Tumors of the Bladder Flashcards
The average age of patients with bladder cancer in the United States is:
a. 65.
b. 69.
c. 73.
d. 76.
e. 78.
c. 73. In the United States, the mean age of diagnosis is 73.
Inverted papillomas are:
a. a benign tumor of the bladder.
b. a precursor to low-grade papillary cancer. c. chemotherapy resistant.
d. an invasive tumor.
e. best treated with antibiotics.
a. A benign tumor of the bladder. When diagnosed according to strictly defined criteria (e.g., lack of cytologic atypia), inverted papillomas behave in a benign fashion with only a 1% incidence of tumor recurrence (Sung etal., 2006; Kilciler etal., 2008). Occasionally, inverted papillomas are present with coexistent urothelial cancer elsewhere in the urinary system, occurring more commonly in the upper tract than the bladder (Asano etal., 2003). The use of fluorescence in situ hybridization to evaluate chromosomal changes can distinguish between an inverted papilloma and a urothelial cancer with an inverted growth pattern (Jones etal., 2007).
The incidence rate of urothelial cancer:
a. has been decreasing recently because of less smoking.
b. is higher in women than in men.
c. is highest in developed countries.
d. peaks in the fifth decade of life.
e. is higher in Asia than Europe.
c. Is highest in developed countries. Sixty-three percent of all bladder cancer cases occur in developed countries, with 55% occurring in North America and Europe. There is a geographic difference in bladder cancer incidence rates across the world, with the highest rates in Southern and Eastern Europe, parts of Africa, Middle East, and North America, and the lowest in Asia and underdeveloped areas in Africa (Ferlay etal., 2007). The incidence of urothelial cancer peaks in the seventh decade of life.
The mortality rate of urothelial cancer:
a. is primarily related to lack of health care access.
b. has been decreasing since 1990.
c. is highest in underdeveloped countries.
d. is proportionally higher in women than in men.
e. is proportionally higher in white men than in African American men.
b. Has been decreasing since 1990. The mortality rate of urothelial cancer has decreased by 5% since 1990, primarily because of smoking cessation, changes in environmental carcinogens, and healthier lifestyles (Jemal etal., 2008).
What is the risk of a white male developing urothelial cancer in his lifetime?
a. Less than 5%
b. 20%
c. 40%
d. 60%
e. 80%
a. Less than 5%. A white male has a 3.7% chance of developing urothelial cancer in his lifetime, which is roughly 3 times the probability in white females or African American males and more than 4.5 times the probability of an African American female (Hayat etal., 2007; Jemal etal, 2008).
The most common histologic bladder cancer cell type is:
a. squamous.
b. adeno.
c. urothelial.
d. small cell.
e. leiomyosarcoma.
c. Urothelial.Histologically, 90% of bladder cancers are of urothelial origin, 5% squamous cell, and less than 2% adenocarcinoma or other variants (Lopez-Beltran, 2008). Urothelial carcinoma is the most common malignancy of the urinary tract and is the second most common cause of death among genitourinary tumors.
The mortality rate from bladder cancer is highest in:
a. the United States.
b. England.
c. South America.
d. China.
e. Egypt.
e. Egypt. The mortality rate from bladder cancer in Egypt is three times higher than in Europe and eight times higher than in North America because squamous cell carcinoma is highly prevalent in Egypt (Parekh etal., 2002).
Recent evidence suggests that physician practice may be related to bladder cancer deaths in the elderly. What percentage of deaths could be avoided?
a. Less than 5%
b. 30%
c. 50%
d. 70%
e. 90%
b. 30%. Mortality from bladder cancer is highest in elderly persons, particularly those past the age of 80, accounting for the third most common cause of cancer deaths in men over the age of 80 (Jemal etal., 2008). Whether this increase in mortality rate is related to tumor biology or changes in physician practice with the elderly is unclear. Recent evidence suggests that physician practice may be related to bladder cancer deaths in the elderly (Morris etal., 2009). These authors estimated that 31% of all bladder cancer deaths were avoidable, more commonly in noninvasive than invasive disease.
Which gene is most commonly mutated in high-grade muscle invasive urothelial cancer?
a. Cyclin A
b. TP53
c. FGFR-3
d. HRAS
e. PTEN
- b. TP53. High-malignant potential, non–muscle-invasive bladder cancer is more likely associated with deletions of tumor suppressor genes such as TP53 and RB (Chatterjee etal., 2004a; George etal, 2007; Sanchez-Carbayo etal, 2007).
- Which gene is most commonly mutated in carcinoma in situ (CIS)?
a. PI3K
b. RB
c. FGFR-3
d. HRAS
e. CD-44
b. RB. All CIS is high grade by definition. The genetic abnormalities associated with CIS include alterations to the RB, TP53, and PTEN genes (Cordon-Cardo etal., 2000; Lopez-Beltran etal, 2002; Cordon-Cardo, 2008).
Which gene is most commonly mutated low-grade papillary urothelial carcinoma (LgTa)?
a. PTEN
b. RB
c. FGFR-3
d. HRAS
e. CD-44
c. FGFR-3. Low-grade urothelial carcinoma is typically papillary in nature with a fibrovascular stalk and frequent papillary branching with increased cellular size, some nuclear atypia, and occasional mitotic figures. These tumors almost universally display alterations of genes in chromosome 9 and frequent mutations in FGFR3, PI3K or, alternatively, Ras genes.
- The chemotherapy proven to cause urothelial cancer is: a. doxorubicin. b. bleomycin. c. ifosfamide. d. etoposide. e. cyclophosphamide.
Wein, Alan J.; Kolon, Thomas F.. Campbell-Walsh-Wein Urology Twelfth Edition Review E-Book (CampbellWalsh) (p. 518). Elsevier Health Sciences. Kindle Edition.
- e. Cyclophosphamide.The only chemotherapeutic agent that has been proven to cause bladder cancer is cyclophosphamide (Travis etal., 1995; Nilsson and Ullen, 2008). The risk of bladder cancer formation is linearly related to the duration and intensity of cyclophosphamide treatment, supporting a causative role. Phosphoramide mustard is the primary mutagenic metabolite that causes bladder cancer in patients exposed to cyclophosphamide.
The increased risk of developing bladder cancer for a man who has a sister with bladder cancer is:
a. twofold.
b. 10-fold.
c. 20-fold.
d. 40-fold.
e. 60-fold.
a. Twofold.First-degree relatives of patients with bladder cancer have a twofold increased risk of developing urothelial cancer themselves, but high-risk urothelial cancer families are relatively rare (Aben etal., 2002; Murta-Nascimento etal., 2007; Kiemeney, 2008).
The risk of a family member developing bladder cancer if a first-degree relative has the disease is:
a. related to secondhand smoke.
b. higher in men.
c. higher in smokers.
d. related to inheritance of low-penetrance genes.
e. most common in high-grade cancer.
d. Related to inheritance of low-penetrance genes. The hereditary risk seems to be higher for women and nonsmokers, but it is not related to secondhand exposure to smoking in families. Most likely, there are a variety of low-penetrance genes that can be inherited to make a person more susceptible to carcinogenic exposure, thus increasing the risk of bladder cancer formation.
The percent of patients presenting with non–muscle-invasive disease is:
a. less than 5%.
b. 20%.
c. 40%.
d. 60%.
e. 80%.
e. 80%.At initial presentation, 80% of urothelial tumors are non–muscle-invasive. There are multiple growth patterns of urothelial cancer, including flat carcinoma in situ (CIS), papillary tumors that can be low or high grade, and sessile tumors with a solid growth pattern. Non–muscle-invasive cancers can be very large because of lack of the genetic alterations required for invasion.
A 30-year-old man has gross hematuria, and cystoscopy reveals a papillary tumor. Transurethral resection of the tumor reveals a noninvasive 2-cm papillary low-malignant-potential urothelial tumor. Muscle is present in the resected specimen. All of the tumor is resected. The best treatment is:
a. intravesical bacille Calmette-Guérin (BCG). b. repeat cystoscopy with random bladder biopsies.
c. radical cystectomy because of the patient’s young age.
d. immediate mitomycin C intravesical therapy.
e. observation.
d. Immediate mitomycin C intravesical therapy.PUNLMP is a papillary growth with minimal cytological atypia that is more than seven cells thick and is generally solitary and located on the trigone (Holmang etal., 2001; Sauter etal., 2004). PUNLMP is composed of thin papillary stalks where the polarity of the cells is maintained and the nuclei are minimally enlarged. PUNLMP has a low proliferation rate and is not associated
The external agent most implicated in causing urothelial cancer is:
a. β-naphthylamine.
b. 4-aminobiphenyl.
c. perchloroethylene.
d. trichloroethylene.
e. 4,4′-methylene bis(2-methylaniline).
a. β-naphthylamine. One of the first and most common chemical agents implicated in the formation of bladder cancer in dye and rubber workers is β-naphthylamine (Case and Hosker, 1954). Activation of aromatic amines allows DNA binding by enzymes that are selectively expressed in the population, making some subjects more susceptible to cancer formation, as described earlier related to the NAT-2 and the GSTM1 polymorphisms.
If a woman stops smoking for 10 years after 30 pack-years of smoking, her risk of developing bladder cancer:
a. is the same as if she still smoked.
b. is the same as if she never smoked.
c. is unrelated to the intensity of smoking.
d. is very low because of her gender.
e. gradually decreases with time.
e. Gradually decreases with time.Smoking cessation does make a difference in urothelial cancer formation. Smokers who have stopped for 1 to 3 years have a 2.6 relative risk, and those who have stopped for more than 15 years have a 1.1 relative risk of bladder cancer formation (Wynder and Goldsmith, 1977; Smoke IAfRoCT, 2004).
A man exposed to high doses of radiation (more than 500 mSv):
a. has the same risk of urothelial cancer formation as a nuclear plant worker.
b. will likely develop urothelial cancer within 5 years.
c. is more likely to develop urothelial cancer if he is younger than 20 years.
d. is two times more likely to develop urothelial cancer.
e. should be quarantined for 3 months.
d. Is two times more likely to develop urothelial cancer. There is a significant increased risk of dying from any cancer if a person is exposed to greater than 50 mSv. The relative risk of urothelial cancer formation is 1.63 in men and 1.74 in women. Interestingly, urothelial cancer formation after radiation is not age related, but the latency period is 15 to 30 years. However, there is no association with low-dose or industrial exposure of radiation therapy and bladder cancer formation. Importantly, urologic technicians and nuclear radiation workers do not have an increased risk of urothelial cancer formation.
One of the main changes between the AJCC 7th edition and AJCC 8th edition for bladder cancer is:
a. there should be two grades of non-muscle-invasive bladder cancer. b. multiple positive pelvic lymph nodes is considered stage 3 disease.
c. perivesical fat involvement by tumors is stage T3.
d. CIS can be low or high grade.
e. Ta grade 1 tumors should be considered cancerous.
b. Multiple positive pelvic lymph nodes is considered stage 3 disease. Broadly speaking, non–muscle-invasive bladder cancer is composed of stage 0 (noninvasive) and stage 1 (invasion into subepithelial connective tissue), muscle-invasive organ-confined bladder cancer is of stage 2, muscle-invasive locally advanced bladder cancer is stage 3, and metastatic disease is stage 4. Whereas prior AJCC editions viewed positive lymph nodes as stage 4 regardless of the quantity or location, the 2017 AJCC staging update now views nodal disease in the absence of systemic metastases as stage 3.
Genetic abnormalities associated with low-malignant potential Ta tumors include:
a. fibroblast growth factor receptor-3 (FGFR-3).
b. TP53.
c. retinoblastoma (RB) gene.
d. PTEN.
e. loss of chromosome 17.
a. Fibroblast growth factor receptor-3 (FGFR-3).Genetic abnormalities associated with low-grade cancer include deletion of 9q and alterations of FGFR-3, HRAS, and PI3K (Holmang etal, 2001; Cordon-Cardo, 2008). Low-grade carcinomas are immunoreactive for cytokeratin-20 and CD-44. The TP53, retinoblastoma (RB), and PTEN genes and loss of chromosome 17 are all associated with high-grade cancer.
A 40-year-old man has a T1 high-grade urothelial cancer on initial presentation. Muscle was present in the biopsy specimen. The next treatment is:
a. BCG.
b. repeat transurethral resection of a bladder tumor (TURBT).
c. radical cystectomy.
d. immediate mitomycin C instillation. e. neoadjuvant chemotherapy followed by radical cystectomy.
b. Repeat transurethral resection of a bladder tumor (TURBT).Because of this understaging, the American Urological Association (AUA) guidelines call for a repeat transurethral resection in patients with T1 tumors to assess for muscle-invasive disease even if muscle was present in the specimen (Hall etal, 2007).
A 73-year-old man with a history of Ta bladder cancer is found to have a 0.5-cm papillary lesion in the prostatic urethra and undergoes extensive transurethral resection of the prostate, revealing high-grade noninvasive disease of the prostatic urethra without ductal or stromal involvement. The next best step is:
a. perioperative mitomycin C.
b. surveillance cystoscopy every 3 months.
c. mitomycin C therapy. d. induction of and maintenance with BCG therapy.
e. radical cystectomy.
d. Induction of and maintenance with BCG therapy. For patients with noninvasive prostatic urethral cancer, transurethral resection of the prostate with BCG therapy is appropriate (Palou etal, 2007). For patients with prostatic ductal disease, a complete TURP is warranted, plus BCG therapy. Although a radical cystectomy could be performed, a more conservative organ-sparing treatment is recommended.
A 62-year-old man undergoes a transurethral biopsy of a bladder tumor at the dome. Final pathology reveals muscle-invasive urothelial and small cell carcinoma. Metastatic workup is negative. The next step is:
a. intravesical gemcitabine therapy.
b. partial cystectomy.
c. radical cystoprostatectomy.
d. external beam radiotherapy.
e. chemoradiation therapy.
e. Chemoradiation therapy. Small cell carcinoma of the bladder should be considered and treated as metastatic disease, even if there is no radiologic evidence of disease outside the bladder. Small cell carcinoma of the bladder accounts for much less than 1% of all primary bladder tumors. In general, small cell carcinoma of the bladder is very chemosensitive, and the primary mode of therapy is chemoradiation therapy or chemotherapy followed by cystectomy.
When cisplatin-based chemotherapy is used, which of the following genetic mutations is associated with the worst prognosis?
a. FGFR-3 mutations
b. PTEN
c. TP53
d. RB
e. PTEN, TP53, and RB
e. PTEN, TP53, and RB. Overall genetic instability is the hallmark of invasive urothelial cancer, but, specifically, alterations of TP53, RB, and PTEN carry a very poor prognosis (Chatterjee etal, 2004a). FGFR-3 mutations are associated with noninvasive bladder cancer.
When cisplatin-based neoadjuvant chemotherapy is used, which of the following genetic mutations is associated with an improved response?
a. FGFR-3 mutations
b. ERCC2
c. TP53
d. RB
e. ERCC2, FANCC, and ATM
e. ERCC2, FANCC, and ATM . The recent application of genomics to large cohorts of MIBCs has produced major breakthroughs in disease heterogeneity with obvious implications for clinical management. Whole transcriptome studies identified basal and luminal molecular subtypes (Choi etal., 2014; TCGAR, 2014; Damrauer et al., 2014), and patients with basal tumors appeared to derive the most benefit from neoadjuvant chemotherapy (NAC) (Seiler etal 2017; McConkey etal., 2018). In parallel, two other groups demonstrated that inactivating mutations in DNA damage repair genes (including ERCC2, FANCC, ATM) were associated with response to NAC (Van Allen etal., 2014; Serebriiskii et al., 2015). These findings are now being prospectively examined within the context of the Southwest Oncology Group’s (SWOG’s) completed S1314 trial. In addition, two groups have designed prospective clinical trials to test whether DDR mutations can be used to guide bladder preservation in patients treated with NAC, and several groups are considering clinical trials to select MIBC patients for NAC based on basal molecular subtype membership.
Tumor suppressor genes are activated by: a. gene amplification.
b. translocation.
c. point mutations.
d. DNA methylation.
e. microsatellite instability.
c. Point mutations. Tumor suppressor genes are mainly activated by allelic deletion of one allele followed by point mutations of the remaining allele. Tumor suppressor genes are recessive or have a negative effect, resulting in unregulated cellular growth. Proto-oncogenes are generally activated by point mutations in the genetic code, gene amplification, and gene translocation. The activated proto-oncogenes become oncogenes that can cause cancer, and this is considered a positive or dominant growth effect (Lengauer etal, 1998; Wolff etal, 2005; Cordon-Cardo, 2008).
The risk of urologic malignancy in a man with recurrent gross hematuria, but who had a previous negative evaluation, is:
a. less than 5%.
b. 20%.
c. 40%.
d. 60%.
e. 80%.
a. Less than 5%.Gross, painless hematuria is the primary symptom in 85% of patients with a newly diagnosed bladder tumor (Khadra etal, 2000; Alishahi etal, 2002; Edwards etal, 2006). The gross hematuria is usually intermittent and can be related to Valsalva maneuvers; therefore any episode of gross hematuria should be evaluated even if subsequent urinalysis is negative. Fifty percent of patients with gross hematuria will have a demonstrable cause, 20% will have a urological malignancy, and 12% will have a bladder tumor (Khadra etal, 2000). The risk of malignancy in patients with recurrent gross or microscopic hematuria that had a full, negative evaluation is near zero within the first 6 years (Khadra etal, 2000).
Which of the following is not a high-risk factor in urothelial cancer formation in patients with microscopic hematuria?
a. Age younger than 40 years
b. Smoking
c. History of pelvic radiation
d. Urinary tract infections
e. Previous urologic surgery
a. Age younger than 40 years. The guidelines recommend consideration for reevaluation of low-risk individuals with microscopic hematuria, but repeat evaluation every 6 months with a urinalysis, cytology, and blood pressure (to detect renal disease) is recommended for high-risk patients. Age younger than 40 years is the only factor that is not associated with an increased risk of malignancy.
A 70-year-old man has microscopic hematuria. Cytology and computed tomography (CT) scan are negative. Cystoscopy reveals a raised 3-mm lesion on the trigone. The lesion is biopsied and is depicted in Fig. 135.1A and B, and is reported as adenocarcinoma. The next step in management is:
a. review the pathology slides with the pathologist.
b. cystectomy.
c. intravesical chemotherapy.
d. bone scan.
e. ask for special stains from pathology.
Wein, Alan J.; Kolon, Thomas F.. Campbell-Walsh-Wein Urology Twelfth Edition Review E-Book (CampbellWalsh) (p. 520). Elsevier Health Sciences. Kindle Edition.
a. Review the pathology slides with the pathologist. This is a classic inverted papilloma, and the inexperienced pathologist might mistake it for an adenocarcinoma. The location of the lesion would be unusual for adenocarcinoma, particularly in a patient with no risk factors, and should alert the clinician to review the slides with the pathologist.
Wein, Alan J.; Kolon, Thomas F.. Campbell-Walsh-Wein Urology Twelfth Edition Review E-Book (CampbellWalsh) (p. 524). Elsevier Health Sciences. Kindle Edition.
A 65-year-old man has gross hematuria. He has a history of tuberculosis. Cytology is suspicious, CT scan is normal, and cystoscopy reveals a papillary lesion cephalad to the trigone. The lesion is visually completely resected (Fig. 135.2) and is reported as high-grade invasive urothelial carcinoma. The next step in management is:
a. intravesical BCG.
b. immediate intravesical mitomycin c. repeat transurethral resection of bladder at the previous biopsied site.
d. a cystectomy.
e. ask the pathologist if there is muscularis propria in the specimen.
Wein, Alan J.; Kolon, Thomas F.. Campbell-Walsh-Wein Urology Twelfth Edition Review E-Book (CampbellWalsh) (p. 520). Elsevier Health Sciences. Kindle Edition.
- e. Ask the pathologist if there is muscularis propria in the specimen. There are clear bundles of muscularis propria in the micrograph making the tumor at least a T2.
Wein, Alan J.; Kolon, Thomas F.. Campbell-Walsh-Wein Urology Twelfth Edition Review E-Book (CampbellWalsh) (p. 524). Elsevier Health Sciences. Kindle Edition.
See Fig. 135.3. The depicted findings have an association with:
a. bladder carcinoma.
b. previous trauma.
c. recurrent urinary tract infections.
d. urolithiasis.
e. ureteral spasm.
Wein, Alan J.; Kolon, Thomas F.. Campbell-Walsh-Wein Urology Twelfth Edition Review E-Book (CampbellWalsh) (p. 520). Elsevier Health Sciences. Kindle Edition.
- a. Bladder carcinoma. Pseudodiverticulosis of the ureter is associated with bladder carcinoma in 30% of cases. This association has led many to recommend that patients with this diagnosis undergo surveillance of their bladder for the development of urothelial neoplasms. The etiology is unknown.
Wein, Alan J.; Kolon, Thomas F.. Campbell-Walsh-Wein Urology Twelfth Edition Review E-Book (CampbellWalsh) (p. 524). Elsevier Health Sciences. Kindle Edition.
Fig. 135.4A is a delayed contrast-enhanced image through the pelvic ureters, and Fig. 135.4B is an early contrast-enhanced image through the bladder. The next step in management is:
a. shockwave lithotripsy.
b. percutaneous nephrostolithotomy.
c. cystoscopy.
d. cystoscopy with ureteroscopy.
e. follow-up with imaging in 6 months.
- d. Cystoscopy with ureteroscopy. There are multiple enhancing masses in the fluid-filled urinary bladder on the early image. On the delayed image, the ureters are opacified with contrast, and there is a filling defect seen in the mildly dilated right ureter, suspicious for a synchronous ureteral lesion.
Wein, Alan J.; Kolon, Thomas F.. Campbell-Walsh-Wein Urology Twelfth Edition Review E-Book (CampbellWalsh) (p. 524). Elsevier Health Sciences. Kindle Edition.
What is cystitis grandularis?
Cystitis glandularis is a rare benign disorder of the urinary bladder characterized by the formation of cysts in the bladder’s submucosa. The cysts are lined by glandular epithelium and can be filled with clear, straw-colored fluid. Symptoms include recurrent urinary tract infections, frequency, urgency and dysuria. The condition is typically diagnosed using cystoscopy and biopsy, and treatment options include observation, medical therapy, or surgery.
What is pelvic lipomatosis?
Pelvic lipomatosis is a rare condition characterized by the abnormal growth of fat within the pelvic region. The condition is benign and usually asymptomatic but it can cause symptoms such as urinary obstruction, constipation, and abdominal pain. Pelvic lipomatosis can be diagnosed by a combination of imaging studies such as CT or MRI and physical examination. Treatment is typically surgical, with the goal of removing the excess fat and relieving any symptoms caused by the condition. In most cases, the condition is benign and non cancerous, but a biopsy is performed to confirm it.
