DOI: https://doi.org/10.21203/rs.3.rs-202220/v1
Background: The inflammatory myofibroblastic tumor (IMT) of urinary bladder is very rare, this case and often misdiagnosed as bladder cancer. We report a patient with atypical clinical features with dysuria and lower abdominal pain.
Case presentation: A 32-year-old man presented with dysuria and lower abdominal pain. Computed tomography (CT) demonstrated that a solitary non-papillary tumor was located at the wall of the bladder dome. Partial cystectomy was successfully managed. Immunohistochemically, positivity of the tumor cells for anaplastic lymphoma kinase (ALK), Actin (SM), vimentin, cytokine (CK), epithelial membrane antigen (EMA) and Ki-67. Based on the the above clinical features、histopathology and immunohistochemical, the tumor was definitively diagnosed as bladder’s IMT. After 24 months, there was no signs of recurrence and metastasis with CT and cystoscopy.
Conclusion: A rare case of inflammatory myofibroblastic tumor of urinary bladder after partial cystectomy was reported. It is essential for urologists and scientists to entirely understand the characteristics of the inflammatory myofibroblastic tumor and make a better clinical guideline, to avoid over treatments.
The inflammatory myofibroblastic tumor (IMT) of urinary bladder is rare in clinical practice. The clinical and radiological features of bladder’s IMT are not specific compared to bladder cancer. After Roth et al[1]. first reported the case in 1980, major medical research centers began to study it. The urology guidelines do not explicitly mention the gold standard for the treatment of the disease at this time. The present case revealed an inflammatory myofibroblastic tumor of urinary bladder of the bladder, pathology features and clinical treatments.
A 32-year-old male patient with a half-month history of dysuria and lower abdominal pain was admitted to The Fourth Hospital Affiliated to China Medical University on March 16, 2018. On physical examination, the patient had no fever with a blood pressure of 130/80 mmHg. There was strong bladder tenderness to palpation. He had no significant previous medical history and denied any surgeries of note. There were no abnormalities in full blood count and serum creatinine levels. The urinalysis tests showed: red blood cells in urine, 14.0/HPF; white blood cell in urine, 0.7/HPF. Computed tomography (CT) demonstrated that a 2.5×4.3×3.3cm solitary non-papillary tumor was located in the bladder dome wall with surrounding edema (Fig. 1), and thickening of the bladder wall and inflammation of adjacent tissues. Chest and abdomen computed tomography showed no evidence of metastatic tumor. These led to suspicion of bladder tumor.
Partial cystectomy was carried out on March 20, 2018. Surgical exploration showed that the tumor was fixed on the bladder wall. No regional lymphadenopathy was noted. Intraoperative frozen sections indicated a low-grade spindle cell tumor. The tumor was completely resected. Surgical samples were formalin fixed, paraffin embedded and cut into 4 micron thick sections for the histological examination with hematoxylin-eosin stain. Histopathologic evaluation of excised specimen revealed proliferation of spindle-shaped cells with inflammatory cell infiltration (Fig. 2). Immunohistochemical analysis indicated positivity of the tumor cells for anaplastic lymphoma kinase (ALK), Actin(SM), vimentin, cytokine (CK), epithelial membrane antigen (EMA) and Ki-67 (20%) (Fig. 3), but negative for CD34, GATA3, Calponin, CK7, P63, S-100, MyoD1, myogenin, and desmin. Based on the histological and immunohistochemical findings, the tumor was clearly diagnosed as inflammatory myofibroblastic tumor (IMT) of urinary bladder. So far, we followed for 24 months and the patient did not show any signs of recurrence.
Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm composed of myofibroblastic and fibroblastic spindle cells, which occurs mainly in soft tissue and viscera. IMTs initially believed to have a reactive or inflammatory pathogenesis, but currently, it is considered to be a tumor with a potentially malignant course due to researches of cytogenetic changes and chromosomal rearrangements[2, 3]. These lesions were originally described by Brunn in pulmonary tissue in 1939[4], and included the presence of spindle cells, fibroblasts, and inflammatory cells composed of plasma cells and lymphocytes. Then IMTs was reported in the retroperitoneal, pelvic and abdominal soft tissues, but its occurrence in the bladder is uncommon.
IMT of urinary bladder was defined as a fibroblast and myofibroblast-derived bladder mesenchymal neoplasm in the 2016 version of the WHO classification of bladder neoplasms. Most of them are benign, but tumor infiltration and metastasis may occur. The pathogenesis of bladder IMT has not yet been clarified. It may be related to infection, trauma and smoking, and it has been reported that 2P23 abnormality on chromosome 2 is closely related to IMT [5]. The most common presentation of the urinary bladder’s IMT is painless hematuria followed by urinary frequency, dysuria, and pelvic pain [6]. A review research indicated that IMT of urinary bladder occurs higher incidence in males and at an average age of 38.9 years. The presence of systemic symptoms of fever or discomfort in 30% of patients with IMTs[7]. In this case, the patient had clinical features of dysuria and lower abdominal pain, without gross hematuria or any systemic symptoms. The clinical manifestations of bladder’s IMT are not specific, and it is often misdiagnosed as bladder urothelial carcinoma and bladder sarcomatoid tumor, which may cause overtreatment[8, 9]. Pathological characteristics are based on spindle cells, myofibroblastic and fibroblasts accompanied by an inflammatory infiltration of plasma cells and lymphocytes. Immunohistochemistry is significantly helpful for the diagnosis, especially the expression of ALK1 is positive. And this case immunohistochemical features represent a typical bladder’s inflammatory myofibroblastic tumor features.
ALK1 staining plays a non-negligible role in distinguishing IMT from other tissues with similar morphology. In 2007, Soda et al. [10]first reported the translocation of the ALK gene in non-small cell lung cancer. Subsequently, it is also noted that IMTs have rearrangements of the ALK gene on chromosome 2p23, and the cytoplasmic reactivity for ALK protein which correlates with the presence of rearrangement of the ALK gene can be detected in 50%-60% of IMTs. It has made IMTs have been distinguish from the wide category of inflammatory pseudotumour that included pseudosarcomatous myofibroblastic proliferation, pseudosarcomatous fibromyxoid tumor and plasma cell pseudotumour into a unique entity with characteristic histological and molecular features. More importantly, it also suggests that IMTs viewed as a true neoplasm, not a reaction process. In recent research, it has been shown that ALK gene was positive in 57–89% of IMTs of the urinary tract, making it an available marker for diagnosis [11].
Because of the rarity of IMT of bladder, no standardized management have been introduced. Bladder IMT is classified as intermediate-grade malignancy with local relapse tendency in the WHO classification of soft tissue tumors. Some scholars have suggested that anti-inflammatory treatment can shrink and even eliminate tumors, however,surgery is generally considered the best option. For small tumors, transurethral resection of bladder tumors can be used. And for the tumors which possess wide stem or cause ureteral obstruction, partial cystectomy can be performed to preserve bladder function. This patient underwent partial cystectomy because of its morphological features, and documented a diagnosis of an IMT by surgical pathology with negative margins. Intraoperative rapid cryopathology helps confirm the diagnosis,and we can avoid over-treatment and make patients better prognosis. There is no evidence to prove the effect of postoperative chemotherapy or radiotherapy. It has been reported that the ALK inhibitors achieves good results in the treatment of IMT.
According to reports in the literature, the cure rate after total resection was 67%, the recurrence rate was 22%, and the metastasis rate of tumors in various sites was 2.5%. Features such as deep location, tumor size and ALK overexpression could increase the likelihood of recurrence [12]. Since approximately 41% of IMTs of urinary bladder had invaded the muscularis propria, it was difficult for us to determine whether the tumor had been completely removed for transurethral resection. Therefore, some cases of tumor recurrence may be caused by residual tumors after transurethral resection. In this case, the tumor was solitary, typical and expressed ALK, and there was no clear vascular invasion and necrosis. Though the patient recovered well after surgery, long-term follow-up is still essential to check for local recurrence or metastasis.
In summary, IMTs of urinary bladder is rare in clinical. Owing to clinical features of it are similar to other malignant tumors, often misdiagnosed before surgery. It should be noted with urinary bladder cancer, teratoma, rhabdomyosarcoma, liposarcoma, etc. The pathological biopsy is a necessary means to avoid overtreatment of radical surgery. With more clinical research, the guidelines for diagnosis and treatment will maybe gradually develop in the near future.
IMT: Inflammatory myofibroblastic tumor; ALK: Anaplastic lymphoma kinase; CK: Cytokine; EMA: Epithelial membrane antigen; CT: Computed tomography
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Authors’ contributions
Zhu XW made substantial contributions to the design of the work. He was involved in acquisition, analysis and interpretation of data, drafting and revision are done by him. Wang YX conducted the literature review. Liu YL supervised and reviewed the manuscript. All authors have read and approved the manuscript
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All data generated or analyzed during this study are included in this published article and its supplementary information files and available from the corresponding author on reasonable request.
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Written informed consent for publication of their clinical details and clinical images was obtained from the Patient's parents. A copy of the consent form is available to the Editor of this journal.
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The authors declare that they have no competing interests.