Hepatic cystic lesions were once thought to be relatively uncommon; however, they are being diagnosed more frequently with the continued advancement and improved access of patients to cross-sectional imaging. Estimates are that cystic liver disease affects 5 to 10% of the world population. The differential for liver disease is broad and includes infectious, inflammatory, malignant, developmental, and traumatic etiologies. Mucinous cystic neoplasm is a unique subset within the hepatic cyst differential and includes the subgroup of mucinous cystic neoplasm, also referred to as biliary cystadenomas (BCA) and cystadenocarcinomas (BCAC). BCAs and BCACs combined comprise less than 5% of all cystic liver diseases. They can present with relatively nonspecific abdominal symptoms and are usually an incidental finding on imaging. Radiologic features of this neoplasm are often suggestive but tend to overlap the findings in other cystic lesions leading to a differential. BCAs are considered to be premalignant. Although only a few reports have demonstrated malignant evolution current consensus on the best treatment is complete surgical resection.
The exact cause of BCAs remains undetermined. One current theory suggests that BCAs may arise from endodermal precursors to the local biliary epithelium. Contrary to this, there is the theory that these neoplasms are secondary to implantation explaining the ovarian like subepithelial stroma, expression of estrogen and progesterone receptors, predilection to be located in segment IV of the liver.
BCACs and BCAs are rare and comprise a small percentage of worldwide cystic liver disease. The incidence of intrahepatic BCAs is reported to be between the ranges of 1 in 20000 and 1 in 100000.  BCAs are seen predominantly in middle-aged women with ages ranging between 40 to 50 years old. Approximately 85% of reported of them arise from the intrahepatic biliary system. They are slow-growing lesions and have been reported to reach sizes up to 30 cm.
On gross pathology, BCAs are multiseptated, and mucin filled lesions surrounded by a dense fibrous capsule that may on occasion includes calcifications. Microscopically, BCAs have three characteristic layers including a mucin-producing, biliary type epithelial layer; a subepithelial layer of cellular stroma; a dense surrounding layering of collagenous connective. There are two separate subsets of cystadenomas based upon the presence of subepithelial ovarian-like mesenchymal stroma. BCAs with mesenchymal stroma occurs exclusively in women and carry a decreased malignant potential to its counterpart without this layer. Furthermore, BCAs contain no proliferating malignant epithelium, unlike BCACs.
The clinical evaluation of patients with BCAs is exceptionally variable and often nonspecific. Many patients are asymptomatic. They only become aware of this lesion incidentally. Of those that do experience symptoms, the typical presentation includes abdominal pain, distension, nausea, and vomiting. Rarely, BCAs may present from symptoms secondary to obstructive jaundice, cholangitis, intracystic hemorrhage, or cyst rupture. Currently, no physical exam signs have been reported to correlate with malignant potential.
The diagnosis of BCAs has its basis a combination of ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and clinicopathologic information. These lesions are typically intrahepatic, solitary, slow-growing, multiloculated cystic tumors filled with a clear mucinous fluid. BCAs have a female predominance and are often present within hepatic segment IV.
Sonographically, they appear as a well defined, anechoic lesion surrounded by an echogenic capsule and containing multiple intrinsic septations. At CT, BCAs are a fluid attenuating cystic mass with a soft tissue attenuating rim, internal septa, and possibly capsular calcifications and mural nodularity. At MRI, signal characteristics are typical for fluid containing cystic lesion, including low T1 and high T2 signal. There may be some variability in both T2 and T1 signal depending on the protein content, presence of hemorrhage, or solid components. BCAs do not communicate with the biliary system. These lesions demonstrate mild capsular and septal enhancement on postcontrast imaging at CT and MRI. The existence of internal debris, bile duct dilation, and enhancing mural nodularity is concerning for BCACs.
Laboratory values are typically normal in patients, although in a minority of case reports elevated liver enzymes can be seen, specifically bilirubin levels. Elevated serum carbohydrate antigen 19-9 and carcinoembryonic antigens can also present, and may reflect malignant transformation, though this is neither sensitive nor specific. Fine-needle aspiration of cyst fluid is no longer the recommendation due to the risk of dissemination of cells and the development of peritoneal carcinomatosis.
BCA is considered a premalignant lesion. Although imaging findings may be suggestive, they often are overlapping and nonspecific. No published guidelines on appropriate therapy of BCAs currently exist due to the limited number of reported cases. Percutaneous ablation and unroofing techniques of BCAs are ineffective and have been shown to have recurrence rates up to 80%. Complete surgical resection is the management of choice given the risk of malignant transformation and recurrence. Enucleation of BCAs is appropriate management only in those cases where complete surgical resection is not possible.
The definitive diagnosis of BCA from BCAC is challenging before surgical resection. Nevertheless, considering the management of these lesions is identical, the role imaging is, therefore, to exclude other benign cystic lesions without malignant potential. Simple hepatic cysts are the most common hepatic cystic lesion. Reliable differentiation of a BCAs from simple cysts is possible due to the lack of internal septations and papillary projections. Differentiating hemorrhagic cysts can often prove to be challenging given their intricate appearance of US. However, given the decrease in spatial resolution on CT, these lesions tend to appear homogenous without internal complexity, unlike BCAs. Furthermore, the clot in hemorrhagic cysts typically appears T1 bright on MR imaging.
Additional diagnostic considerations include pyogenic hepatic abscesses, hydatid disease, mesenchymal hamartomas, and undifferentiated embryonal sarcoma. Unlike BCAs, pyogenic hepatic abscess and hydatid disease typically presents in patients with fever and lacks the female predominance. Furthermore, associated imaging findings, including perilesional edema, segmental perfusion difference, and internal gas, are more suggestive of an infectious etiology. Mesenchymal hamartomas and embryonal sarcoma too lack the characteristic female predominance and are typically seen in children and young adults.
Prognostic data following resection is limited in patients with BCAs due to its rarity. Of those reported, favorable outcomes occur in those with total resection resulting in only 5 to 10% rate of recurrence.
Reported complications from BCAs include obstructive jaundice, cholangitis, intraperitoneal cyst rupture, intracystic hemorrhage, all of which may cause initial patient presentation. The most feared complication of BCAs is a malignant transformation into BCAC, which has been reported to be as high as 20% of cases.
Patients should receive education, informing them that BCAs are a rare entity without any identifiable risk factors. They should receive information regarding the documented risk of recurrence and malignant transformation in the absence of complete resection.
Enhancing patient care and outcomes begin with clinicians awareness of BCAs and the risks associated. The application of clinicopathologic history and multiphasic imaging is paramount to distinguish this entity from other benign hepatic cysts due to their differing clinical management. Upon making the diagnosis, clinicians need to follow the patient with serial imaging to ensure that malignant transformation does not occur. Even after surgical excision, there is a risk of recurrence of BCA; hence, patients require monitoring. Interprofessional communication between the radiologists, referring providers, and surgeons are necessary to minimize diagnostic workup, patient anxiety, and optimize outcomes; this is where oncology-trained nursing staff can be of great assistance to the oncologists and other physicians involved in the case. They can provide post-surgical education wound care, and help the patient monitor for malignant transformation if they opt not to pursue surgery, or recurrence if they do, and report to the physician staff should any of these become a concern. This sort of interprofessional collaboration is crucial to the successful management of BCAs. [Level V]
Because of only anecdotal reports, the outcomes of these lesions remains a mystery.
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