3.1 General information
The characteristics of 112 patients are shown in Table 1. The study participants include more number of women (66/112). The mean age of patients was 40.4 years (range: 18–74 years). Three women had a history of oral contraceptives. Seven patients had a chronic disease, 1 HAML patient with renal AML, and 1 NRH patient with portal hypertension. Forty-one patients showed clinical symptoms, the most common of which were abdominal pain and distension (35/41). The tumor volume increased significantly in two patients during follow-up, abdominal distension accompanied by nausea and vomiting in two patients, abdominal distension accompanied by decreased appetite in 1 patient, and mental tension in 1 patient. The longest duration of symptoms was more than 5 years.
We did not observe abnormality in routine blood tests and coagulation functions in all patients. Liver function was classified as Child-Pugh A for 110 cases, and Child-Pugh B for 2 patients. There were 14 patients with abnormal tumor markers, including 8 patients with abnormal AFP elevation (range: 7.53–15.09 ng/mL, normal: 0–7 ng/mL) and 6 patients with abnormal CA 19-9 elevation (range: 27.21–76.03 U/mL, normal: 0–27 U/mL), all of which were slightly elevated. Seventeen patients were positive for HBsAg.
3.2 Imaging examinations
Computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations were performed in all patients. There were 103 cases of a single tumor, 8 cases with two tumors, and 1 case with three tumors. The distribution of tumor was as follows: left lobe (n = 41), right lobe (n = 59), caudate lobe (n = 6), left and right lobes (n = 6). The tumor diameter ranged from 1.3 to 21.3 cm, with an average of 5.3 ± 3.7 cm. Among the 112 patients, 77 patients underwent CT examination, 77 patients underwent MRI examination (including 26 Gd-EOB-DTPA MRI), and 32 patients underwent two imaging examinations.
The diagnostic accuracies of CT and MRI were 32.5% and 44.2%, respectively (Table 2). The diagnostic accuracy of HCA (CT: 0%, MRI: 11.1%) and other rare benign tumors (CT: 0%, MRI: 12.5%) was low, FNH (CT: 44.7%, MRI: 58.1%) and HAML (CT: 40%, MRI: 41.2%) was also not high; however, Gd-EOB-DTPA MRI showed a 76.9% (20/26) diagnostic accuracy. We found that rare benign liver tumors in this group were most likely to be misdiagnosed as HCC (CT: 16/25, MRI: 16/24). Most of the cases with the unclear diagnosis were difficult to distinguish from HCC (CT: 12/27, MRI: 10/19), especially from well-differentiated HCC. In addition, certain FNH and HCA lesions were indistinguishable.
We analyzed the CT and MRI features of 58 FNHs and 28 HAMLs (Tables 3 and 4). Although certain tumors had characteristic imaging findings (central scar shadow in FNH, intratumoral dysmorphic vascular, and early venous drainage in HAML), most tumors displayed a wide spectrum of imaging findings, especially in the arterial enhancement phase and portal vein phase. The diversity of imaging findings undoubtedly made the diagnosis difficult.
3.3 Surgical methods and results
Before surgery, different treatment options were discussed with the patient and informed consent was obtained. All patients underwent surgical treatment, including laparoscopic hepatectomy in 44 cases and open hepatectomy in 68 cases. There were 97 cases of minor hepatectomy and 15 cases of major hepatectomy. The type of resection include wedge resections (n = 59),bisegmentectomy (n = 7),segmentomy (n = 35),and hemihepatectomy (n = 11). The mean operation time was 180 min (range: 50–385 min) and the mean intraoperative blood loss was 200 mL (range: 50–2000 mL), nine patients received intraoperative blood transfusion (range: 2–8 U red blood cells [RBCs]).
There were 28 postoperative complications including pleural effusion (n = 16), pulmonary infection (n = 4), intraoperative effusion (n = 2), fever (n = 2), biliary leakage (n = 1), incision infection (n = 1), acute renal failure (n = 1), and pleural effusion with pulmonary infection (n = 1). Most of the complications were Grade I-II, and 3 cases were Grade Ⅲ. Patients with postoperative complications recovered and were discharged from the hospital after positive symptomatic treatment. No mortality or second operation was reported.
3.4 Histopathological and immunohistochemical characteristics
All 112 surgical specimens underwent pathological examination, 91 of whom underwent immunohistochemical examination (Table 5 shows the antibody expression of FNH, HCA, and HAML).
Most tumor types showed typical pathological and immunohistochemical features. For example, certain tumors with fat components included HAML, hepatic lipoma, and myelolipoma; these tumors were hypo-vascular. HAML (Figure 1) was composed of abnormal blood vessels, smooth muscles, and mature fat cells in different proportions, accompanied by a few inflammatory cells. Hepatic lipoma was composed entirely of mature adipose tissue. Hepatic myelolipoma consisted of mature adipose tissue and hematopoietic elements, containing erythroid cells and myeloid cells (Figure 2).
Microscopically, SFTL was composed of spindle cells and interspersed collagen, high cellular proliferation of spindle cells arranged in a storiform pattern, with the immunohistochemical staining profile of CD34 (+), vimentin (3+), Bcl-2 (+), and SMA (−). The hepatic schwannoma (Figure 3) was composed of Antoni A and Antoni B areas. The Antoni A area was a hypercellular area, containing numerous closely staggered bundles of fusiform Schwann cells. The Antoni B area was a loose myxoid structure composed of colloidal microcapsules with a few sparse cells. Immunohistochemistry showed that hepatic schwannoma was positive for S-100 and CD56.
The expression of immunohistochemical stains with related antibodies could be well identified as FNH, HCA, and HAML (Table 5). HAMLs showed 100% positive expression of an anti-HMB-45 antibody, whereas the expression of Melan-A, Vimentin, and SMA was over 80%. Unlike HCA, CK19 and CK7 were highly expressed in proliferous small bile ducts in FNHs. Although hepatocytes, CD34, and GS were highly expressed in HCA and FNH, different staining patterns could distinguish the two types of tumors.
We simultaneously analyzed the expression of cell proliferation nuclear antigen Ki-67. The majority of tumors (77/89) displayed a low proliferation index (<5%), and the highest was 20%. The Ki-67 proliferation index was positively correlated with the degree of malignancy of tumor and a marker of tumor invasiveness and prognosis. The low value of the Ki-67 index showed that tumors were less aggressive.
3.5 Follow-up
Postoperative follow-up included returning outpatient and telephone follow-up. The follow-up period was 3 to 102 months, and 17 patients were lost to follow-up. During the follow-up, two patients died of natural causes. The other patients were all alive without tumor recurrence or metastasis.