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Transitional Cell Carcinoma of the Bladder

Bladder Transitional Cell Carcinoma

Transitional cell carcinoma of the bladder (syn. urothelial carcinoma) makes up the majority of bladder cancers. Based on the extent to which the tumor has spread into the bladder wall, it can be categorized as non-muscle invasive (superficial, papillary) or muscle invasive (non-papillary). The most typical symptom, painless hematuria, calls for further cystoscopy investigation, especially in high-risk patients (smokers, workers exposed to carcinogenic chemicals such as aromatic amines, patients exposed to arsenic in water, radiation or cyclophosphamide therapy), whereas computed tomography and magnetic resonance imaging provide additional visualization and staging information.


Presentation

Transitional cell carcinoma of the bladder (syn. urothelial carcinoma) (TCC) constitutes 90% of bladder cancers [1]. Depending on cancer penetration into the bladder wall muscle layer, it is categorized as non-muscle invasive (papillary) or muscle invasive (non-papillary). A majority of bladder TCC are non-muscle invasive on discovery. Being low-grade, this type of cancer has a better prognosis than the high-grade invasive type but is more likely to recur. However, without treatment, non-muscle invasive carcinoma will eventually progress into muscle-invasive type [1] [2].

In both men and women, the most widespread risk factor for developing bladder TCC is smoking [3]. The second major factor is workplace exposure to carcinogens, such as aromatic amines, polycyclic aromatic hydrocarbons, chlorinated hydrocarbons or heavy metals [4] [5]. Oral intake of arsenic is also associated with bladder cancer, with contaminated drinking water being the main source of exposure [6]. Iatrogenic causes of TCC include ionizing radiation and cyclophosphamide therapy [4].

Most patients with TCC display urinary signs and symptoms, predominantly painless hematuria. While usually visible, hematuria can sometimes be microscopic and intermittent, requiring repeated tests in order to be discovered. Additionally, patients can experience urgency or frequency of urination, in some cases accompanied by discomfort or pain. In advanced disease, flank pain, leg swelling or a palpable pelvic mass may occur; non-specific symptoms such as cachexia or bone pain may signal the presence of distant metastases [7].

Weakness
  • The recurrence-free survival time of patients with overexpression of clusterin was significantly shorter than that of patients with weak expression of clusterin (9.8 months vs. 35.2 months).[ncbi.nlm.nih.gov]
  • Diagnosis The prinicpal differential diagnosis is plasmacytoma Usually, awareness of this pattern is enough to permit a diagnosis but stains can be useful if necessary P63 and strong keratin indicate carcinoma Plasma cell processes may sometimes show weak[surgpathcriteria.stanford.edu]
  • Note: In a large series, PSA positivity is reported in 1.4% bladder UCC. [11] In half the cases the staining is weak and in the other half it is strong. [11] IHC for staging Smoothelin immunostain for muscularis propria invasion versus muscularis mucosae[librepathology.org]
Asymptomatic
  • As many benign and malignant glans lesions may be clinically similar, histologic study is necessary to correctly diagnose primary lesions and promptly detect underlying asymptomatic visceral malignancies initially presenting as Paget's disease.[ncbi.nlm.nih.gov]
  • Physicians may consider cystoscopy and/or CT urography in patients 35 years with asymptomatic hematuria who also have risk factors for CIS. These procedures enable diagnostic evaluation of the entire urinary tract, as well as follow-up.[amboss.com]
Pelvic Mass
  • In advanced disease, flank pain, leg swelling or a palpable pelvic mass may occur; non-specific symptoms such as cachexia or bone pain may signal the presence of distant metastases.[symptoma.com]
  • Pelvic pain occurs with advanced cancer, when a pelvic mass may be palpable. Cystoscopy with biopsy Urine cytology Bladder cancer is suspected clinically. Urine cytology, which can detect malignant cells, may be done.[merckmanuals.com]
Abdominal Pain
  • A 48-year-old male with a 30-pack year smoking history was admitted with abdominal pain, nausea, and vomiting. He also complained of a 50-lb weight loss and gross hematuria over one-year period.[ijcasereportsandimages.com]
  • Urinary obstruction, abdominal pain, urinary tract infection, and weight loss are reported occasionally. Rare cases of paraneoplastic syndromes such as ectopic ACTH secretion and hypercalcemia have also been reported.[ccij-online.org]
Diplopia
  • METHODS: A 74-year-old man experienced 2 weeks of red eye, proptosis, diplopia, pain, and visual loss in the right eye.[ncbi.nlm.nih.gov]
Skin Lesion
  • He presented to our outpatient clinic with a 3-month history of skin lesions as multiple, rubbery subcutaneous nodules.[ncbi.nlm.nih.gov]
Subcutaneous Nodule
  • He presented to our outpatient clinic with a 3-month history of skin lesions as multiple, rubbery subcutaneous nodules.[ncbi.nlm.nih.gov]
Hematuria
  • Most patients with TCC display urinary signs and symptoms, predominantly painless hematuria. While usually visible, hematuria can sometimes be microscopic and intermittent, requiring repeated tests in order to be discovered.[symptoma.com]
  • We report a case of amyopathic dermatomyositis in a patient whose painless gross hematuria was due to transitional cell carcinoma of the bladder as well as review this association.[ncbi.nlm.nih.gov]
  • It should be remembered that hematuria could develop after blunt abdominal trauma in children, for reasons other than the trauma itself (e.g. tumors of the urinary tract).[ncbi.nlm.nih.gov]
  • Patients with transitional cell carcinoma of the bladder classically present with irritative voiding symptoms or painless hematuria.[ncbi.nlm.nih.gov]
  • A 67 year old male presented with hematuria. He was diagnosed with left renal cell carcinoma and transitional cell carcinoma of the bladder.[ncbi.nlm.nih.gov]
Dysuria
  • […] urothelial cancer References: [1] [2] [3] [4] [6] [7] [8] [9] Clinical features Location Symptoms Features of advanced/ metastatic disease Bladder carcinoma Painless gross hematuria throughout micturition (most common) Irritative voiding symptoms ( dysuria[amboss.com]
  • Adults aged 60 and over and have unexplained non visible haematuria and either dysuria or a raised white cell count on a blood test.[patient.info]
  • Irritative voiding symptoms (dysuria, burning, frequency) and pyuria are also common at presentation. Pelvic pain occurs with advanced cancer, when a pelvic mass may be palpable.[merckmanuals.com]
  • Patients present with urinary frequency, dysuria or urgency. Microscopic hematuria is very common but gross hematuria is present in an occasional patient.[med-ed.virginia.edu]
Pelvic Pain
  • Bladder cancer care at Mayo Clinic Symptoms Bladder cancer signs and symptoms may include: Blood in urine (hematuria) Painful urination Pelvic pain If you have hematuria, your urine may appear bright red or cola colored.[mayoclinic.org]
  • Pelvic pain: Hypofractionated radiotherapy, nerve block or palliative chemotherapy may be options for those with pelvic pain caused by incurable bladder cancer.[patient.info]
  • Pelvic pain occurs with advanced cancer, when a pelvic mass may be palpable. Cystoscopy with biopsy Urine cytology Bladder cancer is suspected clinically. Urine cytology, which can detect malignant cells, may be done.[merckmanuals.com]
Urinary Incontinence
  • Orthotopic bladders have a risk of urinary incontinence. Prognosis The recurrence rate for superficial transitional cell cancer of the bladder is high (70% within five years). As many as 80% of patients have at least one recurrence.[patient.info]
Nocturia
  • Managing symptoms of locally advanced or metastatic cancer [ 10 ] Bladder symptoms: Palliative radiotherapy may benefit those with symptoms of haematuria, dysuria, urinary frequency or nocturia caused by advanced bladder cancer.[patient.info]

Workup

Cystoscopy and bimanual examination are the golden standards for diagnosis in suspected bladder cancer. Aside from enabling tumor detection and visualization, cystoscopy provides an opportunity for biopsy of the observed abnormalities through all bladder wall layers. The obtained samples can give information on the cell type in addition to cancer stage and grade [8]. Difficulties arise in cystoscopic detection of carcinoma in situ (CIS), which is either invisible or mimics inflammation (appears in red-velvety flat patches) [9]. CIS can be detected through cytology analysis of voided urine. While urine cytology demonstrates high accuracy in diagnosis of CIS and high-grade lesions, its sensitivity is inadequate for low-grade malignancies, which yield too few cells per urine sample. Urine tumor marker analysis, such as fluorescence in situ hybridization (FISH) can increase sensitivity and specificity in TCC detection [10]. In the case of positive cytology, but negative cystoscopy findings, mapping biopsy along with additional diagnostic procedures (e.g. imaging) are recommended for investigation of CIS and upper urinary tract malignancies, respectively [9].

Imaging techniques, primarily computed tomography (CT) and magnetic resonance imaging (MRI) complement cystoscopy in the detection of carcinomas situated in bladder diverticula, disease staging (distinguishing invasive from non-invasive forms) and lymph node visualization [8]. MRI is superior in tumor staging, especially when contrast-enhanced, T2-weighted and diffusion-weighted techniques are combined [1] [11]. Shortcomings of CT and MRI include false positive and false negative findings due to small lymph nodes, reactive lymphadenopathy and variability in bladder wall thickening depending on the degree of bladder extension [1] [8]. [F-18]-Fluorodeoxyglucose positron emission tomography (FDG-PET) can be used for staging of pelvic lymph nodes, discovering distant metastases and differentiating the reactive from tumor tissue. Urinary excretion of FDG limits this method in the diagnosis of primary bladder TCC [12].

The exceptionally high recurrence rate of bladder TCC warrants periodic post-therapeutic surveillance, by using cystoscopy, urinary cytology (including FISH), FDG PET and other imaging techniques [1] [8] [10] [12].

Treatment

  • Despite treatment (mostly surgery and radiotherapy), patients with brain metastases have an especially poor prognosis (median survival 2-5 months), making palliative treatment an important consideration.[ncbi.nlm.nih.gov]
  • Treatment options include debulking surgery, whole brain radiation, stereotactic radiosurgery and chemotherapy. Unfortunately, treatment may not appreciably extend survival and care is often supportive in previously reported cases.[ncbi.nlm.nih.gov]
  • Chemotherapy was stopped immediately but this was not enough to relieve the symptoms of severe myalgia and swelling, and additional treatment consisting of cyclophosphamide and prednisolone was initiated.[ncbi.nlm.nih.gov]
  • GEMOX treatment led to a 36 % response rate in assessable patients. Median progression-free survival was 4.9 months, with a median overall survival (OS) of 10.4 months and a one-year survival rate of 44.4 %.[ncbi.nlm.nih.gov]
  • CONCLUSIONS: Transitional cell carcinoma of the bladder in children is usually benign and endoscopic treatment (TUR-BT) seems to be the treatment of choice.[ncbi.nlm.nih.gov]

Prognosis

  • Literature suggests that these patients present with advanced stage and carry a poor prognosis. The histopathologic features, treatment and prognosis associated with this rare paraneoplastic syndrome are reviewed.[ncbi.nlm.nih.gov]
  • Unfortunately, the prognosis for patients with TCC and CNS metastases is poor. Treatment options include debulking surgery, whole brain radiation, stereotactic radiosurgery and chemotherapy.[ncbi.nlm.nih.gov]
  • In cases of orbital metastasis from TCC, patient prognosis is very poor. Copyright Japanese Ophthalmological Society 2006.[ncbi.nlm.nih.gov]
  • CONCLUSION: These results demonstrate that in contrast to other solid tumours, activation of the Src family members and downstream signalling proteins are associated with a good prognosis in transitional cell carcinoma of the bladder, and activated Src[ncbi.nlm.nih.gov]
  • As most tumors are low-grade and low-stage and are associated with an excellent prognosis, endoscopic TUR is the preferred therapeutic measure. However, recurrence as well as death have been reported in this age group.[ncbi.nlm.nih.gov]

Etiology

  • We discuss the pathogenesis of nephrogenic adenoma and suggest that prolonged cystitis caused by intravesical BCG may play an etiological role.[ncbi.nlm.nih.gov]
  • Among several risk factors, Human Papilloma Virus (HPV) have been presumed to play a causative role in the etiology of bladder cell carcinoma.[ncbi.nlm.nih.gov]
  • INTRODUCTION: Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer.[ncbi.nlm.nih.gov]
  • Brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and octreotide scans were performed to evaluate the underlying etiology of his symptoms.[ncbi.nlm.nih.gov]
  • Studies in migrants may provide valuable insight into the environmental and genetic etiology of cancer.[ncbi.nlm.nih.gov]

Epidemiology

  • INTRODUCTION: Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer.[ncbi.nlm.nih.gov]
  • PATIENTS AND METHODS: Patients with Ta/is/1 N0 M0 TCC of the bladder and no history of previous cancer treated surgically between 1983 and 2002 were studied using the Surveillance, Epidemiology, and End Results (SEER) database.[ncbi.nlm.nih.gov]
  • Epidemiology and etiology of bladder cancer. Urol Clin North Am 1992; 19:421-428. Grant DC, Dee GJ, Yoder IC, Newhouse Sonography of transitional cell carcinoma the renal pelvis.[sonoworld.com]
  • Epidemiology Uncommon before the age of 40, only 5% of cases present before the age of 60. Male to female ratio 4:1 Incidence is about 32 per 100 000 in men, and 10 per 100 000 in women.[almostadoctor.co.uk]
  • […] transitional cell carcinoma of the urinary tract TCCs in other locations: transitional cell carcinoma of the renal pelvis transitional cell carcinoma of the ureter other histologies: squamous cell carcinoma of the bladder adenocarcinoma of the bladder Epidemiology[radiopaedia.org]
Sex distribution
Age distribution

Prevention

  • FNA helped with the diagnosis in this case and prevented unnecessary biopsy.[ncbi.nlm.nih.gov]
  • Elimination of tobacco smoking may prevent about 65 % of TCCs.[ncbi.nlm.nih.gov]
  • A normal healthy cell undergoes an adverse change when it can no longer take in oxygen to convert glucose into energy [compare Otto Warburg On The Prime Cause & Prevention of Cancer ].[healingcancernaturally.com]
  • TUR alone is effective in preventing recurrences in approximately 50% of patients with superficial bladder cancer.[texasoncology.com]
  • Preventing bladder cancer While it is not possible to prevent bladder cancer, it is possible to reduce your risks such as not smoking or quitting smoking, and avoiding exposure to chemicals listed above.[cancer.org.au]

References

Article

  1. Verma S, Rajesh A, Prasad SR, et al. Urinary Bladder Cancer: Role of MR Imaging. RadioGraphics. 2012;32(2):371-387. doi:10.1148/rg.322115125.
  2. Pashos CL, Botteman MF, Laskin BL, Redaelli A. Bladder Cancer. Epidemiology, Diagnosis, and Management. Cancer Practice. 2002;10(6):311-322. doi:10.1046/j.1523-5394.2002.106011.x.
  3. Freedman ND, Silverman DT, Hollenbeck AR. Association Between Smoking and Risk of Bladder Cancer Among Men and Women. Jama. 2011;306(7):737. doi:10.1001/jama.2011.1142.
  4. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. European Urology. 2013;63(2):234-241. doi:10.1016/j.eururo.2012.07.033.
  5. Cumberbatch MGK, Cox A, Teare D, Catto JWF. Contemporary Occupational Carcinogen Exposure and Bladder Cancer. JAMA Oncology. 2015;1(9):1282. doi:10.1001/jamaoncol.2015.3209.
  6. Baris D, Waddell R, Freeman LEB, et al. Elevated Bladder Cancer in Northern New England: The Role of Drinking Water and Arsenic. JNCI: Journal of the National Cancer Institute. 2016;108(9). doi:10.1093/jnci/djw099.
  7. Soloway M, Carmack A, Khoury S. Bladder Tumors. Bladder Cancer: Epidemiology, Staging and Grading, and Diagnosis. In: 1St International Consultation on Bladder Tumors. Health Publication Ltd; 2004:14 - 64.
  8. Vikram R, Sandler CM, Ng CS. Imaging and Staging of Transitional Cell Carcinoma: Part 1, Lower Urinary Tract. American Journal of Roentgenology. 2009;192(6):1481-1487. doi:10.2214/ajr.08.1318.
  9. Babjuk M, Burger M, Zigeuner R, et al. EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2013. European Urology. 2013;64(4):639-653. doi:10.1016/j.eururo.2013.06.003.
  10. Grossman HB, Soloway M, Messing E. Surveillance for Recurrent Bladder Cancer Using a Point-of-Care Proteomic Assay. Jama. 2006;295(3):299. doi:10.1001/jama.295.3.299.
  11. Takeuchi M, Sasaki S, Ito M, et al. Urinary Bladder Cancer: Diffusion-weighted MR Imaging—Accuracy for Diagnosing T Stage and Estimating Histologic Grade. Radiology. 2009;251(1):112-121. doi:10.1148/radiol.2511080873.
  12. Jadvar H, Quan V, Henderson RW, Conti PS. [F-18]-Fluorodeoxyglucose PET and PET-CT in diagnostic imaging evaluation of locally recurrent and metastatic bladder transitional cell carcinoma. International Journal of Clinical Oncology. 2008;13(1):42-47. doi:10.1007/s10147-007-0720-8.

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Last updated: 2019-07-11 19:56