Non-neoplastic reactive, mesenchymal proliferation of the urinary bladder is a rare, but distinctive entity, which has been referred to as inflammatory pseudotumor (IP) or myofibroblastic tumor (IMT), postoperative spindle cell nodule, nodular fasciitis, pseudosarcomatous myofibroblastic proliferation, pseudomalignant spindle cell proliferation, and pseudosarcomatous or atypical fibromyxoid tumor [3, 4]. The unifying feature of these lesions is their tendency to mimic both sarcomas and spindled carcinomas, thus presenting particular diagnostic difficulties in urinary bladder pathology.
The pathogenesis of IMT is still in doubt [4]; some regard this entity as a reactive or inflammatory condition, while others believe that it represents a low-grade mesenchymal malignancy. The latter endorse the low-grade neoplastic nature of this entity owing to (a) the occurrence of cases with deep infiltration of the bladder wall and extension into the perivesical soft tissue and (b) the demonstration of a non-random chromosomal translocation involving 2p23 that results in the expression of anaplastic lymphoma kinase (ALK) [5]. In addition, the relationship of bladder IMT to lesions called IMT in other anatomic sites remains uncertain [3, 6], since bladder lesions are far more likely to express keratin, probably less likely to recur and certainly less likely to metastasize than the latter [3]; albeit, they share similar morphologic features and molecular alterations with these [3, 7].
Pseudosarcomatous myofibroblastic lesions of the bladder may occur at any age (range from childhood to elderly patients), but typically occur in adult males [3, 8, 9]; being in contrast to other reports [10–12] that support a female preponderance. These rare lesions have a non-specific presentation with painless gross hematuria being the most common presenting symptom; other complaints include dysuria, frequency, suprapubic pain, or the discovery of a mass lesion. Their size is quite variable, ranging from a few centimeters up to a reported size of 37.5 cm [9]. Endoscopically and radiographically, these cannot be distinguished from malignant tumors [13]. Cystourethroscopy reveals either an intraluminal (exophytic or polypoid) mass or a submucosal (mural) lesion that may be easily overlooked [10]. When the tumor is sectioned, the mass is relatively gelatinous and soft [11] or has a pale, firm cut surface [10, 14] without areas of hemorrhage or necrosis.
IMT contains a mixture of spindle cells showing myofibroblastic differentiation, admixed with variable numbers of inflammatory cells. These display 3 histologic patterns in varying proportions: (a) the myxoid-vascular pattern, characterized by loosely arranged, stellate-to-plump spindle cells in an oedematous, myxoid background with an irregular network of small blood vessels and inflammatory cells, resembling nodular fasciitis or granulation tissue, (b) the compact spindle cell pattern, which consists of a compact interlacing fascicular or storiform spindle cell proliferation with variable myxoid and collagenized regions, accompanied by an inflammatory infiltrate composed largely of plasma cells, resembling fibrous histiocytoma or smooth muscle neoplasms, (c) the hypocellular-fibrous pattern, characterized by platelike collagen, lower cellularity and relatively sparse inflammation with lymphocytes and plasma cells trapped in a dense eosinophilic matrix, resembling a desmoid or scar [15, 16]. Microscopically, the lesional spindle cells are bipolar with elongated, eosinophilic cytoplasmic processes, which are devoid of cross-striations, and central oval nuclei characterized by smooth nuclear contours, open chromatin pattern, occasional nucleoli and lack of unequivocal malignant features [10, 11]. Anaplastic or pleomorphic features as well as atypical or bizzare mitotic figures are absent; occasional mitoses may be found but the mitotic activity is typically low [11]. Some lesions demonstrate compact cellularity with mitoses, necrosis and bladder wall invasion [3].
Of clinical importance, IMT follows a benign indolent course and conservative management (complete transurethral resection or partial cystectomy) has been reported [1, 3, 13, 17] as treatment of choice. Additional close follow-up (surveillance cystoscopy and biopsy to document resolution) is advised for most cases [3, 18] due to the fact that the biological potential of this entity cannot be accurately assessed and its histologic similarity to malignant neoplasms. Moreover, it is critical not to misdiagnose IMT as rhabdomyosarcoma, leiomyosarcoma or sarcomatoid urothelial carcinoma in order to avoid inappropriate radical surgery and/or adjuvant therapy and their attendant complications.
In fact, some leiomyosarcomas of the urinary bladder can express cytokeratin and are partially or extensively myxoid to such a degree that distinction from IMTs may become impossible; albeit, the presence of (a) prominent cytological atypia, (b) abnormal mitotic figures, (c) preferential reactivity for high-molecular-weight caldesmon and the lack of (a) a delicate vascular network, (b) interspersed inflammatory and red blood cells, and (c) ALK-1 immunostaining (usually demonstrated in IMT) may be of particular value in the differential diagnosis [1, 3–5, 14, 19, 20]. Similarly, sarcomatoid urothelial carcinomas sometimes show weak or focal immunoreactivity for cytokeratin and display myxoid features leading to potential diagnostic confusion with IMT. Of note, the identification of an in situ or invasive "typical" epithelial component usually allows for their diagnosis; other supportive features in favour of sarcomatoid urothelial carcinomas include prominent cytological atypia, atypical mitoses, non-myxoid areas with marked increased cellularity and usually ALK-1 negativity [3, 14]. With regard to embryonal rhabdomyosarcomas in the pediatric setting, these can be distinguished from IMTs by (a) exhibiting greater cellularity and increased numbers of atypical mitotic figures, (b) the presence of rhabdomyoblasts, a uniform population of small hyperchromatic cells, (c) a "cambium layer" (small malignant cells characteristically grouped beneath the epithelium) and (d) positive myogenin (Myf4) and MyoD1 immunostainings [5, 11, 19, 20].
Immunohistochemically, it has become apparent that h-caldesmon, myogenin and ALK-1, in contrast to muscle specific and smooth muscle actins, desmin and cytokeratin, can be of great value in the differential diagnosis of vesical IMTs [4, 14, 20]. As far as ALK-1 cytoplasmic expression is concerned, this has been identified in a range of 8% to 89% of IMT cases in the urinary bladder [20] and in the current report as well; albeit being suggestive of a neoplastic rather than a reactive or inflammatory nature and consistent with abundant mitoses and prominent atypia, the present ALK-positive lesion has neither recurred nor metastasized 3 years post-operatively.