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Inflammatory Pseudotumor: A Rare Cause of Hematuria and Shock
Case Report Inflammatory Pseudotumor: A Rare Cause of Hematuria and Shock Andrea G. Lantz, Nicholas E. Power, Rekha Gupta, and John Grantmyre We report the clinical, radiologic, and pathologic findings of a case of inflammatory pseudotumor in an otherwise healthy 44-year-old woman, who presented with dysuria and hematuria causing hemodynamic instability. Computed tomography revealed a 4.3-cm by 3.5-cm densely enhancing mass arising from the anterior bladder wall. Pathologic examination showed spindle-shaped cells with mild nuclear pleomorphism, rare mitotic activity, and a strong reaction to vimentin, with focal positivity to alpha-actin and S100 protein. Monokeratin, CK7, and CK20 were negative. After two transurethral resections, the patient underwent partial cystectomy. UROLOGY 70: 372.e3–372.e6, 2007. © 2007 Elsevier Inc.
I
nflammatory pseudotumor (IPT) is a rare benign spindle cell tumor of the bladder.1 This lesion must be carefully distinguished from malignant spindle cell lesions, such as sarcomatoid urothelial carcinoma, leiomyosarcoma, and rhabdomyosarcoma to avoid unnecessary radical surgery.2 Although benign, with no reports of metastasis, IPT can be life-threatening, as illustrated in this case.
CASE REPORT A 44-year-old woman presented to our emergency department with a 3-week history of dysuria and 5 days of gross hematuria, with passage of clots the previous night. She had been treated by her family physician for a presumed urinary tract infection, but the urine culture was negative. She denied back pain, fever, and other systemic symptoms. Her past medical history included asthma and a tubal ligation, with no history of surgical trauma to or instrumentation of her bladder. Her family history was noncontributory. She did not smoke, was a social drinker, and worked in an office with no known toxin exposure. She was afebrile with normal vital signs (heart rate 88 beats/min, respiratory rate 14 breaths/min, blood pressure 112/72 mm Hg). The abdominal examination was unremarkable. The electrolyte, glucose, urea, and creatinine (58 mmol/L) levels were normal. Her white blood cell count was 8.7 ⫻ 109/L, hemoglobin 125 g/L, and platelets 237 ⫻ 109/L. The coagulation studies were normal. The urine dip showed gross blood and 2⫹ protein. From the Departments of Urology, and Pathology, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada Reprint requests: Andrea Lantz, M.D., 501 Smyth Road, Box 222, Ottawa General Hospital, Ottawa, ON K1H 8L6 Canada. E-mail: [email protected] Submitted: December 13, 2006, accepted (with revisions): April 13, 2007
© 2007 Elsevier Inc. All Rights Reserved
The patient was discharged by the emergency room physician with a prescription for a cephalosporin and follow-up in the urology clinic the next morning. She was advised to return to the emergency department if she developed increasing pain or fever, passed a concerning amount of blood, or if she were unable to void. The next day, the urine culture was reported positive for group B streptococcus (greater than 100,000 ⫻ 103 colony forming units/L). The patient returned to the emergency department early the next morning complaining of dizziness, weakness, and ongoing hematuria. She had no chest pain or abdominal pain. She had had a syncopal episode at home and had vomited once. She was experiencing urinary frequency, urgency, and urgency urinary incontinence. She was afebrile, but tachycardic (heart rate 102 beats/ min) with a respiratory rate of 16 breaths/min and blood pressure 128/84 mm Hg. The urology service was consulted and saw her immediately in the emergency department. She was pale with dry skin. Her abdomen was soft with suprapubic discomfort. The pelvic examination revealed no palpable abnormality, but the bimanual examination showed suprapubic fullness. The rectal examination findings were normal. Her workup showed negative beta-human chorionic gonadotropin, white blood cell count of 13.7, hemoglobin 102 g/L, creatinine 99 mmol/L, and urea 5.1 mmol/L. She was given intravenous fluids, and a cross-match and blood type and screen were ordered. Continuous bladder irrigation was initiated, with ongoing hematuria and passage of clots. After intravenous fluid resuscitation and workup, the patient’s hemoglobin was 66 g/L, heart rate 108 beats/min, respiratory rate 22 breaths/min, and blood pressure 106/66 mm Hg. Computed tomography of the abdomen and pelvis (Fig. 1) revealed a 4.3-cm by 3.5-cm densely enhancing 0090-4295/07/$32.00 372.e3 doi:10.1016/j.urology.2007.04.006
tion to vimentin and focal positivity with alpha-actin and S100 protein. Monokeratin, CK7, and CK20 were negative. A diagnosis of atypical pseudosarcomatous myofibroblastic proliferation of the bladder, also known as IPT, was made. After a discussion of the treatment options, the patient underwent partial cystectomy 1 month later. The partial cystectomy specimen (Fig. 3) showed residual spindle cell proliferation, with features consistent with atypical pseudosarcomatous myofibroblastic proliferation. The lesion involved the full-thickness muscularis propria. No perivesical fat was involved, and all resection margins were negative. The patient did well postoperatively without hematuria. She has had occasional nocturia and the same preoperative daytime voiding pattern.
COMMENT
Figure 1. (A) Coronal and (B) sagittal enhanced computed tomography images of anterior bladder mass.
mass arising from the anterior bladder wall, reported to be consistent with neoplasm. The mass showed no extravesical extension or metastatic disease within the abdomen or pelvis. Cystoscopy revealed a large, wide-based, sessile tumor arising from the left anterolateral wall of the bladder. Transurethral resection was performed. The patient received 4 U of packed red blood cells perioperatively. She did well postoperatively, with resolution of the hematuria, and she was discharged home 2 days after admission, with repeat cystoscopy and possible repeat resection planned for 2 weeks. Her hemoglobin at discharge was 97 g/L. The patient returned to the emergency department the next morning with weakness, dizziness, and hematuria. Her hemoglobin was 88 g/L. Evacuation of clots, repeat resection, and fulguration were performed. She was well postoperatively and was discharged home with a urology follow-up visit arranged. The pathologic examination of the tumor (Fig. 2) showed spindle cell proliferation, focally involving the muscularis propria. The spindle-shaped cells were separated by edematous stroma and showed mild nuclear pleomorphism and rare mitotic activity, but no atypical forms were seen. Scattered lymphocytes and plasma cells were present in the interstitium. The urothelium showed no evidence of high-grade dysplasia or malignancy. The spindle-shaped cells showed strong reac372.e4
IPT of the bladder has been described by many names, including pseudosarcomatous myofibroblastic proliferation,1 pseudomalignant spindle cell proliferation,2 pseudosarcoma,3 nodular fasciitis of the bladder,4 and reactive pseudosarcomatous response.5 Roth5 first described the lesion as a reactive pseudosarcomatous response in 1980. In 1985, Nochomovitz and Orenstein6 used the term “inflammatory pseudotumor” to describe these lesions. A similar lesion, postoperative spindle cell nodule,7 is known to occur shortly after surgical trauma to the bladder. The distinction between the two is made from the clinical history and time course because the development of a postoperative spindle cell nodule generally occurs within 5 weeks to 3 months after surgery.7 In the past, these lesions have often been initially misdiagnosed as malignancies such as sarcomatoid urothelial carcinoma, leiomyosarcoma, and rhabdomyosarcoma.2 IPT presents with nonspecific symptoms, including hematuria, dysuria, urinary frequency and urgency, urinary obstruction, and pelvic pain.2,8,9 The tumors occur at any age, but are usually seen in young adults.10,11 On cystoscopic examination, IPT usually appears as a polypoid or nodular, sometimes ulcerated, exophytic mass with broad attachment to the bladder wall.2,3,10 On pathologic examination, IPT must be carefully distinguished from similar malignant lesions. In a recent study of 42 cases, Harik et al.10 observed that the most reliable criterion for separating IPT from leiomyosarcoma and carcinoma is the absence of nuclear atypia. They also noted that these lesions may rarely show vascular encroachment but do not show frank vascular invasion.10 “Atypical” features include mitotic activity, necrosis, and extension into muscularis propria or perivesicular fat.10 Treatment of IPT usually consists of transurethral resection or partial cystectomy.1,10,11 Radical cystectomy has been reported,10 but it is not the treatment of choice because IPT is a benign lesion. The natural history of IPT is unclear, because most are resected or excised. Iczkowski UROLOGY 70 (2), 2007
Figure 2. Hematoxylin-eosin stain (original magnification ⫻100) showing (A) normal urothelium, (B) spindle cell proliferation in edematous stroma, (C) immunohistochemical stain–vimentin positive cells, (D) immunohistochemical stain–focally positive alpha actin cells, and (E) immunohistochemical stain–focally positive S100 protein cells.
et al.9 reported the death of 1 patient who was not a candidate for definitive tumor ablation after transurethral resection of his 13.0-cm tumor. His tumor grew to 37.5 cm, resulting in urinary obstruction and urosepsis. IPT can grow extensively through the muscularis propria to invade the perivesicular adipose tissues, peritoneum, and UROLOGY 70 (2), 2007
omentum.10 Recurrence of IPT has recently been reported in 3 cases,10 but it has not been reported to metastasize.9 –11 Sandhu and Iacovou12 reported the case of a patient with full-thickness bladder invasion and tumor fixation to the rectus sheath who was treated with 4 months of oral antibiotics. They saw resolution of the 372.e5
lesion at 9 months of follow-up, and the patient was free of recurrence after 3 years.12
CONCLUSIONS IPT is an uncommon benign bladder lesion that can result in significant and life-threatening symptoms, as illustrated in the case we have described. It should be considered in the differential diagnosis of bladder spindle cell tumors to avoid unnecessary radical surgery. Pathologic examination and special investigations such as immunohistochemical studies are necessary to distinguish these tumors from malignancies that share overlapping characteristics.2 Conservative resection or excision appears to be adequate treatment, with few recurrences and no metastases reported. Given the similarities to malignant tumors, however, these patients should have careful follow-up in the initial postoperative period.
References
Figure 3. Gross partial cystectomy specimen: (A) whole, (B) bisected, and (C) multiple transections.
372.e6
1. Jones EC, Clement PB, and Young RH: Inflammatory pseudotumor of the urinary bladder: a clinicopathological, immunohistochemical, ultrastructural, and flow cytometric study of 13 cases. Am J Surg Pathol 17: 1193–1194, 1993. 2. Lundgren L, Aldenborg F, Angervall L, et al: Pseudomalignant spindle cell proliferations of the urinary bladder. Hum Pathol 24: 181–191, 1994. 3. Stark GL, Fedderson R, Lowe BA, et al: Inflammatory pseudotumor (pseudosarcoma) of the bladder. J Urol 141: 610 – 612, 1989. 4. Das S, Upton JD, and Amar AD: Nodular fasciitis of the bladder. J Urol 140: 1532–1533, 1988. 5. Roth JA: Reactive pseudosarcomatous response in urinary bladder. Urology 16: 635– 637, 1980. 6. Nochomovitz LE, and Orenstein JM: Inflammatory pseudotumor of the urinary bladder: possible relationship to nodular fasciitis—two case reports, cytologic observations, and ultrastructural observations. Am J Surg Pathol 9: 366 –373, 1985. 7. Young RH: Spindle cell lesions of the urinary bladder. Histol Histopathol 5: 505–512, 1990. 8. Bulusu AD, and Hopkins T: Inflammatory pseudotumor of the bladder. Urology 51: 487– 488, 1998. 9. Iczkowski KA, Shanks JH, Gadaleanu V, et al: Inflammatory pseudotumor and sarcoma of the urinary bladder: differential diagnosis and outcome in thirty-eight spindle cell neoplasms. Mod Pathol 14: 1043–1051, 2001. 10. Harik LR, Merino C, Coindre JM, et al: Pseudosarcomatous myofibroblastic proliferations of the bladder: a clinicopathologic study of 42 cases. Am J Surg Pathol 30: 787–794, 2006. 11. Ricchiuti DJ, Ricchiuti VS, Ricchiuti RR, et al: Fibrous inflammatory pseudotumor of the bladder. Rev Urol 2: 232–235, 2000. 12. Sandhu SS, and Iacovou JW: Pseudotumor of the bladder. J R Soc Med 90: 46 – 47, 1997.
UROLOGY 70 (2), 2007
I
nflammatory pseudotumor (IPT) is a rare benign spindle cell tumor of the bladder.1 This lesion must be carefully distinguished from malignant spindle cell lesions, such as sarcomatoid urothelial carcinoma, leiomyosarcoma, and rhabdomyosarcoma to avoid unnecessary radical surgery.2 Although benign, with no reports of metastasis, IPT can be life-threatening, as illustrated in this case.
CASE REPORT A 44-year-old woman presented to our emergency department with a 3-week history of dysuria and 5 days of gross hematuria, with passage of clots the previous night. She had been treated by her family physician for a presumed urinary tract infection, but the urine culture was negative. She denied back pain, fever, and other systemic symptoms. Her past medical history included asthma and a tubal ligation, with no history of surgical trauma to or instrumentation of her bladder. Her family history was noncontributory. She did not smoke, was a social drinker, and worked in an office with no known toxin exposure. She was afebrile with normal vital signs (heart rate 88 beats/min, respiratory rate 14 breaths/min, blood pressure 112/72 mm Hg). The abdominal examination was unremarkable. The electrolyte, glucose, urea, and creatinine (58 mmol/L) levels were normal. Her white blood cell count was 8.7 ⫻ 109/L, hemoglobin 125 g/L, and platelets 237 ⫻ 109/L. The coagulation studies were normal. The urine dip showed gross blood and 2⫹ protein. From the Departments of Urology, and Pathology, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada Reprint requests: Andrea Lantz, M.D., 501 Smyth Road, Box 222, Ottawa General Hospital, Ottawa, ON K1H 8L6 Canada. E-mail: [email protected] Submitted: December 13, 2006, accepted (with revisions): April 13, 2007
© 2007 Elsevier Inc. All Rights Reserved
The patient was discharged by the emergency room physician with a prescription for a cephalosporin and follow-up in the urology clinic the next morning. She was advised to return to the emergency department if she developed increasing pain or fever, passed a concerning amount of blood, or if she were unable to void. The next day, the urine culture was reported positive for group B streptococcus (greater than 100,000 ⫻ 103 colony forming units/L). The patient returned to the emergency department early the next morning complaining of dizziness, weakness, and ongoing hematuria. She had no chest pain or abdominal pain. She had had a syncopal episode at home and had vomited once. She was experiencing urinary frequency, urgency, and urgency urinary incontinence. She was afebrile, but tachycardic (heart rate 102 beats/ min) with a respiratory rate of 16 breaths/min and blood pressure 128/84 mm Hg. The urology service was consulted and saw her immediately in the emergency department. She was pale with dry skin. Her abdomen was soft with suprapubic discomfort. The pelvic examination revealed no palpable abnormality, but the bimanual examination showed suprapubic fullness. The rectal examination findings were normal. Her workup showed negative beta-human chorionic gonadotropin, white blood cell count of 13.7, hemoglobin 102 g/L, creatinine 99 mmol/L, and urea 5.1 mmol/L. She was given intravenous fluids, and a cross-match and blood type and screen were ordered. Continuous bladder irrigation was initiated, with ongoing hematuria and passage of clots. After intravenous fluid resuscitation and workup, the patient’s hemoglobin was 66 g/L, heart rate 108 beats/min, respiratory rate 22 breaths/min, and blood pressure 106/66 mm Hg. Computed tomography of the abdomen and pelvis (Fig. 1) revealed a 4.3-cm by 3.5-cm densely enhancing 0090-4295/07/$32.00 372.e3 doi:10.1016/j.urology.2007.04.006
tion to vimentin and focal positivity with alpha-actin and S100 protein. Monokeratin, CK7, and CK20 were negative. A diagnosis of atypical pseudosarcomatous myofibroblastic proliferation of the bladder, also known as IPT, was made. After a discussion of the treatment options, the patient underwent partial cystectomy 1 month later. The partial cystectomy specimen (Fig. 3) showed residual spindle cell proliferation, with features consistent with atypical pseudosarcomatous myofibroblastic proliferation. The lesion involved the full-thickness muscularis propria. No perivesical fat was involved, and all resection margins were negative. The patient did well postoperatively without hematuria. She has had occasional nocturia and the same preoperative daytime voiding pattern.
COMMENT
Figure 1. (A) Coronal and (B) sagittal enhanced computed tomography images of anterior bladder mass.
mass arising from the anterior bladder wall, reported to be consistent with neoplasm. The mass showed no extravesical extension or metastatic disease within the abdomen or pelvis. Cystoscopy revealed a large, wide-based, sessile tumor arising from the left anterolateral wall of the bladder. Transurethral resection was performed. The patient received 4 U of packed red blood cells perioperatively. She did well postoperatively, with resolution of the hematuria, and she was discharged home 2 days after admission, with repeat cystoscopy and possible repeat resection planned for 2 weeks. Her hemoglobin at discharge was 97 g/L. The patient returned to the emergency department the next morning with weakness, dizziness, and hematuria. Her hemoglobin was 88 g/L. Evacuation of clots, repeat resection, and fulguration were performed. She was well postoperatively and was discharged home with a urology follow-up visit arranged. The pathologic examination of the tumor (Fig. 2) showed spindle cell proliferation, focally involving the muscularis propria. The spindle-shaped cells were separated by edematous stroma and showed mild nuclear pleomorphism and rare mitotic activity, but no atypical forms were seen. Scattered lymphocytes and plasma cells were present in the interstitium. The urothelium showed no evidence of high-grade dysplasia or malignancy. The spindle-shaped cells showed strong reac372.e4
IPT of the bladder has been described by many names, including pseudosarcomatous myofibroblastic proliferation,1 pseudomalignant spindle cell proliferation,2 pseudosarcoma,3 nodular fasciitis of the bladder,4 and reactive pseudosarcomatous response.5 Roth5 first described the lesion as a reactive pseudosarcomatous response in 1980. In 1985, Nochomovitz and Orenstein6 used the term “inflammatory pseudotumor” to describe these lesions. A similar lesion, postoperative spindle cell nodule,7 is known to occur shortly after surgical trauma to the bladder. The distinction between the two is made from the clinical history and time course because the development of a postoperative spindle cell nodule generally occurs within 5 weeks to 3 months after surgery.7 In the past, these lesions have often been initially misdiagnosed as malignancies such as sarcomatoid urothelial carcinoma, leiomyosarcoma, and rhabdomyosarcoma.2 IPT presents with nonspecific symptoms, including hematuria, dysuria, urinary frequency and urgency, urinary obstruction, and pelvic pain.2,8,9 The tumors occur at any age, but are usually seen in young adults.10,11 On cystoscopic examination, IPT usually appears as a polypoid or nodular, sometimes ulcerated, exophytic mass with broad attachment to the bladder wall.2,3,10 On pathologic examination, IPT must be carefully distinguished from similar malignant lesions. In a recent study of 42 cases, Harik et al.10 observed that the most reliable criterion for separating IPT from leiomyosarcoma and carcinoma is the absence of nuclear atypia. They also noted that these lesions may rarely show vascular encroachment but do not show frank vascular invasion.10 “Atypical” features include mitotic activity, necrosis, and extension into muscularis propria or perivesicular fat.10 Treatment of IPT usually consists of transurethral resection or partial cystectomy.1,10,11 Radical cystectomy has been reported,10 but it is not the treatment of choice because IPT is a benign lesion. The natural history of IPT is unclear, because most are resected or excised. Iczkowski UROLOGY 70 (2), 2007
Figure 2. Hematoxylin-eosin stain (original magnification ⫻100) showing (A) normal urothelium, (B) spindle cell proliferation in edematous stroma, (C) immunohistochemical stain–vimentin positive cells, (D) immunohistochemical stain–focally positive alpha actin cells, and (E) immunohistochemical stain–focally positive S100 protein cells.
et al.9 reported the death of 1 patient who was not a candidate for definitive tumor ablation after transurethral resection of his 13.0-cm tumor. His tumor grew to 37.5 cm, resulting in urinary obstruction and urosepsis. IPT can grow extensively through the muscularis propria to invade the perivesicular adipose tissues, peritoneum, and UROLOGY 70 (2), 2007
omentum.10 Recurrence of IPT has recently been reported in 3 cases,10 but it has not been reported to metastasize.9 –11 Sandhu and Iacovou12 reported the case of a patient with full-thickness bladder invasion and tumor fixation to the rectus sheath who was treated with 4 months of oral antibiotics. They saw resolution of the 372.e5
lesion at 9 months of follow-up, and the patient was free of recurrence after 3 years.12
CONCLUSIONS IPT is an uncommon benign bladder lesion that can result in significant and life-threatening symptoms, as illustrated in the case we have described. It should be considered in the differential diagnosis of bladder spindle cell tumors to avoid unnecessary radical surgery. Pathologic examination and special investigations such as immunohistochemical studies are necessary to distinguish these tumors from malignancies that share overlapping characteristics.2 Conservative resection or excision appears to be adequate treatment, with few recurrences and no metastases reported. Given the similarities to malignant tumors, however, these patients should have careful follow-up in the initial postoperative period.
References
Figure 3. Gross partial cystectomy specimen: (A) whole, (B) bisected, and (C) multiple transections.
372.e6
1. Jones EC, Clement PB, and Young RH: Inflammatory pseudotumor of the urinary bladder: a clinicopathological, immunohistochemical, ultrastructural, and flow cytometric study of 13 cases. Am J Surg Pathol 17: 1193–1194, 1993. 2. Lundgren L, Aldenborg F, Angervall L, et al: Pseudomalignant spindle cell proliferations of the urinary bladder. Hum Pathol 24: 181–191, 1994. 3. Stark GL, Fedderson R, Lowe BA, et al: Inflammatory pseudotumor (pseudosarcoma) of the bladder. J Urol 141: 610 – 612, 1989. 4. Das S, Upton JD, and Amar AD: Nodular fasciitis of the bladder. J Urol 140: 1532–1533, 1988. 5. Roth JA: Reactive pseudosarcomatous response in urinary bladder. Urology 16: 635– 637, 1980. 6. Nochomovitz LE, and Orenstein JM: Inflammatory pseudotumor of the urinary bladder: possible relationship to nodular fasciitis—two case reports, cytologic observations, and ultrastructural observations. Am J Surg Pathol 9: 366 –373, 1985. 7. Young RH: Spindle cell lesions of the urinary bladder. Histol Histopathol 5: 505–512, 1990. 8. Bulusu AD, and Hopkins T: Inflammatory pseudotumor of the bladder. Urology 51: 487– 488, 1998. 9. Iczkowski KA, Shanks JH, Gadaleanu V, et al: Inflammatory pseudotumor and sarcoma of the urinary bladder: differential diagnosis and outcome in thirty-eight spindle cell neoplasms. Mod Pathol 14: 1043–1051, 2001. 10. Harik LR, Merino C, Coindre JM, et al: Pseudosarcomatous myofibroblastic proliferations of the bladder: a clinicopathologic study of 42 cases. Am J Surg Pathol 30: 787–794, 2006. 11. Ricchiuti DJ, Ricchiuti VS, Ricchiuti RR, et al: Fibrous inflammatory pseudotumor of the bladder. Rev Urol 2: 232–235, 2000. 12. Sandhu SS, and Iacovou JW: Pseudotumor of the bladder. J R Soc Med 90: 46 – 47, 1997.
UROLOGY 70 (2), 2007