25/04/2018 Massimo Milione MD, PhD Department of Pathology and Laboratory Medicine Fondazione IRCCS Istituto Nazionale Tumori Milano- Italy massimo.milione@istitutotumori.mi.it OUTLINE General Features and Classifications Ki67 role? OUTLINE General Features and Classifications 1
25/04/2018 Morphology -Prognosis- Molecular pathogenesis 1980 2015 WELL DIFFERENTIATED NEUROENDOCRINE NEOPLASMS POORLY DIFFERENTIATEDNEUROENDOCRINE CARCINOMAS MITOTIC INDEX <2/2/10HPF MITOTIC INDEX 2-10/10HPF MITOTIC INDEX >10/10HPF (mediana70mm 2 ) MITOTIC INDEX >10/10HPF (mediana80mm 2 ) NECROSIS ABSENT NECROSIS RARE NECROSI ALWAYS PRESENT Ki67% suggested useful.not a pillar DIAGNOSTIC CATEGORIES ACCORDING WHO 2015 TYPICAL CARCINOID ATYPICAL LARCE CELLS SMALL CELLS NEUROENDOCRINE NEUROENDOCRINE CARCINOID CARCINOMA CARCINOMA 7 Synaptophyisin Typical Carcinoid Mitotic Index:1 Necrosis absent Ki67:1% Chromogranin-A Ki-67 2
Slide 6 7 titolo centrale per tipo Massimo Milione, 24/09/2017
25/04/2018 8 Synaptophysin Atypical Carcinoid Mitotic Index:3 NECROSIS: focal Ki67:3% Chromogranin-A Ki-67 9 Large Celle Neuroendocrine Carcinoma MITOTIC INDEX 12 NECROSIS: PRESENT Ki67: 40-70% Synaptophyisin Cromogranina-A 10 SMALL CELL NEUROENDOCRINE CARCINOMA MITOTIC INDEX 45 NECROSIS: PRESENT Ki67:80% Synaptophyisin Cromogranina-A 3
Slide 7 8 titolo centrale per tipo Massimo Milione, 24/09/2017 Slide 8 9 titolo centrale per tipo Massimo Milione, 24/09/2017 Slide 9 10 titolo centrale per tipo Massimo Milione, 24/09/2017
25/04/2018 OUTLINE Ki67 role? Ki67 is NOT accepted a prognostic tool ONLYas a diagnostic tool in order to distinguish (in biopsies) Carcinoid against Small Cells Neuroendocrine Carcinoma Levels Mitotic Index NECROSIS G1 G2 G3 At least 2 markers At least 2 markers All markers at level 1 at level 2 at level 3 Typical Carcinoid Atypical Carcinoid Large/Small Carcinoma 4
25/04/2018 Ki67 Synaptophysin G1 G2 G3 At least 2 markers at level 1 At least 2 markers at level 2 All markers at level 3 Ki-67:30%=Level 3 Mitotic Index:1=Level 1 Necrosis: Absent=Level 1 WHO Typical Carcinoid G1 At least 2 markers at level 1 Mitotic Index Levels NECROSIS 5
25/04/2018 Is right time for Lung? massimo.milione@istitutotumori.mi.it grazie Milione M, ESMO PreceptorshipMilione, LuganoBari 14 April 2018 14 giugno 6
25/04/2018 LOH SAGA FOREGUT MIDGUT OUTLINE Differential Diagnosis Well Differentiated METASTASES INTESTINAL PATTERN MORPHOLOGY Ki67 <2% Serotonin + Cdx-2 + PANCREATIC PATTERN MORPHOLOGY Ki67 5% Islet-1+ Cdx-2 +/- Hormones (site dependent)) NO CLEAR PATTERN MORPHOLOGY Cdx-2 + TTF-1 - Cdx-2- TTF-1 + LUNG Cdx-2+ Serotonin + Cdx-2+/- Serotonin - Ileocecal Region Islet-1 + Ki67 5% MilioneM et al Journal of Oncopathology2014 PANCREAS (HORMONES (site dependent) GEP TRIANGLE (HORMONES (site dependent) Islet-1 - STOMACH LARGE BOWEL RECTUM 7
25/04/2018 Abate-Shen C. Nat Rev Cancer 2002 NO TTF-1 Islet-1 CDX-2 SMALL OR LARGE CELL NEUROENOCRINE CARCINOMA? MERKEL CELLS CARCINOMA! Sinaptofisina Islet-1 TTF1 NF CK20 Ki-67 PolV LUNG PRIMITIVE TUMOR Sinaptofisina Ki-67 URINARY BLADDER! Sinaptofisina Ki-67 TTF1 TTF1 8
25/04/2018 WHO 1980 Prognosis Poor Prognosi GastricCarcinoids Functioning Pancreatic Carcinoids Microcitoma Ileal Carcinoids RectalCarcinoids Lung Typical Carcinoids Ampulla Carcinoids MetastaticCarcinoids Non Functioning PancreaticCarcinoids Atypical Lung Carcinoids 9