Liver & intrahepatic bile ducts
Hepatocellular carcinoma
Macrotrabecular massive
Editorial Board Member: Raul S. Gonzalez, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 10 October 2019
Minor changes: 25 December 2020
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PubMed Search: Macrotrabecular Hepatocellular Carcinoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology | Diagnosis | Laboratory | Prognostic factors | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Xia R, Zhang X. Macrotrabecular massive. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/macrotrabecularhepatocellularcarcinoma.html. Accessed January 17th, 2021.
Definition / general
- Subtype of hepatocellular carcinoma with macrotrabecular pattern (≥ 6 - 10 cells thick) (IARC: Digestive System Tumours, 5th Edition, 2019, Am J Surg Pathol 2019;43:943, Hepatology 2018;68:103)
- Macrotrabecular pattern > 50% of the tumor (IARC: Digestive System Tumours, 5th Edition, 2019)
Essential features
- Hepatocellular carcinoma with > 50% growth of macrotrabecular pattern (≥ 6 - 10 cells thick) (IARC: Digestive System Tumours, 5th Edition, 2019, Am J Surg Pathol 2019;43:943, Hepatology 2018;68:103)
- Present with higher grade and stage compared to conventional hepatocellular carcinoma (Am J Surg Pathol 2019;43:943)
- Associated with high serum AFP (Am J Surg Pathol 2019;43:943, Hepatology 2018;68:103)
- Poor prognosis with early recurrence and poor overall survival (Hepatology 2018;68:103, J Hepatol 2017;67:727)
- Vascular invasion common (J Hepatol 2017;67:727)
- Associated with TP53 mutations and FGF19 amplification (J Hepatol 2017;67:727)
Terminology
- Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC)
- Macrotrabecular hepatocellular carcinoma (MT-HCC)
ICD coding
- ICD-O: 8170/3 - Hepatocellular carcinoma
- ICD-11: 2C12 - H00048 - Hepatocellular carcinoma
Epidemiology
- Relative frequency: 5% (1.7% - 12%) (Am J Surg Pathol 2019;43:943, Hepatology 2018;68:103)
- Male predominant (71 - 79%)
Sites
- Liver
Etiology
- HBV infection, HCV infection, alcohol intake, nonalcoholic steatohepatitis (NASH) or other / undetermined etiologies (Am J Surg Pathol 2019;43:943, Hepatology 2018;68:103)
Diagnosis
- Based on light microscopic examination of tissue with compatible histomorphology findings (hepatocellular carcinoma with > 50% growth of macrotrabecular pattern (≥ 6 - 10 cells thick))
Laboratory
- Serum AFP level (> 100 ng/mL) is elevated in 40 - 73% patients (Am J Surg Pathol 2019;43:943, Hepatology 2018;68:103)
Prognostic factors
- Worse prognosis with larger tumor size, macrovascular invasion, microvascular invasion, poor differentiation; these are frequent findings (Hepatology 2018;68:103, J Hepatol 2017;67:727)
- High tumor stage compared to conventional hepatocellular carcinoma
- High early recurrence, overall recurrence and poor recurrence free and overall survival (Hepatology 2018;68:103, Am J Surg Pathol 2019;43:943, J Hepatol 2017;67:727)
Treatment
- Surgical resection
- Radiofrequency ablation
- Transarterial chemoembolization (TACE)
- Transplantation
Gross description
- Large tumor size (66% > 50 mm) with satellite nodules or macrovascular invasion (Hepatology 2018;68:103, J Hepatol 2017;67:727)
- Background liver with or without cirrhosis
Microscopic (histologic) description
- Hepatocellular carcinoma with > 50% growth of macrotrabecular pattern (≥ 6 - 10 cells thick) (IARC: Digestive System Tumours, 5th Edition, 2019, Am J Surg Pathol 2019;43:943, Hepatology 2018;68:103)
- Trabeculae observed in cross sections are bordered by a complete rim of CD34 positive endothelial cells in more than half of the tumor area (vessels encapsulating tumor clusters (VETC)) (Hepatology 2019 Jun 17 [Epub ahead of print])
- Associated with micro and macrovascular invasion (> 60%) (Am J Surg Pathol 2019;43:943, J Hepatol 2017;67:727)
- Associated with higher tumor cell grade and presence of anaplastic tumor cells (Am J Surg Pathol 2019;43:943)
Microscopic (histologic) images
Contributed by Xuchen Zhang, M.D., Ph.D.
Macrotrabeculae with anaplastic cells
Macrotrabecular pattern
Macrotrabecular pattern
Macrotrabeculae with cytologic atypia
Positive stains
- Same as markers for conventional hepatocellular carcinoma (variably positive): hepatocytic differentiation markers (HepPar1, arginase1, polyclonal CEA and CD10 in canalicular pattern, AFP and albumin mRNA ISH), cytokeratin CAM 5.2 and malignant markers (glypican 3, glutamine synthetase and p53)
- Endothelial specific molecule 1 (ESM1) stains the sinusoidal stromal cells forming nearly a continuous positive surrounding of macrotrabeculae (Clin Cancer Res. 2019 Jul 29 [Epub ahead of print])
Negative stains
- CK7, CK19, mucin (mucicarmine), MOC31 and BerEP4
Molecular / cytogenetics description
- Often harbor TP53 mutations or FGF19 amplifications (J Hepatol 2017;67:727)
- Positive for albumin mRNA ISH
Sample pathology report
- Liver, segment 5, mass, biopsy:
- Hepatocellular carcinoma, poorly differentiated, with macrotrabecular pattern (see comment)
- Comment: Histologic sections show thickened cords are composed of polygonal tumor cells with distinct cell membranes, eosinophilic cytoplasm, high N/C ratio, prominent nucleoli, conspicuous mitoses and necrosis. The thickened cords contain more than 6 - 10 cells thick tumor cells consistent with macrotrabecular pattern. This pattern of hepatocellular carcinoma has been recently categorized as macrotrabecular massive subtype.
- Liver, right lobe, right hepatectomy:
- Poorly differentiated hepatocellular carcinoma, macrotrabecular massive subtype (see comment and synoptic report)
- Nonneoplastic background liver with chronic hepatitis B and portal fibrosis (grade 1 of 4, stage 1 of 4)
- Comment: The current hepatocellular carcinoma shows mixed histologic growth pattern with acinar, trabecular and macrotrabecular patterns. The tumor cells in the macrotrabeculae (≥ 6 - 10 cells thick) show marked nuclear pleomorphism with numerous mitoses and prominent nucleoli. Anaplastic giant tumor cells are present. Immunohistochemical stains show that the tumor cells are positive for arginase1, HepPar1 and focally positive for glypican 3. Peritumoral microvascular invasion is present. Also noted grossly is that there is a tumor thrombus in one of the portal vein branches and this is confirmed microscopically.
Differential diagnosis
- Trabecular hepatocellular carcinoma: hepatocellular carcinoma with trabecular growth pattern of < 6 cells thick
Board review style question #1
- Which of the following hepatocellular carcinoma subtypes is associated with worse
prognosis?
- Clear cell subtype
- Macrotrabecuar massive subtype
- Fibrolamellar
- Lymphocyte rich
- Steatohepatitic
Board review style answer #1
B. Macrotrabecuar massive subtype
Reference: Macrotrabecular massive hepatocellular carcinoma
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Reference: Macrotrabecular massive hepatocellular carcinoma
Comment Here
Board review style question #2
- Which of the following molecular features is associated with macrotrabecular massive
hepatocellular carcinoma?
- TP53 mutation or FGF19 amplification
- CTNNB1 mutations
- RB1 mutation
- Chromosomal alteration
- TERT promoters mutation
Board review style answer #2
A. TP53 mutation or FGF19 amplification
Reference: Macrotrabecular massive hepatocellular carcinoma
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Reference: Macrotrabecular massive hepatocellular carcinoma
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