adenocarcinoma (Fig.19) [191]. …”