The Stem Cell Marker Bmi-1 Is Sensitive in Identifying Early Lesions of Carcinoma ex Pleomorphic Adenoma

Abstract

In the present study, we evaluated and described the sensitivity of the stem cell marker B cell-specific moloney murine leukemia virus integration site 1 (Bmi-1) in identifying early lesions of carcinoma ex pleomorphic adenoma (CXPA). While invasive CXPAs are tumors with a prominent and easily recognizable malignant component, the identification of early carcinomatous changes in PA remains a diagnostic challenge due to the lack of objective morphological criteria. The immunohistochemical expression of Bmi-1 was assessed in both adenomatous and carcinomatous components of 9 CXPA cases at an early phase of histological progression (6 intracapsular and 3 minimally invasive) grouped according to the cellular differentiation as luminal (7 cases) or myoepithelial (2 cases). A selective nuclear expression of Bmi-1 was found exclusively in the malignant component of 8 cases (6 luminal type and 2 myoepithelial type), including intraductal carcinoma areas, except for 1 case in which scarce cells of the remnant PA were positive. Thus, Bmi-1 is expressed from the earliest morphologically detectable stages of PA malignant transformation. When faced with atypical features in PA, evaluation of Bmi-1 expression can provide more objective criteria for identification and diagnosis of early lesions of CXPA. This is applied to carcinomas with luminal or myoepithelial differentiation.

FIGURE 1

(A) Occasional double-layered ductiform structures and cords of modified myoepithelial cells in a myxoid stroma compose residual pleomorphic adenoma areas. No cellular pleomorphism is present (hematoxylin and eosin (H&E), original magnification ×400). (B) Scarce Bmi-1-positive cells in remnant pleomorphic adenoma areas (original magnification, ×400). (C) Intraductal carcinoma area characterized by expanded ductiform structures lined by highly pleomorphic transformed ductal cells, occasionally with individual necrotic cells, externally bounded by a rim of bland-looking myoepithelial cells (arrows) (H&E, original magnification, ×400). (D) Bmi-1 expression in luminal transformed cells (original magnification, ×400).

FIGURE 2

Intracapsular luminal-type carcinoma ex pleomorphic adenoma with extraductal component. (A) Numerous irregular duct-like structures replacing the “maternal” pleomorphic adenoma (myxoid area), but respecting the capsule (hematoxylin and eosin (H&E), original magnification ×100). (B) In a high-power view, juxtaposed duct-like structures lined by pleomorphic cells (H&E, original magnification ×400). (C) Nuclear Bmi-1 expression in carcinomatous cells (original magnification, ×400).

FIGURE 3

Intracapsular myoepithelial-type carcinoma ex pleomorphic adenoma. (A) Blocks of clear to eosinophilic cells pushing the capsule. A neoplastic islet is infiltrating the capsular connective tissue (arrows) (hematoxylin and eosin (H&E), original magnification, ×100). (B) In detail, myoepithelial carcinoma composed by compact nests of clear cells lacking pleomorphism, ductal formation, and mitotic activity (H&E, original magnification, ×400). (C). Diffuse nuclear Bmi-1 expression in malignant myoepithelial cells (original magnification, ×400).