The pathology of urinary bladder lesions with an inverted growth pattern

Abstract

Inverted lesions in the urinary bladder have been the source of some difficulty in urological pathology. The two common ones are von Brunn's nests and cystitis cystic/cystitis glandularis, which are considered normal variants of urothelium. Apart from them, a number of other rare urothelial lesions with inverted growth pattern occur in the urinary bladder. Some of them are only reactive conditions, just as pseudocarcinomatous hyperplasia. Some are benign tumors, namely inverted papilloma. Whereas others are malignant neoplasms, including inverted papillary urothelial neoplasm of low malignant potential (PUNLMP), non-invasive inverted papillary urothelial carcinoma (low-grade and high-grade), and invasive urothelial carcinoma (inverted, nested and big nested variants). Because of the overlapping morphological features of all the inverted lesions mentioned above, even between high-grade invasive carcinoma and pseudocarcinomatous hyperplasia which are only a kind of reactive conditions, it is very important for the surgical pathologist to recognize and be familiar with these inverted lesions in urinary bladder. In this article, we review these spectrums of inverted lesions of the urinary bladder. Emphasis is placed on histogenesis, morphology, differential diagnosis of these lesions, and the pathologic grading of the non-invasive inverted neoplasms, such as inverted papilloma, inverted PUNLMP, non-invasive inverted papillary urothelial carcinoma with low-grade, and non-invasive inverted papillary urothelial carcinoma with high-grade.

Keywords: Von Brunn’s nests; inverted papillary urothelial neoplasm of low malignant potential (PUNLMP); inverted papilloma; inverted urothelial carcinoma; pseudocaicinomous hyperplasia.

Figure 1

Von Brunn nests and cystitis cystica. (A) Von Brunn nests proliferating and forming significant solid cell nodules, with cystic or adenoid lacunae in the center of some nests (HE, ×40); (B) cystitis cystica connecting with the surface of the urothelium (HE, ×40); (C, D) cystitis cystica having smooth edges, locating on the superficial layer of the lamina propria, having relatively identical lesion depth, occurring with concurrently with von Brunn nests and being lined with the true urothelium (C: HE, ×40; D: HE, ×100).

Figure 2

Inverted papilloma. (A) Non-hyperplastic and non-atypical tumor cells growing endophytically to the lamina propria and forming different-sized epithelial nests and trabecular with a surface of thin normal layer of urothelium (HE, ×40); (B) inverted papilloma with peripheral palisading and central paralleling with the basal lamina (HE, ×200); (C) in the center of the nest, micro cystic structure formed lining with typical surface “umbrella” cells of the urothelium (HE, ×100); (D) the stroma within the trabecular structure is mainly loose connective tissue (HE, ×100).

Figure 3

Similar to exophytic one, Inverted PUNLMP is composed of large and mild irregular trabeculae, an increased thickness, presence of central “umbrella” cells, mild atypia and rare mitoses within an urothelium with preserved polarity. PUNLMP, papillary urothelial neoplasm of low malignant potential (HE, ×40).

Figure 4

Inverted papillary urothelial carcinoma, non-invasive, low grade. (A) The neoplasm shows large and moderate irregular trabeculae with inconsistent size, a degree of cellularity and loss of polarity (HE, ×40); (B) mild to moderate cytologic atypia is apparent (HE, ×100).

Figure 5

Inverted papillary urothelial carcinoma, high grade. The neoplasm shows large and severe irregular trabeculae with inconsistent size, a degree of cellularity, even greater loss of polarity, severe cytologic atypia (HE, ×40).

Figure 6

Inverted urothelial carcinoma with micro-nested, cluster-like, or individual cellular invasion (HE, ×100).

Figure 7

Nested variant of urothelial carcinoma is characterized by bland morphology which mimics von Brunn nests (A) and deeper invasion (B) (HE, ×40).

Figure 8

Large nested variant of urothelial carcinoma. The large nested variant of urothelial carcinoma always is an aggressive neoplasm with deep muscularis propria invasion (A) (HE, ×40) but with a milder morphological cellular appearance (B) (HE, ×100).