Large nested urothelial carcinoma: A clinicopathological study of 22 cases on transurethral resection materials

Large nested urothelial carcinoma (LNUC) is a recently recognized variant of urothelial carcinoma (UC), which is characterized with inverted growth pattern and bland cytology. Diagnosis can be extremely challenging, especially in transurethral resection (TUR) materials. Haematoxylin-eosin stained slides of TUR materials with UC, submitted to our department between 2008 and 2017 were re-examined. Twenty-two LNUC cases were found. LNUC frequency was 0.7%. Mean age was 69.9, 82% were male. Mean tumor diameter was 4.9 cm. Non-invasive UC was present in all cases; low-grade in 6, high-grade in 1, low and high-grade in 15. Five and 16 cases were pT1 and pT2, respectively, no invasion was detected in one case. In addition to medium-large nests, small nests and conventional UC areas was present in 2 and 3 cases, respectively. Stroma-tumor interface was irregular in 19 cases and 3 cases had invasive nests with rounded contours. Fibrous stromal reaction and/or stromal lymphoid infiltration were present in 21 cases. Budding, described as small nests in stromal interface of medium-large nests was found in 16 cases. Follow-up was available for 18 cases with an average of 59 months. Four cases had metastasis, 1 patient died of disease. LNUC causes diagnostic difficulty, especially in TUR materials. Large size of tumor, irregularity of nests, presence of stromal reaction and budding can be clues for correct diagnosis.