膽囊肝樣腺癌的鏡下特征：相互交織移行的肝樣分化區和腺癌區_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

方會娟 ,  徐小艷

河南中醫藥大學第五臨床醫學院（鄭州人民醫院）病理科（鄭州 450053）;

Corresponding?author：

徐小艷, Email: xxy123com@sina.com

Keywords：

膽囊肝樣腺癌; 病理診斷; 治療; 預后

DOI：

10.7507/1007-9424.202312053

Video：

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目的總結膽囊肝樣腺癌（hepatoid adenocarcinoma，HAC）的臨床及病理學特點、鑒別診斷、治療、預后等情況。方法收集鄭州人民醫院收治的1例膽囊HAC患者的臨床表現、病理特征及治療和預后情況并復習國內外文獻。結果患者為一57歲男性。CT見膽囊占位；血清甲胎蛋白（alpha-fetoprotein，AFP）207.23 μg/L；術后組織病理學檢查結果顯示腫瘤由95%的實性片狀區域和5%的腺樣結構組成，實性片狀區域胞漿透亮或嗜堿性，胞核大、核仁明顯，核分裂象易見，部分區域血管豐富，可見腫瘤性壞死。免疫表型顯示實性片狀區域AFP、細胞角質蛋白19、熱休克蛋白70、谷氨酰胺合成酶、Glypican-3均彌漫陽性，Hepatocyte少量陽性；腺樣結構細胞角質蛋白19陽性。診斷膽囊HAC伴少量腺癌。術后隨訪21個月，患者死亡。復習文獻報道36例膽囊HAC（包括本例），男14例，女22例，男∶女約為1∶1.57；年齡38～80歲。腫瘤長徑1.1～12.0 cm。位于膽囊底6例、膽囊體8例、膽囊頸6例、底-頸或底-體2例。血清AFP正常9例，升高18例。免疫表型AFP、Glypican-3、Hepatocyte至少1項陽性。隨訪1～60個月，死亡11例，2例發生肝轉移。結論膽囊HAC是一種高度惡性腫瘤，治療以手術切除為主，預后差，該腫瘤形態學少見，鑒于其臨床表現、治療及預后有別于普通腺癌，其最終依賴于病理診斷，因此認識其形態學及免疫表型至關重要。

Citation： 方會娟, 徐小艷. 膽囊肝樣腺癌的鏡下特征：相互交織移行的肝樣分化區和腺癌區. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2024, 31(4): 474-478. doi: 10.7507/1007-9424.202312053 Copy

1.	Watanabe M, Hori Y, Nojima T, et al. Alpha-fetoprotein-producing carcinoma of the gallbladder. Dig Dis Sci, 1993, 38(3): 561-564.
2.	Vardaman C, Albores-Saavedra J. Clear cell carcinomas of the gallbladder and extrahepatic bile ducts. Am J Surg Pathol, 1995, 19(1): 91-99.
3.	李樹慶, 鐘延豐, 廖松林. 膽囊肝樣腺癌一例. 中華病理學雜志, 1999, 28(5): 399.
4.	Nakashima H, Nagafuchi K, Satoh H, et al. Hepatoid adenocarcinoma of the gallbladder. J Hepatobiliary Pancreat Surg, 2000, 7(2): 226-230.
5.	Sakamoto K, Kimura N, Tokumura H, et al. Hepatoid adenocarcinoma of the gallbladder. Histopathology, 2005, 47(6): 649-651.
6.	van den Bos IC, Hussain SM, Dwarkasing RS, et al. Hepatoid adenocarcinoma of the gallbladder: a mimicker of hepatocellular carcinoma. Br J Radiol, 2007, 80(960): e317-e320. doi: 10.1259/bjr/97773297.
7.	Gakiopoulou H, Givalos N, Liapis G, et al. Hepatoid adenocarcinoma of the gallbladder. Dig Dis Sci, 2007, 52(12): 3358-3362.
8.	Koswara T, Marwoto W, Siregar NC, et al. Hepatoid carcinoma of the gallbladder. Acta Med Indones, 2007, 39(4): 179-182.
9.	林敏, 葉欽, 陳健, 等. 膽囊肝樣腺癌一例. 中華醫學雜志, 2008, 88(1): 69-70.
10.	Sakamoto K, Monobe Y, Kouno M, et al. Hepatoid adenocarcinoma of the gallbladder: Case report and review of the literature. Pathol Int, 2004, 54(1): 52-56.
11.	Ellouze S, Slim C, Ahmad G, et al. Hepatoid adenocarcinoma of the gallbladder. World J Surg Oncol, 2011, 9: 103. doi: 10.1186/1477-7819-9-103.
12.	Karayiannakis AJ, Kakolyris S, Giatromanolaki A, et al. Hepatoid adenocarcinoma of the gallbladder : case report and literature review. J Gastrointest Cancer, 2012, 43 Suppl 1: S139-S144. doi: 10.1007/s12029-011-9326-5.
13.	Lee JH, Lee KG, Paik SS, et al. Hepatoid adenocarcinoma of the gallbladder with production of alpha-fetoprotein. J Korean Surg Soc, 2011, 80(6): 440-444.
14.	楊岳, 孫冬林, 鄒巖, 等. 膽囊肝樣腺癌合并甲胎蛋白升高一例. 中華肝膽外科雜志, 2014, 20(9): 643, 669.
15.	李揚, 劉志艷, 劉新農, 等. 膽囊肝樣腺癌伴肝臟、網膜多發轉移一例. 中華肝膽外科雜志, 2015, 21(4): 247, 252.
16.	Devi NR, Sathyalakshmi R, Devi J, et al. Hepatoid adenocarcinoma of the gall bladder—A rare variant. J Clin Diagn Res, 2015, 9(8): ED09-ED10. doi: 10.7860/JCDR/2015/10799.6324.
17.	狄純嬋, 周平. 膽囊肝樣腺癌并淋巴結轉移一例. 中華病理學雜志, 2016, 45(2): 125-126.
18.	張鵬, 王禹, 廖佳樺, 等. 膽囊肝樣腺癌行膽囊癌根治術1例. 癌癥進展, 2017, 15(12): 1493-1494.
19.	司友嬌, 趙凱凱, 黃九寧, 等. 膽囊肝樣腺癌1例. 中國醫學影像技術, 2017, 33(9): 1440.
20.	Yoshioka S, Ishida M, Okano K, et al. Cytological features of hepatoid adenocarcinoma of the gallbladder: A case report with immunocytochemical analyzes. Diagn Cytopathol, 2018, 46(8): 711-715.
21.	Qian X, Zhou D, Gao B, et al. An alpha-fetoprotein-negative hepatoid adenocarcinoma of the gallbladder with squamous differentiation. Hepatobiliary Surg Nutr, 2020, 9(1): 116-118.
22.	陳佳菁, 林慧, 陳婷婷, 等. 膽囊肝樣腺癌1例. 診斷病理學雜志, 2020, 27(5): 359-360.
23.	吳嫣, 周先榮, 袁靜萍, 等. 肺、膽囊、膀胱原發肝樣腺癌三例臨床病理學觀察. 中華病理學雜志, 2021, 50(2): 137-139.
24.	張娟, 馮亞園, 霍雷, 等. 膽囊肝樣腺癌的臨床影像病理分析. 中華消化病與影像雜志(電子版), 2022, 12(4): 210-214.
25.	Li Z, Jiang Q, Chen X, et al. Primary hepatoid adenocarcinoma of gallbladder with MB21D2/GALNT12/ARID2 mutations: a case report. Front Endocrinol (Lausanne), 2022, 12: 791153. doi: 10.3389/fendo.2021.791153.
26.	Iwasaki S, Hidaka H, Uojima H, et al. A case of successful treatment with lenvatinib in primary hepatoid adenocarcinoma of the gallbladder that was difficult to distinguish from hepatocellular carcinoma. Clin J Gastroenterol, 2022, 15(6): 1108-1114.
27.	李巧轉, 周志華, 王倩, 等. 膽囊肝樣腺癌4例臨床病理分析. 武警醫學, 2023, 34(1): 54-57.
28.	王鶴霖, 戴朝六. 膽囊肝樣腺癌的診斷與治療現狀. 中華消化外科雜志, 2017, 16(11): 1163-1166.
29.	Metzgeroth G, Str?bel P, Baumbusch T, et al. Hepatoid adenocarcinoma—review of the literature illustrated by a rare case originating in the peritoneal cavity. Onkologie, 2010, 33(5): 263-269.

1. Watanabe M, Hori Y, Nojima T, et al. Alpha-fetoprotein-producing carcinoma of the gallbladder. Dig Dis Sci, 1993, 38(3): 561-564.
2. Vardaman C, Albores-Saavedra J. Clear cell carcinomas of the gallbladder and extrahepatic bile ducts. Am J Surg Pathol, 1995, 19(1): 91-99.
3. 李樹慶, 鐘延豐, 廖松林. 膽囊肝樣腺癌一例. 中華病理學雜志, 1999, 28(5): 399.
4. Nakashima H, Nagafuchi K, Satoh H, et al. Hepatoid adenocarcinoma of the gallbladder. J Hepatobiliary Pancreat Surg, 2000, 7(2): 226-230.
5. Sakamoto K, Kimura N, Tokumura H, et al. Hepatoid adenocarcinoma of the gallbladder. Histopathology, 2005, 47(6): 649-651.
6. van den Bos IC, Hussain SM, Dwarkasing RS, et al. Hepatoid adenocarcinoma of the gallbladder: a mimicker of hepatocellular carcinoma. Br J Radiol, 2007, 80(960): e317-e320. doi: 10.1259/bjr/97773297.
7. Gakiopoulou H, Givalos N, Liapis G, et al. Hepatoid adenocarcinoma of the gallbladder. Dig Dis Sci, 2007, 52(12): 3358-3362.
8. Koswara T, Marwoto W, Siregar NC, et al. Hepatoid carcinoma of the gallbladder. Acta Med Indones, 2007, 39(4): 179-182.
9. 林敏, 葉欽, 陳健, 等. 膽囊肝樣腺癌一例. 中華醫學雜志, 2008, 88(1): 69-70.
10. Sakamoto K, Monobe Y, Kouno M, et al. Hepatoid adenocarcinoma of the gallbladder: Case report and review of the literature. Pathol Int, 2004, 54(1): 52-56.
11. Ellouze S, Slim C, Ahmad G, et al. Hepatoid adenocarcinoma of the gallbladder. World J Surg Oncol, 2011, 9: 103. doi: 10.1186/1477-7819-9-103.
12. Karayiannakis AJ, Kakolyris S, Giatromanolaki A, et al. Hepatoid adenocarcinoma of the gallbladder : case report and literature review. J Gastrointest Cancer, 2012, 43 Suppl 1: S139-S144. doi: 10.1007/s12029-011-9326-5.
13. Lee JH, Lee KG, Paik SS, et al. Hepatoid adenocarcinoma of the gallbladder with production of alpha-fetoprotein. J Korean Surg Soc, 2011, 80(6): 440-444.
14. 楊岳, 孫冬林, 鄒巖, 等. 膽囊肝樣腺癌合并甲胎蛋白升高一例. 中華肝膽外科雜志, 2014, 20(9): 643, 669.
15. 李揚, 劉志艷, 劉新農, 等. 膽囊肝樣腺癌伴肝臟、網膜多發轉移一例. 中華肝膽外科雜志, 2015, 21(4): 247, 252.
16. Devi NR, Sathyalakshmi R, Devi J, et al. Hepatoid adenocarcinoma of the gall bladder—A rare variant. J Clin Diagn Res, 2015, 9(8): ED09-ED10. doi: 10.7860/JCDR/2015/10799.6324.
17. 狄純嬋, 周平. 膽囊肝樣腺癌并淋巴結轉移一例. 中華病理學雜志, 2016, 45(2): 125-126.
18. 張鵬, 王禹, 廖佳樺, 等. 膽囊肝樣腺癌行膽囊癌根治術1例. 癌癥進展, 2017, 15(12): 1493-1494.
19. 司友嬌, 趙凱凱, 黃九寧, 等. 膽囊肝樣腺癌1例. 中國醫學影像技術, 2017, 33(9): 1440.
20. Yoshioka S, Ishida M, Okano K, et al. Cytological features of hepatoid adenocarcinoma of the gallbladder: A case report with immunocytochemical analyzes. Diagn Cytopathol, 2018, 46(8): 711-715.
21. Qian X, Zhou D, Gao B, et al. An alpha-fetoprotein-negative hepatoid adenocarcinoma of the gallbladder with squamous differentiation. Hepatobiliary Surg Nutr, 2020, 9(1): 116-118.
22. 陳佳菁, 林慧, 陳婷婷, 等. 膽囊肝樣腺癌1例. 診斷病理學雜志, 2020, 27(5): 359-360.
23. 吳嫣, 周先榮, 袁靜萍, 等. 肺、膽囊、膀胱原發肝樣腺癌三例臨床病理學觀察. 中華病理學雜志, 2021, 50(2): 137-139.
24. 張娟, 馮亞園, 霍雷, 等. 膽囊肝樣腺癌的臨床影像病理分析. 中華消化病與影像雜志(電子版), 2022, 12(4): 210-214.
25. Li Z, Jiang Q, Chen X, et al. Primary hepatoid adenocarcinoma of gallbladder with MB21D2/GALNT12/ARID2 mutations: a case report. Front Endocrinol (Lausanne), 2022, 12: 791153. doi: 10.3389/fendo.2021.791153.
26. Iwasaki S, Hidaka H, Uojima H, et al. A case of successful treatment with lenvatinib in primary hepatoid adenocarcinoma of the gallbladder that was difficult to distinguish from hepatocellular carcinoma. Clin J Gastroenterol, 2022, 15(6): 1108-1114.
27. 李巧轉, 周志華, 王倩, 等. 膽囊肝樣腺癌4例臨床病理分析. 武警醫學, 2023, 34(1): 54-57.
28. 王鶴霖, 戴朝六. 膽囊肝樣腺癌的診斷與治療現狀. 中華消化外科雜志, 2017, 16(11): 1163-1166.
29. Metzgeroth G, Str?bel P, Baumbusch T, et al. Hepatoid adenocarcinoma—review of the literature illustrated by a rare case originating in the peritoneal cavity. Onkologie, 2010, 33(5): 263-269.

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膽囊肝樣腺癌的鏡下特征：相互交織移行的肝樣分化區和腺癌區

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