Urothelial Tumors of the Urinary Bladder

in Young Patients
A Clinicopathologic Study of 59 Cases
Melissa L. Stanton, MD; Li Xiao, MD; Bogdan A. Czerniak, MD, PhD; Charles C. Guo, MD 

Context.—Urothelial tumors are rare in young patients.
Because of their rarity, the natural history of the disease in
young patients remains poorly understood.
Objective.—To understand the pathologic and clinical
features of urothelial tumors of the urinary bladder in
young patients.
Design.—We identified 59 young patients with urothelial tumors of the urinary bladder treated at our institution
and analyzed the tumors’ pathologic features and the
patients’ clinical outcomes.
Results.—All patients were 30 years or younger, with a
mean age of 23.5 years (range, 4–30). Thirty-eight patients
(64%) were male, and 21 (36%) were female. Most tumors
were noninvasive, papillary urothelial tumors (49 of 59;
83%), including papillary urothelial neoplasms of low
malignant potential (7 of 49; 14%), low-grade papillary
urothelial carcinomas (38 of 49; 78%), and high-grade
papillary urothelial carcinomas (4 of 49; 8%). Only a few
(n ¼ 10) of the urothelial tumors were invasive, invading
the lamina propria (n ¼ 5; 50%), muscularis propria (n ¼ 4;

40%), or perivesical soft tissue (n ¼ 1; 10%). Clinical
follow-up information was available for 41 patients (69%),
with a mean follow-up time of 77 months. Of 31 patients
with noninvasive papillary urothelial tumors, only 1
patient (3%) later developed an invasive urothelial
carcinoma and died of the disease, and 30 of these
patients (97%) were alive at the end of follow-up,
although 10 (32%) had local tumor recurrences. In the
10 patients with invasive urothelial carcinomas, 3 patients
(30%) died of the disease and 5 others (50%) were alive
with metastases (the other 2 [20%] were alive with no
recurrence).
Conclusion.—Urothelial tumors in young patients are
mostly noninvasive, papillary carcinomas and have an
excellent prognosis; however, a small subset of patients
may present with high-grade invasive urothelial carcinomas that result in poor clinical outcomes.
(Arch Pathol Lab Med. 2013;137:1337–1341; doi:
10.5858/arpa.2012-0322-OA)

B

Recent studies have indicated that papillary and nonpapillary urothelial carcinomas may use different molecular
pathways, which may contribute to their distinct biologic
behaviors.3
Urothelial tumors are typically a disease of elderly people,
with a male predominance. The median ages of patients at
the time of the initial diagnosis are 69 years in men and 71
years in women.4 Urothelial tumors are rare in young
patients. Previous studies of patients with this disease have
used different definitions of young age, ranging from 20 years
to 40 years.5–18 These differences have led to inconsistent
results regarding the clinicopathologic features of this
disease in young patients. Some studies6,10–12 have reported
that younger patients with urothelial tumors had a more
favorable prognosis than older patients, but other studies5,8,13,14 have shown that the clinical course of the disease
in younger patients is similar to that in older patients.
Furthermore, because urothelial tumors are rare in young
patients, most studies5–18 of urothelial tumors in such
patients have been small series with the number of reported
cases ranging from 12 to 50. To better characterize the
clinicopathologic features of urothelial tumor in young
patients, we retrospectively evaluated a large series of

ladder cancer is the fourth most common cancer in men
and the ninth most common cancer in women in the
United States.1 Its incidence has been steadily increasing
during the past years. It is estimated that 73 510 patients are
newly diagnosed with bladder cancer and 14 880 patients
die of this disease in the United States every year.1 Most
bladder cancers consist of urothelial carcinoma, which can
be classified into different categories with distinct clinical
behavior.2 Low-grade, papillary urothelial carcinomas usually do not invade the bladder wall but often recur locally,
necessitating long-term surveillance. In contrast, highgrade, nonpapillary urothelial carcinomas are more likely
to be deeply invasive into the bladder wall and to
metastasize, resulting in significantly higher mortality.
Accepted for publication December 11, 2012.
From the Department of Pathology, University of Texas M. D.
Anderson Cancer Center, Houston.
The authors have no relevant financial interest in the products or
companies described in this article.
Reprints: Charles C. Guo, MD, Department of Pathology,
University of Texas M. D. Anderson Cancer Center, 1515 Holcombe
Blvd, Unit 085, Houston, TX 77030 (e-mail: ccguo@mdanderson.
org).
Arch Pathol Lab Med—Vol 137, October 2013

Urothelial Tumors in Young Patients––Stanton et al 1337

and another showed focal small cell carcinoma features. medical history. the incidence of low-grade urothelial tumors decreases.5–10 The average ages of young patients with urothelial tumors in most previous reports were older than 30 years but younger than 40 years. D. smoking history. 3–225 months). Clinical histories were available for 36 patients (61%). We reviewed the patients’ archived slides for histologic features.18 In the current study. papillary urothelial carcinomas. but 3 of them (60%) developed metastases in lymph nodes. D). 2 (33%) had recurrent urinary tract infections. 25 (96%) were alive after a mean of 71 months (range. 1%). 71%) were 21 to 30 years old. The noninvasive urothelial tumors included papillary urothelial neoplasms of low malignant potential (PUNLMPs) (7 of 49 [14%]. 1 invasive urothelial carcinoma showed a focal. accounting for 3% to 9% of urothelial tumors in young patients.5 years (range. including inverted type  Papillary urothelial neoplasm of low malignant potential  Low-grade. All 5 patients (100%) with tumors invading the lamina propria in the bladder were alive after a mean of 85 months (range. Of 26 patients with low-grade. Anderson Cancer Center (Houston) from 1985 to 2011 and found 59 patients who were initially diagnosed with urothelial tumors in the urinary bladder at 30 years or younger. tumor recurrence. Two (100%) of the patients with PUNLMPs who had follow-up data available were alive with no evidence of disease after 13 and 37 months. In addition. Table 1. More than 95% of patients younger than 30 years with urothelial tumors have low-grade (grade 1 or 2) papillary tumors. Table 3). Forty-two patients (71%) were 21 to 30 years old. 14%). although urothelial papillomas were relatively common in previous reports. Thirty-eight patients (64%) were male. the muscularis propria died of the disease after 15 and 102 months. respectively. A). with a mean age of 23. grade. 14 patients (24%) were 11 to 20 years old.2 2004. we searched the surgical pathology files at the University of Texas M. The invasive urothelial carcinomas (n ¼ 10) invaded the lamina propria (n ¼ 5.8. 1 (33%) had local tumor recurrence. Figure. The most common presenting symptom was gross hematuria (31 of 59. papillary urothelial carcinoma Nonpapillary type  Urothelial carcinoma in situ Invasive Urothelial Carcinoma MATERIALS AND METHODS After obtaining approval for our study from the institutional review board. B). stage. metastasis.0% to 2. and 21 (36%) were female. whereas the incidence of high-grade urothelial tumors increases. 3–250 months.5–18 Most of urothelial tumors in young patients are noninvasive. of those 36 patients. followed by the group of patients who were 11 to 20 years old (14 of 59. whereas 13 of 42 patients (31%) who were 21 to 30 years old had high-grade urothelial carcinoma. and perivesical soft tissue (n ¼ 1.6. Only 5% of our patients (n ¼ 3) were younger than 10 years at diagnosis.patients initially diagnosed at 30 years or younger at a single institution. This age distribution suggests that the incidence of urothelial tumors in young patients increases with age. papillary urothelial carcinoma  High-grade. The urothelial tumors were noninvasive in 49 cases (83%) and invasive in 10 cases (17%). of those 6 patients. which had required bilateral ureteral implantations. low-grade. 40%.5 years. the patients in our series had a male to female ratio of 1. and clinical outcome. Figure. We determined the tumor grade using the 2004 World Health Organization classification system (Table 1)2 and the pathologic stage using the 2010 American Joint Committee on Cancer staging system. including tumor type. 24%). Furthermore. all 17 patients (100%) who were 20 years old or younger had low-grade papillary urothelial tumors. treatment. Although 1. papillary urothelial carcinomas (38 of 49 [78%]. invasive urothelial carcinoma and died of the disease after 160 months. 37– 238 months).2 Urothelial tumors in younger patients often have a lower grade and stage than those in older patients. and the other 2 (50%) were alive with metastases to the lungs and lymph nodes after 12 and 166 months. Figure. including low-grade. papillary urothelial carcinomas were alive after a mean of 129 months (range. papillary urothelial carcinomas (4 of 49 [8%]. with a mean follow-up time of 77 months (range. COMMENT Urothelial tumors are rare in young patients.8:1. 53%). 21 (58%) had a history of smoking tobacco and 2 (6%) had a family history of bladder cancer. and only 3 patients (5%) were 10 years old or younger (Table 2). papillary urothelial carcinomas and PUNLMPs. but the exact incidence depends on the criteria defining the young age group. resulting in a higher rate (31%) than that previously reported in this age group. however. Follow-up information was available for 41 patients (69%). a tumor grade distribution more like that of older patients than that of younger patients. whereas 20% were high grade (grade 2 or 3). As patient age increases. Two of 4 patients (50%) with tumors invading 1338 Arch Pathol Lab Med—Vol 137. October 2013 a Excerpted from Eble et al. C).4% of urothelial tumors are found in patients younger than 20 years. Seven (70%) of the 10 patients with invasive urothelial carcinomas underwent radical cystoprostatectomy or cystectomy. and any unusual features.19 We also reviewed the patients’ records to collect data on demographics.14.1. we did not find any urothelial papillomas in the patients we studied. RESULTS The mean age of the 59 patients at initial diagnosis was 23. All 3 patients (100%) with high-grade. Simplified 2004 World Health Organization Histologic Classification of Urothelial Tumorsa Noninvasive Urothelial Neoplasm Papillary type  Urothelial papilloma. Figure. 4–30 years). and high-grade. Six (17%) of the 36 patients had a history of urinary tract infections. lowgrade papillary urothelial neoplasms. The 1 patient (100%) with a tumor invading the perivesical soft tissue died after 10 months despite cystoprostatectomy and chemotherapy.20 The differences are Urothelial Tumors in Young Patients––Stanton et al .4% of urothelial tumors are found in patients younger than 40 years. 80% of urothelial carcinomas were low grade. 16–250 months). which was lower than the ratio of 4:1 reported in older patients. In the current study. and another (33%) developed bone metastasis. but 9 (35%) had local tumor recurrences. only 0. muscularis propria (n ¼ 4. nested variant. Only 1 patient (4%) later developed high-grade. 50%). all patients were 30 years old or younger when they were first diagnosed. followed by abdominal pain (8 of 59.20 In patients 30 to 40 years old.1% to 0. Most of these patients (42 of 59. In addition.

a Age.Table 2. High-grade. Yossepowitch and Dalbagni13 found that younger (median age. However. 34. Papillary urothelial neoplasm of low malignant potential. and only 1 (6%) had a high-grade. LGPUC. (%) 2 11 25 38 (5) (29) (66) (100) HGPUC. No. INVUC.20 Fine et al17 reported that 23 patients younger than 20 years with urothelial tumors were all (100%) alive with no evidence of disease after a mean follow-up of 4. Studies have suggested that younger patients with urothelial tumors are likely to have more favorable outcomes than older patients.17. high-grade papillary urothelial carcinoma. PUNLMP. No. D. No. papillary urothelial carcinoma. B. No patients (0%) in this age group died of the disease.3 years) patients with superficial urothelial tumors had similar outcomes. high-grade invasive urothelial carcinoma. likely due to the referral nature of our institution. No. (%) 0 0 4 4 (0) (0) (100) (100) INVUC. October 2013 Urothelial Tumors in Young Patients––Stanton et al 1339 . papillary urothelial carcinoma. Urothelial carcinoma invading the muscularis propria (hematoxylin-eosin.9–12. papillary urothelial neoplasm of low malignant potential. No. Our results suggest that the Urothelial tumors in young patients.6 years) and older (median age.13 although we note that the latter series included many patients who were 30 to 40 years old. a Patient’s age at the initial diagnosis.5 years. (%) 3 14 42 59 (5) (24) (71) (100) Abbreviations: HGPUC. which tends to treat patients with aggressive oncologic diseases. noninvasive. (%) 0 1 9 10 (0) (10) (90) (100) Total. lowgrade papillary urothelial carcinoma. although local tumor recurrences were not uncommon. In the current study. invasive urothelial carcinoma. C. original magnifications 3100 [A through D]). 65. 16 of the 17 patients (94%) diagnosed at 20 years old or younger had low-grade. y 10 11–20 21–30 Total Distribution of Patients With Urothelial Tumors by Patient Age and Tumor Type PUNLMP. Arch Pathol Lab Med—Vol 137. all 4 patients (100%) who died of the disease were in the age group of 21 to 30 years. (%) 1 2 4 7 (14) (29) (57) (100) LGPUC. A. noninvasive urothelial tumors. Low-grade. an age group that tends to have urothelial tumors that are more similar to those of older patients than those of younger patients in grade and stage.

Migaldi M. 1340 Arch Pathol Lab Med—Vol 137. 10. Rossi G. Occupational exposure is another known risk factor for urothelial tumors in old patients. INVMP. (%).23 Because urine cytology is generally not effective for detecting low-grade. Outcomes for Young Patients With Urothelial Tumorsa Noninvasive. Tobacco smoking is a major known risk factor for bladder cancer in old patients. CA Cancer J Clin. France: IARC Press. World Health Organization Classification of Tumours. (%). No. 2010. Javadpour N. J Urol. papillary urothelial neoplasm of low malignant potential. but diagnosis is often delayed in young patients because clinical suspicion of urothelial tumors is generally low for this age group. bladder section. 9. Cancer. 94(3):311–316. n ¼ 31 PUNLMP. in whom these tumors predominate. Goldwasser B. (%). Although the oncogenesis of urothelial tumors in young patients is not clear. Thus. Urothelial Tumors in Young Patients––Stanton et al . 12. n¼4 74 0 0 2 2 (15–166) (0) (0) (50) (50) INVPS. J Urol.44(2):81–83. 6. such as polypoid cystitis and nephrogenic adenomas. 2004:90–157. low-grade. 14.Table 3. 8. n¼1 10 0 (0) 0 (0) 0 (0) 1 (100) Abbreviations: PUNLMP. et al. Eble JN.130(1):54–55. and the risk is increased with duration of smoking. Nephrogenic adenomas may show papillary structures. 3. it has limited value for young patients. Transitional cell carcinoma of the bladder in young adults: presentation. low-grade papillary urothelial carcinoma. Carcinoma of the bladder in patients less than 40 years old. Cancer Biomark. Grossman HB. Noone AM. we analyzed the clinical and pathologic features of urothelial tumors in a large series of young patients from a single institution. Accessed November 7. This patient later developed invasive. Dalbagni G. Anderson Cancer Center is supported in part by Cancer Center Support Grant CA16672 from the National Institutes of Health. HGPUC. the use of the diagnostic category of PUNLMP can avoid labeling a significant number of young patients with carcinoma. Bladder carcinoma in patients less than 40 years of age. particularly those younger than 20 years. Thus. Reda M. Madgar I. Sauter G. Molecular pathology and biomarkers of bladder cancer. J Urol. INVPS. suggesting that tobacco smoking is likely to contribute to the development of urothelial tumors in young patients. et al. 2011. No. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. 11. The incidence of tobacco smoking is also high in young patients with bladder cancer. M. natural history and outcome. 2. Wan J.24 Several benign papillary lesions in the urinary bladder. INVLP.21. high-grade urothelial carcinomas. Another pitfall in diagnosis is overestimating the tumor grade. McGuire EJ. Bethesda. noninvasive. urothelial carcinoma invading the perivesical soft tissue. Krapcho M. high-grade urothelial carcinomas often develop metastases and may die of disease.cancer. but its role is uncertain in young patients.9(1–6):159–176. 15. (%). Neoplasms of transitional cell origin in first twenty years of life. Naishadham D. Maiorana G. Johnson DE. Long-term followup of patients less than 30 years old with transitional cell carcinoma of bladder. (%). Witjes JA. No. Lyon.64(1):178–181. 1989. 2004. 1989. Patients with noninvasive papillary urothelial tumors have an excellent prognosis. Urol Int. Epstein JI. Transitional cell carcinoma of the bladder in children and adolescents. 7. Tomera KM. Jemal A. Weiss RM. Czerniak B. should be differentiated from papillary urothelial carcinomas.101(5):706–710.1(1):57–59. n¼5 85 2 0 3 0 (16–250) (40) (0) (60) (0) INVMP. 13. urothelial carcinoma invading the muscularis propria. 1993. eds. 1975–2008. Most urothelial tumors in this age group were noninvasive. D. Nativ O. flat. and only a few of the tumors were invasive. n¼3 129 1 1 1 0 (37–238) (33) (33) (33) (0) INVLP. Mostofi FK. multiple environmental and genetic factors may contribute to the etiology. Baskin AM. In the cohort studied by Fine et al. prognosis for urothelial carcinoma is excellent in young patients. In the current study. 1988. Polypoid cystitis usually forms broad-based papillary or polypoid structures with edema and inflammation in the stroma. Primary epithelial tumors of the bladder in the first two decades of life. Patients with invasive. SEER cancer statistics review.gov/csr/1975_2008/. papillary urothelial neoplasms. LGPUC. low-grade. vol 6. 1978. 1969. Sesterhenn IA. papillary urothelial neoplasms in this age group.22 genetic factors are likely to play an important role in the early onset of urothelial tumors in young patients. Kelalis PP. No. eds. high-grade papillary urothelial carcinoma. Urology. n ¼ 10 HGPUC. n ¼ 26 71 16 9 0 1 (3–225) (62) (35) (0) (3)b Invasive. 1983. J Urol. urothelial carcinoma invading the lamina propria. pt 2):749–755. Benson RC Jr. J Urol. Br J Urol. mo (range) Alive with no recurrence Alive with local recurrence Alive with metastasis Died of disease 25 2 0 0 0 (13–37) (100) (0) (0) (0) LGPUC. Bladder carcinoma in patients 40 years old or less.139(5):933–934. An early study14 reported that 67% of patients younger than 30 years had a history of tobacco smoking and the rate was increased to 96% of patients between 30 and 40 years old. J Urol. The pathologic diagnosis of urothelial tumors is not difficult. high-grade urothelial carcinoma with metastasis and died after 160 months. Yossepowitch O. October 2013 In summary.168(1):61– 66. http://seer. 2012. Kutarski PW. Cancer statistics. indicating an aggressive behavior in this age group.120(2):172–173. Jonas P. Fitzpatrick JM. No. 5.135(1):53–54. 4. Debruyne FM. Howlader N. Hanani Y. Padwell A. 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