Urethral cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [6], Vindhya BellamKonda, M.B.B.S [7]

Overview

Urethral cancer must be differentiated from bladder cancer, cervical cancer, bladder stones, ureteral stones, cystitis, neurogenic bladder, and urethritis.

Differentiation

Urethral cancer must be differentiated from other diseases that cause lower urinary tract irritation symptoms (e.g., dysuria, urgency and frequency in addition to urethral discharge); these include Bladder cancer, Cervical cancer, urethritis, Bladder stones, cystitis, urethrolithiasis, Neurogenic bladder, cervicitis, vulvovaginitis, and epididymitis.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11]

The following table summarizes the differential diagnosis for Urethral cancer:

Diseases	Hematuria	Pyuria	Frequency	Urgency	Dysuria	Weak urine stream	Mass	Fever	Tenderness	Discharge	Inguinal Lymphadenopathy	Urinalysis	Urine Culture	Gold Standard	Past medical history
Diseases	Symptoms							Physical Examination				Diagnostic tests			Past medical history
Urethral Cancer	+	–	+/–	+/–	+/–	+	+	–	–	–	–	Malignant cells RBC	–	Biopsy	Personal history of bladder cancer. Conditions that cause chronic inflammation in the urethra, including: Sexually transmitted diseases (STDs), including human papillomavirus (especially HPV type 16) Frequent urinary tract infections (UTIs) White female Age 60
Bladder cancer	+	–	+/–	+/–	–	–	+/–	–	–	–	–	Malignant cells RBC	–	Biopsy	Smoking Occupational exposure to chemicals: Textiles, Rubber, Paint, Leather, Dye, Metal, Machining, Plastics, Arsenic, Aristolochic acids Chronic bladder irritation Chronic urinary tract infection Bladder stones Schistosoma haematobium Trauma Chemotherapy: yclophosphamide, Ifosfamide Radiation therapy Personal history of cancer in the urinary tract Congenital bladder anomalies such as rachus, Exstrophy
Cervical cancer	–	–	+/–	+/–	–	–	+/–	–	–	–	–	–	–	Biopsy	Specific risk factor: Human papillomavirus (HPV) infection:^[12]^[13]^[14]^[15] Other risk factors for cervical cancer include the following: ^[16]^[17] Smoking HIV infection Increased number of sexual partners Young age at time of first sexual intercourse Hormonal contraception High parity DES (diethylstilbestrol):
Bladder stones	+	–	+	+/–	+/–	–	–	–	–	–	–	RBC	–	CT scan without contrast	Common risk factors in the development of nephrolithiasis include: Dietary habits Low urinary pH Hypercalcemia Hypercalciuria Hyperoxaluria Hyperuricemia Hyperuricosuria Metabolic syndrome Obesity Diabetes mellitus Environmental – such as hot climate Drugs Thiazide Furosemide Sulfadiazine Indinavir
Ureterolithiasis	+	–	+	+	+/–	–	–	–	–	–	–	RBC	–	CT scan without contrast	Same as bladder cancer
Neurogenic bladder	–	–	+/–	+/–	–	–	–	–	–	–	–	–	–	Urodynamic study (UDS)	Spinal cord diseases, injuries Neural tube defects including spina bifida. Brain tumors
Urethritis	–	+	–	–	+	+/–	–	+	–	Urethral discharge	+	Positive leukocyte esterase test or >10 WBCs Mucous threads in the morning urine	–	Gram stain & mucoid or purulent discharge	Prior STDs Urinary tract infections New sexual partner Recent intercourse Recent catheterization
Cystitis	+	+	+	+	+	–	–	+	Suprapubic	–	+	Nitrite +ve Leukocyte esterase +ve WBCs RBCs	>100,000CFU/mL	Urine culture	Recent catheterisation Pregnancy Recent intercourse Diabetes Personal or family history of UTI Known abnormality of the urinary tract BPH HIV
Diseases	Symptoms							Physical Examination				Diagnostic tests			Past medical history
Diseases	Hematuria	Pyuria	Frequency	Urgency	Dysuria	Weak urine stream	Mass	Fever	Tenderness	Discharge	Inguinal Lymphadenopathy	Urinalysis	Urine Culture	Gold Standard	Past medical history
Vulvovagintis	–	–	–	–	+			+	–	Vaginal discharge	+	–	–	Gram stain & culture of discharge	Number and type of sexual partners (new, casual, or regular) Prior STDs Previous history of symptomatic BV in female partner (in homosexual women)
Cervicitis	–	+	–	–	+			+	Cervical	Endocervical exudate	–	–	–	Culture for gonococcal cervicitis	Abnormal vaginal bleeding after intercourse or after menopause Abnormal vaginal discharge Painful sexual intercourse Pressure or heaviness in the pelvis
Epididymitis	+	–	+	+	+			+	Testicular & suprapubic	+/– urethral discharge	+	Hematuria may be seen	+	Culture	Unilateral, gradual, and localized scrotal pain posterior to the testis Scrotal swelling Scrotal wall erythema Constitutional symptoms: feeling warm, chills, nausea and vomiting

References

↑ Stephen Bent, Brahmajee K. Nallamothu, David L. Simel, Stephan D. Fihn & Sanjay Saint (2002). “Does this woman have an acute uncomplicated urinary tract infection?”. JAMA. 287 (20): 2701–2710. PMID 12020306. Unknown parameter |month= ignored (help)
↑ W. E. Stamm (1981). “Etiology and management of the acute urethral syndrome”. Sexually transmitted diseases. 8 (3): 235–238. PMID 7292216. Unknown parameter |month= ignored (help)
↑ W. E. Stamm, K. F. Wagner, R. Amsel, E. R. Alexander, M. Turck, G. W. Counts & K. K. Holmes (1980). “Causes of the acute urethral syndrome in women”. The New England journal of medicine. 303 (8): 409–415. doi:10.1056/NEJM198008213030801. PMID 6993946. Unknown parameter |month= ignored (help)
↑ Leonie G. M. Giesen, Grainne Cousins, Borislav D. Dimitrov, Floris A. van de Laar & Tom Fahey (2010). “Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs”. BMC family practice. 11: 78. doi:10.1186/1471-2296-11-78. PMID 20969801.
↑ Taylor-Robinson D (1996). “The history of nongonococcal urethritis. Thomas Parran Award Lecture”. Sex Transm Dis. 23 (1): 86–91. PMID 8801649.
↑ Bennett, John (2015). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.
↑ Brill JR (2010). “Diagnosis and treatment of urethritis in men”. Am Fam Physician. 81 (7): 873–8. PMID 20353145.
↑ Daniel V. Landers, Harold C. Wiesenfeld, R. Phillip Heine, Marijane A. Krohn & Sharon L. Hillier (2004). “Predictive value of the clinical diagnosis of lower genital tract infection in women”. American journal of obstetrics and gynecology. 190 (4): 1004–1010. doi:10.1016/j.ajog.2004.02.015. PMID 15118630. Unknown parameter |month= ignored (help)
↑ Felix Millan-Rodriguez, J. Palou, Anna Bujons-Tur, Mireia Musquera-Felip, Carlota Sevilla-Cecilia, Marc Serrallach-Orejas, Carlos Baez-Angles & Humberto Villavicencio-Mavrich (2006). “Acute bacterial prostatitis: two different sub-categories according to a previous manipulation of the lower urinary tract”. World journal of urology. 24 (1): 45–50. doi:10.1007/s00345-005-0040-4. PMID 16437219. Unknown parameter |month= ignored (help)
↑ Kim TH, Kim SY, Moon KC, Lee J, Cho JY, Kim SH (April 2017). “Clear Cell Adenocarcinoma of the Urethra in Women: Distinctive MRI Findings for Differentiation From Nonadenocarcinoma and Non-Clear Cell Adenocarcinoma of the Urethra”. AJR Am J Roentgenol. 208 (4): 805–811. doi:10.2214/AJR.16.16929. PMID 28140610.
↑ Cantiello F, Cicione A, Salonia A, Autorino R, Tucci L, Madeo I, Damiano R (May 2013). “Periurethral fibrosis secondary to prostatic inflammation causing lower urinary tract symptoms: a prospective cohort study”. Urology. 81 (5): 1018–23. doi:10.1016/j.urology.2013.01.053. PMID 23608423.
↑ [1] American Cancer Society
↑ [2]
↑ [3]
↑ [4]
↑ Kim JJ, Burger EA, Regan C, Sy S. PMID 30212064. Missing or empty |title= (help)
↑ Tatar O, Thompson E, Naz A, Perez S, Shapiro GK, Wade K, Zimet G, Gilca V, Janda M, Kahn J, Daley E, Rosberger Z (November 2018). “Factors associated with human papillomavirus (HPV) test acceptability in primary screening for cervical cancer: A mixed methods research synthesis”. Prev Med. 116: 40–50. doi:10.1016/j.ypmed.2018.08.034. PMID 30172799.

[:0-1] Stephen Bent, Brahmajee K. Nallamothu, David L. Simel, Stephan D. Fihn & Sanjay Saint (2002). “Does this woman have an acute uncomplicated urinary tract infection?”. JAMA. 287 (20): 2701–2710. PMID 12020306. Unknown parameter |month= ignored (help)

[:1-2] W. E. Stamm (1981). “Etiology and management of the acute urethral syndrome”. Sexually transmitted diseases. 8 (3): 235–238. PMID 7292216. Unknown parameter |month= ignored (help)

[:2-3] W. E. Stamm, K. F. Wagner, R. Amsel, E. R. Alexander, M. Turck, G. W. Counts & K. K. Holmes (1980). “Causes of the acute urethral syndrome in women”. The New England journal of medicine. 303 (8): 409–415. doi:10.1056/NEJM198008213030801. PMID 6993946. Unknown parameter |month= ignored (help)

[:3-4] Leonie G. M. Giesen, Grainne Cousins, Borislav D. Dimitrov, Floris A. van de Laar & Tom Fahey (2010). “Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs”. BMC family practice. 11: 78. doi:10.1186/1471-2296-11-78. PMID 20969801.

[pmid8801649-5] Taylor-Robinson D (1996). “The history of nongonococcal urethritis. Thomas Parran Award Lecture”. Sex Transm Dis. 23 (1): 86–91. PMID 8801649.

[:4-6] Bennett, John (2015). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.

[pmid20353145-7] Brill JR (2010). “Diagnosis and treatment of urethritis in men”. Am Fam Physician. 81 (7): 873–8. PMID 20353145.

[:5-8] Daniel V. Landers, Harold C. Wiesenfeld, R. Phillip Heine, Marijane A. Krohn & Sharon L. Hillier (2004). “Predictive value of the clinical diagnosis of lower genital tract infection in women”. American journal of obstetrics and gynecology. 190 (4): 1004–1010. doi:10.1016/j.ajog.2004.02.015. PMID 15118630. Unknown parameter |month= ignored (help)

[:7-9] Felix Millan-Rodriguez, J. Palou, Anna Bujons-Tur, Mireia Musquera-Felip, Carlota Sevilla-Cecilia, Marc Serrallach-Orejas, Carlos Baez-Angles & Humberto Villavicencio-Mavrich (2006). “Acute bacterial prostatitis: two different sub-categories according to a previous manipulation of the lower urinary tract”. World journal of urology. 24 (1): 45–50. doi:10.1007/s00345-005-0040-4. PMID 16437219. Unknown parameter |month= ignored (help)

[pmid28140610-10] Kim TH, Kim SY, Moon KC, Lee J, Cho JY, Kim SH (April 2017). “Clear Cell Adenocarcinoma of the Urethra in Women: Distinctive MRI Findings for Differentiation From Nonadenocarcinoma and Non-Clear Cell Adenocarcinoma of the Urethra”. AJR Am J Roentgenol. 208 (4): 805–811. doi:10.2214/AJR.16.16929. PMID 28140610.

[pmid23608423-11] Cantiello F, Cicione A, Salonia A, Autorino R, Tucci L, Madeo I, Damiano R (May 2013). “Periurethral fibrosis secondary to prostatic inflammation causing lower urinary tract symptoms: a prospective cohort study”. Urology. 81 (5): 1018–23. doi:10.1016/j.urology.2013.01.053. PMID 23608423.

[12] [1] American Cancer Society

[13] [2]

[14] [3]

[15] [4]

[pmid30212064-16] Kim JJ, Burger EA, Regan C, Sy S. PMID 30212064. Missing or empty |title= (help)

[pmid30172799-17] Tatar O, Thompson E, Naz A, Perez S, Shapiro GK, Wade K, Zimet G, Gilca V, Janda M, Kahn J, Daley E, Rosberger Z (November 2018). “Factors associated with human papillomavirus (HPV) test acceptability in primary screening for cervical cancer: A mixed methods research synthesis”. Prev Med. 116: 40–50. doi:10.1016/j.ypmed.2018.08.034. PMID 30172799.

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