Proliferações biliares intra-hepáticas: histopatologia e potenciais marcadores imuno-histoquímicos

HIRAYAMA, André Bubna; MELLO, Evandro Sobroza de; ALVES, Venâncio Avancini Ferreira

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Brasil

Arquivos de Gastroenterologia

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Brasil

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Sumário

REVIEW • Arq. Gastroenterol. 60 (3) • Jul-Sep 2023 • https://doi.org/10.1590/S0004-2803.23032023-107 copiar

Proliferações biliares intra-hepáticas: histopatologia e potenciais marcadores imuno-histoquímicos

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

As proliferações biliares intra-hepáticas representam um espectro que abrange desde entidades reativas (reação ductular, algumas com arquitetura atípica), hamartomatosas (complexo de von Meyenburg), benignas (adenoma de ductos biliares) e precursoras/limítrofes (neoplasia intraepitelial biliar, neoplasia papilar intraductal de ducto biliar) até neoplasias totalmente malignas (colangiocarcinoma). Os quadros clínicos e até mesmo os padrões de imagem podem ser semelhantes, exigindo estudos refinados visando critério histológicos e imuno-histoquímicos para diagnósticos mais precisos, essenciais para o correto manejo do paciente. Este artigo discute conceitos atualizados e definições das entidades mais relevantes visando mais especificamente ao diagnóstico diferencial na prática, com foco na morfologia e imuno-histoquímica, com discussão de potenciais marcadores para ajudar na distinção entre lesões benignas e malignas.

Palavras-chave:
Neoplasia; vias biliares; cholangiocarcinoma

	Ductular reaction	Bile duct adenoma	Intrahepatic cholangiocarcinoma, small-duct subtype
p16⁶⁶66. Sasaki M, Matsubara T, Kakuda Y, Sato Y, Nakanuma Y. Immunostaining for polycomb group protein EZH2 and senescent marker p16INK4a may be useful to differentiate cholangiolocellular carcinoma from ductular reaction and bile duct adenoma. Am J Surg Pathol . 2014;38:364-9. doi:10.1097/PAS.0000000000000125. https://doi.org/10.1097/PAS.000000000000...	+	+	-
CD56/N-CAM⁶⁷67. Gütgemann I, Haas S, Berg JP, Zhou H, Büttner R, Fischer HP. CD56 expression aids in the differential diagnosis of cholangiocarcinomas and benign cholangiocellular lesions. Virchows Arch. 2006;448:407-11. doi:10.1007/s00428-005-0145-6. https://doi.org/10.1007/s00428-005-0145-...	+	+	+
EZH2⁶⁶66. Sasaki M, Matsubara T, Kakuda Y, Sato Y, Nakanuma Y. Immunostaining for polycomb group protein EZH2 and senescent marker p16INK4a may be useful to differentiate cholangiolocellular carcinoma from ductular reaction and bile duct adenoma. Am J Surg Pathol . 2014;38:364-9. doi:10.1097/PAS.0000000000000125. https://doi.org/10.1097/PAS.000000000000...	-	-	+
p53⁵⁰50. Bickenbach K, Galka E, Roggin KK. Molecular mechanisms of cholangiocarcinogenesis: are biliary intraepithelial neoplasia and intraductal papillary neoplasms of the bile duct precursors to cholangiocarcinoma?. Surg Oncol Clin N Am . 2009;18:215-vii. doi:10.1016/j.soc.2008.12.001. https://doi.org/10.1016/j.soc.2008.12.00... ^,⁶³63. Lee KB. Histopathology of a benign bile duct lesion in the liver: Morphologic mimicker or precursor of intrahepatic cholangiocarcinoma. Clin Mol Hepatol. 2016;22:400-5. doi:10.3350/cmh.2016.0105. https://doi.org/10.3350/cmh.2016.0105...	-	-	+
BCL2⁶⁵65. Bertram S, Padden J, Kälsch J, Ahrens M, Pott L, Canbay A, et al. Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions. J Clin Pathol. 2016;69:619-26. doi: 10.1136/jclinpath-2015-203418. https://doi.org/10.1136/jclinpath-2015-2...	+	+	- (or faintly positive)
HSP27⁶⁵65. Bertram S, Padden J, Kälsch J, Ahrens M, Pott L, Canbay A, et al. Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions. J Clin Pathol. 2016;69:619-26. doi: 10.1136/jclinpath-2015-203418. https://doi.org/10.1136/jclinpath-2015-2...	-	+ (weak)	+ (strong)
HSP70⁶⁵65. Bertram S, Padden J, Kälsch J, Ahrens M, Pott L, Canbay A, et al. Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions. J Clin Pathol. 2016;69:619-26. doi: 10.1136/jclinpath-2015-203418. https://doi.org/10.1136/jclinpath-2015-2...	-	+ (weak)	+ (strong)
STIP1⁶⁵65. Bertram S, Padden J, Kälsch J, Ahrens M, Pott L, Canbay A, et al. Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions. J Clin Pathol. 2016;69:619-26. doi: 10.1136/jclinpath-2015-203418. https://doi.org/10.1136/jclinpath-2015-2...	-	+	+
SerpinH1⁶⁵65. Bertram S, Padden J, Kälsch J, Ahrens M, Pott L, Canbay A, et al. Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions. J Clin Pathol. 2016;69:619-26. doi: 10.1136/jclinpath-2015-203418. https://doi.org/10.1136/jclinpath-2015-2...	-	-	+
14-3-3Sigma⁶⁵65. Bertram S, Padden J, Kälsch J, Ahrens M, Pott L, Canbay A, et al. Novel immunohistochemical markers differentiate intrahepatic cholangiocarcinoma from benign bile duct lesions. J Clin Pathol. 2016;69:619-26. doi: 10.1136/jclinpath-2015-203418. https://doi.org/10.1136/jclinpath-2015-2...	-	+	+
Ki67 ¹1. WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France): International Agency for Research on Cancer; 2019. (WHO classification of tumours series, 5th ed.; vol. 1).^,⁶⁹69. Sasaki M, Sato Y, Nakanuma Y. Bile duct adenoma and small-sized small duct type intrahepatic cholangiocarcinoma show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components. Histopathology. 2023;83:298-309. doi: 10.1111/his.14932. https://doi.org/10.1111/his.14932... ^,⁷²72. Tsokos CG, Krings G, Yilmaz F, Ferrell LD, Gill RM. Proliferative index facilitates distinction between benign biliary lesions and intrahepatic cholangiocarcinoma. Hum Pathol. 2016;57:61-7. doi:10.1016/j.humpath.2016.06.019. https://doi.org/10.1016/j.humpath.2016.0...	low	low	high (usually higher than 10%)

	Small duct cholangiocarcinoma	Large duct cholangiocarcinoma
C reative protein²2. Chung T, Park YN. Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma. Front Med (Lausanne). 2022;9:857140. doi:10.3389/fmed.2022.857140. https://doi.org/10.3389/fmed.2022.857140... ^,⁷⁵75. Lin F, Shi J, Wang HL, Ma XJ, Monroe R, Luo Y, et al. Detection of Albumin Expression by RNA In Situ Hybridization Is a Sensitive and Specific Method for Identification of Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas. Am J Clin Pathol . 2018;150:58-64. doi: 10.1093/ajcp/aqy030. PMID: 29746696. https://doi.org/10.1093/ajcp/aqy030. PMI...	+ (especially if a cholangiolocellular component is present)	-
Fibrinopeptide B⁷⁵75. Lin F, Shi J, Wang HL, Ma XJ, Monroe R, Luo Y, et al. Detection of Albumin Expression by RNA In Situ Hybridization Is a Sensitive and Specific Method for Identification of Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas. Am J Clin Pathol . 2018;150:58-64. doi: 10.1093/ajcp/aqy030. PMID: 29746696. https://doi.org/10.1093/ajcp/aqy030. PMI...	+ (especially if a cholangiolocellular component is present)	-
pVHL⁷⁶76. Lok T, Chen L, Lin F, Wang HL. Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol . 2014;45:394-400. doi:10.1016/j.humpath.2013.10.004. https://doi.org/10.1016/j.humpath.2013.1...	+++	-
S100p⁷⁶76. Lok T, Chen L, Lin F, Wang HL. Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol . 2014;45:394-400. doi:10.1016/j.humpath.2013.10.004. https://doi.org/10.1016/j.humpath.2013.1...	+/-	+++
Maspin⁷⁶76. Lok T, Chen L, Lin F, Wang HL. Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol . 2014;45:394-400. doi:10.1016/j.humpath.2013.10.004. https://doi.org/10.1016/j.humpath.2013.1...	+/-	+++
MUC5AC⁷⁶76. Lok T, Chen L, Lin F, Wang HL. Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol . 2014;45:394-400. doi:10.1016/j.humpath.2013.10.004. https://doi.org/10.1016/j.humpath.2013.1...	+/-	+++
K17⁷⁶76. Lok T, Chen L, Lin F, Wang HL. Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol . 2014;45:394-400. doi:10.1016/j.humpath.2013.10.004. https://doi.org/10.1016/j.humpath.2013.1...	+/-	+++
CD56/N-CAM²2. Chung T, Park YN. Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma. Front Med (Lausanne). 2022;9:857140. doi:10.3389/fmed.2022.857140. https://doi.org/10.3389/fmed.2022.857140...	+	-

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[1] Corresponding author: André Bubna Hirayama. E-mail: a.hirayama@hc.fm.usp.br