neoplasie del colon-retto sequenza adenoma- carcinoma
TRANSCRIPT
![Page 1: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/1.jpg)
Neoplasie del colon-rettoNeoplasie del colon-rettoSequenza Adenoma-Sequenza Adenoma-
CarcinomaCarcinoma
![Page 2: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/2.jpg)
![Page 3: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/3.jpg)
Neoplasie Epiteliali del Colon-Retto
• Benigne– Amartoma– Polipo iperplastico– Adenoma– Polipo misto iperplastico-adenomatoso
• Maligne– Adenocarcinoma colorettale– Carcinomi neuroendocrini– Lesioni metastatiche
![Page 4: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/4.jpg)
POLIPI del COLON-RETTO
• Polipo: ogni protuberanza che si eleva al di sopra della mucosa
• Polipi del colon– Iperplastici– Infiammatori– Amartomatosi– Neoplastici
• Adenoma: proliferazione neoplastica clonale della mucosa colica
![Page 5: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/5.jpg)
ADENOMA
• Aspetto macroscopico– Elevati– Piatti– Depressi
• Aspetti istopatologici– Tubulare– Villoso– Serrato
![Page 6: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/6.jpg)
• Adenomi • Polipi iperplastici
SSA
TSA
Mixed
![Page 7: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/7.jpg)
Sequenza Adenoma-Carcinomacolorettale
• Il carcinoma colo-rettale insorge nella maggioranza dei casi da un preesistente adenoma– Adenoma e Carcinoma spesso coesistono– La sistematica rimozione degli adenomi porta
ad una riduzione del numero dei carcinomi invasivi
![Page 8: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/8.jpg)
Sequenza Adenoma-Carcinomacolorettale
– Adenomi e carcinomi hanno una distribuzione similare nei vari segmenti dell’intestino, massima nel retto-sigma
– L’età di incidenza degli adenomi ha un picco massimo di 5 anni antecedente quello dei carcinomi
– Il rischio di sviluppare adenomi colorettali è associato con gli stessi fattori (dieta e stile di vita) correlati al rischio di carcinoma colorettale.
– Adenomi e Carcinomi del grosso intestino mostrano alterazioni molecolari simili
![Page 9: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/9.jpg)
Polipo iperplastico
![Page 10: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/10.jpg)
ADENOMA TUBULAREADENOMA TUBULARE
![Page 11: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/11.jpg)
ADENOMA TUBULAREADENOMA TUBULARE
![Page 12: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/12.jpg)
ADENOMA TUBULAREADENOMA TUBULARE
![Page 13: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/13.jpg)
ADENOMA TUBULAREADENOMA TUBULARE
![Page 14: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/14.jpg)
TSA Traditional Serrated Adenoma
![Page 15: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/15.jpg)
Sessile Serrated Adenoma
![Page 16: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/16.jpg)
Sessile Serrated Adenoma
![Page 17: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/17.jpg)
Polipi serrati: vie evolutive
![Page 18: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/18.jpg)
ADENOMA VILLOSOADENOMA VILLOSO
![Page 19: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/19.jpg)
ADENOMA VILLOSOADENOMA VILLOSO
![Page 20: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/20.jpg)
ADENOMA VILLOSOADENOMA VILLOSO
![Page 21: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/21.jpg)
ADENOMA VILLOSOADENOMA VILLOSO
![Page 22: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/22.jpg)
ADENOCARCINOMA IN ADENOMA VILLOSOADENOCARCINOMA IN ADENOMA VILLOSO
![Page 23: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/23.jpg)
ADENOMI MULTIPLIADENOMI MULTIPLI
![Page 24: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/24.jpg)
ADENOCARCINOMA in ADENOMA VILLOSOADENOCARCINOMA in ADENOMA VILLOSO
![Page 25: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/25.jpg)
ADENOCARCINOMAADENOCARCINOMA
![Page 26: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/26.jpg)
ADENOCARCINOMAADENOCARCINOMA
![Page 27: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/27.jpg)
ADENOCARCINOMAADENOCARCINOMA
![Page 28: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/28.jpg)
ADENOCARCINOMAADENOCARCINOMA
![Page 29: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/29.jpg)
ADENOCARCINOMAADENOCARCINOMA
![Page 30: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/30.jpg)
ADENOCARCINOMAADENOCARCINOMA
![Page 31: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/31.jpg)
ADENOCARCINOMAADENOCARCINOMA
![Page 32: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/32.jpg)
ADENOCARCINOMAADENOCARCINOMA
![Page 33: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/33.jpg)
Sindromi Genetiche predisponenti al Carcinoma
colorettale• Poliposi Adenomatosa Familiare
– APC >90% entro 40 aa <0.5%
• Sindrome dei polipi giovanili– SMAD4 <<0.5%
• Sindrome di Peutz-Jeghers– STK/LKB1 40-60% 25-60 aa <<0.05%
• Sindrome di Cowden– PTEN <<0.05%
• HNPCC– MLH1, MSH2, PMS2, MSH6 50-90% entro 70aa 2-
3%
![Page 34: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/34.jpg)
ADENOMATOSI FAMILIARE-FAPADENOMATOSI FAMILIARE-FAP
![Page 35: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/35.jpg)
ADENOMATOSI FAMILIARE-FAPADENOMATOSI FAMILIARE-FAP
![Page 36: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/36.jpg)
Adenomatosi Poliposa Adenomatosi Poliposa FamiliareFamiliare
• Malattia Autosomica dominante• Presentazione con carcinoma colorettale in età
giovane adulta• Multipli adenomi colorettali• Adenomi anche in altre sedi: stomaco e duodeno• Neoplasie anche in altri parenchimi: SNC e tiroide• Lesioni pigmentate della retina, cisti mandibolari,
cisti sebacee• Mutazione del gene APC • APC cromosoma 5q21
![Page 37: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/37.jpg)
![Page 38: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/38.jpg)
![Page 39: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/39.jpg)
Beta Catenina: meccanismi di attivazione
![Page 40: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/40.jpg)
APC ed Instabilità cromosomicaAPC ed Instabilità cromosomica
![Page 41: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/41.jpg)
![Page 42: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/42.jpg)
Alterazioni genetiche nella sequenza adenoma-carcinomaAlterazioni genetiche nella sequenza adenoma-carcinoma
![Page 43: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/43.jpg)
CRC: modello tradizionale
![Page 44: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/44.jpg)
CRC: classificazione molecolare
![Page 45: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/45.jpg)
CRC MSS Meth-
• 80% colon sx retto
• Maschi
• Risposta al 5FU
• Rara la molteplicità (eccetto FAP)
![Page 46: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/46.jpg)
CRC MSS: alterazioni CRC MSS: alterazioni molecolarimolecolari
![Page 47: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/47.jpg)
CRC: aspetti morfologici
• Rare le forme mucinose• Rari i linfociti intraepiteliali• Budding tumorale• Necrosi “sporca”• Beta-catenina nucleare
![Page 48: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/48.jpg)
CRC MSS tumor budding
![Page 49: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/49.jpg)
CRC MSS Meth-
![Page 50: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/50.jpg)
Carcinomi Colici conInstabilità dei Microsatelliti
• Difetto dei meccanismi di riparo del DNA mismatch– CRC sporadici e HNPCC– Tumori sincroni e metacroni– Tumori extracolici– Prognosi relativamente favorevole– Pazienti giovani
![Page 51: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/51.jpg)
Instabilità dei Microsatelliti
• Sequenze ripetitive nel genoma ACACACACAC…..
• Difetti nei meccanismi di riparo del DNA mismatch
• Inserzione e delezione di nucleotidi– Meccanismo Velcro
• DNA mismatch genes– MLH1, MSH2, MSH6
![Page 52: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/52.jpg)
CRC MSI aspetti cliniciCRC MSI aspetti clinici
• Colon dx• Prevalenza femminile• Fumo• Fattore prognostico favorevole• Fattore predittivo favorevole
– Scarsa risposta 5-FU– risposta immunitaria
![Page 53: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/53.jpg)
CRC MSI aspetti morfologici
• Mucinosi• Scarsa differenziazione• Linfociti intratumorali• Crescita espansiva• Scarso budding• Aspetti “serrati”• Beta-catenina di membrana
![Page 54: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/54.jpg)
![Page 55: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/55.jpg)
CRC MSITIL
![Page 56: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/56.jpg)
MLH1
![Page 57: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/57.jpg)
CRC MSI beta catenin
![Page 58: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/58.jpg)
CRC MSI aspetti molecolari
![Page 59: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/59.jpg)
![Page 60: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/60.jpg)
CRC Meth+ MSS
• 60% colon dx• Prevalenza femminile• Aggressivi• Risposta al 5FU• Storia familiare• Fasce di età più giovani
![Page 61: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/61.jpg)
CRC Meth+ MSS aspetti morfolgici
• Mucinosi
• Scarsa differenziazione
• Pochi linfociti infiltranti il tumore
• Adenomi serrati
![Page 62: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/62.jpg)
CpG methylation
![Page 63: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/63.jpg)
CRC Meth+ MSS aspetti molecolari
![Page 64: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/64.jpg)
![Page 65: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/65.jpg)
Classificazione molecolare dei CRC
![Page 66: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/66.jpg)
CRC HNPCC
• 60% colon dx• Maschi> femmine• Storia familiare• Età di insorgenza precoce• Multiple neoplasie
![Page 67: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/67.jpg)
CRC HNPCC aspetti molecolari
![Page 68: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/68.jpg)
![Page 69: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/69.jpg)
CRC HNPCC aspetti morfologici
• Linfociti intratumorali• Scarsa differenziazione• Mucinosi• Budding tumorale• Pochi adenomi
![Page 70: Neoplasie del colon-retto Sequenza Adenoma- Carcinoma](https://reader036.vdocument.in/reader036/viewer/2022081421/5542eb4d497959361e8bbc47/html5/thumbnails/70.jpg)
MSH2MSH2 MLH1MLH1