Microscopic description:

Lesion consists of invasive urothelial carcinoma, high grade with nested pattern and invasion into the muscularis propria

IHC showed positivity for GATA3, CK7, AE1/AE3, CAM5.2 and p63

Based on the histopathological features and IHC stains, finding is consistent with persistent invasive high grade urothelial carcinoma with nested features

Discussion:

The nested variant of urothelial carcinoma is a very rare type of cancer, making up just 0.8% of all invasive bladder carcinoma

It is known for the deceptively bland histologic appearance, despite aggressive behavior and poor prognosis (70% mortality between 4 and 40 months)

Nested pattern can be identified by losely packed, haphazardly arranged, and poorly defined urothelial cells infiltrating the lamina propria and the muscularis propria (which is differential from other possible diagnoses)

The nested pattern of the recurrent bladder lesion was not originally identified on prior research, which highlights the difficulty in accurate diagnosis

Difficult to diagnose due to resemblance of foci to benign processes, and infiltrative patterns being hard to assess on small biopsies

Common stains used for positivity include CK7, CK20, p63, Ki-67, CK903 and variable for P53. Some research suggests p53 positivity, and possible subsequent p21 loss, may indicate a higher rate of recurrence and worse survival rate

Accurate and early diagnosis is essential to begin treatment, as diagnosis at advanced stages often have poor prognosis

Treatment is uncertain due to the rarity of the variant, and also but research suggests multimodality therapy including platinum based chemotherapy may be beneficial, as well as cystectomy for early stage tumors

References:

Dhall D, Al-Ahmadie H, Olgac S. Nested variant of urothelial carcinoma. Arch Pathol Lab Med. 2007 Nov;131(11):1725-7. doi: 10.5858/2007-131-1725-NVOUC. PMID: 17979494.

Lin O, Cardillo M, Dalbagni G, Linkov I, Hutchinson B, Reuter VE. Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases. Mod Pathol. 2003 Dec;16(12):1289-98. doi: 10.1097/01.MP.0000094091.04541.FC. PMID: 14681330.

Venyo AK. Nested variant of urothelial carcinoma. Adv Urol. 2014;2014:192720. doi: 10.1155/2014/192720. Epub 2014 Jan 22. PMID: 24587796; PMCID: PMC3920611

Wang J, Talmon G, Kazmi SA, Siref LE, Morris MC. Metastases from nested variant urothelial carcinoma of the urinary bladder in pancreatic allograft mimicking graft rejection. J Clin Med Res. 2012 Apr;4(2):145-8. doi: 10.4021/jocmr798w. Epub 2012 Mar 23. PMID: 22505990; PMCID: PMC3320126.