해외 증례(Japan) Gastric adenocarcinoma of fundic gland type with autoimmune gastritis

관리자
2023-02-12
조회수 169

2023년 1월, Clin J Gastroenterol에 실린 올해 첫 case report 입니다. 

AIG에서 neuroendocrine tumors, hyperplastic polyps (malignant potential) 및 adenocarcinoma와 같은 neoplasms이 발생할 수 있습니다. Fundic galnd type의 adenocarcinoma (GAFG)의 경우 ESD를 받은 EGC환자의 약 1%에서 발생하는 well-differentiated adenocarcinoma로 H. pylori 감염이나 atrophic change나 intestinal metaplasia와는 관계없이 발생하는 것으로 알려져 있습니다. AIG에서 파괴된 parietal cells로 인해 위 체부의 심한 atrophy가 발생하기 때문에 남아 있는 fundic glands에서 GAFG가 발생하기는 어려운 것으로 보이지만, 최근 case가 있어 보고 하게 되었습니다. 


Case report

87 years / Male, C/Cx: Dysphagia

No EGD, H. pylori or PPI medication history

Medical P/Hx: Type 2 DM, Anigna pectoris

Laboratory findings: Anti-H. pylori Ig G (-), H. pylori stool Ag(-), Hb/TFT (WNL), Gastrin (3992 pg/ml), APCA(+), AIFA (1:40)

Fig. 1 Conventional white-light endoscopic fndings of typical autoimmune gastritis. 

a> The greater curvature in the middle gastric corpus. b> Sticky adherent dense mucus in the upper gastric corpus. c> The antrum area shows discolored mucosa. d> The tumor is on the greater curvature of the middle corpus. e & f> Magnifed endoscopy with narrow-band imaging fndings of the tumor. A small structure resembling a fundic gland with dilated blood vessels.

두 가지 형태의 병변이 관찰되어 조직검사를 시행하였습니다. 

* GAFG: Whitish, fat, elevated submucosal tumor-like lesion, approximately 5 mm in diameter was detected on the greater curvature of the middle corpus. (Fig. 1C)

* Well-differentiated adenocarcinoma: Whitish, elevated lesion on the posterior wall of the lower corpus measuring 10 mm in diameter. ME-NBI revealed the tumor area to be brownish and demarcated with an irregular microvascular pattern. (No endoscopic image)

<Resect specimen: en bloc resection by ESD>

1. GAFG (Gastric adenocarcinoma of the fundic gland type) (30x20mm, elevated lesion: 5x3 mm)

Fig. 2 The histopathological fndings of the endoscopic submucosal dissection (ESD) resected specimen of gastric adenocarcinoma of the fundic gland type (H&E staining). a> The low power view of the ESD resected specimen includes the tumor (red line including blue box) and the surrounding mucosae (green box). b> Magnifed view around the red line lesion of histopathological fndings of the tumor.

Fig. 3 The immunohistochemical fndings of the gastric adenocarcinoma of the fundic gland type. a> The magnifed image of the tumor in the blue box. Abnormal fundic glands are increased in the middle to deep layer of the lamina propria mucosae. b> Negative for MUC5AC. c> Partially positive for MUC6. d> Positive for pepsinogen-I. e> Partially positive for H+/K+-ATPase. f> Negative for MUC2

진단: Low-grade GAFG, Type 0–IIb, pT1a(M), pUL0, ly0, v0, pHM0, and pVM0 (according to the Japanese classifcation of gastric carcinoma)

Gastric mucosa surrounding tumor: fundic glands (Fig 4.)

Fig. 4 The immunohistochemical fndings in the gastric mucosa around the gastric adenocarcinoma of the fundic gland type. a> H&E staining. b> positive for MUC5AC. c> positive for MUC6. d> positive for pepsinogen-I. e> Positive for H+/K+-ATPase. f> Negative for MUC2.

2. Well-differentialted adenocarcinoma (20x20 mm, elevated lesion: 7x5 mm)

진단: Type 0–IIa, pT1a(M), pUL0, ly0, v0, pHM0, and pVM0

Gastric mucosa surrounding tumor: Intestimal metaplasia

 

Discussion

이번 case에서 살펴보면 parietal cell의 감소로 인해 gastric mucosa의 적은 부분에서 H+/K+-ATPase 가 관찰되고 있습니다. 또한, Pepsinogen-I과 MUC6가 양성으로 확인 되는데 이는 mucous neck cells의 존재를 의미하며, AIG의 전형적인 fundic glands의 손상이 관찰되고 있었습니다. 

AIG에서의 조직학적 특징을 살펴보면, (Watanabe H. Histological diagnosis and stages of autoimmune gastritis–a new proposal. Nihon Shokakibyo Gakkai Zasshi. 2022;119:528–39.) 

(i) parietal cell changes (altered, reduced, or absent)

(ii) mucus neck cells and pyloric gland changes (increased, reduced, or displaying intestinal metaplasia)

(iii) hyperplasia of enterochromafin-like cells. 

이며, AIG의 조직학적 pahse는 이러한 조직학적 특징을 바탕으로 three phases (early, advanced forid, and advanced end stage)로 구분되어 집니다. 이번 case의 경우는 parietal cells의 수는 reduced, chief and mucous neck cells은 유지되고 있어서 “advanced forid stage” (Fig. 4b–d)로 볼 수 있습니다. 이번 case에서 GAFG는 remaining chief cells에서 기인한 것으로 생각되는데, AIG에서의 carcinogenic pathways가 아직 분명하지는 않지만, 위산 분비의 저하로 nitrosamine이 carcinogenic nitrogen compounds의 존재와 hypergastrinemia로 인한 finduic glands의 trophic action이 원인으로  보여집니다. AIG는 또한 H. pylori 감염되지 않은 경우보다는 높은 carcinogenic risk를 가지고 있습니다. AIG에서 tubular adenocarcinoma에 대한 report 들이 있기는 하지만 AIG에서 GAFG/GAFGM의 발생은 매우 드물게 보고 되고 있습니다 (Table 1). 


Our study has some limitations. First, the diagnostic criteria for AIG are still under consideration. The sensitivity and specifcity of PCA and IFA are not suffcient. In addition, the cut-off values of gastrin and histopathological diagnosis do not correspond. Second, conclusively proving the absence of H. pylori infection in AIG is diffcult. Therefore, based on previous reports, we made a diagnosis based on the criteria that could be used at this present time. 

Cnclusion

We report a case of GAFG with AIG. During AIG progression, the chief cells may remain and develop into a malignancy. Therefore, even with AIG, careful observation is required when considering the occurrence of GAFG/GAFGM.


Abstract

 An 87-year-old man with dysphagia presented to our hospital. He was diagnosed with autoimmune gastritis (AIG) with severe atrophy and hypergastrinemia. The patient was positive for parietal cell antibody (PCA) and anti-intrinsic factor antibody (IFA), without evidence of H. pylori infection. A fat elevated tumor was detected in the middle corpus, and therapeutic endoscopic submucosal dissection was performed. Histopathological examination revealed atypical cells mimicking the fundic glands, which were positive for pepsinogen-I and partially positive for MUC6 and H +/K+-ATPase, proliferating to the deep layer. The fnal diagnosis was gastric adenocarcinoma of the fundic gland type (GAFG). AIG is expected to be difcult to develop GAFG because the basal gastric glands are highly atrophic due to the production of PCA. However, some chief cells may remain and could have the potential to develop into malignancy during AIG progression. Therefore, careful observation is required in patients with AIG when considering the occurrence of GAFG.

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대한자가면역성위염연구회

주소 : 경기도 용인시 기흥구 중부대로 579, 508-23호 (구갈동, 강남대프라자)

대표전화 : 070-8080-0453  이메일 : autogastritis@gmail.com 


Copyright (c)대한자가면역성위염연구회. All Rights Reserved. Design Hosting By 위멘토.