Lesioni ghiandolari: il punto di vista molecolare

Giovanni Negri, Bolzano

GiSCI, Firenze 2014

Lesioni ghiandolari: il punto di vista molecolare

• Quali sono i problemi maggiori nella diagnostica delle lesioni ghiandolari? – Neoplasia ghiandolare vs. negativo – AIS vs. adenocarcinoma – Lesione ghiandolare vs. squamosa

• In che modo la biologia molecolare può essere di aiuto?

Lesioni ghiandolari: il punto di vista molecolare

• Quali sono i problemi della diagnosi di lesione ghiandolare? – Neoplasia ghiandolare vs. negativo – AIS vs. adenocarcinoma – Lesione ghiandolare vs. squamosa

• In che modo la biologia molecolare può essere di aiuto?

(...) HPV DNA was detected in all cases with the exception of one case of CIN3 and three cases of ADCA

Among AIS cases, the probability of being positive forHPV 16 or 18 increased as time to diagnosis decreased, from about 35%, 14 years or more before diagnosis to about 57% just before diagnosis. For AC cases, the probability of HPV 16 or 18 positivity was 20%, 14 years or more before diagnosis, and increased to 47% close to diagnosis

G.Negri, AP Bolzano

G.Negri, AP Bolzano

G.Negri, AP Bolzano

G.Negri, AP Bolzano

G.Negri, AP Bolzano

AGC endocervicali •Materiale scarso, non più di 1 criterio per AIS (palizzate/feathering/ rosette) es: cellule endocervicali con accenno di palizzate nucleari; citoplasma conservato; pochi gruppi endocervicali abnormi •Ev. test HPV •AGC non è un tentativo di grading di lesione ghiandolare!

G.Negri, AP Bolzano

TBS 2014 Update http://bethesda.soc.wisc.edu/

1. LSIL and HPV-positive ASC-US on cervical cytology; each yields the same cancer risk, and can be considered as equivalent for management

2. Some have suggested using terminology such as “LSIL cannot exclude HSIL” or “LSIL with a few cells suggestive of HSIL” for these problematic Pap tests

3. There are no changes to terminology being considered for glandular lesions at this time

Int J Gynecol Pathol 2011

G.Negri AP Bolzano

Displasia endocervicale in istologia

G.Negri AP Bolzano

• WHO 2003: – Glandular Dysplasia: glandular lesion with significant nuclear

abnormalities that are more striking than those in glandular atypia but fall short of the criteria for AIS.

– Glandular atypia: alteration which does not fulfil the criteria for glandular dysplasia or AIS and which may be associated with inflammation or irradiation

• WHO 2014: – Lesions with cytological atypia less than AIS have sometimens

been referred as dysplasia or LG-CGIN. This is a poorly reproducible diagnosis for which criteria are not well defined.

– Lesions showing diffuse strong p16 and ki67 index and lack of Hormone receptor (...) should be classified as AIS/HGCGIN for management purposes.

(...) HPV DNA was detected in all cases with the exception of one case of CIN3 and three cases of ADCA (...) Variants of cervical adenocarcinoma known not to be associated with HPV (...) were excluded

Overall prevalence of HPV: 62.8% (Tenti et al: 84.8% AmJClinPathol 1996, Tornesello et al: 72% Gyn Oncol 2011) HPV 16 (50.9%),18 (31.6%),45 (11.6%)-> 94% dei casi HPV+

AdvAnatPathol 2013

Mucinous carcinoma, gastric type

• Synonyms: minimal deviation adenocarcinoma (if extremely well differentiated)

• Fino al 25% degli adenocarcinomi endocervicali

• MDA: 1% degli adenocarcinomi • Talvolta associato a sindrome di

Peutz-Jeghers • Non HPV-associato, p16- • P53 frequentemente mutato

G.Negri AP Bolzano

Minimal deviation adenocarcinoma

•WHO 2003: “adenocarcinoma in which most of the glands are impossible to distinguish from normal” •La diagnosi puó essere impossibile su materiale bioptico (Young e Clement 2002) •Concordanza diagnostica in istologia 23% (Tsuda, 2003) •Granter e Lee 1996: 6/7 casi con pap precedente negativo. Alla revisione: 3 casi con cellule abnormi “classiche” •HPV e p16 negativi •Immunoistochimica con CEA, p53, HIK1083, CA-IX

G.Negri AP Bolzano

BJC 2013

Cancer, 2013

Take-home message

• La maggior parte delle neoplasie ghiandolari condivide la carcinogenesi HPV-indotta con le lesioni squamose.

• Fino al 25% delle neoplasie endocervicali sono tuttavia non hpv-associate. Queste neoplasie non potranno essere individuate con test dell’HPV o markes surrogati come p16.

• Biomarcatori alternativi affidabili e già validati non sono ancora disponibili.