Most patients with a focal hepatic lesion, especially those with a history of previous malignancy, will undergo extensive preoperative radiodiagnostic tests, such as ultrasonography, computed tomography, and magnetic resonance imaging. These techniques usually offer an accurate clinical diagnosis14,15
; however, in certain circumstances, such as in patients amenable to resection or when the surgeon unexpectedly finds a liver mass, frozen section diagnosis is mandatory for the proper management of the patient. The accuracy and diagnostic value of frozen sections has been evaluated in tumours of different tissues. However, previous studies of the accuracy of frozen section in the diagnosis of focal hepatic masses are lacking. Thus in the present study we aimed to evaluate the value of frozen section in the histopathological diagnosis of surgically resected liver lesions and to determine causes of error and any pitfalls that might occur.
Overall, malignant tumours were found in 32% of cases and benign tumours in 9%, other benign lesions in 26%, and no evidence of malignancy in 33%. Regarding diagnostic accuracy of frozen section in determining malignancy status, after excluding the four deferred cases in which the definite diagnosis was made on paraffin sections, we found that the overall accuracy of the test was 95% and the negative predictive value was 98%. These results are similar to that of previous studies of frozen sections in other tissues.11,12,13,16
Errors were one false negative diagnosis because of sampling error and two false positive diagnoses. Among these three error cases, one had major implications for the management of the patient, in whom the surgeon had to undertake another operation to remove the resectable tumour which turned out to be malignant. Although, we regarded the cause of error in the two false positive cases as an overdiagnosis error, as evidenced by the permanent sections, pathological misinterpretation has been reported as a well recognised pitfall in the distinction between bile duct adenoma and metastatic adenocarcinoma.17,18
Our results are consistent with other studies such as that of Prey et al
, who undertook an extensive review of frozen sections of 4057 tissue blocks from various organs and found an accuracy of 91.5%. Almost all of the misdiagnoses were because of sampling errors and misinterpretation.19
Take home message
- Frozen section is an accurate and reliable method for intraoperative diagnosis of suspected liver lesions
As there were some pitfalls making the diagnosis less than perfect, we explored the influence of the various factors involved. We found that the major pitfall in frozen sections occurred in the distinction between Von Meyenberg complex or bile duct hamartoma and well differentiated adenocarcinoma, which is a well recognised problem in the diagnosis of focal hepatic lesions,20
and in cases of metastatic carcinoma that show abundant desmoplastic stromal response with a paucity of malignant cells. We noted that certain types of metastatic carcinomas in the liver are difficult to diagnose, especially in frozen section, such as metastatic signet ring carcinoma of the stomach and lobular carcinoma of the breast. Thus previous knowledge of the primary tumour of the patient, if any, has a substantial impact on the interpretation of frozen sections of liver masses. We also found that bile duct epithelium may be lost during processing of frozen sections, and in some cases of bile duct hamartoma, for example, the bile ducts may appear as cystic spaces or holes without discernable lining or content in the frozen section.
With regard to the quality of the frozen sections, although we found approximately 8% to be of poor quality, this did not interfere significantly with the diagnosis, and in most cases a correct diagnosis was made regardless of the quality of the section. The number of biopsies was also explored as an influencing factor. Although we did not find an association between number of biopsies and a benign or malignant diagnosis, we noticed that the yield of malignant diagnoses increased with increasing numbers of biopsies. For example, in some cases, malignancy was diagnosed on the third biopsy and one case it was diagnosed using nine blocks. In agreement with this observation, Tangjitgamol et al
did not find an association between the numbers of frozen sections of ovarian masses and malignant diagnosis.11
Other studies found that underdiagnoses were caused by sampling error and recommended that a greater number of frozen sections should be taken.21,22
In conclusion, frozen section appears to be an accurate and reliable test for intraoperative diagnosis of focal liver lesions in general. However, some problems persist and histopathologists should remain vigilant.