Inverted urothelial carcinoma: a series of 12 cases with a wide morphologic spectrum overlapping with the large nested variant

Summary The current series presents 12 cases of invasive urothelial carcinoma (UC) with inverted growth pattern that fulfill the architectural criteria of the recently described “large nested” variant of UC, but which display a wider spectrum of morphologic and cytologic changes. All cases had an associated component of usual invasive UC, and 10 had an associated surface papillary component. Although many areas within the tumors were indistinguishable from a noninvasive endophytic growth pattern, at least some had an irregular ragged contour, and all showed haphazard arrangement with variable amount of intervening stroma at least focally. Inflammatory stromal reaction was noted in 11 cases, and desmoplasia and retraction artifact were present in 8 cases each. Although major areas showed mild atypia, many tumors showed marked hyperchromasia, prominent nucleoli, marked irregular nuclear membranes, and brisk mitotic activity. Final pathological stage on cystectomy specimens was T2 in 4 cases, T3 in 2 cases, and T4 in 3 cases. In 3 cases, lymph node metastases were documented histologically. Review of the literature shows that the “large nested,” “inverted,” “endophytic,” and “inverted papilloma-like” variants of invasive UC are interrelated entities and should probably be considered as one variant with a wide spectrum of cytoarchitectural features. They should also be separated from the “nested” variant with which they rarely coexist and which shows different characteristics at the morphologic level.