【膵臓】前癌病変の分類コンセンサス：WHO2019 の背景知識として

A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas

Olca Basturk, Seung-Mo Hong, Laura D Wood, N Volkan Adsay, Jorge Albores-Saavedra, Andrew V Biankin, Lodewijk A A Brosens, Noriyoshi Fukushima, Michael Goggins, Ralph H Hruban, Yo Kato, David S Klimstra, Günter Klöppel, Alyssa Krasinskas, Daniel S Longnecker, Hanno Matthaei, G Johan A Offerhaus, Michio Shimizu, Kyoichi Takaori, Benoit Terris, Shinichi Yachida, Irene Esposito, Toru Furukawa, Baltimore Consensus Meeting

Am J Surg Pathol. 2015 Dec;39(12):1730-41.

膵臓の前癌病変に関して、現行の WHO 分類（2019）の元となっているコンセンサスミーティングの内容である。現状の内容を理解するために最も最適な論文と考える。興味がある方は、歴史を知るためにも是非これの引用論文を孫引きして読んでいただきたい。

Abstract
International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following:

(1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade. Thus, "high-grade dysplasia" is to be reserved for only the uppermost end of the spectrum ("carcinoma in situ"-type lesions).

(2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined.

(3) Intraductal lesions 0.5 to 1 cm can be either large PanINs or small IPMNs. The term "incipient IPMN" should be reserved for lesions in this size with intestinal or oncocytic papillae or GNAS mutations.

(4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the "associated" group) ought to be genetically distinct from an IPMN elsewhere in the gland.

(5) "Intraductal spread of invasive carcinoma" (aka, "colonization") is recommended to describe lesions of invasive carcinoma invading back into and extending along the ductal system, which may morphologically mimic high-grade PanIN or even IPMN.

(6) "Simple mucinous cyst" is recommended to describe cysts >1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN.

(7) Human lesions resembling the acinar to ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist and may reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study.

These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas.

以下に、日常診断で特に重要な点のみを抜粋し、現行の WHO 分類（2019）での問題点や日本での取扱いについて※太字で付け加える。

【SANOTIC SUMMARY】
１．すべての前癌病変で２段階分類を採用した。
▶ low-grade: PanIN-2 / intermediate-grade dysplasia まで
▶ high-grade: PanIN-3 / carcinoma in situ まで

２．切除断端について
▶ 浸潤癌の症例では、切除断端の PanIN の存在は予後に関与しない
※ 日本では PanIN-3 / CIS については報告する
▶ 浸潤癌併存のない IPMN では、断端部の病変の有無と予後の関係は不明

３．0.5～1.0 cm 大の PanIN と IPMN の境界的サイズの病変について
▶ 腸型、オンコサイト型あるいは GNAS 変異例を incipient IPMN とした
※ WHO2019 ではオンコサイト型が Intraductal oncocytic papillary neoplasm (IOPN) として独立したが、これについては時期尚早であるとの意見もある。

４．IPMN 由来の浸潤癌と IPMN が同時に存在しているのみの浸潤性膵管癌は遺伝子的背景に異なるので、きちんと切り出して、その浸潤癌成分と IPMN 成分の関係をみるべきである。（IPMN 由来癌の方が予後良好）

５．浸潤性膵管癌の膵管内進展（Intraductal spread of invasive carcinoma、colonization あるいは ductal cancerization）について記載する。ただし、PanIN や IPMN との区別が難しいことがある。

PubMed と PMC free article にリンクはこちら👇

A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas - PubMed

A REVISED CLASSIFICATION SYSTEM AND RECOMMENDATIONS FROM THE BALTIMORE CONSENSUS MEETING FOR NEOPLASTIC PRECURSOR LESIONS IN THE PANCREAS

肝胆膵の目次はこちら👇

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