Gastric cancer epidemiology and pathology Gábor Cserni, MD, PhD, DSc Bács-Kiskun County Teaching Hospital Kecskemét, Hungary
Incidence estimates ‘06 <ul><li>Europe </li></ul><ul><ul><li>96.1 thousand (men) </li></ul></ul><ul><ul><li>63.8 thousand ...
Mortality ‘06 <ul><li>Europe </li></ul><ul><ul><li>70.4 thousand (men) </li></ul></ul><ul><ul><li>47.8 thousand (women) </...
ACS Facts and Figures 2010 n=12730 n=8270 Estimated deaths: 6350 Estimated deaths: 4220
Risk factors <ul><li>Atrophic gastritis, intestinal metaplasia, chronic Helicobacter pylori infection / autoimmunity (inte...
Gastric dysplasia <ul><li>L ow  G rade (LG) : </li></ul><ul><li>Mild alterations in mucosal architecture (tubular structur...
Gastric dysplasia Gut 2000;47:251
Histological classification  I.  (Laurén) <ul><li>Intestinal  (53% in the original description) </li></ul><ul><ul><li>Glan...
Histological classification  II.  ( WHO ) WHO 3rd Edition, 2000
Very well differentiated intestinal GC <ul><li>Associated with complete (type I) intestinal metaplasia </li></ul><ul><li>R...
Other rare types of GC <ul><li>GC with lymphoid stroma ( medullary  carcinoma) </li></ul><ul><ul><li>Poorly differentiated...
Histological classification  III.  ( Ming ) <ul><li>Expanding  (67%) </li></ul><ul><ul><li>Pushing borders (roughly equiva...
Histological classification  IV.  ( Goseki ) <ul><li>Based on tubule (gland) formation and intracellular mucin production:...
Histological classification  V.  ( Carneiro ) <ul><li>-  Glandular  carcinomas ( ≈ intestinal) </li></ul><ul><li>-  Isolat...
Histological classification  VI. ( Mucin IHC ) <ul><li>G : MUC5AC+ &/or MUC6+, MUC2-, CD10- </li></ul><ul><li>I: MUC5AC-, ...
Primary  tumor: (c)T & pT <ul><li>T & pT   </li></ul><ul><ul><li>TX: Not assessable  (to be minimized) </li></ul></ul><ul>...
Regional lymph nodes: pN <ul><li>pNX:  Not assessable  (eg: removed formerly / not removed / no lymph node identified) </l...
Early gastric cancer (EGC)  pT1a and pT1b any pN <ul><li>Japanese classification </li></ul><ul><li>(s i non y ms) </li></u...
Advanced gastric cancer (AGC)  invading muscularis propria & beyond <ul><li>Borrmann’s classification </li></ul><ul><li>Ty...
Spread of GCs <ul><li>Direct spread </li></ul><ul><ul><li>proximal: to esophagus </li></ul></ul><ul><ul><li>distal: to duo...
Pathol. prognostic factors <ul><li>Stage </li></ul><ul><ul><li>EGC (size and pT1a 90-100% 5y OS vs pT1b 80-90% 5y OS) vs A...
 
<ul><li>16 IHC studies (n ≥ 50) </li></ul><ul><li>3264 cases overall </li></ul><ul><li>17,6% (6,8% - 34%) incidence </li><...
Altered scoring system for GC
ToGA -  Thomas Henkel, Kassel Tucson Symposium <ul><li>HER-2 positivity per histological type </li></ul><ul><li>33,4%  int...
Based on 3803 cases <ul><li>Scor ing  a ltere d (biopsy, basolateral pattern, 10%) </li></ul><ul><li>30,5% focal overexpre...
 
Resection specimen
Same resection specimen
Same resection specimen
HER2 3+ resection specimen
Reminder: Same resection specimen could yield biopsies negative or positive for HER2
Evaluation summary The above pattern , if well visible at  medium (x10, x20) power  in  at least 5 clustered cells The abo...
Further personal suggestions … <ul><li>If a  biopsy  (there is a need for multiple samples) is  negative , and there is a ...
Gastric tumor in a biopsy
Gastric tumor IHC
Lobular breast cancer in the stomach i n view of IHC : GCDFP-15  +  and  ER  +  a
Histological report <ul><li>GROSS </li></ul><ul><li>Tumor  location , macroscopic  appearance ,  size , distace from dista...
THE END
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BALKAN MCO 2011 - G. Cserni - Epidemiology and pathology

  1. 1. Gastric cancer epidemiology and pathology Gábor Cserni, MD, PhD, DSc Bács-Kiskun County Teaching Hospital Kecskemét, Hungary
  2. 2. Incidence estimates ‘06 <ul><li>Europe </li></ul><ul><ul><li>96.1 thousand (men) </li></ul></ul><ul><ul><li>63.8 thousand (women) </li></ul></ul><ul><ul><li>159.9 thousand cases </li></ul></ul><ul><ul><li>approx. 5% of all cancer cases </li></ul></ul>EUROPE EU Ann Oncol 2007;18:531
  3. 3. Mortality ‘06 <ul><li>Europe </li></ul><ul><ul><li>70.4 thousand (men) </li></ul></ul><ul><ul><li>47.8 thousand (women) </li></ul></ul><ul><ul><li>118.2 thousand cases </li></ul></ul><ul><ul><li>approx. 6.9% of all cancer deaths </li></ul></ul>EUROPE EU Ann Oncol 2007;18:531
  4. 4. ACS Facts and Figures 2010 n=12730 n=8270 Estimated deaths: 6350 Estimated deaths: 4220
  5. 5. Risk factors <ul><li>Atrophic gastritis, intestinal metaplasia, chronic Helicobacter pylori infection / autoimmunity (intestinal type) </li></ul><ul><li>Gastric ulcers </li></ul><ul><li>Gastric polyps (adenomatous > hyperplastic) </li></ul><ul><li>Menetrier’ s hyperplastic gastritis </li></ul><ul><li>Operated stomach (B-II resection – stump cancer) </li></ul><ul><li>Diet (salted, smoked) </li></ul><ul><li>Hereditary DGC (germline mutation of the CDH-1 gene) </li></ul><ul><li>FAP, HNPCC, Peutz-Jeghers syndrome , Li-Fraumeni syndrome, hereditary hyperplastic polyposis </li></ul>
  6. 6. Gastric dysplasia <ul><li>L ow G rade (LG) : </li></ul><ul><li>Mild alterations in mucosal architecture (tubular structures with budding and branching, papillary enfolding, crypt lengthening, serration, and cystic changes). Enlarged columnar cells with minimal or no mucin. Homogeneously blue vesicular, rounded or ovoid nuclei, usually pseudostratified in the proliferation zone, located at the superficial portion of the dysplastic tubules </li></ul><ul><li>High Grade ( HG ) : </li></ul><ul><li>Irregularly shaped tubules (branching, folding). Mucin absent to minimal. Nuclear crowding, hyperchromasia, pleomorphism, cigare-shaped or rounded nuclei. Prominent nucleoli. Proliferation through the epithelium. </li></ul>
  7. 7. Gastric dysplasia Gut 2000;47:251
  8. 8. Histological classification I. (Laurén) <ul><li>Intestinal (53% in the original description) </li></ul><ul><ul><li>Gland formation (tubular, papillary and solid patterns) </li></ul></ul><ul><li>Diffuse (33% in the original description) </li></ul><ul><ul><li>Poorly cohesive widely infiltrating tumor cells (often signet ring type) </li></ul></ul><ul><ul><li>Gland formation absent or minimal and limited to superficial areas </li></ul></ul><ul><li>Indeterminate </li></ul><ul><ul><li>Either having relatively equal proportions of the intestinal and diffuse type (mixed) OR undifferentiated solid tumors </li></ul></ul>
  9. 9. Histological classification II. ( WHO ) WHO 3rd Edition, 2000
  10. 10. Very well differentiated intestinal GC <ul><li>Associated with complete (type I) intestinal metaplasia </li></ul><ul><li>Resembles regenerative changes </li></ul><ul><li>Minimal cytological atypia </li></ul><ul><li>Architectural glandular distorsion </li></ul>Endoh Y et al Human Pathol 1999;30:826
  11. 11. Other rare types of GC <ul><li>GC with lymphoid stroma ( medullary carcinoma) </li></ul><ul><ul><li>Poorly differentiated (mainly solid) </li></ul></ul><ul><ul><li>Majority EBV associated </li></ul></ul><ul><li>Hepatoid ( AFP and bile producing / glandular variant too ) </li></ul><ul><li>Choriocarcinoma </li></ul><ul><li>Parietal cell carcinoma </li></ul>
  12. 12. Histological classification III. ( Ming ) <ul><li>Expanding (67%) </li></ul><ul><ul><li>Pushing borders (roughly equivalent with the intestinal type of Lauren) </li></ul></ul><ul><li>Infiltrative (33%) </li></ul><ul><ul><li>Diffusely infiltrative pattern </li></ul></ul>Cancer 1977; 39: 2475
  13. 13. Histological classification IV. ( Goseki ) <ul><li>Based on tubule (gland) formation and intracellular mucin production: </li></ul><ul><li>I: Well differentiated tubules IC mucin poor </li></ul><ul><li>II: Well differentiated tubules IC mucin rich </li></ul><ul><li>III: Poorly differentiated tubules IC mucin poor </li></ul><ul><li>IV: Poorly differentiated tubules IC mucin rich </li></ul><ul><li>Mucin rich and poorly differentiated tumors have worse prognosis. </li></ul>Gut 1992; 33: 606
  14. 14. Histological classification V. ( Carneiro ) <ul><li>- Glandular carcinomas ( ≈ intestinal) </li></ul><ul><li>- Isolated cell carcinomas ( ≈diffuse) </li></ul><ul><li>- Mixed </li></ul><ul><li>- Solid (sheets, trabeculae, islands of undifferentiated cells) </li></ul>Curr Diagn Pathol 1997; 4: 51
  15. 15. Histological classification VI. ( Mucin IHC ) <ul><li>G : MUC5AC+ &/or MUC6+, MUC2-, CD10- </li></ul><ul><li>I: MUC5AC-, MUC6-, MUC2+ &/or CD10+ </li></ul><ul><li>GI: mixed positivity </li></ul><ul><li>N: (null) negativity </li></ul>
  16. 16. Primary tumor: (c)T & pT <ul><li>T & pT </li></ul><ul><ul><li>TX: Not assessable (to be minimized) </li></ul></ul><ul><ul><li>T0: No tumor </li></ul></ul><ul><ul><li>Tis: intraepithelial tumor without invasion of the lamina propria </li></ul></ul><ul><ul><li>T1a: Tumor invades into lamina propria or muscularis mucosae. ( TNM6 : T1) </li></ul></ul><ul><ul><li>T1b: Tumor invades into submucosa. ( TNM6 : T1) </li></ul></ul><ul><ul><li>T2: Tumor invades into muscularis propria. ( TNM6 : T2a) </li></ul></ul><ul><ul><li>T3: Tumor invades into subserosa. ( TNM6 : T2b) </li></ul></ul><ul><ul><li>T4: Tumor involves the peritoneum or adjacent structures: </li></ul></ul><ul><ul><li>T4a: Tumor invades into peritoneum. ( TNM6 : T3) </li></ul></ul><ul><ul><li>T4b: Tumor involves adjacent structures (spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal, kidney, small bowel, retroperitoneum). ( TNM6 : T4) </li></ul></ul>Upper 5 cm and GEJ staged according to the esophagus related categories.
  17. 17. Regional lymph nodes: pN <ul><li>pNX: Not assessable (eg: removed formerly / not removed / no lymph node identified) </li></ul><ul><li>pN0: No regional LN metastasis (incl. isolated tumor cells) </li></ul><ul><li>pN1: Metastasis in 1-2 regional LN(s) ( TNM6 : 1-6 LN) </li></ul><ul><li>pN2: Metastasis in 3-6 regional LNs ( TNM6 : 7-15 LN) </li></ul><ul><li>pN3a: Metastasis in 7-15 regional LNs ( TNM6 : pN2) </li></ul><ul><li>pN3b: Metastasis in 16 or more regional LNs ( TNM6 : pN3) </li></ul>
  18. 18. Early gastric cancer (EGC) pT1a and pT1b any pN <ul><li>Japanese classification </li></ul><ul><li>(s i non y ms) </li></ul><ul><li>I Protruding </li></ul><ul><li>II Superficial </li></ul><ul><ul><li>IIa Twice as thick as the mucosa </li></ul></ul><ul><ul><li>IIc Not more than the submucosa </li></ul></ul><ul><li>III excavating </li></ul>Chen C et al. Radiology 2007;242:472-482 .
  19. 19. Advanced gastric cancer (AGC) invading muscularis propria & beyond <ul><li>Borrmann’s classification </li></ul><ul><li>Type IV: linitis plastica when it involves a large part of the stomach. </li></ul>Chen C et al. Radiology 2007;242:472-482 .
  20. 20. Spread of GCs <ul><li>Direct spread </li></ul><ul><ul><li>proximal: to esophagus </li></ul></ul><ul><ul><li>distal: to duodenum or even deeper </li></ul></ul><ul><ul><li>serosal: omentum, transverse colon, pancreas, spleen, liver; transperitoneal : peritoneum, omentum, ovaries, intestines </li></ul></ul><ul><li>Lymphatic </li></ul><ul><ul><li>regional LNs or more distant LNs (para-aortic, mesenteric, pancreatic, splenic, mediastinal, left scl - Virchow) </li></ul></ul><ul><li>Hematogeneous </li></ul><ul><ul><li>Liver, lung, adrenals, skin … ovaries…etc </li></ul></ul>
  21. 21. Pathol. prognostic factors <ul><li>Stage </li></ul><ul><ul><li>EGC (size and pT1a 90-100% 5y OS vs pT1b 80-90% 5y OS) vs AGC (25-35% 5y OS ↔ 50% in Japan ) </li></ul></ul><ul><ul><li>esp. serosal involvement and LN status </li></ul></ul><ul><ul><li>(a minimum of 15 LNs recommended) </li></ul></ul><ul><li>HER-2 (predictive for anti-HER2 therapies) </li></ul>
  22. 23. <ul><li>16 IHC studies (n ≥ 50) </li></ul><ul><li>3264 cases overall </li></ul><ul><li>17,6% (6,8% - 34%) incidence </li></ul><ul><li>9 ISH studies (n ≥ 50) </li></ul><ul><li>1232 cases overall </li></ul><ul><li>19,2% (7,1% - 42,6%) incidence </li></ul>HER-2 positivity in gastric cancer
  23. 24. Altered scoring system for GC
  24. 25. ToGA - Thomas Henkel, Kassel Tucson Symposium <ul><li>HER-2 positivity per histological type </li></ul><ul><li>33,4% intestinal </li></ul><ul><li>5,5% diffuse </li></ul><ul><li>19,6% mixed </li></ul>
  25. 26. Based on 3803 cases <ul><li>Scor ing a ltere d (biopsy, basolateral pattern, 10%) </li></ul><ul><li>30,5% focal overexpression (heterogeneity) </li></ul><ul><li>25% FISH+ IHC- </li></ul><ul><li>7,5% IHC+ FISH- </li></ul><ul><li>Polysomy less common: 27,2% (HERA) vs 3,8% ToGA </li></ul><ul><li>IHC+ response ; FISH+/IHC- no or lesser response </li></ul><ul><li>Algorithm is the same, but IHC recommended as first test </li></ul>ToGA - Thomas Henkel, Kassel Tucson Symposium 2010
  26. 28. Resection specimen
  27. 29. Same resection specimen
  28. 30. Same resection specimen
  29. 31. HER2 3+ resection specimen
  30. 32. Reminder: Same resection specimen could yield biopsies negative or positive for HER2
  31. 33. Evaluation summary The above pattern , if well visible at medium (x10, x20) power in at least 5 clustered cells The above pattern , if well visible at medium (x10, x20) power IHC 2+ Strong circumferential, basolateral or lateral staining (visible at low power ) in at least 5 clustered cells Strong circumferential, basolateral or lateral staining (visible at low power ) in at least 10% of the cells IHC 3+ Biopsy Resection HER2 result
  32. 34. Further personal suggestions … <ul><li>If a biopsy (there is a need for multiple samples) is negative , and there is a resection that follows : the latter cannot be considered negative on the basis of the report of the former because of heterogeneity. </li></ul><ul><li>In case of a mixed tumor , composed of a positive and a negative component, and overall positivity would be <10% in a resection specimen, it seems better to go against the rule and describe the tumor as e.g. having a HER-2 positive intestinal component and a HER2 negative diffuse component . </li></ul>
  33. 35. Gastric tumor in a biopsy
  34. 36. Gastric tumor IHC
  35. 37. Lobular breast cancer in the stomach i n view of IHC : GCDFP-15 + and ER + a
  36. 38. Histological report <ul><li>GROSS </li></ul><ul><li>Tumor location , macroscopic appearance , size , distace from distal and proximal margins </li></ul><ul><li>MICRO </li></ul><ul><li>Histological type (e.g. Laurén), differentiation , margins , depth of invasion ( pT ), number of examined and involved LNs (pN) . </li></ul><ul><li>HER2 status </li></ul><ul><li>(Other relevant, nearby pathology – including Helicobacter pylori infection, gastritis, fungi… etc.) </li></ul>
  37. 39. THE END

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