PCCCL is a particular and relatively rare histological type of HCC. Microscopically, it is similar to the clear cell cancers (kidney, ovarian or adrenal), which makes it difficult to differentiate from the metastatic clear cell cancers of the liver. Murakata et al[11
] have recommended hepatocyte antibody as a screening immunostain in working up a clear cell tumor in the liver when diagnostic histological criteria of HCC are absent. In this setting, it distinguishes PCCCL from other clear cell malignancies with a sensitivity of 90% and specificity of 100%. Some other studies have indicated in situ
hybridization for albumin mRNA as a useful method to distinguish PCCCL from other clear cell tumors metastasizing to the liver[12
]. In the present study, we made the diagnosis using features that point toward the diagnosis of HCC. This study integrated the patient’s pathological features, biopsy, and clinical manifestations, imaging studies, endoscope bile stasis and postoperative long-term follow-up to make a clear diagnosis[4,13
]. There was no misdiagnosis in our study. Some authors consider < 30% of clear cells within the tumor as sufficient[9
], whereas others diagnose PCCCL when the tumor contains > 30% clear cells, however, tumors with clear cells ranging from 90% to 100% are extremely rare[14
]. We used the diagnostic criteria generally accepted by pathologists in China to diagnose PCCCL, that is, only when it contained > 50% clear cells[10
]. In our further studies, we formed a group according to whether the clear cell count was 70% of all cells. We found that the group with > 70% clear cells had significantly longer survival (χ2
= 7.432, P
= 0.006). This shows that the prognosis was related to the proportion of clear cells. The greater the number of clear cells, the better the prognosis.
Surgical resection is an effective way to achieve favorable outcomes and long-term survival of patients with PCCCL. Lao et al[15
] have reported 1- and 3-year survival rates of 76.5% (13/18) and 47.1% (8/18), in all 13 surgical resection patients; the longest survival was 97 mo, and surgical resection was an effective treatment to achieve long-term survival. Compared with HCC, PCCCL has a slower development process, good differentiation, lower grade malignancy, and easier capsule formation, therefore, the tumor is more limited and prone to resection. Surgical resection is the most important means of achieving long-term survival. If there is recurrence after resection, tumor re-resection is possible, but if it cannot be removed, development is slower than for HCC. In the present study, there were 24 patients in the surgical resection and chemotherapy group; the median survival period was 38.2 mo, and the median survival of the curative surgical resection group was 39.1 mo. The difference between these two groups was not significant (χ2
= 0.196, Ρ
= 0.658), which indicated that postoperative adjuvant chemotherapy with calcium folinate and tegafur was not sensitive to PCCCL and had no obvious effect on the survival time of patients. Other postoperative chemotherapy regimens for PCCCL were not investigated in this study. The prognosis of patients with postoperative chemotherapy requires further study.
Pecorella et al[16
] have reported that a 35-year-old patient who was treated with liver transplantation survived for 17 mo, which was lower than the median survival in our study. Emile et al[17
] have shown that prognosis was better in a large series of transplanted Caucasian patients with PCCCL than in those with other liver malignancies. In the present study, the prognosis of patients with surgical resection was better than for HCC, which may be related to better tumor differentiation, capsule formation, less vascular invasion and lymph node metastasis, and high resectability rate. The prognosis of patients with PCCCL is still controversial. Many studies have reported PCCCL has better prognosis than other HCCs[8,18
]. Lai et al[9
] have reported that the outcome for patients with PCCCL is better than those with common-type cancers, and survival improves with an increasing proportion of clear cells. Conversely, other investigators have found that the prognosis of patients with PCCCL is similar to that of their common-type counterparts and perhaps even worse[19,20
]. Yang et al[14
] have reported that the 3- and 5-year survival rate was 54.5% and 33.3%, respectively, which was slightly lower than the rate for non-PCCCL patients (including HCC). However, all these data failed to disclose any statistical significance, or were not statistically analyzed according to the number of cases. Our study confirmed the former results in a series of postoperative patients, and showed significantly higher 1-, 3- and 5-year survival rates in PCCCL patients. The Kaplan-Meier method showed that capsule formation, preoperative liver function, HCV infection, large vascular invasion and multiple tumor occurrences were related to disease-free survival. The prognosis of patients in the PCCCL group was related to clear cell ratio, preoperative liver function, liver cirrhosis, HCV infection, capsule formation, large vascular invasion and multiple tumor occurrences. In this study, lymph node metastasis did not significantly affect survival, which may have been related to the comparatively small number of cases in this study, therefore, we need to increase the number of sample cases for further study. Cox multivariate analysis showed that clear cell ratio, capsule formation, preoperative liver function and large vascular invasion were independent risk factors for survival. In this study, capsule formation of PCCCL was different from the clinical characteristics of HCC. Capsule formation may limit tumor growth and spread and is conducive to tumor resection and treatment. Lower malignancy and better differentiation of clear cells may have contributed to the improved prognosis. The higher the proportion of clear cells, the better was the prognosis. Preoperative Child-Pugh classification was an independent risk factor for survival. High HCV prevalence led to poor liver function and shorter survival.
In summary, postoperative chemotherapy with calcium folinate and tegafur had no obvious effect on survival time of patients with PCCCL. Patients with a high clear cell ratio had improved prognosis. Capsule formation, poor preoperative liver function, HCV infection, large vascular invasion, and multiple tumor occurrence were risk factors for metastasis and postoperative recurrence of PCCCL. Patients with capsule formation, no large vascular invasion, high clear cell ratio, and better liver function had improved prognosis.