DOI: 10.1148/rg.255045205
RadioGraphics 2005;25:1397-1403
© RSNA, 2005
Best Cases from the AFIP
Intradiverticular Bladder Carcinoma1
Eduardo J. Matta, MD,
Arthur J. Kenney, MD,
Gregg M. Barré, MD and
Richard M. Vanlangendonck, Jr, MD
1 From the Department of Radiology, Ochsner Clinic Foundation, Jefferson, La. Received November 24, 2004; revision requested January 5, 2005, and received February 16; accepted February 25. All authors have no financial relationships to disclose.
Address correspondence to E.J.M., 723 Pecan Grove Ln, Jefferson, LA 70121 (e-mail: ematta{at}tulanealumni.net).
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History
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A previously healthy 56-year-old man presented to our clinic with a complaint of painless gross hematuria. The patient had experienced an isolated episode of hematuria 6 months earlier after use of over-the-counter sinus medication. He had been asymptomatic since. The second episode occurred in the morning 2 days before his clinic visit after use of ibuprofen. However, this time symptoms persisted for 48 hours. The patient denied having any other genitourinary symptoms. His medical history was unremarkable for genitourinary disease, but his family history was positive, with his father having had "kidney cancer" at 69 years of age. He was a 45 pack-year tobacco smoker and drank about six beers per night. A review of systems revealed a history of knee arthritis treated with indomethacin.
The work-up for hematuria showed the following results: The level of prostate-specific antigen was within normal limits. Urine cytology demonstrated urothelial atypia, which was suspicious for neoplastic disease. Ultrasonography (US), intravenous urography, and cystoscopy demonstrated a mass within a bladder diverticulum. Computed tomography (CT) was performed for staging of bladder cancer. After a discussion of treatment options, the patient opted for diverticulectomy.
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Imaging Findings
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At intravenous urography, a large bladder diverticulum was identified on the right side (Fig 1). US performed the same day showed the 7.7 x 7.3 x 2.7-cm right-sided diverticulum, which contained an anteriorly located 3.3 x 3.0 x 2.0-cm solid mass confined within its lumen (Fig 2a). Color flow and spectral Doppler analysis demonstrated blood flow within the mass (Fig 2b). Subsequently, the patient underwent CT of the abdomen and pelvis before and after administration of intravenous contrast material. Precontrast images showed the right-sided bladder diverticulum with the anterosuperior mass of soft-tissue attenuation (Fig 3a). Postcontrast images revealed enhancement of the mass from 31 to 51 HU (Fig 3b). No gross extension into the perivesical fat, lymphadenopathy, or distant metastasis was noted.
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Figure 1. Anteroposterior intravenous urogram obtained 15 minutes after injection of contrast material shows a large right-sided bladder diverticulum with a somewhat irregular lateral border superiorly (arrow).
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Figure 3a. (a) Axial unenhanced CT scan shows the intradiverticular mass, which has an attenuation value of 31 HU. (b) Contrast-enhanced CT scan shows homogeneous enhancement of the mass to 51 HU.
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Figure 3b. (a) Axial unenhanced CT scan shows the intradiverticular mass, which has an attenuation value of 31 HU. (b) Contrast-enhanced CT scan shows homogeneous enhancement of the mass to 51 HU.
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Pathologic Evaluation
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Cystoscopy demonstrated the right-sided bladder diverticulum with the large papillary mass, which was approximately 4 cm in diameter (Fig 4; see also radiographics.rsnajnls.org/cgi/content/full/25/5/1397/DC1). Erythematous mucosa was evident surrounding the mass. The bladder diverticulum specimen from diverticulectomy exhibited tan to brown mucosa with several slightly raised, rubbery, gray to white lesions and two distinct masses (Fig 5). The first measured 4.5 x 2.0 x 1.8 cm; the second measured 1.5 x 1.4 x 1.0 cm. Both were rubbery, lobulated, tan to brown solid masses. Microscopic evaluation demonstrated synchronous transitional cell carcinomas (TCCs). The first lesion was a high-grade TCC with squamoid features (Fig 6a). The second was also a high-grade TCC but with mucinous/signet ring cell differentiation (Fig 6b). Both lesions invaded deep into, but not through, the bladder wall. In addition, TCC in situ was found.
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Figure 4a. (a) Cystoscopic image shows the diverticular ostium. The intradiverticular mass can be faintly seen in the center of the ostium. (b) Cystoscopic image obtained inside the diverticulum shows the mass (top) with surrounding mucosal erythema (bottom left).
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Figure 4b. (a) Cystoscopic image shows the diverticular ostium. The intradiverticular mass can be faintly seen in the center of the ostium. (b) Cystoscopic image obtained inside the diverticulum shows the mass (top) with surrounding mucosal erythema (bottom left).
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Figure 5a. (a) Photograph shows the resected bladder diverticulum. The diverticular ostium (arrow) is better visualized when the tissues are lifted up with a hemostat (inset). (b) Photograph obtained after dissection shows the lobulated mass within the diverticular cavity.
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Figure 5b. (a) Photograph shows the resected bladder diverticulum. The diverticular ostium (arrow) is better visualized when the tissues are lifted up with a hemostat (inset). (b) Photograph obtained after dissection shows the lobulated mass within the diverticular cavity.
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Figure 6a. (a) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows papillary urothelial carcinoma (right) with papillary fronds (black arrows). Squamous differentiation (left) is associated with eosinophilic keratinous debris (white arrow). (b) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows papillary urothelial carcinoma (right) with papillary fronds (black arrows). Glandular signet ring cell differentiation (left) is associated with blue mucin-filled intracytoplasmic vacuoles (white arrow).
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Figure 6b. (a) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows papillary urothelial carcinoma (right) with papillary fronds (black arrows). Squamous differentiation (left) is associated with eosinophilic keratinous debris (white arrow). (b) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows papillary urothelial carcinoma (right) with papillary fronds (black arrows). Glandular signet ring cell differentiation (left) is associated with blue mucin-filled intracytoplasmic vacuoles (white arrow).
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Discussion
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The urinary bladder is the most frequent site for urinary tract cancers. More than 95% of primary bladder cancers are of epithelial origin, most commonly TCC. Squamous cell carcinoma and adenocarcinoma account for a minority of epithelial tumors. Mesenchymal neoplasms are rare (1). TCC, also known as urothelial carcinoma, represents 90% of all bladder tumors. These range from solitary benign masses to highly invasive tumors with metastases.
There is controversy about the appropriate way to determine the histologic grade of these cancers. A classification scheme from the World Health Organization was created in 1973. More recently, an attempt at a scheme with wider acceptance was made with the development of the World Health Organization/International Society of Urological Pathology consensus classification of urothelial neoplasms of the urinary bladder. This classification includes hyperplastic lesions, flat lesions with atypia, and papillary neoplasms. Each of these is further subdivided. The last category includes papillomas, neoplasms of low malignant potential, and low- and high-grade carcinomas (2).
Staging schemes include the Jewett-Strong-Marshall system and the TNM system of the International Union against Cancer. Both rate local disease on the basis of tumor spread along the different layers of the bladder wall (Table 1, Fig 7) (3–5). Lymphadenopathy or distant metastases are not commonly associated with superficial tumors, but the chances of spread increase significantly after muscle layer invasion (3). Thus, the staging of diverticular tumors presents a unique difficulty, as bladder diverticula are formed by mucosal herniations through muscular defects and the diverticular walls lack a muscle layer. Indeed, some authors suggest skipping the T2 stage altogether when staging diverticular tumors (6).
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Figure 7. Correlation of the extent of tumor invasion with the TNM staging system of the International Union against Cancer and the Jewett-Strong-Marshall (JSM) staging system. The muscular layer is missing in bladder diverticula. The reflection of peritoneum that makes up the serosal layer of the upper bladder is not shown.
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Bladder cancer is two to five times more common in men than in women. Its prevalence increases with age (7). There is a relationship between bladder cancers and exposure to aniline dyes and other chemicals used in several industries. Studies on cigarette smoking show a dose-response relation between pack-years and relative risk of bladder cancer, ranging from two to 10 (7,8). It is postulated that these substances, after being metabolized in the liver and excreted in the urine, become carcinogens that may interact locally with detoxifying enzymes, tumor suppressor genes, and oncogenes (9). Long-term analgesic abuse may increase the risk of bladder cancer, placing patients with chronic pain at risk. Cyclophosphamide and similar chemotherapeutic agents have also been implicated (7,9). There is also a relationship between bladder cancer and infection with Schistosoma haematobium. Presumably, there is an inflammatory process with regenerative hyperplasia and increased cell proliferation. The same process may be responsible for the small increase in bladder cancer, especially squamous cell carcinoma, found with recurrent urinary tract infections, indwelling catheters, and chronic urolithiasis (7).
There is a well-documented relationship between urinary bladder diverticula and bladder cancer. Intradiverticular tumors have a prevalence of 1%–10% (6). It is thought that urinary stasis produces chronic mucosal irritation and prolonged exposure to urinary carcinogens. Thus, there is a predisposition to malignant degeneration of the diverticular urothelium (10).
Most patients present with hematuria or microhematuria. Unfortunately, this may be intermittent, so a negative sample has little meaning. Other symptoms may include vesical irritability; urgency; dysuria; and, less commonly, flank pain from obstruction, leg edema, or a pelvic mass. Results of physical examination are usually unremarkable, especially with disease confined to the bladder, but abdominal tenderness or induration or an abdominal mass may be present (4,8).
Cytologic results from urine specimens may provide a diagnosis or steer the differential diagnosis in the right direction. However, cystoscopy is deemed of more value than cytologic analysis. The final diagnosis of bladder cancer is usually established with cystoscopy and biopsy of the lesion. Aside from cystoscopy, imaging studies are an indispensable adjunct in the diagnosis, staging, and management of bladder cancer (4).
Conventional radiography is of limited use in bladder cancer. Calcifications visible at plain radiography are rare. A pelvic mass needs to be large before it is visible on a plain radiograph. Alongside cystoscopy, intravenous urography has been the primary method of evaluating patients with hematuria for many years. Bladder position or tethering, wall irregularities, and filling defects may offer clues pointing to the presence of neoplastic disease (11). Unfortunately, intravenous urography demonstrates only 60% of all known bladder tumors (4).
Cross-sectional imaging may demonstrate a vesical mass or focal wall thickening. Cross-sectional imaging is also an essential tool for detecting intradiverticular masses. The only clue to these at intravenous urography may be an irregularly shaped diverticulum (compare Figs 1 and 3). Moreover, an obstructed diverticulum can remain occult during intravenous urography. Intradiverticular masses may also be difficult to see or altogether missed during cystoscopy (12,13).
US is inexpensive and allows detailed visualization of the bladder. With the advent of color Doppler US, determination of vascularity within a lesion is possible. Although no statistical relationship between the characterization of vascularity at color Doppler US and tumor grade or stage has been found, color Doppler US remains a powerful way to determine the nature of a lesion: Nonneoplastic mass lesions, such as a clot, may appear as a filling defect at intravenous urography, but detection of vascularity at color Doppler US would favor the diagnosis of a neoplastic mass (Fig 2b) (14). Unlike other modalities, US does not allow evaluation of the entire genitourinary tract.
Aside from adequate visualization of the bladder, CT allows recognition of vesical, ureteral, and renal synchronous lesions, as well as local spread, lymphadenopathy, and metastatic disease. Like color Doppler US, contrast-enhanced CT allows differentiation of vascular lesions from other masses if preceded by an unenhanced scan (Fig 3). Although tumor attenuation is similar to that of the bladder wall at nonenhanced CT, postcontrast images show relative hyperenhancement of the neoplasm. This is most reproducible with a 60-second scanning delay (15). Calcification or soft-tissue thickening may suggest a local mass. Flat tumors are not easily detectable with CT. Thus, any suggestion of a filling defect should be followed by delayed excretory views of the bladder in the supine and prone positions to outline the internal lining of the bladder. An irregular interface, haziness, or stranding of the perivesical fat suggests tumor spread (15). Nevertheless, the role of CT in staging is limited by its inability to resolve the different layers of the bladder wall.
Magnetic resonance (MR) imaging of the bladder provides direct multiplanar capabilities and unparalleled soft-tissue contrast. T2-weighted images demonstrate a difference in signal intensity between the inner and outer layers of the muscularis propria, aiding in gross assessment of tumor depth. Gadolinium enhancement allows further evaluation of tumor extent and spread to adjacent organs. MR imaging will likely improve on and extend the current usefulness of imaging in staging bladder cancer (5,16). Ultimately, tumor resection or biopsy is needed for adequate staging, but these methods cannot detect extravesical disease.
Local endoscopic resection is the treatment of choice for superficial tumors. These tumors are also treated with intravesical instillation of adjuvant chemotherapeutic agents after transurethral resection. Bacillus Calmette-Guérin is an immunomodulating agent also used in the treatment of superficial bladder cancer after transurethral resection (17). More invasive tumors are treated with cystectomy, chemotherapy, and/or radiation (3). Treatment for cancers within diverticula may include transurethral resection, but this is complicated by narrow ostia and thin diverticular walls. Diverticulectomy, partial cystectomy, and radical cystectomy with or without intravesical instillations are other modes of treatment for intradiverticular disease (6). Common treatments of bladder cancer are summarized in Table 2.
In our case, the diverticulectomy was followed by intravesical instillation of bacillus Calmette-Guérin a few weeks later. The results of 3-month follow-up cystoscopy were negative. Six months after surgery, however, cystoscopy demonstrated a 2-cm mass in the right lateral bladder wall. The patient subsequently underwent transurethral resection of the bladder tumor and instillation of intravesical mitomycin C. No further recurrences have been detected at follow-up cystoscopies.
Bladder tumors are well known for having a high frequency of synchronous and metachronous lesions, more commonly seen in tumors of higher grade. The prognosis is most influenced by the histologic grade at diagnosis. Ten-year survival can range from 98% for papillomas and low malignant potential tumors to 40% for high-grade neoplasms. Staging also affects the prognosis, as the vast majority of patients who develop metastases have concomitant or prior muscle layer invasion (8). Previously, the prognosis was thought to be grimmer for tumors arising in diverticula, mainly because the thinner diverticular wall would allow earlier spread (10,12). Resection of these tumors can be technically challenging (6). However, recent studies suggest that complete resection with careful follow-up may be successful in the treatment of intradiverticular cancers (6). Different therapies, such as bacillus Calmette-Guérin, have been able to alter the natural history of bladder cancer (17). Improvements in cytologic, cystoscopic, and radiologic evaluations will allow better staging and management and, ultimately, better results in treating this illness.
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Acknowledgments
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We thank Barbara Siede, medical illustrator, for her graphic representation of tumor invasion through the bladder wall (Fig 7).
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Footnotes
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Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases are published, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
SUPPLEMENTAL MATERIAL
A movie clip to supplement this article is available online at radiographics.rsnajnls.org/cgi/content/full/25/5/1397/DC1.
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History
Imaging Findings
