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Recurrent Superficial Papillary Adenocarcinoma of the Bladder
0022-5347/02/1686-2538/0 THE JOURNAL OF UROLOGY® Copyright © 2002 by AMERICAN UROLOGICAL ASSOCIATION, INC.®
Vol. 168, 2538 –2539, December 2002 Printed in U.S.A.
DOI: 10.1097/01.ju.0000034846.77358.6c
RECURRENT SUPERFICIAL PAPILLARY ADENOCARCINOMA OF THE BLADDER HOSSAM H. YAKOUT, NABIL K. BISSADA
AND
F. L. PICKLESIMER
From the Department of Urology, Division of Urologic Oncology, Medical University of South Carolina, Charleston, South Carolina KEY WORDS: bladder neoplasms; adenocarcinoma, papillary; neoplasm recurrence, local
Primary adenocarcinoma of the bladder is the third most common type of bladder carcinoma after transitional and squamous cell carcinomas. This neoplasm comprises 0.5% to 2% of all epithelial malignant bladder tumors. Primary vesical adenocarcinomas are most frequently single lesions with a predilection for the trigone and bladder dome. Most of these lesions are muscle invasive at presentation. Papillary adenocarcinoma, a rare subtype of bladder adenocarcinoma, was first reported in 1985.1 We report a unique case of recurrent superficial papillary adenocarcinoma of the bladder that was managed conservatively without progression for more than 5 years. CASE REPORT
A 60-year-old white female presented with moderate persistent irritative bladder symptoms. Medical history was remarkable for grade 1 colon carcinoma that was resected in 1981, breast cancer with lymph node involvement that was treated with modified radical mastectomy, axillary node dissection, chemotherapy and 8 to 9 years of hormonal therapy (tamoxifen); neurofibromatosis of the trunk and limbs; temporal lobe seizures and Hashimoto’s thyroiditis. The patient also had a history of allergic reaction (hives) to certain drugs. She was initially diagnosed with interstitial cystitis. However, cystourethroscopy in November 1995 showed a papillary tumor involving the left anterolateral bladder wall with several small satellite lesions. The tumor was resected and pathological examination demonstrated low grade papillary adenocarcinoma with clear cell features with invasion to the lamina propria but no muscle invasion. Differential diagnosis was supported by positive mucicarmine and CA 125 staining (figs. 1 and 2). Evaluation for metastasis was negative. Accepted for publication June 28, 2002.
FIG. 2. Higher power magnification of original biopsy reveals hobnailed architecture, and cells with anaplastic nuclei and vacuolated cytoplasm. Reduced from ⫻200.
Surveillance cystoscopy in February 1996 revealed a slightly papillary appearance in the left lateral bladder wall, which was biopsed. Pathological analysis showed papillary epithelial hyperplasia with focal atypia but no evidence of malignancy. Recurrent papillary tumor in an area 4 to 5 cm. in diameter in the left posterolateral bladder wall appeared in August 1999. Since then, the patient has had multiple recurrences managed by endoscopic resection. Pathological evaluations have demonstrated recurrent superficial noninvasive papillary adenocarcinoma. However, these biopsy specimens have lacked many of the features evident in the diagnostic specimen. To date there has been no evidence of progression or metastatic disease during 64 months of followup. DISCUSSION
Papillary adenocarcinoma of the bladder is a rare primary malignant epithelial tumor. A review of the literature reveals few previously reported cases.1–3 One such case involved papillary adenocarcinoma of the bladder associated with bladder stone.2 This patient was managed by transurethral resection of the bladder tumor and cystolithotripsy. In the series of primary nonurachal bladder adenocarcinoma reported by Gill et al in 1989, 2 patients had papillary adenocarcinoma.3 These cases were treated as classic adenocarcinoma with total cystectomy. To our knowledge O’Brien and Urbanski described the only case of noninvasive papillary adenocarcinoma of the bladder.1 The tumor displayed significant cytological atypia. The authors outlined the difference between papillary adenocarcinoma of the bladder and cystitis glandularis and classic bladder adenocarcinoma. Microscopically this tumor demonstrated papillary projections covered by 2 to 3 cells of thick
FIG. 1. Original biopsy shows complex, predominantly papillary neoplasm lined by 2 to 3 cell layers of cuboidal cells with occasional hobnailed cells. Reduced from ⫻40. 2538
RECURRENT SUPERFICIAL PAPILLARY BLADDER ADENOCARCINOMA
epithelium with distinct goblet cells and no evidence of invasion. Examination for mucopolysaccharides showed prominent neutral and acid mucoid production. Sialomucins and sulfomucins were present within the goblet cells (on high iron diamine and alcian blue staining). Carcinoembryonic antigen production was not detected either within the cytoplasm or on the cell surface. Electron microscopy confirmed the presence of goblet cells with well defined mucin pools in the apical portion of the cells, and the free surface revealed distinct microvilli without rootlets. On cystoscopy the papillary features were indistinguishable from those of papillary transitional cell carcinoma.1 In our case the original diagnostic biopsy reviewed at referral demonstrated an unusual, predominantly papillary neoplasm with invasion of the lamina propria (fig. 1). The tumor showed short papillae, and focally hyalinized and tubulocystic structures lined by vacuolated cuboidal and hobnailed eosinophilic cells (fig. 2). The papillae displayed true fibrovascular cores lined by 1 to 3 cell layers. In addition, there were closely packed tubules with scattered small cysts and focal necrosis. Throughout the tumor the majority of the cells had anaplastic nuclei and prominent nucleoli. Mitotic figures were identified at up to 3 per high power field. Having been recognized to possess unusual histological features, the tumor was examined by several consultants before referral. Histochemical and immunohistochemical staining performed at 1 consultation revealed the tumor was positive for mucicarmine and CA 125, and suggested a diagnosis of clear cell adenocarcinoma. Recent literature indicates that CA 125 positivity is a nonspecific finding. Prostate specific antigen testing was negative. Subsequent bladder biopsies have not demonstrated a tu-
2539
bulocystic pattern, but have been more strictly papillary. The tumor continues to show papillae lined by epithelium 2 to 3 cell layers thick. The malignant cells display eosinophilic and clear cytoplasm, and anaplastic nuclei with prominent nucleoli. The most recent biopsy revealed mitotic figures and apoptotic bodies. However, no invasion has been evident in these subsequent biopsies. Periodic acid-Schiff staining with and without diastase demonstrated mucin within the most recent papillary lesion. Thus, followup histology continues to support the diagnosis of papillary adenocarcinoma with clear cell features. Our patient exhibited a long history of slow indolent superficial well differentiated papillary adenocarcinoma. However, despite tumor recurrence since the diagnosis, no progression to muscle invasion or distant metastases developed during 5 years of conservative therapy. To our knowledge this is the only reported case of low grade papillary adenocarcinoma of the bladder treated solely with transurethral resection of the tumor with no signs of progression during a lengthy followup. Our case underscores the fact that the natural history of these rare tumors can be variable, with some exhibiting an aggressive course while others recur but remain stable for many years. REFERENCES
1. O’Brien, A. M. and Urbanski, S. J.: Papillary adenocarcinoma in situ of bladder. J Urol, 134: 544, 1985 2. Tanaka, S., Yasumoto, R., Morikawa, Y., Nakatani, T. and Mackawa, M.: Adenocarcinoma of the urinary bladder with a bladder stone: report of a case. Hinyokika Kiyo, 35: 881, 1989 3. Gill, H. S., Dhillon, H. K. and Woodhouse, C. R.: Adenocarcinoma of the urinary bladder. Br J Urol, 64: 138, 1989
Vol. 168, 2538 –2539, December 2002 Printed in U.S.A.
DOI: 10.1097/01.ju.0000034846.77358.6c
RECURRENT SUPERFICIAL PAPILLARY ADENOCARCINOMA OF THE BLADDER HOSSAM H. YAKOUT, NABIL K. BISSADA
AND
F. L. PICKLESIMER
From the Department of Urology, Division of Urologic Oncology, Medical University of South Carolina, Charleston, South Carolina KEY WORDS: bladder neoplasms; adenocarcinoma, papillary; neoplasm recurrence, local
Primary adenocarcinoma of the bladder is the third most common type of bladder carcinoma after transitional and squamous cell carcinomas. This neoplasm comprises 0.5% to 2% of all epithelial malignant bladder tumors. Primary vesical adenocarcinomas are most frequently single lesions with a predilection for the trigone and bladder dome. Most of these lesions are muscle invasive at presentation. Papillary adenocarcinoma, a rare subtype of bladder adenocarcinoma, was first reported in 1985.1 We report a unique case of recurrent superficial papillary adenocarcinoma of the bladder that was managed conservatively without progression for more than 5 years. CASE REPORT
A 60-year-old white female presented with moderate persistent irritative bladder symptoms. Medical history was remarkable for grade 1 colon carcinoma that was resected in 1981, breast cancer with lymph node involvement that was treated with modified radical mastectomy, axillary node dissection, chemotherapy and 8 to 9 years of hormonal therapy (tamoxifen); neurofibromatosis of the trunk and limbs; temporal lobe seizures and Hashimoto’s thyroiditis. The patient also had a history of allergic reaction (hives) to certain drugs. She was initially diagnosed with interstitial cystitis. However, cystourethroscopy in November 1995 showed a papillary tumor involving the left anterolateral bladder wall with several small satellite lesions. The tumor was resected and pathological examination demonstrated low grade papillary adenocarcinoma with clear cell features with invasion to the lamina propria but no muscle invasion. Differential diagnosis was supported by positive mucicarmine and CA 125 staining (figs. 1 and 2). Evaluation for metastasis was negative. Accepted for publication June 28, 2002.
FIG. 2. Higher power magnification of original biopsy reveals hobnailed architecture, and cells with anaplastic nuclei and vacuolated cytoplasm. Reduced from ⫻200.
Surveillance cystoscopy in February 1996 revealed a slightly papillary appearance in the left lateral bladder wall, which was biopsed. Pathological analysis showed papillary epithelial hyperplasia with focal atypia but no evidence of malignancy. Recurrent papillary tumor in an area 4 to 5 cm. in diameter in the left posterolateral bladder wall appeared in August 1999. Since then, the patient has had multiple recurrences managed by endoscopic resection. Pathological evaluations have demonstrated recurrent superficial noninvasive papillary adenocarcinoma. However, these biopsy specimens have lacked many of the features evident in the diagnostic specimen. To date there has been no evidence of progression or metastatic disease during 64 months of followup. DISCUSSION
Papillary adenocarcinoma of the bladder is a rare primary malignant epithelial tumor. A review of the literature reveals few previously reported cases.1–3 One such case involved papillary adenocarcinoma of the bladder associated with bladder stone.2 This patient was managed by transurethral resection of the bladder tumor and cystolithotripsy. In the series of primary nonurachal bladder adenocarcinoma reported by Gill et al in 1989, 2 patients had papillary adenocarcinoma.3 These cases were treated as classic adenocarcinoma with total cystectomy. To our knowledge O’Brien and Urbanski described the only case of noninvasive papillary adenocarcinoma of the bladder.1 The tumor displayed significant cytological atypia. The authors outlined the difference between papillary adenocarcinoma of the bladder and cystitis glandularis and classic bladder adenocarcinoma. Microscopically this tumor demonstrated papillary projections covered by 2 to 3 cells of thick
FIG. 1. Original biopsy shows complex, predominantly papillary neoplasm lined by 2 to 3 cell layers of cuboidal cells with occasional hobnailed cells. Reduced from ⫻40. 2538
RECURRENT SUPERFICIAL PAPILLARY BLADDER ADENOCARCINOMA
epithelium with distinct goblet cells and no evidence of invasion. Examination for mucopolysaccharides showed prominent neutral and acid mucoid production. Sialomucins and sulfomucins were present within the goblet cells (on high iron diamine and alcian blue staining). Carcinoembryonic antigen production was not detected either within the cytoplasm or on the cell surface. Electron microscopy confirmed the presence of goblet cells with well defined mucin pools in the apical portion of the cells, and the free surface revealed distinct microvilli without rootlets. On cystoscopy the papillary features were indistinguishable from those of papillary transitional cell carcinoma.1 In our case the original diagnostic biopsy reviewed at referral demonstrated an unusual, predominantly papillary neoplasm with invasion of the lamina propria (fig. 1). The tumor showed short papillae, and focally hyalinized and tubulocystic structures lined by vacuolated cuboidal and hobnailed eosinophilic cells (fig. 2). The papillae displayed true fibrovascular cores lined by 1 to 3 cell layers. In addition, there were closely packed tubules with scattered small cysts and focal necrosis. Throughout the tumor the majority of the cells had anaplastic nuclei and prominent nucleoli. Mitotic figures were identified at up to 3 per high power field. Having been recognized to possess unusual histological features, the tumor was examined by several consultants before referral. Histochemical and immunohistochemical staining performed at 1 consultation revealed the tumor was positive for mucicarmine and CA 125, and suggested a diagnosis of clear cell adenocarcinoma. Recent literature indicates that CA 125 positivity is a nonspecific finding. Prostate specific antigen testing was negative. Subsequent bladder biopsies have not demonstrated a tu-
2539
bulocystic pattern, but have been more strictly papillary. The tumor continues to show papillae lined by epithelium 2 to 3 cell layers thick. The malignant cells display eosinophilic and clear cytoplasm, and anaplastic nuclei with prominent nucleoli. The most recent biopsy revealed mitotic figures and apoptotic bodies. However, no invasion has been evident in these subsequent biopsies. Periodic acid-Schiff staining with and without diastase demonstrated mucin within the most recent papillary lesion. Thus, followup histology continues to support the diagnosis of papillary adenocarcinoma with clear cell features. Our patient exhibited a long history of slow indolent superficial well differentiated papillary adenocarcinoma. However, despite tumor recurrence since the diagnosis, no progression to muscle invasion or distant metastases developed during 5 years of conservative therapy. To our knowledge this is the only reported case of low grade papillary adenocarcinoma of the bladder treated solely with transurethral resection of the tumor with no signs of progression during a lengthy followup. Our case underscores the fact that the natural history of these rare tumors can be variable, with some exhibiting an aggressive course while others recur but remain stable for many years. REFERENCES
1. O’Brien, A. M. and Urbanski, S. J.: Papillary adenocarcinoma in situ of bladder. J Urol, 134: 544, 1985 2. Tanaka, S., Yasumoto, R., Morikawa, Y., Nakatani, T. and Mackawa, M.: Adenocarcinoma of the urinary bladder with a bladder stone: report of a case. Hinyokika Kiyo, 35: 881, 1989 3. Gill, H. S., Dhillon, H. K. and Woodhouse, C. R.: Adenocarcinoma of the urinary bladder. Br J Urol, 64: 138, 1989