Answer: Atypical inflammatory myofibroblastic tumor

Histology: The lesion, in areas, has a classic tissue-culture-like pattern seen with inflammatory myofibroblastic tumors (IMT). Within a myxoid background, cells have relatively uniform nuclei with longer tapering fibroblastic-like cells. Within the myxoid matrix, extravasated red blood cells and inflammatory cells are noted. In areas, the lesion is more cellular with a greater degree of pleomorphism. These pleomorphic cells contain large hypochromatic nuclei. Numerous mitotic figures are identified, a few which appear somewhat atypical. The lesion extends into muscularis propria.

Discussion: This patient, several months ago, had a classic IMT confirmed by positive staining for ALK-1. IMTs of the bladder are rare and have been called by various other names in the past, most commonly pseudosarcomatous fibromyxoid tumors. The recognition that IMTs have shown clonal abnormalities involving the ALK gene and are immunoreactive for ALK protein supports the hypothesis that some IMTs of the bladder are neoplastic rather than reactive lesions. Approximately 2/3 of bladder IMTs will show ALK-1 expression. The most important differential diagnosis includes sarcomatoid urothelial carcinoma and leiomyosarcoma. IMT often shows strong or extensive immunoreactivity for cytokeratin, which can lead to a misdiagnosis of sarcomatoid carcinoma. The presence of marked cytologic atypia, atypical mitotic figures, and non-myxoid areas with marked increased cellularity or the presence of malignant epithelial components are key features to diagnose sarcomatoid carcinoma. Some leiomyosarcomas show myxoid features and can also stain positive for cytokeratin. The lack of a delicate vascular network, interspersed inflammatory cells and extravasated red blood cells which are usually observed in IMT, and the presence of marked cytological atypia and atypical mitoses seen in leiomyosarcomas may be helpful in the differential diagnosis. Leiomyosarcomas are usually negative for ALK-1 protein. IMT of the bladder usually shows a benign clinical course and even local recurrence is rare. Treatment of choice is usually transurethral resection or, if the lesion is amenable, partial cystectomy. The current case is unusual in that this patient experienced several rapid recurrences of the IMT following TUR with the most recent recurrence showing a greater degree of cytologic atypia and increased cellularity. Because of these worrisome histological features and the difficulty in clinical management of the patient, we diagnosed this lesion as an atypical IMT and recommended that this patient undergo radical cystectomy. As the behavior of IMTs are not entirely well-characterized, even in classic cases I always recommend, as I did in this case, close clinical follow-up to make sure that the lesion does not progress or continues to regress. One must also be extremely careful making the diagnosis of IMT on a limited biopsy from the bladder as sarcomatoid carcinomas and sarcomas may have areas resembling IMTs.