This document discusses benign bladder tumors and non-urothelial bladder malignancies. It provides information on various benign tumors of the bladder including epithelial metaplasia, leukoplakia, inverted papilloma, nephrogenic adenoma, leiomyoma, and inflammatory pseudotumor. It also discusses non-urothelial bladder malignancies such as squamous cell carcinoma, adenocarcinoma, small cell carcinoma, sarcoma, and others. Treatment options and characteristics of different tumor types are covered. The document is intended as an educational guide for medical professionals.

1. BENIGN BLADDER TUMOURS
AND NON UROTHELIAL
BLADDER MALIGNANCIES
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
1

2. MODERATORS:
Professors:
• Prof. Dr. G. Sivasankar, M.S., M.Ch.,
• Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
• Dr. J. Sivabalan, M.S., M.Ch.,
• Dr. R. Bhargavi, M.S., M.Ch.,
• Dr. S. Raju, M.S., M.Ch.,
• Dr. K. Muthurathinam, M.S., M.Ch.,
• Dr. D. Tamilselvan, M.S., M.Ch.,
• Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai.
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3. BENIGN BLADDER
TUMOURS
3
Dept of Urology, GRH and KMC, Chennai.

4. BENIGN BLADDER TUMOURS
• Epithelial metaplasia
• Leukoplakia
• Inverted papilloma
• Nephrogenic adenoma
• Leiomyoma
• Cystitis cystica/glandularis
• Inflammatory pseudotumour
4
Dept of Urology, GRH and KMC, Chennai.

5. EPITHELIAL METAPLASIA
• Focal areas of transformed urothelium with normal nuclear and cellular
architecture.
• It is surrounded by normal urothelium.
• Located usually on trigone
• Can be of two types: Squamous metaplasia or Glandular metaplasia
5
Dept of Urology, GRH and KMC, Chennai.

6. SQUAMOUS METAPLASIA
• Incidence 40% of women and 5% men
• More common in women of child bearing age.
• Related to infection, trauma and surgery.
• No racial differences seen.
• Squamous metaplasia has a knobby appearance
• Covered by white, flaky, easily disrupted material lying on the trigone.
• Spinal cord injury patients are more liable due to chronic catheterization and
UTIs.
6
Dept of Urology, GRH and KMC, Chennai.

7. SQUAMOUS METAPLASIA
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Dept of Urology, GRH and KMC, Chennai.

8. GLANDULAR METAPLASIA
• Glandular metaplasia appears as clumps of raised red areas appearing
inflammatory and often confused with cancer.
• Can extensively involve the bladder, particularly trigone
• Biopsy not required
• Treatment unnecessary
• No preventive agents available.
8
Dept of Urology, GRH and KMC, Chennai.

9. LEUKOPLAKIA
• Similar to squamous metaplasia
• Additional keratin deposition appears as a white flaky substance floating in
the bladder.
• Eventhough leukoplakia of other organs are often premalignant, bladder
leukoplakia are benign.
• No treatment is necessary.
9
Dept of Urology, GRH and KMC, Chennai.

10. LEUKOPLAKIA
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Dept of Urology, GRH and KMC, Chennai.

11. INVERTED PAPILLOMA
• It is a benign proliferative lesion.
• Comprises <1% of bladder tumours.
• Associated with chronic inflammation or bladder outlet obstruction.
• Can be located through out the bladder but most common on trigone.
• Has an inverted growth pattern with anastomosing islands of histologically
and cytologically normal urothelial cells
• Cells invaginate from the surface urothelium into the lamina propria but not
into muscularis propria.
11
Dept of Urology, GRH and KMC, Chennai.

12. INVERTED PAPILLOMA
• Can coexist with urothelial cancer elsewhere, more commonly with upper
tract tumours.
• FISH can distinguish inverted papilloma and urothelial cancer with inverted
growth pattern.
• Transurethral resection is the treatment of choice.
• After resection, 1% chance of recurrence.
12
Dept of Urology, GRH and KMC, Chennai.

13. INVERTED PAPILLOMA
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Dept of Urology, GRH and KMC, Chennai.

14. PAPILLOMA
• Benign proliferative growth
• Composed of delicate stalks lined by normal urothelium.
• Previously categorized as Grade 1 Ta tumours.
• Rarely have mitotic figures.
• 75% have FGFR-3 mutations
• No TP53 or RB mutations.
• May recur but do not progress or invade
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Dept of Urology, GRH and KMC, Chennai.

15. PAPILLOMA
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Dept of Urology, GRH and KMC, Chennai.

16. NEPHROGENIC ADENOMA
• Cause: chronic urothelial irritation
• Trauma, previous surgery, renal transplantation, intravesical chemotherapy,
stones, catheters and infection.
• Mechanism: Nests of displaced mesonephric tissue in urothelium activated
with mucosal injury.
• Most cases have gross hematuria.
• No racial or gender association.
16
Dept of Urology, GRH and KMC, Chennai.

17. NEPHROGENIC ADENOMA
• Composed of glandular-appearing tubules similar to renal tubules involving
mucosa and submucosa of bladder.
• Covered by cuboidal cells with clear or eosinophilic cytoplasm with normal
nuclei.
• Treatment: Transurethral resection and elimination of chronic irritation.
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Dept of Urology, GRH and KMC, Chennai.

18. NEPHROGENIC ADENOMA
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Dept of Urology, GRH and KMC, Chennai.

19. NEPHROGENIC ADENOMA
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Dept of Urology, GRH and KMC, Chennai.

20. CYSTITIS CYSTICA AND
GLANDULARIS
• Common finding in normal bladders.
• Usually associated with inflammation or chronic obstruction.
• Represent cystic nests lined by columnar or cuboidal cells, associated with
Von Brunn nests.
• May be associated with pelvic lipomaosis and may occupy majority of the
bladder.
• May develop into or coexist with intestinal metaplasia (benign, goblet cells,
similar to colonic epithelium).
• Few reports of carcinoma conversion present.
20
Dept of Urology, GRH and KMC, Chennai.

21. CYSTITIS CYSTICA/GLANDULARIS
• Recommendation: Regular endoscopic evaluation.
• Most common presenting feature: Irritative voiding symptoms and
hematuria.
• Treatment: Transurethral resection, relief of obstruction or inflammatory
condition.
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Dept of Urology, GRH and KMC, Chennai.

22. VON BRUNN’S NEST
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Dept of Urology, GRH and KMC, Chennai.

23. CYSTITIS GLANDULARIS
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Dept of Urology, GRH and KMC, Chennai.

24. LEIOMYOMA
• Most common nonepithelial benign tumor of bladder.
• Composed of benign smooth muscle.
• Most common in women of child bearing age.
• Histologically similar to leiomyomas of uterus.
• Appear as smooth indentations of bladder.
• Can be confused with bladder tumour.
• MRI can confirm the diagnosis.
• Treatment: In case of large and painful leiomyomas, surgical excision may
be required.
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Dept of Urology, GRH and KMC, Chennai.

25. LEIOMYOMA
25
Dept of Urology, GRH and KMC, Chennai.

26. INFLAMMATORY PSEUDOTUMOUR
• Rare, spindle-cell type neoplasms, also referred as pseudosarcomatous
tumors or myofibroblastic tumors.
• Combine pathological features of both inflammatory and neoplastic
processes
• Bladder sarcoma is a differential diagnosis.
• A subset of these tumors present within 3 months of a surgical procedure and
are referred to as “postoperative spindle-cell tumors”.
• Histology: The absence of significant nuclear atypia, less than 3 mitotic
figures per high power field and spindle-cell like cells with myxoid
degeneration and eosinophilic cytoplasm.
26
Dept of Urology, GRH and KMC, Chennai.

27. NON UROTHELIAL BLADDER
MALIGNANCIES
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Dept of Urology, GRH and KMC, Chennai.

28. NON UROTHELIAL BLADDER
MALIGNANCIES
• Squamous cell carcinoma
• Adenocarcinoma
• Small cell carcinoma
• Sarcoma
• Carinosarcoma and sarcomatoid tumours
• Pheochromocytoma
• Melanoma
• Lymphoma
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Dept of Urology, GRH and KMC, Chennai.

29. 29
Dept of Urology, GRH and KMC, Chennai.

30. 30
Dept of Urology, GRH and KMC, Chennai.

31. SQUAMOUS CELL CANCER
• Second to urothelial carcinoma, squamous cell carcinoma (SCC) is the most
prevalent epithelial neoplasm of the bladder, accounting for an
approximate 3–5% of bladder tumors in Western countries.
• Can be Schistoma related or Non schistosoma related
• Mechanism: Increased proliferation rate, chronic inflammation and exposure
to environmental agents.
• Microscopically the tumor may be well differentiated or poorly
differentiated.
31
Dept of Urology, GRH and KMC, Chennai.

32. SCHISTOSOMA RELATED SCC
• SCC of the bladder in countries of the Middle East and Egypt is linked to
chronic infections with schistosoma haematobium.
• SCC not only represents the most common histological type of bladder
tumor, but also the most prevalent form of cancer in men overall,
accounting for 30% of cancers.
• It is also the second most common type of malignant neoplasm in women
after breast cancer in middle east.
32
Dept of Urology, GRH and KMC, Chennai.

33. SCHISTOSOMA RELATED SCC
• Age of presentation is lower, affecting mainly men in their fifth decade of
life.
• Potentially preventable disease, affecting mainly patients who are
repeatedly exposed and re-infected by the schistosoma parasite.
• Chronic infection with schistosoma hematobium or other bacteria, to a lesser
degree leads to squamous cell formation of the bladder.
• Schistoma ova are deposited in the bladder wall and produce chronic
inflammation that converts urothelium to squamous cell epithelium.
• N-butyl-N-nitrosamine is produced in high levels in chronic schistosoma
infection.
33
Dept of Urology, GRH and KMC, Chennai.

34. SCHISTOSOMA RELATED SCC
• In a series of 1026 cystectomy patients in endemic region, Ghoneim et al.,
reported that, 22% urothelial carcinoma and 11% adenocarcinoma.
• The overall 5-yea59% of bladder tumors were SCCr survival rate of SCC
patients was 50.3%.
• Only T- and N-stage as independent predictors of survival.
• Standard treatment of bilharzia-related SCC is radical cystectomy and
urinary diversion.
• A potential role for neo-adjuvant or adjuvant radiation and chemotherapy
remains poorly defined.
34
Dept of Urology, GRH and KMC, Chennai.

35. NON SCHISTOSOMA RELATED SCC
• Pure SCC of the bladder is a rare finding in Western countries.
• Should be distinguished from urothelial bladder cancer with partial
squamous differentiation, which is relatively common.
• In a large recent cystectomy series from the Memorial Sloan Kettering
Cancer Center (MSKCC), only 2.8% of patients demonstrated pure SCC.
• Chronic bladder irritation is the main etiology.
35
Dept of Urology, GRH and KMC, Chennai.

36. NON SCHISTOSOMA RELATED SCC
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Dept of Urology, GRH and KMC, Chennai.

37. NON SCHISTOSOMA RELATED SCC
• Spinal cord injury patients develop squamous cell carcinoma due to chronic
catheter irritation and infection. (Commonest cause of SCC in USA)
• Older studies: 2.5-10% of patients with mean delay of 17 years.
• New studies 0.38% (? Better care)
37
Dept of Urology, GRH and KMC, Chennai.

38. NON SCHISTOSOMA RELATED SCC
• Preoperative radiation has been proposed to improve local control, but
remains of uncertain benefit.
• Standard chemotherapy regimens appear to have limited impact on the
disease due to the relative chemo-resistance of SCC.
• Combination of paclitaxel, carboplatin and gemcitabine that have
demonstrated efficacy in patients with SCC of head and neck may offer
promise for the future.
38
Dept of Urology, GRH and KMC, Chennai.

39. NON SCHISTOSOMA RELATED SCC
• Has unfavorable prognosis, in large due to locally advanced disease at the
time of presentation.
• A study of 25 patients treated with bilateral pelvic node dissection and
radical cystectomy reported by Richie et al. found a 5-year survival rate of
48% and identified tumor stage as the most important predictor of outcome.
39
Dept of Urology, GRH and KMC, Chennai.

40. SQUAMOUS CARCINOMA IN
UROTHELIAL CANCER
40
Dept of Urology, GRH and KMC, Chennai.

41. ADENOCARCINOMA
• Third most common type of epithelial tumor
• comprises 0.5–2.0% of all bladder tumors.
• More frequent in geographic regions where schistosomiasis is endemic
• Most common tumor arising in the bladder of exstrophy patients, who have
a reported 4% life-time risk for developing this type of malignancy.
• Histology: Cells form glandular structures that resemble colonic
adenocarcinoma (enteric type) and/or may produce large amounts of
intra- (signet cell type) or extracellular mucin (mucinous type)
• Can be divided into Urachal and Non urachal origin.
41
Dept of Urology, GRH and KMC, Chennai.

42. ADENOCARCINOMA
• Urachal adenocarcinoma - one-third of primary adenocarcinomas
• Non-urachal adenocarcinoma – two thirds of primary adenocarcinoma and
are associated with chronic bladder irritation and exposure to certain ill-
defined carcinogens.
• Urachal adenocarcinoma criteria:
• presence of an urachal remnant,
• an intact or ulcerated urothelium without metaplastic changes,
• a predominant invasion of the muscularis or deeper structures of the bladder or
extension to the space of Retzius, anterior abdominal wall or umbilicus
• For practical purposes all adenocarcinomas of the dome should be
considered as urachal in origin until proven otherwise.
42
Dept of Urology, GRH and KMC, Chennai.

43. ADENOCARCINOMA
• Treatment:
Vesical adenocarcinoma - radical cystectomy and pelvic node dissection,
Locally invasive urachal adenocarcinoma - En bloc surgical removal of the
urachal ligament, umbilicus and part of the anterior abdominal wall.
Chemotherapy-not generally useful.
• Prognosis:
Generally unfavorable with 5-year survival rates ranging between 11% and
55%.
Survival correlates with local extent.
43
Dept of Urology, GRH and KMC, Chennai.

44. STAGING OF URACHAL
ADENOCARCINOMA
44
Dept of Urology, GRH and KMC, Chennai.

45. URACHAL ADENOCARCINOMA
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Dept of Urology, GRH and KMC, Chennai.

46. SIGNET RING CELL CARCINOMA
• Primary tumour is extremely rare, < 1% of all epithelial bladder neoplasms.
• Urachal orgin and directly extend into the bladder.
• High grade tumours, high stage tumors and have a uniformly poor diagnosis.
• Primary treatment: Radical cystectomy.
• Mean survival time: < 20 months
• Elevated carcinoembroyonic antigen in some patients.
• Understaging is common, peritoneal studding common in peritoneal
exploration.
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Dept of Urology, GRH and KMC, Chennai.

47. SARCOMA
• Most common mesenchymal tumor of bladder.
• <1% of bladder cancers.
• Male:Female 2:1, average age 6th decade of life.
• Subtypes: Leiomyosarcoma > rhabdomyosarcoma, rarely angiosarcoma,
osteosarcoma and carcinosarcoma.
• Association: Pelvic radiation, systemic chemotherapy for other cancers
• Not smoking related.
47
Dept of Urology, GRH and KMC, Chennai.

48. SARCOMA
• Majority high grade, >75% confined to bladder muscle.
• Most common symptom: Gross painless hematuria 76%, Local irritative
symptoms 16%
• Diagnosis: Transurethral resection, abdominal and chest imaging.
• Prognostic factor: Grade
• Treatment: Radical cystectomy
• 5 year disease free survival rate of leiomyosarcoma 52-62%.
• Poor prognostic factors: Angiolymphatic invasion, metastatic disease
48
Dept of Urology, GRH and KMC, Chennai.

49. SARCOMA
• Chemotherapy: Doxorubicin, ifosphamide and cisplatin
• Metastasis: Bone > Liver rarely soft tissue organs.
• Rhabdomyosarcoma occur at any age, in young children, produce
polypoid lesions at the base of the bladder. (Botryoides tumors).
• Pediatric rhabdomyosarcoma: Combination therapy with surgical resection
and radiation
49
Dept of Urology, GRH and KMC, Chennai.

50. CARCINOSARCOMA AND
SARCOMATOID TUMOR
• Carcinosarcoma - primary bladder tumor composed of an intimate
admixture of both malignant epithelial (carcinoma) and malignant soft tissue
elements (sarcoma).
• Sarcomatoid tumor - malignant primarily spindle cell type tumor with
epithelial differentiation.
• Predominantly elderly, male patients.
• Local extent correlated with outcome, yet most patients had locally
advanced tumors at the time of diagnosis.
• Poor outcome with patients succumbing to their disease within 1–2 years
despite aggressive surgical management.
50
Dept of Urology, GRH and KMC, Chennai.

51. SMALL CELL CARCINOMA
• Primarily arises in the lung, can occur in extrapulmonary sites including
bladder, prostate and colon.
• <1% of bladder tumours.
• Common in men older than 70 years, slightly more in smokers.
• Should be considered as a metastatic disease even if no radiologic
evidence of disease outside the bladder.
• Highly chemosensitive and primary therapy is chemo radiation.
• Most common presenting symptom: Painless gross hematuria > Local
irritation and pain.
• At transurethral resection, tumour indistinguishable from urothelial
carcinoma.
51
Dept of Urology, GRH and KMC, Chennai.

52. • Histologic diagnosis is required.
• Common cellular pattern is diffuse sheets of dark blue cells with necrosis and
mitosis.
• Chromogranin A distinguish small cell cancer from Urothelial carcinoma.
• Chemotherapy: Carboplatin/Cisplatin and etoposide
• Complete relapse is common with initial therapy, but clinical relapse >80%
cases.
• Theory: Multipotential undifferentiated stem cells producing small cell
carcinoma and other histologic types of bladder cancer.
• Identical patterns of allelic loss in small cell carcinoma and coexisting
urolothelial cancers suggest a common clonal origin.
52
Dept of Urology, GRH and KMC, Chennai.

53. • Exists both epithelial and neuroendocrine differentiation.
• Neuron specific enolase, chromogranin A and synaptophysin are markers.
• Surgery may be combined with chemoradiation.
• 5 year cancer specific survival 16-18% with chemoradiation or
chemotherapy and radical cystectomy respectively.
53
Dept of Urology, GRH and KMC, Chennai.

54. SMALL CELL BLADDER
CARCINOMA
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Dept of Urology, GRH and KMC, Chennai.

55. PHEOCHROMOCYTOMA
• Bladder pheochromocytomas are exceedingly rare, accounting for less than
0.05% of bladder tumors.
• Represent approximately 10% of extraadrenal pheochromocytomas.
• 10% are malignant.
• Mostly sporadic, may be associated with NF 1.
• Histologically they are characterized by cells arranged in discrete nests
(“Zellballen”) separated by a prominent sinusoidal network.
• Theory: Arise from embryonic rests of chromaffin cells in the sympathetic
plexus of the detrusor muscle.
55
Dept of Urology, GRH and KMC, Chennai.

56. PHEOCHROMOCYTOMA
• Symptoms mostly non-specific
• May include micturional attacks (paroxysmal hypertension, headaches,
palpitations, blurred vision, diaphoresis) resulting from catecholamine excess
triggered by voiding.
• If suspected, cystoscopy should be done only after adrenergic blockade.
• Macroscopic appearance - a solitary submucosal or intramural nodule.
• Biopsy should be avoided.
• Computed tomography and/or magnetic resonance imaging are useful.
• MIBG scan is the investigation of choice.
56
Dept of Urology, GRH and KMC, Chennai.

57. PHEOCHROMOCYTOMA
• Treatment: Complete local excision by partial cystectomy combined with
pelvic lymph node dissection.
• Surgery is planned in a similar fashion as in adrenal pheochromocytomas
and involves volume expansion and adrenergic blockade.
• No defined histological features have been identified to safely distinguish
benign and malignant pheochromocytomas.
• Lifelong follow-up is warranted in view of metachronous metastasis.
57
Dept of Urology, GRH and KMC, Chennai.

58. MELANOMA
• Most commonly a secondary presentation from widespread metastatic
melanoma originating from the skin.
• Rare cases of primary melanoma of the bladder and female urethra,
noted.(From Neural crest cells?)
• Histology: large malignant cells arranged in nests with variable amounts of
pigment.
• No association between malignant melanoma and melanosis of the
bladder, a benign condition characterized by hyperpigmentation of the
urothelium due to an enrichment of cytoplasmatic melanin granula.
• Treatment of the rare localized primary melanoma of the bladder is radical
surgery. The prognosis is guarded.
58
Dept of Urology, GRH and KMC, Chennai.

59. LYMPHOMA
• Most frequently, bladder lymphoma reflects widespread metastatic disease
of systemic hematological disease.
• Rare primary lymphomas of the bladder occur.
• Histology: Tumors consist of a diffuse, infiltrative proliferation of lymphoid cells
surrounding and permeating normal structures rather than replacing them.
59
Dept of Urology, GRH and KMC, Chennai.

60. PRIMARY LYMPHOMA OF
BLADDER
• Primary lymphoma - more common in women than men (3:1)
• In large proportion represented so-called Lymphoma of the Mucosa-
Associated Lymphoid Tissue (MALT).
• Mostly localized and of low grade and carry an excellent prognosis.
• In contrast to most other primary bladder tumors, primary treatment consists
in local radiation, which achieves remissions in a high percentage of patients
and can result in extended recurrence-free survival.
60
Dept of Urology, GRH and KMC, Chennai.

61. THANK YOU
61
Dept of Urology, GRH and KMC, Chennai.