위 선종/이형성 Gastric adenoma/dysplasia

Jun Haeng Lee. Department of Medicine

Sungkyunkwanuniversity School of Medicie, Seoul, Korea

Dysplasia in Barrett’s esophagus

• Ideally, the management of a disorder is based on

– an unequivocal diagnosis,

– a firm understanding of the natural history, and

– definitive data regarding the risks and benefits of the

treatment options.

• Unfortunately, none of these prerequisite factors

may be available to guide the management of

patients with dysplasia in Barrett’s esophagus.

Spechler SJ. Am J Gastroenterol 2005;100:927-935

Issues regarding gastric adenoma/dysplasia

Jun Haeng Lee. Department of Medicine

Sungkyunkwanuniversity School of Medicie, Seoul, Korea

Problem 1: What is dysplasia?

• Abnormality of development; in pathology, alteration in

size, shape, and organization of adult cells (Dorlands’

dictionary 24th ed.)

• Unequivocal neoplastic transformation of the

epithelium (Riddell RH. Hum Pathol 1983)

• Histological expression of genetic alterations that favor

cell growth and neoplasia (Spechler. Gastroenterology 2001)

• In Japan, some authorities defined biopsies with marked

reactive and regenerative histological features as

dyplasia (Goldstein NS. Hum Pathol 1997)

What is adenoma? - Adenoma = dysplasia

소화기병리학연구회. 위암 병리보고서 기재사항 표준화. 대한병리학회지 2005;39:106

Regenerating atypia vs. dysplasia

• Changes in epithelial cells (e.g. increased N/C ratio

+/- structural disarray) may occur in two situations.

• Regenerating atypia - when the eithelium has

been injured and is undergoing repair

• Dysplasia - when genetic alterations have

transformed the cells in a neoplastic growth

• Significant overlap exist between the two.

Regenerating

atypia Dysplasia

Conceptual model

Regenerating

atypia Dysplasia

In clinical practice

위궤양 scar의 조직검사에서 adenoma with low grade dysplasia

관찰자간 차이에 대하여

Atypia에 대한 설명 (2017/3)

• 비전형적 세포(Atypia)는 세포의 모양이 비전형적이라는, 즉

정상이 아니라는 뜻입니다. 여기에는 많은 원인이 있습니다.

좋은 것부터 나쁜 것까지 상당히 다양합니다. 먼저 좋은 쪽을

보자면 단순한 위염 또는 위궤양 때문에 세포의 모양이 비전

형적(atypical)으로 변할 수 있습니다. 반대로 전암성 병소 또

는 위암의 조직검사에서 비전형적이라는 결과가 나오는 경우

도 있습니다. 그 비율을 정확히 말하기는 어렵지만 보통 암과

관련되지 않은 것(위염이나 궤양)이 절반, 암과 관련된 것(선

종이나 암)이 절반 정도입니다. 외부 슬라이드 재판독과 내시

경 재검을 권합니다. 첫 평가에서 큰 이상이 아닌 것으로 나와

도 재검이 필요합니다.

현실적인 접근

• Adenoma의 진단에는 모양은 고려하지 않습니다.

융기형, 평탄형, 함몰형이 모두 포함됩니다.

• 광의의 adenoma = adenoma with LGD + adenoma

with HGD

• 좁은 의미의 adenoma = adenoma with LGD

• 병리과 의사가 dysplasia라고만 보고한 경우:

dysplasia = adenoma (광의)

Problem 2: Inter-continental variation

Normal

Superficial Gastritis

Atrophic Gastritis

Intestinal metaplasia

Dysplasia

Stomach Cancer

Correa. Scand J Gastroenterol Suppl 1984;104:131-136

Dysplasia에 대한 다양한 분류법

Rugge. Eur J Gastroenterol Hepatol 2005;17:1191-1196

Group classification of JRSGC since 1971

Group Diagnosis

Group I Normal mucosa and benign lesions with no

atypia

Group II Lesions showing atypiaa but are diagnosed as

benign (non-neoplastic)

Group III Borderline lesions between benign (non-

neoplastic) and malignant

Group IV Lesions strongly suspected of carcinoma

Group V Carcinoma

Nagano T. Gann Monogr Cancer Res 1971;11:245-256

Kato. Stomach & Intestine 2004;39:1443-1447

5. invasive carcinoma invasive carcinoma

4.3 suspicion of invasive

carcinoma

suspicious for invasive

carcinoma

4.2 carcinoma in situ 5. carcinoma

4. lesions strongly

suspected of carcinoma

4.1 high-grade

adenoma/dysplasia

high grade

adenoma/dysplasia

3. noninvasive low-grade

neoplasia

low grade

adenoma/dysplasia

2. indefinite indefinite for dysplasia 3. borderline lesion

2. benign non-

neoplastic lesion

1. negative for

neoplasia/dysplasia

negative for dysplasia 1. normal and benign

lesion with no atypia

Vienna, 1998 Western Japanese

Schlemper. Gut 2000;47:251-255

Western vs. Japanese view - pathologic diagnosis of 35 cases

Schlemper RJ. Lancet 1997;349:1725-1729

Willis & Riddell. Gastrointest Endosc 2003;57:369-376

♠ Korean endoscopists are treating a lot of patients with gastric adenomas, and some of them may be considered as well-differentiated gastric adenocarcinomas in Japan.

우리나라의 고도선종은 아마도 일본에서는 암으로 분류되고 있는 것 같습니다.

Problem 3: Inter-observer variation - Referred due to high grade dysplasia (M/71)

Outside review: adenocarcinoma (W/D)

ESD using needle knife for EGC - W/D adenocarcinoma, SM2, RM(-), L(+), V(-)

자연사

Jun Haeng Lee. Department of Medicine

Sungkyunkwanuniversity School of Medicie, Seoul, Korea

8년간 치료 안한 선종

History of gastric dysplasia - from a very famous textbook

Moderate

Dysplasia

High Grade

Dysplasia

Gastric

Cancer

5 years

10%

5 years

10%

3 months – 2 years

50-90%

Mild

Dysplasia

60% 10%

Luk GD. Sleisenger’s. 6th ed. page 736

Progression to invasive carcinoma (cat 5) - significant difference between authors

Author LGD (Vienna category 3) HGD (Vienna category 4)

% fraction interval % fraction Interval

Saraga (1987) 2% (1/64) 4 years 81% (7/21) 4 months

Lansdown (1990) 0% (0/7) 85% (11/13) 5 months

Rugge (1991) 17% (12/69) 1 year 75% (6/8) 4 months

Fertitta (1993) 23% (7/30) 10 months 81% (25/31) 5 months

Di Gregorio (1993) 7% (6/89) 2 years 60% (6/10) 11 months

Rugge (1994) 14% (13/90) 2 years 78% (14/18) 9 months

Kokkola (1996) 0% (0/96) 67% (2/3) 1.5 year

Yamada (2004) 0% (0/38) 10% (1/10) 4.6 year

Biopsy

Resected LGD HGD Total

LGD 83 3 86

HGD 12 12 24

Carcinoma 1 7 8

Total 96 22 118

Park DI. Endoscopy 2001;33:501-506

자연사인지 조직검사의 한계인지 명확하지 않습니다.

저도 선종 ESD 후 위암 (LP암)

위 선종의 진단과 치료

Jun Haeng Lee. Department of Medicine

Sungkyunkwanuniversity School of Medicie, Seoul, Korea

저도 선종 2개

고도 선종

Endoscopic or surgical resection of gastric neoplasms in SMC (2012) - Excluding palliative surgeries

AGC (505)

Beyond absolute indication EGC (949)

Absolute indication EGC (327)

Adenoma with HGD (122)

Adenoma with LGD (141)

EGCs among all gastric cancers: 71.6% (327/1,781) Absolute indication EGCs among all EGCs: 25.6% (327/1,276)

Diagnostic group classifications before and after the treatment

ESD or surgery

LGD HGD AI-EGC EI-EGC BEI-EGC AGC

Pre-treatment diagnostic groups

LGD HGD AI-EGC EI-EGC BEI-EGC AGC

Post-treatment diagnostic groups

Post-treatment analysis of EI-EGCs (2012)

LGD 1

HGD 12

AI-EGC 67

EI-EGC 31

BEI-EGC AGC

ESD 111

LGD HGD AI-EGC EI-EGC 111

BEI-EGC AGC

Lee JH. Surg Endosc 2016;30:3987-93

Pre-treatment analysis of AI-EGCs (2012)

LGD HGD AI-EGC

396 EI-EGC BEI-EGC AGC

ESD 355

LGD 1

HGD 4

AI-EGC 229

EI-EGC 67

BEI-EGC 53

AGC 1

Lee JH. Surg Endosc 2016;30:3987-93

Absolute indication EGC by pre-treatment diagnostic groups

Pre-Tx AI EGC 396

ESD 355

Operation 41

LGD 1

HGD 4

AI EGC 229

AGC 1

LGD 1

BAI EGC 120

AI EGC 29

BAI EGC 11

ESD 1 Surgery 53

Surgery 1 ♠Reason for surgery (multiple) Suspicious lymphadenopathy on CT (18) Multiple lesions (6) Patient’s wish (18) Difficult location (3) Suspicious SM invasion on EUS (2)

* BAI: beyond absolute indications Lee JH. Surg Endosc 2016;30:3987-93

선종의 33%는 upgrade 됩니다.

Lee JH. Surg Endosc 2016;30:3987-93

Villous adenoma with high grade dysplasia, 4.0x3.6cm

먼 과거에는 선종으로 수술하기도 했습니다.

Tubular adenoma, elevated type, 4x3.5cm, negative RM

거의 전부 내시경으로 치료하고 있습니다.

작고 납작한 저도선종은 소작술로 치료

• High grade dysplasia는 원칙적으로 내시경적 절제술을

시행한다. 위암을 동반하고 있는 경우가 많으므로 가급

적 en bloc resection을 위하여 노력한다. ESD 등의 방법

을 적극적으로 이용한다.

• Low grade dysplasia의 치료방침은 HGD 보다는 less

invasive하게 선택한다. 큰 병소, 뚜렷한 함몰부위나 돌출

부위가 있는 경우는 내시경 절제술을 선택한다. 그러나,

작고 납작한 병소와 전신상태가 나쁜 경우는 APC를 이

용한 ablation을 하고 선택적으로 follow-up도 가능하다.

위 선종의 치료

새로운 접근법은 없는가?

Jun Haeng Lee. Department of Medicine

Sungkyunkwanuniversity School of Medicie, Seoul, Korea

Genetic changes in early gastric carcinogenesis

• Min et al. investigated the genomic and

transcriptomic landscape of adenoma with LGD,

adenoma with HGD, and EGC.

• Several genetic changes have been identified

in advanced gastric cancer, but the genetic

alterations associated with early gastric

carcinogenesis remain unclear.

Min BH. J Pathol 2016;240:304-314

Genetic changes in early gastric carcinogenesis

Min BH. J Pathol 2016;240:304-314

He found that the expression pattern clearly divided into normal, LGD, and EGC, whereas those of HGD overlapped with LGD or EGC. RNF 43 mutation were present only in HGD and EGC.

Adenoma-carcinoma model of gastric multistep carcinogenesis

Min BH. J Pathol 2016;240:304-314

결론 – 위 선종

• 조직검사에서 dysplasia가 있으면 선종으로 진단

합니다.

• 선종 중 일부는 (저도 선종의 10%, 고도 선종의

33%) 절제술 후 암으로 진단이 바뀐다. 그 중 일

부는 수술이 필요합니다.

• 작고 납작한 저도 선종은 소작술 혹은 경과관찰

을 선택할 수 있습니다.

감사합니다.