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[Mucinous adenocarcinoma]

0. 들어가는 증례

On the greater curvature side of the proximal antrum, there was a 4 cm-sized, round, dome-like, elevated mass with central shallow ulceration and spontaneous bleeding. Although the ulceration was not deep, the endoscopist's impression was (1) Borrmann type 2 advanced gastric cancer and (2) lymphoma (less likely). However, the final pathology after surgical resection was mucinous adenocarcinoma with deep submucosal (SM3) invasion. Therefore, it is a case of AGC-like EGC.

1. Depth of invasion is difficult to guess in mucinous adenocarcinoma

Endoscopic differentiation between EGC and AGC is not easy. According to the experience at our institution (Shin 2010), 9.3 % of pathologically confirmed AGCs were initially considered as EGC by endoscopy. Similarly, 8.1 % of pathologically confirmed EGCs were initially considered as AGC by endoscopy. EUS (endoscopic ultrasonography) may help evaluate the depth of invasion, but routine use of EUS before surgery or ESD is not supported by quality evidences.

WHO definition of mucinous adenocarcinoma is "an adenocarcinoma in which a substantial amount of extracellular mucin (more than 50% of the tumor) is retained within the tumor". Japanese definition is "an adenocarcinoma characterized by a substantial number of mucous lakes due to mucin pooling in the tumor stroma."

Mucinous adenocarcinoma is one of important types of AGC-like EGC. There is an abundant mucin pool between tumor cells, so the cancer lesion commonly looks like an elevated mass lesion. Some cases with AGC-like EGC (mucinous adenocarcinoma) can be found in the literature.

One interesting point of mucinous adenocarcinom is that it is also a common type of EGC-like AGC. So the endoscopic evaluation of invasion depth is very difficult for mucinous adenocarcinoma.

Mucinous adenocarcinom (PM invasion)

Mucinous adenocarcinom (PM invasion)

2. Mucinous adenocarcinom can mimick SMT (submucosal tumor)

Mucinous adenocarcinoma can mimick submucosal tumor. Followings are two typical cases from a recent case report (Yu. J Korean Surg Soc 2013;84:118?122).

3. Two types of mucinous adenocarcinoma

Mucinous gastric adenocarcinoma can be devided into two groups -- differentiated (= low grade) vs undifferentiated (= high grade).

Two types of mucinous gastric adenocarcinoma were discussed in a recent Korean study (Lee, 2012). The conclusion of the study was that compared with patients with poorly differentiated adenocarcinoma, the overall survival of patients with undifferentiated mucinous adenocarcinoma was statistically significantly worse and those with signet ring cell carcinoma had a better prognosis. See one paragraph in the introduction section.

"According to the World Health Organization (WHO) classification, the four predominant histological types of gastric adenocarcinoma are tubular adenocarcinoma, papillary adenocarcinoma, mucinous adenocarcinoma (MAC) and signet ring cell carcinoma (SRC). Unlike tubular adenocarcinoma, which is graded as well-, moderately- or poorly-differentiated according to the degree of glandular formation, papillary adenocarcinoma is usually classified as well-differentiated, and SRC as poorly-differentiated. The Japanese classification system categorizes gastric adenocarcinomas into two groups: differentiated and undifferentiated. The differentiated group consists of well-differentiated, moderately-differentiated and papillary adenocarcinoma. The undifferentiated group consists of poorly differentiated adenocarcinoma (PDAC) and SRC. Interestingly, MAC can be regarded as either a differentiated or undifferentiated type depending on the predominant components. In the same context, Nakamura categorized all gastric cancer as either differentiated or undifferentiated."

According to a report from Japan (Kunisaki, 2006), undifferentiated mucinous gastric adenocarcinoma has following characteristics.

  1. Higher frequency of metastasis to lymph nodes and lymphatic and venous invasion
  2. Anatomical extent of metastatic spread to lymph nodes was more widespread
  3. Advanced tumor stage
  4. More frequent peritoneal metastasis at the initial diagnosis was more frequent
  5. Poor curability

4. Difficult to make diagnosis using forcep biopsy.

Other challenging aspect of mucinous adenocarcinoma is that the pre-treatment pathologic diagnosis is impossible in most cases. The pretreatment biopsy is usually poorly differentiated adenocarcinoma or signet ring cell carcinoma. It is because the existence of mucin pool is difficult to see in tiny biopsy specimens. Followings are some more examples of mucinous adenocarcinoma.

Mucinous adenocarcinoma는 조직검사에서 암이 나오지 않을 수 있습니다. Mucin pool에 암세포가 둥둥 떠 있는 경우가 많으므로...

5. Some examples of mucinous adenocarcinoma

Mucinous adenocarcinoma (M, muscularis mucosa)

Mucinous adenocarcinoma (SM1)

Mucinous adenocarcinoma (SM2) presented as intractable gastric ulcer

Mucinous adenocarcinoma (SM3)

Mucinous adenocarcinoma (SM3)

Mucinous adenocarcinoma (Proper muscle, LN positive)

Mucinous adenocarcinoma (Subserosa)

Mucinous adenocarcinoma (Subserosa, LN positive)

Mucinous adenocarcinoma (Subserosa, LN positive)

Mucinous adenocarcinoma (Subserosa)

Mucinous adenocarcinoma (penetrates serosa, LN positive)

Mucinous adenocarcinoma (penetrates serosa, LN positive)

Mucinous adenocarcinoma (penetrates serosa, LN positive)

Mucinous adenocarcinoma (direct extension to adjacent structure (mesocolon), LN positive)

Stomach, subtotal gastrectomy:
Advanced gastric carcinoma
1. Location : [1] lower third, [2] duodenum, Center at antrum and lesser curvature, anterior wall
2. Gross type : Borrmann type 2
3. Histologic type : mucinous adenocarcinoma (mucinous carcinoma portion: 100%)
4. Histologic type by Lauren : diffuse
5. Size : 4.5x4 cm
6. Depth of invasion : subserosal connective tissue (pT3)
7. Resection margin: free from carcinoma; safety margin: proximal 4.5 cm, distal 1.5 cm
8. Lymph node metastasis : metastasis to 9 out of 38 regional lymph nodes (pN3a), (perinodal extension: present) (9/38: "3", 2/8; "4", 0/4; "5", 3/4; "6", 2/5; "7", 0/5; "9", 1/1; "8a", 0/8; "11p", 0/0; "12a", 1/1; "4sb", 0/1; "1", 0/0; "12p", 0/1)
9. Lymphatic invasion : present (+++)
10. Venous invasion : not identified
11. Perineural invasion : present
12. Peritoneal cytology : negative
13. AJCC stage by 7th edition: pT3 N3a

위암 의심이나 첫 조직검사에서 암으로 나오지 않았다는 소견으로 의뢰되셨습니다. 외부 슬라이드 재판독 결과 chronic gastritis with lymphoepithelial lesion-like change로 보고되었습니다. 즉시 내시경 조직검사 재검을 하였고 mucin pool with some atypical cells, suspected mucin-producing adenocarcinoma로 보고되어 수술을 하였습니다. 매우 심했습니다.
Stomach, total gastrectomy:
. Advanced gastric carcinoma
1. Location : upper third, Center at body and lesser curvature
2. Gross type : Borrmann type 4
3. Histologic type : mucinous adenocarcinoma
4. Histologic type by Lauren : diffuse
5. Size : 12.5x7 cm
6. Depth of invasion : invades serosa (pT4a)
7. Resection margin: free from carcinoma, safety margin: proximal 3cm, distal 15cm
8. Lymphatic invasion : present
9. Venous invasion : present (extramural)
10. Perineural invasion : present
11. Lymph node metastasis : metastasis to 23 out of 59 regional lymph nodes (pN3b) (perinodal extension: present) (23/59: "1", 1/9; "3", 14/18; "4", 0/2; "4sb", 0/1; "5", 0/0; "6", 0/5; "7", 3/12; "8a", 3/8; "9", 0/0; "11p", 2/3; "12a", 0/1; "2", 0/0; "10", 0/0)
12. Peritoneal cytology : negative
13. AJCC stage by 7th edition: pT4a N3b


[2014-3-31. 애독자 증례 (M병원 M선생님)]

저도 최근 어려운 mucinous adenocarcinoma 증례를 경험하였습니다. 저는 최근에 크기가 애매한 SMT(1.5-2 cm)의 진단을 위하여 precut & biopsy를 하는 연구를 진행중입니다. FNA하기 어려운 경우입니다. EUS는 비싼 검사임에도 정확한 조직진단이 안되니 화내는 환자가 있기도 하구요...

70대 여자 환자였습니다. 내시경에서는 전형적인 SMT였습니다. 위치는 전정부 소만, 크기는 1.5 cm 정도였고, EUS에서 heterogenous mixed echoic mass였습니다. 그래서 Dual knife로 precut을 살짝하고 조직검사를 하였습니다. 그랬더니 젤라틴 같은 물질이 나왔습니다. 조직검사 결과는 다음과 같았습니다.

Stomach, antrum, endoscopic biopsy; Tiny pieces of fibrovascular tissue with mucinous material (See note)
(Note) No epithelial component is present in mucin. Differential diagnosis includes mucin containing benign lesions and mucinous adenocarcinoma. Further evaluation is recommended.

고민하다가 ESD를 하자고 했습니다. 조직검사를 다시 해도 결과가 달라지지 않을 것 같아 아예 ESD를 하자고 했습니다. 초음파상에서 3번째 층에 국한되었다는 것을 알았기 때문에 정확한 진단을 위해 권했습니다. 조직검사는 첨단에서 했기 때문에 시술에는 영향이 없었습니다. 다음과 같은 결과가 나왔습니다.

Stomach, endoscopic submucosal dissection; MUCINOUS ADENOCARCINOMA with signet ring cell feature
1) Location of tumor: lesser curvature of antrum
2) Tumor size: 1.8x1.4x0.4 cm
3) Depth of invasion: submucosa (sm3)
4) Surgical margins: involved by carcinoma at deep resection margin, and involved by mucin pool at lateral resection margin
5) Lymphatic invasion: not identified
6) Venous invasion: not identified
7) Perineural invasion: not identified
8) Preexisting adenoma: not identified
Note) Epicenter of tumor is submucosa. A part of tumor extends to mucosa. Definite cancer cells are not identified in foveolar epithelium. Differential diagnosis includes gastric adenocarcinoma and metastatic adenocarcinoma. Further evaluation is recommended.

결국 수술을 했고, 임파선 전이나 위에 남아있는 조직은 없었습니다.

[2014-3-31. 이준행 의견]

내시경은 하면 할수록 어려워집니다. 그냥 평범한 SMT 중에 mucinous adenocarcinoma가 숨어있다는 것을 생각하면 오싹합니다. 그렇다고 모든 경우 ESD와 같은 적극적인 방법을 취할 수도 없고... 뚫어지게 살펴보고 적절히 추적관찰할 수 밖에 없을 것 같습니다. 적절히 추적관찰을 하면 큰 문제가 나기 전에 진단되는 예가 많을 것으로 믿습니다.

위장관 진단 EUS에 대해서는 저는 별로 좋은 경험이 없습니다. 가격은 둘째 문제로 치더라도, 개인적으로 도움받은 적이 별로 없습니다. 헷갈린 경우만 많았지요. 크게 손해본 환자 이야기도 종종 듣습니다. 그래서 저는 거의 처방하지 않습니다. 한달에 1-2개 정도 처방합니다. 좋은 증례 감사합니다.

© 일원내시경교실 바른내시경연구소 이준행. EndoTODAY Endoscopy Learning Center. Lee Jun Haeng.