With more than 380,000 new cases and 150,000 deaths occurring every year in the world, bladder neoplasm is ranked among the most common malignancies in medical practice [1]. It was considered as the fourth most common cause of cancer in males [1]. But in 2016, data from the United States indicates that its incidence has risen to third place amongst malignant diseases in males (after prostate and lung cancer), with more than 75,000 new cases, of which almost 60,000 are in males [2]. Apart from male gender, cigarette smoking, known as the single most important risk factor for bladder neoplasm, as well as occupational exposure to aromatic amines (frequently in rubber and cable manufacturing) are well-established risk factors [3]. The main clinical presentation is gross painless hematuria, seen in almost 85% of patients when the diagnosis is made [4] [5]. The second important feature of bladder neoplasm is the appearance of asymptomatic microscopic hematuria [4]. In addition, lower urinary tract symptoms (LUTS), such as dysuria, frequent urination, nocturia, etc., have been strongly associated with the development of bladder neoplasms [3], and their unexplained occurrence must be evaluated thoroughly [4]. Unfortunately, their poor follow-up and misdiagnosis as infections or kidney stones are the main factors for a delayed diagnosis [5], and pelvic pain or a palpable pelvic mass, are signs of metastatic dissemination. A very important feature of bladder neoplasms is their recurrence after excision, often at sites rather than at the primary site of the lesion, making long-term monitoring of operated patients mandatory [6].

• Hematuria

  The main clinical presentation is gross painless hematuria, seen in almost 85% of patients when the diagnosis is made. The second important feature of bladder neoplasm is the appearance of asymptomatic microscopic hematuria. [symptoma.com]

  Herein, we reported a 59-year-old female patient consulted to our outpatient clinic with the incidents of hematuria. [ncbi.nlm.nih.gov]

  Clinical features  Often vague  Gross or microscopic hematuria. [slideshare.net]

  This blood in the urine may be visible to the naked eye (gross/macroscopic hematuria) or detectable only by microscope (microscopic hematuria). Hematuria is the most common symptom in bladder cancer. [checkorphan.org]

• Nocturia

  In addition, lower urinary tract symptoms (LUTS), such as dysuria, frequent urination, nocturia, etc., have been strongly associated with the development of bladder neoplasms, and their unexplained occurrence must be evaluated thoroughly. [symptoma.com]

  Other symptoms may include suprapubic pain after voiding, bladder irritability, dribbling, and nocturia. Physical examination The physical examination is usually normal. [medical-dictionary.thefreedictionary.com]

  Less commonly, patients may complain of urinary frequency, nocturia, and dysuria, symptoms that are more common in patients with carcinoma in situ. [cancer.gov]

Signs and symptoms of bladder neoplasm may be insidious and are often absent in its early stages, making the diagnosis difficult. In the setting of macroscopic hematuria, however, bladder cancer must be excluded as the underlying cause. A detailed patient history regarding the onset of symptoms and their progression is the first step, followed by a thorough physical examination of the abdomen and a prostate exam, as prostate cancer must be excluded as well. Urinalysis is also a valuable diagnostic procedure that can reveal microscopic hematuria, which is particularly valuable in the absence of other symptoms [5]. Urine cytology is also an important diagnostic method used to detect the presence of malignant cells that have been shed from the tumor into urine [5]. However, cystoscopy is considered to be the gold standard, although it is invasive and highly unpleasant [1] [5]. Cystoscopy provides a viable sample for biopsy and enables adequate classification according to TNM staging [7]:

• Tumor (T) - Depending on the depth of tissue infiltration, tumors are divided into the following stages: Noninvasive papillary lesions (Ta), carcinoma in situ (Tis), lesions that invade the subepithelial connective tissue (T1), muscle (either superficial or deep, demarcated as T2a and T2b, respectively), perivesicular tissue, either microscopic or macroscopic (T3a and T3b), and tumors that invade adjacent organs (infiltration of the prostate, uterus, or vagina are designated as T4a, whereas T4b denotes invasion of the pelvic or abdominal wall).
• Nodal involvement (N) - Infiltration of adjacent lymph nodes by the tumor is not seen in the initial stages of the disease (N0), but further development results in infiltration of only one node in the pelvis (N1), 2 or more in the same area (N2) or 1 or more iliac nodes (N3).
• Metastasis (M) - Presence of metastases (M1) confirms the advanced stage of the disease and carries a very poor prognosis.

In order to define the tumor stage, histopathological findings must be supported by imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI). However, the diagnosis primarily relies on the extent of the primary tumor and its spread such as nodal and metastatic involvement indicating advanced (IV) disease [7]. Recent studies have evaluated several markers that may be of use in the diagnostic workup such as apolipoprotein E (APOE), fibrinogen β chain precursor (FGB) and polymerase (RNA) I polypeptide E (POLR1E) which have shown promising results [1].

1. Lindén M, Segersten U, Runeson M, Wester K, Busch C, Pettersson U, et al. Tumour expression of bladder cancer-associated urinary proteins. BJU Int. 2013;112(3):407-415.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30.
3. Zhou J, Kelsey KT, Smith S, Giovannucci E, Michaud DS. Lower Urinary Tract Symptoms and Risk of Bladder Cancer in Men: Results from the Health Professionals Follow-Up Study. Urology. 2015;85(6):1312-1318.
4. Dobbs RW, Hugar LA, Revenig LM, Al-Qassab S, Petros JA, Ritenour CW, et al. Incidence and clinical characteristics of lower urinary tract symptoms as a presenting symptom for patients with newly diagnosed bladder cancer. Int Braz J Urol. 2014;40(2):198-203.
5. Garg T, Pinheiro LC, Atoria CL, et al. Gender Disparities in Hematuria Evaluation and Bladder Cancer Diagnosis: A Population-Based Analysis. J Urol. 2014;192(4):1072-1077.
6. Aster, JC, Abbas, AK, Robbins, SL, Kumar, V. Robbins basic pathology. Ninth edition. Philadelphia, PA: Elsevier Saunders; 2013.
7. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.