Benign tumors and Mimickers of UB tumors.pptx
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Benign tumor of UB
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Benign tumors and Mimickers of UB tumors.pptx
- 1. Benign lesions and mimickers of UB CANCER Dr Hemanta Pun Mch Resident 1st year
- 2. Epithelial Metaplasia • Defn: – focal area of transformed urothelium, – normal nuclear and cellular morphology • Features: – Site: Trigone of UB – Squamous or glandular metaplasia • v/s UB ca: – Glandular m.: inflammatory areas – Squamous m.: H/O UTI, trauma, prior surgery • Role of Bx and Rx: none
- 3. Urothelial Papilloma • Incidence: <1% • Age: younger • Site : usu. Trigone of UB (usu solitary) • Cause: chronic inflammation or BOO • C/F : Painless hematuria/ Irritative voiding symptoms • Behaviour : Benign (<1% recurrence) • Genetics: FGFR-3 mutation (lack p53 and RB mutation) • Pathology: exophytic papillary lesions with delicate stalks – edematous stroma, covered by a normal-in-thickness multilayer coat of benign- appearing transitional cells
- 4. Inverted Urothelial Papilloma (IUP) • Benign lesion • Site : usu. Trigone of UB • Cause: chronic inflammation or BOO • Recurrence: r/t incomplete resection • Pathology: – Surface: flat and smooth (occ papillae) – Urothelial cells with peripheral palisading – No atypia/inflamm/fibrosis – No invasion beyond submucosa [v/s UC: large cells with muscular propria invasion with reactive stroma]
- 5. Although initially related with human papillomavirus, the last findings using IHC and different FISH probes exclude this causal link
- 6. Nephrogenic Adenoma • Rare tumor • Cause : chronic irritation of urothelium – Trauma – Prior surgery – Renal transplantation – Intravesical chemo – Stones – Catheters – Infection
- 7. • C/F : – dysuria – Hematuria • Cystoscopy: – Papillary neoplasm (? Aggressive UB neoplasm) • Pathology: – Wide histological spectrum – microcystic, cystic, papillary, solid, and flat architectures, as well as clear cell, oncocytic, and fibro-myxoid changes • Genetics: +ve for PAX-8/Napsin A and –ve for p63/GATA-3 • Potential malignant simulator • Treatment : Resection
- 8. Leukoplakia • C/F: – Incidental diagnosis (asymptomatic) – Recurrent infection – Frequency and urgency – characteristic white, flaky plaques floating in the bladder • Cause: – UTI – Trauma – Prior surgery
- 10. Cystitis Cystica and/or Glandularis (with Int metaplasia); CCGIM • Benign lesion • Cause: UB inflammation or chronic BOO • HPE: – cystic nests that are lines by columnar or cuboidal cells and are generally associated with proliferation of Von Brunn nests – lacks cytological atypia, necrosis, signet ring cells and brisk or atypical mitotic activity
- 11. • Cystoscopy: – broad based mass – Cystic transformation • Malignant potential: – Low – Need of regular endoscopic evaluation • Treatment: Transurethral resection
- 12. BCG-Induced Inflammatory Reaction (BCGitis) • Cause: BCG admin intravesically in previous TURBT patient---- + local host defense mechanism • Cystoscopy: florid inflammation • Diagnosis: TUR Bx
- 13. Endocervicosis (EC)/Endometriosis (EM) (Müllerianosis) • presence of endocervical and endometrial tissue outside the endocervix and endometrium, respectively. • MC site: UB • C/F: hypogastric pain, dysuria, and transient hematuria during menstruation • USG: UB mass
- 14. • Pathology: – Glands (EC/EM type) within UB with an infiltrative pattern • Behaviour: – Benign with low risk of malignant potential – recurrent and resistant to therapy
- 15. Malakoplakia (MK) • chronic granulomatous inflammation • Site: Urinary tract (can inv other organs) • Risk Factor: Immunocompromised • USG: bladder mass • Patho: – +nce of Michaelis-Gutmann bodies with chronic inflammation mainly composed of abundant histiocytes, the so-called von Hansemann’s macrophages
- 16. IgG4-related disease (IGG4) • Systemic autoimmune dz • Pathogenesis: not clear • Site: Urinary tract (with different organs). • Pathology: diagnostic criterias a) dense lymphoplasmacytic infiltrate b) storiform-type fibrosis c) Obliterative phlebitis d) IgG4 population (among total IgG plasma cell infiltrate): >40% e) No arteritis
- 17. Schistosomiasis • aka Bilharziasis/Snail fever • Causative agents: Schistosoma sps. – Schistosoma haematobium – S. japonicum – S. mansoni • MC site: UB • Pathogenesis (in UB ca) : IL-4 mediated – Increased risk of SCC in endemic regions
- 18. • HPE: – Chronic inflamm with abundant eosinophils – Hyperplastic changes without atypia – Varied quantity of parasitic eggs • Treatment : Anti-protozoal agents [Praziquantel, Metronidazole]
- 19. Post-radiation changes • Site: UB • C/F: Intermittent Hematuria/Irritative voiding symptoms • HPE: – hyperplastic pseudo-carcinomatous changes – No atypia or mitoses – Stroma: Hyperemic and edematous – Occ, multinucleated giant cells
- 20. Papillary urothelial neoplasm of low malignant potential (PUNLMP) • Site: Trigone of UB • Behaviour: contorversial !!! – 5 year recurrence rate: 20% – Progression to MIBC : <1% • Genetics: – TERT promoter mutations and FGFR3 mutations (>60%) – HRAS mutation (3%) [vs 33% in non-invasive UCC] – s/o indolent course • Patho: – papillary growth; usu solitary – minimal cytologic atypia that is more than seven cells thick – Maintained cell polarity – Mildly enlarged nuclei
- 21. Precursor Malignant Lesions • Normal urothelium: – multilayered mucosa (4 to 7 cells thick) • BBM • Intermediate • Superficial umbrella – nonkeratinizing squamous and pseudostratified columnar epithelium
- 22. WHO classification 1. Urothelial hyperplasia (flat and papillary) 2. Reactive atypia 3. Urothelial atypia of unknown significance (AUS) 4. Urothelial dysplasia 5. low-grade intraurothelial neoplasia
- 23. Reactive atypia • Nuclear abnormalities in the background of an inflamed urothelium • Causes: – chronic inflammation – Noxious stimuli • C/F: Irritative voiding symptoms • Cystoscopy: mucosa edematous and inflammed • HPE: – Prominent and enlarged nuclei; maintained nuclear polarity • Behavior : – No Malignant potential – Coexists with dysplasia and CISs
- 24. Atypia of unknown significance(AUS) • Diagnosis of limited clinical utility. • ?????premalignant or reactive. • HPE: – Inflammation of the lamina propria – Nuclear atypia disproportionate to the degree of atypia • IHC staining : +ve for CK20 and CK44
- 25. Urothelial dysplasia • Def: Normal urothelial thickness and an altered cytologic appearance • Indication of urothelial instability and a marker of recurrence or progression in those with a history of urothelial cancer. – Progression to UCC: 15-20% – Progressioon to CIS : 60% • HPE: – loss of nuclear polarity – nuclear enlargement – Hyperchromasia – nuclear membrane irregularity.
Editor's Notes
- A broad spectrum of lesions, including hyperplastic, metaplastic, inflammatory, infectious, and reactive, may mimic cancer all along the urinary tract. This presantation collects most of them from a clinical and pathologic perspective, offering urologists and general pathologists their most salient definitory features. Some of these diagnoses are problematic for both the urologists and pathologists. Interestingly, the right identification of their definitive features will allow their correct diagnoses, thus, avoiding overtreatment. In this practical context, urologists and pathologists must bear in mind a long list of conditions that, eventually, may cause diagnostic problems.
- There are numerous benign tumors of the bladder, each with its own clinical presentation and disease burden. Defined as focal area of transformed urothelium, with otherwise normal nuclear and cellular morphology Typically, epithelial metaplasia is located on the trigone and may be composed of either squamous metaplasia or glandular metaplasia. Glandular metaplasia in particular consists of clumps of raised, red inflammatory areas that can be confused for cancer. Squamous metaplasia is very common, affecting up to 40% of women and 5% of men, and can be attributed to a history of urinary tract infection, trauma, and prior surgery A biopsy to diagnose glandular or squamous metaplasia is unnecessary and no treatment is required or efficacious.
- An inverted papilloma (Fig. 135.6) is a benign proliferative lesion that is associated with chronic inflammation or bladder outlet obstruction and can be located throughout the bladder but most commonly on the trigone, accounting for less than 1% of all bladder tumors. 4. Painless gross hematuria is the most common representing symptom, with microscopic hematuria and irritative voiding symptoms also common. 5. When diagnosed according to strictly defined criteria (e.g., lack of cytologic atypia), inverted papillomas behave in a benign fashion with a 1% chance of recurrence. Previously, characterized as low-grade Ta malignant bladder tumors but are now thought to be benign with no risk of local or systemic invasion. Although papillomas have fibroblast growth factor receptor-3 (FGFR3) mutations, which are commonly found in bladder cancer, they lack markers of aggressive behavior, including TP53 and RB mutations. Specifically, UPs are strict exophytic papillary lesions with delicate stalks, and sometimes edematous stroma, covered by a normal-in-thickness multilayer coat of benign- appearing transitional cells (Figure 1a)
- IUP is a classically recognized entity characterized by a benign clinical course in which recurrences are related to incomplete resections IUP appears as slightly elevated lesions, mainly in the bladder trigone, on cystoscopy. However, some cases have been also described in the upper urinary tract as pedunculated (polypoid) masses. Although the surface is usually flat and smooth, occasional papillary projections can be detected. Wavy small urothelial nests of cells without atypia displaying peripheral palisading immersed in a stroma without inflammation or fibrosis, and without invasion beyond the submucosa is the characteristic hallmark in IUP [By contrast, large, rigid, and round urothelial nests with invasion into the muscular propria layer and accompanied by reactive stroma and/or inflammatory infiltrates strongly favor the diagnosis of urothelial carcinoma with an inverted growth pattern] Interestingly, IUP share with UP the RAS pathway activation in its genesis without FGFR3, TERT, TP53, or RB1 gene implications, otherwise typical in urothelial carcinomas
- Although initially related with human papillomavirus, the last findings using immunohistochemistry and different FISH probes exclude this causal link
- 1. Nephrogenic adenoma is a rare tumor caused by chronic irritation of the urothelium and can arise from trauma, prior surgery, renal transplantation, intravesical chemotherapy, stones, catheters, and infection.
- Lesions may cause dysuria hematuria, prompting cystoscopic investigation. The largest series of NA published so far [16] illustrates the varied histology of this condition and confirms its proven malignant simulator potentiality Cystoscopically, nephrogenic adenoma may appear like a papillary neoplasm and may be hard to distinguish from more aggressive bladder neoplasms. combined expression of PAX-8 and absence of p63 and GATA-3 should solve diffcult cases [16]. Very recently, napsin A has been proposed as a sensitive marker in NA useful as well in the differential diagnosis Recurrence does occur but is uncommon and can be safely managed with repeat resection
- If not diagnosed incidentally, presenting symptoms are typically frequent, recurrent infections with urinary urgency and frequency. Leukoplakia of the bladder has similar features to squamous metaplasia with the additional characteristic of white, flaky plaques floating in the bladder.
- Historic reports described leukoplakia as premalignant, However, more recently a connection between leukoplakia as an independent risk factor for bladder cancer has been disproven. Staack et al. (2006) performed cytogenic studies of bladder leukoplakia in 77 cases using DNA analysis for tumor suppressor gene TP53 and found no evidence to suggest that this condition was premalignant; therefore cystoscopy, biopsy, and further treatment were unnecessary.
- Cystitis cystica and/or glandularis is a common finding in normal bladders, typically associated with inflammation or chronic obstruction. The presence of intestinal metaplasia has been show to bear no increased risk of cancer. In contrast,adenocarcinomas arising in the bladder are usually intestinal type and feature significant cytological atypia and prominent mitotic activity, infiltrative growth pattern, and desmoplastic reaction
- CCGIM may demonstrate mucus extravasation, sometimes extensive, which may be mistaken for invasive adenocarcinoma Although cystitis glandularis (Fig. 135.9) can transform into adenocarcinoma, the risk is low; however, regular endoscopic evaluation of these entities is recommended. Treatment is transurethral resection and relief of the obstruction or inflammatory condition.
- Intravesical instillations of BCG (Mycobacterium bovis strains) is a common urological practice in patients who have received a previous transurethral resection (TUR) for high-grade urothelial carcinoma (UC). The goal of this practice is to activate local host defenses as an inflammatory antitumoral instrument. florid inflammation caused is endoscopically indistinguishable from a neoplastic lesion. A TUR biopsy usually resolves the dilemma, since the typical tuberculoid granulomas (Figure 1e) are easily seen in the context of a chronic inflammatory infiltrate. However, A diagnosis of BCGitis does not preclude the presence of a concomitant UC recurrence or persistent carcinoma in situ.
- The urinary tract,esp UB is the most frequently reported site for these conditions. Clinically, EM in the bladder presents in women with hypogastric pain, dysuria, and transient hematuria during menstruation, directly related to the hormonal cycle, which remains a key point for the correct diagnosis. Bladder EC and endometriosis rise serious diagnostic concerns to clinicians and urologists since they usually appear as tumor masses on radiological exams.
- Both EC and EM are histologically well characterized [46,48,49]. Glands, either mucinous endocervical-type (Figure 1i) or endometrial (Figure 2a), appear within the bladder or ureteric wall with an infiltrative pattern accompanied by specialized stroma The capacity of malignant transformation is minimal but does exist at least from a theoretical viewpoint. Although benign, EC and EM may be recurrent and resistant to therapy
- MK may reach occasionally a large size in the bladder closely mimicking a malignancy both radiologically (Figure 2b) and histologically. However, the diagnosis of this condition does not preclude a concomitant diagnosis of urothelial carcinoma
- IgG4 is a systemic autoimmune disorder that may affect many different organs and whose pathophysiological bases and intimate mechanisms are still badly known [54]. It frequently inv the urinary tract from the renal pelvis to urethra along with many different organs. IGG4 simulates malignancy everywhere since it develops tumor masses that are detectable on radiological exams. Besides, IgG4 subpopulation among the total IgG plasma cell infiltrates must be higher than 40%. Phlebitis can be accompanied by thrombosis. Arteritis is not a feature. IgG4-related disease showing a tumor mass in the right ureter in CT scan (a) affecting ureter wall and periureteral soft tissues with a dense lymphoplasmacytic infiltrate (10) (b) and displaying the typical storiform-type fibrosis (40) (c), and dense IgG4 subpopulation higher than 40% (250) (e)
- Schistosomiasis (Bilharziasis) is chronic parasitic disease caused by some species of blood trematodes (flukes) in the genus Schistosoma. The three main species infecting humans are Schistosoma haematobium, S. japonicum, and S. mansoni Schistosoma haematobium, one of the five species infecting humans, typically affects the urinary tract, most commonly the urinary bladder, where the trapped eggs induce chronic inflammation manifesting as hematuria and scarring The relationship between SC and bladder carcinogenesis has been largely reported. The local immune response produced by Schistosoma hematobium seems to be mediated by IL-4 signaling, which is responsible for the hyperplasia occurring in this infection, which seems to be a key precursor of bladder carcinogenesis in the form of squamous cell carcinoma. chronic non-treated infection promotes an increased risk for squamous cell carcinoma development, particularly in Egypt where this infection is endemic and this neoplasm more frequent.
- An exuberant chronic inflammation with abundant eosinophils is detected on the histological analysis. Urothelium shows hyperplastic changes, but cytologic atypia is not a prominent feature. Depending on the stage of the disease and the extent of the biopsy specimens, a varied quantity of parasitic eggs, either calcified or not, can be seen in between a dense inflammatory infiltrate as seen in the fig. However, the histological diagnosis is impossible if parasitic eggs are not present in the sample.
- Despite the significant advances obtained in radiotherapy, the bladder is frequently affected secondarily when cancers arising in neighbor organs, for example, prostate, rectum, and uterus, are treated with this kind of therapy [39]. These changes are more frequently seen within the first two years after radiation and present as episodes of intermittent hematuria. PRC may be puzzling and confounding for the pathologist when analyzing small biopsies or transurethral resection specimens.
- constitutes a diagnosis with particularly good prognosis, and there is controversy as to whether it should carry the label of cancer. TERT promoter mutations and FGFR3 mutations have been identified in more than 60% of PUNLMP cases, which creates a similar profile to low-grade papillary Ta lesions. low rate of HRAS mutations (3%) compared with the 33% incidence in other noninvasive urothelial tumors, however, may speak to the relative indolent, non-aggressive course of PUNLMP lesions PUNLMP is a papillary growth with minimal cytologic atypia that is more than seven cells thick, generally solitary, and typically located on the trigone.
- Firstly talking about the Normal urothelium comprises multilayered mucosa, 4 to 7 cells thick….Cells mature from the basal basement membrane cells, which are small and cuboidal, to intermediate cells to superficial umbrella cells in an orderly fashion. These umbrella cells form a urine bladder barrier preventing toxins from transforming urothelial cells. Normal epithelium features the transition between nonkeratinizing squamous and pseudostratified columnar epithelium.
- 2004 World Health Organization classification system for urothelial neoplasia classifies pre-malignant lesions as………..
- Reactive atypia is characterized by nuclear abnormalities occurring in the background of an inflamed urothelium Typically patients have a history of chronic inflammation, regeneration,or reaction from noxious stimuli and have irritative voiding symptoms. Similar to hyperplasia, reactive atypia does not appear to independently evolve into carcinoma; however, atypia often coexists with dysplasia and carcinoma in situ and thus mandates rigorous investigation.
- (AUS) is used when it is unclear whether observed urothelial changes are premalignant or reactive. Microscopically, AUS is characterized by inflammation of the lamina propria and nuclear atypia disproportionate to the degree of atypia. CK20 and CK44 immunohistochemical staining, which are positively expressed in AUS, can aid in distinguishing AUS from dysplasia. AUS independently does not appear to lead to urothelial carcinoma and is a diagnosis of limited clinical utility.
- Approximately 14% to 19% of patients with urothelial dysplasia will progress to urothelial cancer; however, in the setting of a prior history of bladder cancer, urothelial dysplasia will lead to CIS in 60% of cases