Changing role of histopathology in the diagnosis and management of hepatocellular carcinoma

Table 1 Role of tumour tissue analysis in hepatocellular carcinoma

Diagnostic	Prognostic/theragnostic
Distinguishing HCC from metastasis	Prognostic histomorpholic parameters-tumour grade, vessel invasion, pTNM stage
Distinguishing benign/preneoplastic lesions from HCC	Identification of Histological variants of prognostic importance
Diagnosis confirmation of small HCC	Tissue biomarkers-for prognostication
Diagnosis of liver nodules in non-cirrhotic background	Tissue biomarkers-for assessing presence of therapeutic targets and drug development
Diagnosis of atypical variants of HCC, which have atypical Imaging findings	Histologic surrogates of clinically relevant molecular signatures-for predicting prognosis
Combined HCC-CC	Histologic surrogates of clinically relevant molecular signatures-as predictors of potential responders for targeted therapies
Diagnosis confirmation of HCC in phase III trials of new drugs

HCC: Hepatocellular carcinoma.

Table 2 Based on the evidence from published literature, algorithm based on the role of tissue diagnosis is inserted

Mandatory	Potentially necessary/helpful	Unwarranted
Lesion in a cirrhotic patient that lacks typical imaging characteristics	Well-differentiated HCC	HCC, if typical features are present on dynamic imaging technique
All nodules developing in the non-cirrhotic background	< 2 cm sized HCC, due to hypovascularity in small HCC and lack of typical imaging findings	AFP levels very high in the absence of other known causative tumours
Combined hepato-cholangiocarcinoma	Predictors of prognosis	Curative resection possible due to risk of needle tract seeding, if biopsied
Atypical variants of HCC	Teaching and biobanking
Identifying stem cell phenotypes	Distinguishing HCC from regenerative nodule, dysplastic nodule, hepatic adenoma, FNH
Phase III trials of novel drugs	Morphologic surrogates of molecular signatures
Tissue biomarker development and studies	Surrogate biomarkers of MVI in liver biopsy

HCC: Hepatocellular carcinoma; MVI: Micro vascular; AFP: α-fetoprotein.