IBC and IBAC are kinds of rare liver cystic tumours, occupying only about 5% of liver cystic lesions. In 2010, IBC and IBAC were redefined as H-MCNs by WHO new classification according to the presence of an ovarian-like stoma (OS).[7, 8] BAC tends to transform into IBAC at about 20%. Thus, the treatment of H-MCNs should be more radical, and the accurate diagnosis of H-MCNs and HSC is of great significance. However, due to the lack of specific biochemical markers and imaging features, the identification of H-MCNs was still challenging. To improving the differential diagnosis between H-MCNs and HSC, previous researchers make their effects on finding some markers. [9, 12-14]. Nevertheless, these small-sample studies can hardly find significant differences between HSC and H-MCNs. Labib et at. reported that H-MCNs was often found as a single cyst (p=0.006); Koffron et at. reported that the elevation of CA19-9 and CEA level in the cystic fluid were useful; while Choi et al. found that cystic fluid analysis was useless to diagnose H-MCNs. At present, the imaging examination is still the most effective method to diagnose H-MCNs, although lacking reliably specific feature. Frozen section after the fenestration is also an accurate method of diagnosing H-MCN, it would be a risk to perform such a technique if the lesion harboured a carcinoma focus. In a word, the data on the preoperative diagnosis of H-MCNs remains scarce, and few studies were based on the new classification of H-MCNs.[4-6, 8, 10, 15, 16]
In our cohort, a total of 29 patients diagnosed as H-MCNs with the presence of OS in pathology were reviewed. Major of H-MCNs occurred in women (20/29, 69%), particularly younger age women (≤60yr,79%), which is consistent with the previous study, although it didn’t reach significant differences.[9, 13] There are many studies compared the tumour markers between HSC and H-MCNs.[9, 13, 14, 17] In our study, we found that serum CA19-9 level was increased in many patients with H-MCNs, but the difference was not statistically significant (p=0.053). Cyst fluid tumour markers analysis of H-MCNs remains controversial and needs more extensive sample sizes study to verify.[9, 13] Radiographic examination was still the primary tool to diagnose H-MCNs. However, we revealed that only about half of patients with H-MCNs could be accurately diagnosed by the CT (12/26,46.1%) and MRI (8/14,57.1%), while the US was nearly no help to diagnose H-MCNs (1/29,3.4%). (Table 1) The imaging characteristics of H-MCNs, reported previously, were solitary, large, thick-wall, multilocular cystic with internal septation and calcification.[11, 18] Nevertheless, the imaging finding of many H-MCNs were are atypical, and some HSCs may also exhibit these features, which cause great difficulty of diagnosing H-MCNs.
In multivariate analysis, three factors, including biliary ductal dilation, enhancement in CT and intrahepatic location, were significantly associated with H-MCNs. H-MCNs originate from congenitally aberrant bile ducts, and the cyst fluid is secreted by these abnormal bile duct cells. Compared with HSC, there is more blood supply in the wall, nodules and septa of H-MCNs. Thus, the H-MCNs was often combined with bile duct dilatation and enhanced after contrast in imaging. What’s interesting was that although the normal right lobe of the liver is much bigger than the left, most lesions of H-MCNs (23/29,79.3%) located in the left lobe of the liver which was statistically significant in multivariate analysis. Zen et al. and Albores-Saavedra et al. found a similar phenomenon.[19, 20] In our view, this may because the high degree of left liver freeness, the tumour is prong to outward compression growth in the loose tissue, the mechanism need to be further explored.
The preoperative distinguish of H-MCNs and HSC was crucial to make the surgical plan. Because of the high rate of recurrence and premalignant progression, H-MCNs were recommended to undergo radical resection, such as complete cyst resection or anatomical liver resection, even liver transplantation.[10, 21, 22] It was reported that complete cyst resection could bring to long-term survival and a low rate of recurrence.[10, 23] According to a multi-institutional study, if the H-MCNs were performed fenestration, the recurrence could reach 48.6%, and might enhance the risk of malignant-transformation. The treatment of large HSC is usually laparoscopic fenestration or unroofing when patients have the symptom of compression. As a result, several HSC misdiagnosed as H-MCNs may undergo radical excision to suffer unnecessary surgical trauma.
Since the preoperative diagnosis of H-MCNs remains quite tricky, it is essential to establish a preoperative diagnosis model to enhance the differential ability of H-MCNs and HSC. We created a diagnosis nomogram that facilitates accurate identification and screening of H-MCNs preoperatively. Nomogram is a visualized tool that could vividly display the logistic regression model and help to make clinical decisions. In our Nomogram, three factors (Enhancement after contrast, intrahepatic location, and biliary dilation) were significantly associated with H-MCNs in the multivariate logistic regression analysis were included. Besides, serum CA19-9 level was widely reported to associate with H-MCNs in previous studies.[10, 24, 25] In our analysis, serum CA19-9 level was increased in many patients with H-MCNs, but the difference was not statistically significant in multivariate analysis (p=0.053). In consideration of improving the sensitivity of the diagnostic model, we also included the CA19-9 as a significant factor. This is the first Nomogram of H-MCNs in liver cystic lesions. The advantages of the Nomogram were that it provides individualized risk assessment in a dynamic manner, and all the factors included are routinely reached in clinical practice. By utilizing this Nomogram, the patients with a high probability of H-MCNs would be recommended to undergo a complete resection. And some preoperatively invasive tests like biopsy or fluid aspiration would be replaced by using the Nomogram to get a risk probability.
There were some limitations to this study. First of all, the current study was a retrospective study with some inevitable selection bias. Second, although the H-MCNs were a rare disease, the sample size of the present study was too small and we have no ability to include enough samples for impeccable logistic regression. Thus, the Nomogram based on these 29 positive cases may not fully reflect the reality, and large-sample multicenter studies were still expected in the future. Before the wide acceptance of this Nomogram, it is desirable to validate this result from other centres. Third, considering whether the cystic fluid tumour marker level could help in the diagnosis of H-MCNs remains controversial, and not all of the liver cystic patients were routinely performed aspiration paracentesis, we didn’t include fluid tumour marker level as a predictive factor. Meanwhile, other specific markers understudy might further improve the accuracy of the prediction model of H-MCNs.