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LE NEOPLASIE DELLA VESCICA

LE NEOPLASIE DELLA VESCICA. Normal Urothelium.

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LE NEOPLASIE DELLA VESCICA

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  1. LE NEOPLASIE DELLA VESCICA

  2. Normal Urothelium • Normal urothelium consists of a flat mucosa lined by less than approximately seven layers of urothelial cells covered by an umbrella cell layer. There is no need to count the number of cell layers in order to distinguish normal urothelium from flat urothelial hyperplasia. Rather, only overt thickening should be designated as hyperplasia. The size of normal urothelial cells is approximately 3 times the size of lymphocytes, which can almost always be found in the underlying lamina propria. Flat lesions with benign cytology and minimal disorder should not be designated as mild dysplasia but rather as normal urothelium. Atypia in umbrella cells should not be overdiagnosed as dysplasia or CIS

  3. UROTELIONORMALE

  4. Papillary Hyperplasia • Papillary hyperplasia is characterized by slight “tenting”, undulating, or an elevated configuration of the urothelium of varying thickness, lacking nuclear atypia. The lesion often has one or a few small, dilated capillaries at its base but it lacks a well-developed fibrovascular core.

  5. IPERPLASIA PAPILLARE

  6. Urothelial Papilloma • Urothelial papilloma is defined as discrete papillary growth with a central fibrovascular cores lined by urothelium of normal thickness and cytology. There is no need for counting the number of cell layers.

  7. PAPILLOMA UROTELIALE

  8. Papillary Urothelial Neoplasm of Low Malignant Potential • Papillary urothelial neoplasm of low malignant potential is a papillary urothelial lesion with an orderly arrangement of cells within papillae with minimal architectural abnormalities and minimal nuclear atypia irrespective of the number of cell layers. The urothelium in papillary urothelial neoplasms of low malignant potential is much thicker than in papillomas and/or the nuclei are significantly enlarged and somewhat hyperchromatic. Mitotic figures are infrequent in papillary urothelial neoplasms of low malignant potential, and usually confined to the basal layer.

  9. PUNLMP • Queste lesioni sono ad un rischio un maggiore del papilloma di recidivare o formare altre lesioni papillari. • Queste nuove lesioni sono occasionalmente ad alto grado e possono progredire.

  10. PUNLMP

  11. PUNLMP

  12. PUNLMP

  13. Low-grade Papillary Urothelial Carcinoma • Low-grade papillary urothelial carcinomas are characterized by an overall orderly appearance but with easily recognizable variation of architectural and or cytologic features even at scanning magnification. Variation of polarity and nuclear size, shape, and chromatin texture comprise the minimal but definitive cytologic atypia. Mitotic figures are infrequent and usually seen in the lower half, but may be seen at any level of the urothelium. It is important to recognize that there may be a spectrum of cytologic and architectural abnormalities within a single lesion, such that the entire lesion should be examined, with the highest grade of abnormality noted.

  14. LOW GRADE PAPILLARY UROTHELIAL CARCINOMA

  15. LG-papillare

  16. High-grade Papillary Urothelial Carcinoma • High-grade papillary urothelial carcinomas are characterized by a predominantly or totally disorderly appearance at low magnification. The disorder results from both architectural and cytologic abnormalities. Architecturally, cells appear irregularly clustered and the epithelium is disorganized. Cytologically, there is a spectrum of pleomorphism ranging from moderate to marked. The nuclear chromatin tends to be clumped and nucleoli may be prominent. Mitotic figures, including atypical forms, are frequently seen at all levels of the urothelium. There is an option in the diagnosis of high-grade papillary urothelial carcinoma to comment on whether there is marked nuclear anaplasia.

  17. HG-papillare

  18. HG-Papillare

  19. HG-papillare

  20. Flat Urothelial Hyperplasia • Flat uothelial hyperplasia consists of a markedly thickened mucosa without cytological atypia. Rather than requiring a specific number of cell layers, marked thickening is needed to diagnose flat hyperplasia. This lesion may be seen in the flat mucosa adjacent to low-grade papillary urothelial lesions. When seen by itself there is no data suggesting that it has any premalignant potential.

  21. Iperplasia piatta

  22. Reactive Urothelial Atypia • Reactive (inflammatory) atypia consists of nuclear abnormalities occurring in acutely or chronically inflamed urothelium. In reactive atypia, nuclei are uniformly enlarged and vesicular, with central prominent nucleoli. Mitotic figures may be frequent. A history of instrumentation, stones, or therapy is often present. In the absence of appreciable nuclear hyperchromasia, pleomorphism, and irregularity in the chromatin pattern, the lesion should not be considered neoplastic.

  23. Urothelial Atypia of Unknown Significance • In some cases it is difficult to differentiate between reactive and neoplastic atypia. There may be a greater degree of pleomorphism and/or hyperchromatism out of proportion to the extent of the inflammation, such that dysplasia can not be ruled out with certainity. These cases should be designated as "atypia of unknown significance" so that the patients may be followed more closely and re-evaluated once the inflammation subsides.

  24. Dysplasia • Dysplastic urothelium has appreciable cytologic and architectural changes felt to be preneoplastic, yet falling short of the diagnostic threshold for carcinoma in situ.

  25. DISPLASIA

  26. Carcinoma in situ • Carcinoma in situ is a flat lesion of the urothelium that is a documented precursor of invasive cancer in some cases. The lesion is characterized by the presence of cells with large, irregular, hyperchromatic nuclei that may be either present in the entire thickness of the epithelium or only part of it. Mitotic activity is frequently observed, often in the mid to upper urothelium. Carcinoma in situ encompasses lesions which in the past were designated as severe dysplasia or marked atypia.

  27. CIS

  28. CIS

  29. Carcinoma uroteliale infiltrante la lamina propria

  30. Carcinoma uroteliale infiltrante la tonaca muscolare

  31. Invasione endovascolare linfatica

  32. Montironi R, Lopez-Beltran A. • The 2004 WHO classification of bladder tumors: a summary and commentary. • Int J Surg Pathol. 2005 Apr;13(2):143-53.

  33. Lopez-Beltran A, Luque RJ, Alvarez-Kindelan J, Quintero A, Merlo F, Requena MJ, Montironi R. • Prognostic Factors in Survival of Patients With Stage Ta and T1 Bladder Urothelial Tumors The Role of G1-S Modulators (p53, P21Waf1, p27Kip1, Cyclin D1, and Cyclin D3), Proliferation Index and Clinicopathologic Parameters • Am J Clin Pathol. 2004 Sep;122(3):444-52.

  34. Friedrich MG, Toma MI, Petri S, Cheng JC, Hammerer P, Erbersdobler A, Huland H. • Expression of Maspin in non-muscle invasive bladder carcinoma: correlation with tumor angiogenesis and prognosis. • Eur Urol. 2004 Jun;45(6):737-43.

  35. Sugimoto S, Maass N, Takimoto Y, Sato K, Minei S, Zhang M, Hoshikawa Y, Junemann KP, Jonat W, Nagasaki K • Expression and regulation of tumor suppressor gene maspin in human bladder cancer. • Cancer Lett. 2004 Jan 20;203(2):209-15.

  36. Papilloma uroteliale invertito • Sebbene non faccia propriamente parte delle lesioni papillari propriamente dette, questa entità condivide alcuni aspetti con il papilloma esofitico. In alcuni casi ci sono aspetti ibridi in cui una quota della lesione è costituita da una componente esofitica. • In questi casi si dovrebbe classificare la lesione come papilloma con aspetti endo-ed esofitici. • Quando completamente escissa la lesione ha un basso rischio di recidiva.

  37. Percentuale di ricorrenza, progressione di grado, di stadio e sopravvivenza tra le differenti categorie di carcinoma papillare non invasivo Papilloma PUNLMP LG-PC HG-PC Recidiva 0-8% 27-47% 48-71% 55-58% Progr-G 2% 11% 7% not applicable Stage prog. 0% 0-4% 2-12% 27-61% Sopravv. 100% 93-100% 82-96% 74-90%

  38. Neoplasie uroteliali invasive • L’invasione della lamina propria è caratterizzata dalla presenza di nidi, clusters o cellule uniche dentro la lamina propria; questa invasione può essere associata ad una reazione di tipo desmoplastico dello stroma e ad un infiltrato infiammatorio cospicuo. • Nei carcinomi papillari di basso grado, si possono trovare dei nidi cellulari di grandi dimensioni nella lamina propria, con disposizione a palizzata degli elementi periferici, circondati da stroma, che rappresentano un pattern di crescita invertito piuttosto che una invasione.

  39. Pattern di invasione della lamina propria CIS con microinvasione: la microinvasione nel CIS è definita da Farrow et al.(Clin Oncol 1982;1:609-14), come una componente invasiva inferiore ai 5 mm in profondità. La microinvasione può conferire a questi tumori la capacità di metastatizzare.

  40. Pattern istologici di invasione nella lamina propria • -Carcinoma in situ con microinvasione • -Carcinoma papillare uroteliale con microinvasione • -Carcinoma papillare uroteliale con invasione dell’asse stromale • -Invasione certa della lamina propria -invasione fino alla muscolaris mucosae -invasione attraverso la muscolaris mucosae -invasione della lamina propria non meglio precisata • -Carcinoma uroteliale con patter di crescita endofitica o a fronte ampio, con invasione stromale distruttiva

  41. TNM • I linfonodi regionali sono quelli della piccola pelvi, vale a dire quelli al di sotto della biforcazione delle arterie iliache comuni. • La lateralità non incide sulla classificazione N.

  42. TNM • Tx Tumore primitivo non definibile • T0 Tumore primitivo non evidenziabile • Ta Carcinoma papillare non invasivo • Tis Carcinoma in situ: “tumore piatto”

  43. TNM • T1 Tumore che invade il tessuto connettivo sottoepiteliale • T2 Tumore che invade la parete muscolare • T2a: invasione superficiale della parete muscolare • T2b: invasione profonda della parete muscolare

  44. TMN • T3 tumore che invade i tessuti perivescicali • T3a: Microscopicamente • T3b: Macroscopicamente (massa extravescicale)

  45. TNM • T4 Tumore che invade qualsiasi delle seguenti strutture: prostata, utero, vagina, parete pelvica, parete addominale • T4a: tumore che invade prostata, utero, vagina • T4b: tumore che invade la parete pelvica o parete addominale

  46. TNM • Nx Linfonodi regionali non valutabili • N0 Linfonodi regionali liberi da metastasi • N1 Metastasi ad un singolo lnf della dimensione massima di 2 cm • N2 Metastasi in 1 o più lnf, delle dimensioni comprese fra 2 e5 cm • N3 Metastasi in 1 lnf della dimensione massima superiore a 5 cm

  47. TMN • Mx Metastasi a distanza non accertabili • M0 Metastasi a distanza assenti • M1 Metastasi a distanza presenti

  48. Raggruppamento in stadi • Stadio I • T1 N0 M0

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