Introduction

Bladder carcinoma has been reported to be a common malignancy with an estimated 15580 deaths and 74690 new cases globally in 2013 (1). It is typically a disease of older individuals; the majority of patients are above 60 years of age at the time of diagnosis. Urothelial bladder carcinoma (UBC) is a rare condition in patients aged below 40 years, furthermore, much rarer in the first two decades of life with reported incidence rates of only 0.1% to 0.4% (2). There is controversy regarding the clinical behavior and prognosis of UBC in young patients.

Case Presentation

The patient was a healthy 24-year-old male who had no history of smoking or exposure to chemicals. He presented to our clinic after having painless macroscopic hematuria. Physical examination was unremarkable. The urinalysis was positive for blood cells and there were no signs of infection and, other laboratory tests were normal. Initially, the patient was sent for a urinary ultrasound scan which revealed a 2x2 centimeters hyper-echoic lesion on the right side of the bladder; both of the kidneys were normal. His urine was confirmed to be sterile by urine culture and cytology of the urine was negative for aberrant cells. Diagnostic cystoscopy confirmed the papillomatous lesion on the right side of the bladder at the 8 o’clock position (Figure 1). Soon after, deep transurethral resection of the lesion was carried out down to the muscle. The postoperative period was uneventful. Pathology of the lesion was reported as papillary urothelial neoplasm of low malign potential (PUNLMP) (Figure 2). Control cystoscopy at the 3^rd month has shown no recurrence in the follow-up; the next cystoscopy was planned for the 12^th month. The informed consent was obtained from the patient for publication.

Discussion

UBC in young individuals is very rare and only 1% of cases are detected in the first 40 years of life. Its incidence dramatically increases with age. In people aged over the 70 years, the incidence rate of UBC is 15-20 times higher than in those aged 30-50 years (3).

Nearly all patients with UBC typically present with macroscopic and painless hematuria (4). In this age group, the clinicians have less inclination to perform cystoscopy. In a study, cystoscopy was performed in 40% of children who presented with macroscopic hematuria and UBC was detected in only 1% (5). Therefore, diagnostic delays of up to one year may occur. Ultrasound imaging is very sensitive for detecting UBC and proven to be a reliable diagnostic tool. Computed tomography is particularly useful for assessing the upper urinary system and distant metastasis. Urine cytology has limited use in the diagnosis of UBC because it has very low sensitivity.

There is controversy on the clinical behavior and prognosis of UBC in young patients which can be explained with several reasons. Firstly, the definitions of “young patient” are highly variable. The vast majority of the studies have included patients below 40 years of age as “young patient”, while others have used 20 or 30 years of age as a cut-off point. Recently, in the age group below 20 years, the disease was found to have clinical and pathological features different from that in olders (6). Secondly, different World Health Organization (WHO) pathological classification systems have been used for reporting. The histopathological reporting classification system was last overhauled by the WHO in 2016.

The younger patients with UBC have low-stage and -grade disease while the incidence of high-grade tumors gradually increases with age. Na et al. (7) analyzed 42 patients and found pTa in 33, pT1 in 4, pT2 or higher in 5 and low-grade in 31, high-grade in 11 patients. Moreover Wang et al. (8) found that 5-year survival was better in young patients (93.8%) than in older ones (85.1%). The largest study, with more than 150 patients, showed that the vast majority of patients had PUNLMP (40.3%), furthermore, UBC could be highly aggressive in 18% of high-grade and muscle-invasive type tumors (9).

It is widely accepted that conversion of the 1973 WHO classification to the 2004 WHO classification would result in down-grading of a significant proportion of grade 1 tumors to PUNLMP (10). Especially in patients under 30 years of age, in whom grade 1 tumors predominate, it is likely that majority of urothelial carcinomas from studies published before the 2004 WHO system would have been classified as PUNLMP, as reported by Fine et al. (11). In that study, 23 UBC patients were reclassified according to the 2004 WHO classification system and more than half of tumors were found to be PUNLMP. It is reasonable to conclude that PUNLMP dominates in patients under 30 years of age. Even if PUNLMP may recur in up to 36% of patients, it has a low risk of progression (3.7%) and this progression generally occurs as a low-grade pTa lesion (12). Another importance of the term is that the diagnosis of “cancer” can be avoided in young patients.

There have been some studies investigating the relationship between recurrence of UBC and age. Na et al. (7) showed that only 7.1% of patients under 40 years of age had recurrences, while 38% of patients over 60 years of age had recurrence. Moreover, Ozbey et al. (13) reported that the mean time to first relapse was 37.7 months in young patients and 9.9 months in older patients, therefore the older age group may have more rapid recurrence.

Several studies were conducted to understand the molecular level why young patients had more low-grade and -stage tumors. Wild et al. (14) reported that genetic alterations which are frequently found in older patients are extremely rare under 20 years of age. Similarly, Owen et al. (15) showed lower epigenetic alteration rates in individuals under the age of 20 years.

Hematuria in young patients should be investigated in detail. By using the term PUNLMP, the diagnosis of “cancer” can be avoided and it is particularly important in young patients who usually have favorable outcomes. In the management of UBC in young patients, the grade and stage of the tumor are more critical than the age factor, as in older patients.

Ethics

Informed Consent: The informed consent was obtained from the patient.

Peer-review: Internally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: H.D., H.Ş., Concept: İ.A., H.Ş., Design: İ.A., M.Ç., Data Collection or Processing: İ.A., H.T., Analysis or Interpretation: İ.A., Literature Search: İ.A., H.T., H.D., Writing: İ.A.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.