Answer: Inflammatory myofibroblastic tumor (IMT)

Histology: The lesion consists of at low power a large mass which is invading muscularis propria. The lesion has variable morphology. In some areas the lesion consists of spindle cells arranged in shorts of fascicles. In other areas the lesion has a more epithelioid appearance. Individual cells consist of long spindle cells with abundant eosinophilic cytoplasm with cytoplasmic tails extending on both sides of the nuclei. The nuclei are vesicular with central prominent nucleoli. Throughout the lesion are interspersed neutrophils with less frequently lymphocytes and plasma cells. In areas the lesion has a somewhat myxoid appearance. Focal necrosis is identified.

Discussion: The major differential diagnosis of this spindle cell lesion is inflammatory myofibroblastic tumor (IMT) vs. leiomyosarcoma. Sarcomatoid sarcoma (carcinosarcoma) could also have a similar morphology. IMT, in contrast to both of these malignant differential diagnoses, has tissue-culture-like fibroblasts with long cytoplasmic extensions on either side of the nuclei. Furthermore, the lack of nuclear hyperchromasia is critical in distinguishing IMT from sarcomas and sarcomatoid carcinomas. Although the nuclei are enlarged, they are vesicular with prominent nucleoli and are not dark and are not pleomorphic. Some IMTs can have frequent mitotic figures although the current case does not. The presence of scattered neutrophils also throughout the lesion is classic for IMT and is not a typical finding within sarcomas or sarcomatoid carcinomas. These lesions can mimic malignancies due to their large growth, destruction of muscularis propria, and necrosis. These lesions may even extend out of the bladder into perivesicular adipose tissue. Despite this alarming morphology, these lesions tend to self regress over time such that the correct treatment is to do TUR and then follow the patient closely whereby most lesions do not need additional surgery. However, on occasion these lesions may cause local problems or regrowth such that uncommonly radical cystectomy may still need to be performed. There is somewhat of a controversy regarding the nomenclature for these lesions. We prefer the term IMT as two-thirds of these lesions have an ALK gene rearrangement and are positive for ALK immunohistochemically. These lesions may occur in 2 different scenarios. One may be following a benign TUR several months earlier which in some cases people use the term post-operative spindle cell nodule. The other is when these lesions occur de novo which some people use the term pseudosarcomatous fibromyxoid tumor. However, regardless whether these lesions arise de novo or following a benign TUR, they have the exact morphology, same immunohistochemistry, and same molecular findings. Consequently, we prefer a more unifying concept of IMT. On a limited biopsy IMTs may closely resemble sarcomas or sarcomatoid carcinoma such that I would never establish a diagnosis of IMT on a small biopsy but would request a larger TUR sample to more fully characterize the lesion. It is worth trying to do an ALK which was positive in this case to verify the diagnosis. However as one-third of these cases are negative for ALK, one can still establish a definitive diagnosis of IMT based on histology in the absence of ALK positivity.