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A 57-year-old man presents to general medical clinic with hematuria. He first noticed the color of his urine darkening several weeks ago, and it has recently worsened. He denies any pain. Vital signs are stable. Physical examination is within normal limits. He has no costovertebral angle tenderness. Urinalysis is positive for heme and urine culture is negative. Urine cytology reveals malignant cells. An image from subsequent cystoscopy is shown in figure A. Biopsy confirms this is the most common tumor of the genitourinary tract. All of the following are risk factors for this tumor EXCEPT?
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Transitional cell carcinoma is the most common tumor of the genitourinary tract. HIV is not a risk factor for transitional cell carcinoma.
It is highly associated with smoking as well as the other risk factors listed except for HIV.
Bladder cancer is the most common tumor of the genitourinary tract. 90% of these cancers are transitional cell carcinomas. This type of tumor may occur at any point in the genitourinary tract - from the kidney to the bladder. However, most of the time the tumors reside in the bladder. Although often resectable, transitional cell carcinomas often recur after removal. Risk factors include cigarette smoking, industrial carcinogens (aniline dye, azo dyes), radiation, and long-term treatment with cyclophosphamide.
Sharma et al. discuss the diagnosis and treatment of bladder cancer. Bladder cancer is the sixth most prevalent malignancy in the U.S. Cystoscopy remains the mainstay of diagnosis and surveillance. Fluorescence cystoscopy offers improvement in the detection of flat neoplastic lesions such as carcinoma in situ. Non-muscle-invasive cancers are typically managed with transurethral resection and intravesical chemotherapy.
Burger et al. discuss epidemiology and risk factors of bladder cancer. Smoking is the most common risk factor and accounts for almost half of all tumors. Occupational exposures to aromatic amines and aromatic hydrocarbons are other important risk factors.
Image A depicts a transitional carcinoma of the bladder on cystoscopy. Illustration A depicts the classic pathological appearance of transitional cell carcinoma.
Answers 1-3, 5: All of these are known risk factors for transitional cell carcinoma.
Sharma S, Ksheersagar P, Sharma P.
Am Fam Physician. 2009 Oct 01;80(7):717-23. PMID: 19817342 (Link to Abstract)
Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y.
Eur Urol. 2013 Feb;63(2):234-41. Epub 2012 Jul 25. PMID: 22877502 (Link to Abstract)
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A 67-year-old male presents to his primary care physician for his annual physical examination. He has no significant past medical history and is generally healthy. At the conclusion of the visit, he mentions, embarrassingly, that he has noted some intermittent bloody discharge from his penis not related to urination, which concerns him. Which of the following is the most likely diagnosis?
Renal cell carcinoma
Transitional cell carcinoma of the bladder
Bloody urethral discharge occurring in an older man is urethral carcinoma (UC) until proven otherwise.
Urethral cancer is cancer originating from any segment of the urethra. This cancer is relatively rare, with the most common histologic type being papillary transitional cell carcinoma. The symptom of gross hematuria (visible blood in the urine during micturition) may suggest upper or lower urinary tract sources, while a urethral discharge is most likely not from a bladder or upper urinary source.
Sharp et al. discuss asymptomatic microscopic hematuria, which can be discovered incidentally in routine primary care situations (defined as the presence of three or more red blood cells per high-power field visible in a properly collected urine specimen without evidence of infection). Notably, the most common causes of microscopic hematuria are not malignancy related and include urinary tract infections, benign prostatic hyperplasia, and urinary calculi. They estimate the risk of malignancy to be 5% in patients with asymptomatic microscopic hematuria.
Gakis et al. discuss primary UC. They report pelvic magnetic resonance imaging is the preferred imaging study to determine the local extent of the urethral tumor. Management is determined by location and extent, with a localized anterior UC, noninvasive UC or carcinoma in situ treated with urethra-sparing surgery is an alternative to primary urethrectomy in both sexes, provided negative surgical margins can be achieved. Bacillus Calmette-Guérin (BCG) also has a role in treatment in certain cases.
Illustration A shows a histomicrograph of papillary urothelial carcinoma, the most common type of urethral cancer.
Answers 1-3: Cancers of the upper urinary tract and bladder present with hematuria not urethral discharge.
Answer 4: Prostate cancer does not commonly present with hematuria.
Sharp VJ, Barnes KT, Erickson BA.
Am Fam Physician. 2013 Dec 01;88(11):747-54. PMID: 24364522 (Link to Abstract)
Gakis G, Witjes JA, Compérat E, Cowan NC, De Santis M, Lebret T, Ribal MJ, Sherif AM, European Association of Urology.
Eur Urol. 2013 Nov;64(5):823-30. Epub 2013 Apr 2. PMID: 23582479 (Link to Abstract)
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A 72-year-old man presents to his primary care physician complaining of blood in his urine. He states that there is blood present throughout the void, but that he does not experience any pain or burning on urination. He smoked 1 pack per day for 50 years, but quit 6 years ago. Vital signs are within normal limits. Urinalysis is significant for 10 RBC/hpf, but no white cells and no casts. Urine culture is negative, and basic chemistries are within normal limits. Of the following, which is the best next step in management?
Kidney, ureter, bladder plain film series
Cystoscopy and intravenous pyelography
MRI abdomen and pelvis
The patient’s clinical presentation is suspicious for a urinary-tract malignancy. A full urologic evaluation of the entire urinary tract is required with cystoscopy and intravenous pyelography (IVP).
Hematuria can have multiple etiologies, but risk factors for malignancy includes advanced age, smoking history, occupational exposure to chemicals or dyes (benzenes, aromatic amines), chronic cystitis, pelvic irradiation, cyclophosphamide exposure, chronic indwelling foreign body, and history of analgesic abuse. In this vignette, the patient has two risk factors (advanced age, smoking). Bladder cancer is the most common malignancy of the urinary tract, and commonly presents with hematuria (with or without pain), dysuria, frequency, urgency, and constitutional symptoms.
Choyke discusses the recommended imaging studies for the presentation of hematuria. While IVP has traditionally been a standard modality of upper tract visualization, ultrasonography and CT have recently been investigated as viable alternatives and are gaining traction. CT urography is a new technique produces images similar to IVP while also giving traditional CT images as well.
Loo et al. conducted a prospective cohort study of patients evaluated for asymptomatic microscopic hematuria and report the development of a Hematuria Risk Index to identify patients at high risk, which include those risk factors previously mentioned. They suggest that more extensive evaluations for malignancy only be conducted in patients who have been risk stratified and identified as high risk individuals.
Illustration A is an IVP study. After injection of contrast, a radiograph is taken to show excretion into the lower ureters and bladder. Note the mass-like filling defect (arrows), suggestive of a large bladder carcinoma.
Answer 1: A kidney, ureter, bladder plain film series is used to identify nephrolithiasis.
Answer 3: MRI of the abdomen and pelvis is not the first imaging study ordered in the workup of urinary tract malignancy.
Answer 4: Urine cytology can be helpful as an adjunct to cystoscopy.
Answer 5: Antibiotics are not an appropriate first choice in management without confirmation of infection.
Am Fam Physician. 2008 Aug 01;78(3):347-52. PMID: 18711950 (Link to Abstract)
Loo RK, Lieberman SF, Slezak JM, Landa HM, Mariani AJ, Nicolaisen G, Aspera AM, Jacobsen SJ.
Mayo Clin Proc. 2013 Feb;88(2):129-38. Epub 2013 Jan 9. PMID: 23312369 (Link to Abstract)
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