Macrotrabecular-Massive Hepatocellular Carcinoma: Light and Shadow in Current Knowledge

Anna Sessa,1– 3 Sébastien Mulé,2– 4 Raffaele Brustia,2,3,5 Hélène Regnault,1,3 Athena Galletto Pregliasco,4 Rami Rhaiem,6,7 Vincent Leroy,1– 3 Daniele Sommacale,2,3,5 Alain Luciani,2– 4 Julien Calderaro,2,3,8 Giuliana Amaddeo1– 3 1Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France; 2Université Paris-Est Créteil, Faculté de Médecine, Créteil, France; 3Inserm, U955, Team 18, Créteil, France; 4Medical Imaging Department, AP-HP, Henri Mondor University Hospital, Créteil, France; 5Department of Digestive and Hepato-Pancreato-Biliary Surgery, AP-HP, Henri Mondor University Hospital, Créteil, France; 6Department of Hepato-Biliary Pancreatic and Digestive Oncological Surgery, Robert Debré University Hospital, Reims, France; 7Reims Champagne-Ardenne University, Reims, France; 8Department of Pathology, APHP, Henri Mondor University Hospital, Créteil, FranceCorrespondence: Giuliana Amaddeo; Anna Sessa, Hepatology Department, APHP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, Créteil, 94000, France, Tel +33 149812353, Email giuliana.amaddeo@aphp.fr; asessa1990@gmail.comAbstract: The subject of this narrative review is macrotrabecular-massive hepatocellular carcinoma (MTM‐HCC). Despite their rarity, these tumours are of general interest because of their epidemiological and clinical features and for representing a distinct model of the interaction between the angiogenetic system and neoplastic cells. The MTM‐HCC subtype is associated with various adverse biological and pathological parameters (the Alfa-foetoprotein (AFP) serum level, tumour size, vascular invasion, and satellite nodules) and is a key determinant of patient prognosis, with a strong and independent predictive value for early and overall tumour recurrence. Gene expression profiling has demonstrated that angiogenesis activation is a hallmark feature of MTM-HCC, with overexpression of both angiopoietin 2 (ANGPT2) and vascular endothelial growth factor A (VEGFA).Keywords: hepatocellular carcinoma, macrotrabecular, angiopoietin 2 inhibitors, TP53, immunotherap