The ancillary role of D2-40 in demonstration of muscularis propria invasion vs desmoplastic reaction in invasive urothelial carcinoma of the bladder.

Abstract

The presence or absence of muscularis propria (MP) invasion carries significant implications in bladder carcinoma treatment. Identification of MP is mainly based on morphology, with occasional application of immunohistochemical stains, including desmin, H-caldesmon, and smooth muscle actin (SMA), all aimed to stain smooth muscle. The specificity of these stains is imperfect. We evaluate the ancillary role of D2-40 in separating MP from desmoplastic reaction. We first examined immunoreactivity of muscularis mucosae and MP with the above markers in nonneoplastic specimens to establish their staining patterns. We then studied 33 cases of muscle-invasive urothelial carcinoma in which a desmoplastic reaction and MP were both present and clearly identifiable by routine hematoxylin and eosin morphology, with the goal of determining the sensitivity and specificity of these stains in identifying MP vs desmoplastic reaction. Both muscularis mucosae and MP stained uniformly positive for desmin, H-caldesmon, and SMA and lacked expression of D2-40. The desmoplastic reaction showed positivity with desmin in 30 cases (91%), H-caldesmon in 29 cases (88%), SMA in 33 cases (100%), and D2-40 in 33 cases (100%). Expression of desmin, H-caldesmon, and SMA identified MP with 100% sensitivity, but their specificity dropped to 9%, 12%, and 0%, respectively. In contrast, D2-40 demonstrated 100% sensitivity and specificity in distinguishing MP vs desmoplastic reaction. We suggest using an immunohistochemical panel composed of D2-40 and a smooth muscle marker, preferably desmin or H-caldesmon, to help distinguish muscularis propria from desmoplastic reaction when morphology alone is equivocal.