Preoperative assessment of hepatocellular carcinoma tumor grade using needle biopsy: implications for transplant eligibility

Abstract

Objective: To examine the diagnostic agreement of preoperative needle core biopsy (NCB) grading of hepatocellular carcinoma (HCC) compared with the final surgical pathologic tumor grade.

Summary background data: Some centers have adopted protocols for selecting patients with HCC for transplantation based on tumor grade as determined by preoperative NCB. The validity of NCB to predict final tumor grade has not been previously assessed.

Methods: A total of 211 patients who underwent hepatic resection, open radiofrequency, or transplantation for HCC between 1998 and 2004 were identified. Clinicopathologic, NCB, and surgical data were collected and analyzed using chi and kappa statistics.

Results: A total of 120 (67.4%) of the 178 who underwent resection or transplantation had an NCB. On preoperative NCB, the majority of HCC cases were classified as well-differentiated (n = 35; 37.6%) or moderately differentiated (n = 44; 47.3%), while 14 (15.1%) cases were categorized as poorly differentiated. In contrast, when tumor grading was based on the final surgical specimen, there was a significantly higher proportion of HCC cases graded as poorly differentiated (well-differentiated, n = 34; 36.6%; moderately differentiated, n = 33; 35.5%; poorly differentiated, n = 26; 27.9%) (P < 0.05). The overall percent agreement of NCB and surgical pathology to determine tumor grade was poor (kappa = 0.18, P < 0.0001). Whereas final pathologic tumor grade predicted the presence of microscopic vascular invasion (well, 15.7%; moderate; 31.9%, poor; 58.4%; P = 0.001), NCB grade did not (well, 23.7%; moderate, 28.0%; poor, 25.4%; P = 0.65).

Conclusions: Selection of candidates for transplantation based on NCB tumor grade may be misleading, as NCB tumor grade often did not correlate with grade or presence of microscopic vascular invasion on final pathology. Clinicomorphologic criteria (tumor size, number) should remain the major determinants of eligibility for transplantation.

FIGURE 1. Tumor grade was scored using the modified Edmonson and Steiner nuclear grading scheme in which grades 1 and 2 were defined as well-differentiated, grade 3 as moderately differentiated, and grade 4 as poorly differentiated.

FIGURE 2. ROC curve analysis displaying the limited ability of NCB to discriminate poor tumor grade on the final surgical specimen (AUC = 0.74).

FIGURE 3. Although preoperative NCB tumor grade was not associated with microscopic vascular invasion, tumor grade on the final surgical specimen was significantly associated with the presence of microscopic vascular. *P = 0.001.

FIGURE 4. Tumor grade in HCC can be heterogeneous. A, A portion of tumor is well-differentiated while an adjacent area, which contains markedly enlarged oncocytic hepatocytes with some nuclear pleomorphism and angulation, is moderately differentiated. B, In this example, an area of moderate differentiation is adjacent to an area of poor differentiation.