The Biliary Cystadenoma: Evolving and Updated

Ryan Wolfe, DO; Francis Scholz, MD; Yevgeniy Arshanskiy, MD; Jeremy Wortman, MD

Department of Radiology, Lahey Hospital and Medical Center, Burlington MA

DisclosuresFSpoon Company: Francis Scholz is the sole owner – No conflict of interest

Biliary Cystadenoma (BCA) – How common?● Approximately 5-10% of patients have hepatic cysts for which most are simple cysts● ~5% of all hepatic cysts are a biliary cystic tumor (BCT)

○ Biliary cystic tumors include BCAs, biliary cystadenocarcinomas (BCACs), and intraductal papillary mucinous neoplasms (IPMNs)

● Majority arise from the intrahepatic biliary ducts while a minority, ~10%, are found in the extrahepatic ducts

Prior Interval growth

Introduction -Epidemiology

PresenterPresentation NotesSource: Soares KC, Arnaoutakis DJ, Kamel I, Anders R, Adams RB, Bauer TW, Pawlik TM. Cystic neoplasms of the liver: biliary cystadenoma and cystadenocarcinoma. J Am Coll Surg. January 2014; 218(1):119-128.

Pictures:Javors 03522525 (right)1217400 Sch (left and mid)

BCA – What is it?● Hypothesized to develop from embryonic ectopic rests of

bile ducts● However, since ~50% of BCAs contain endocrine cells then

the origins may be from intrahepatic peribiliary glands● Solitary, multilocular cystic lesions containing mesenchymal

stroma

○ Epithelial mucin-producing layer, undifferentiated mesenchymal cells beneath the epithelium, and a fibrous, collagenous connective tissue layer

PresenterPresentation NotesPicture folder: 4766971 69 M

BCA – Mostly Females

● Classically, BCAs have ovarian-type stroma with expression of estrogen and progesterone receptors, which accounts for the large female predominance

○ Mean age is ~ 40-45 years

● In those lacking the classic mesenchymal stroma, there is no sex predilection

BCA – New classification● Biliary cystic tumors with ovarian-like stroma in the cyst wall without biliary ductal

communication are now what has been advocated to be classified as BCA/BCAC● Mucin production by BCA or BCAC is contained within the cystic tumor and does not enter the

bile ducts

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Evolving classification

BCA of the same patient on ultrasound with color doppler(left), gross surgical specimen (middle), and on T2W MRI (right)

PresenterPresentation NotesPicture folder: Case from or for AIRP WHAT IS DX OF WHAT THIS SLIDE IS SHOWING

Intraductal papillary neoplasms of the Bile Ducts (IPNBs)Biliary cystic tumors that demonstrate ductal communication and lack ovarian-like stroma are now classified as IPNBs and not as BCAs or BCACs● Papillary or villous neoplasms project into the bile ducts by a fibrovascular stalk

○ Thought that mucinous retention leads to cystic dilatation of duct● Counterpart to pancreatic intraductal papillary mucinous neoplasm (IPMN) ● Develop from biliary epithelium, progressing from low grade dysplasia to invasive carcinoma● Only about 33% of biliary IPMNs demonstrate visible mucus production unlike pancreatic main

duct IPMNs, which almost all show visible mucus

PresenterPresentation NotesThought that mucinous retention leads to cystic dilatation of duct instead of being a true cystic neoplasmBUT IT MUST BE A NEOPLASM BECAUSE progressing from low grade dysplasia to invasive carcinoma

BCAPlain film – US – CT – MRI

Mass Effect:• Exerts mass effect on surrounding structures. Notice

the subtle bulge of the left hepatic contour by the biliary cystadenoma (blue arrows)

• Also note thin septa (yellow arrows) creating polygonal shaped cysts

Imaging

BCAPlain film – US – CT – MRI

Cystic:• Cystic lesions vary from anechoic to mild low-level echogenicity depending on

hemorrhagic, mucin and proteinaceous content. Has through transmissionSeptations:• Multiple thin septations and mural nodularity (arrows)Calcification in wall or septa:• Thin wall or septum may demonstrate acoustic shadowingMass Effect:• Exerts mass effect on surrounding structures, including adjacent viscera, can

compress bile ducts causing duct dilatation

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BCA Plain film – US – CT – MRI

Cystic:• Usually fluid density. However, can be hyperattenuating depending on

degree of proteinaceous or hemorrhage contentSeptations:• Multiple thin septations and mural nodularityEnhancement:• Septations and mural nodules may enhance and cannot reliably be used to

differentiate BCA from BCACCalcification:• Thin within wall or septumMass Effect:• Exerts mass effect on surrounding structures, including adjacent viscera if

exophytic, can compress bile ducts causing duct dilatationPearls:• We have not observed simple hepatic cysts coexisting in patients with BCA!• Additional BCAs as well as other liver lesions may coexist. Note a

hemangioma (arrows) adjacent to a BCA

6 patients

BCAPlain film – US – CT – MRI

Cystic:• Appearance variable on T1 and T2 weighted sequences depending on degree

of proteinaceous or hemorrhage contentSeptations:• Multiple thin septations and mural nodularityEnhancement:• Septations and mural nodules may enhance and cannot reliably be used to

differentiate BCA from BCACMass Effect:• Exerts mass effect on surrounding structures, including adjacent viscera if

exophytic, can compress bile ducts causing duct dilatation

T2W FS

T1W FS with contrast

MRCP

‘Cysts-in-cyst’ Appearance: Rad + Path CorrelateA classic BCA CT image of “cysts-in-cyst” appearance with dominant cyst and multiple internal cysts. It bulges liver cortex on CT and at surgery.

Note careful surgical removal, ensuring an intact resection of cyst.

Notice the removed specimen with multiple cysts (yellow arrows). The movie on next slide shows wall incision followed by incisions into successive cysts to evaluate for malignancy.

PresenterPresentation NotesPicture folder: 2170660 ALL

BCA - ‘Cyst-in-cyst’● The wall of a BCA contains one or more

germinal centers that produce cysts that enlarge and may contain more germinal centers (each making “bubble blowing” sites)

● See a tiny cyst forming inside a cyst growing inside another cyst (arrow)

● A BCA must be completely removed, marsupialization may allow recurrence

PresenterPresentation NotesIntra-op Clip

BCA: Bile Duct Involvement

BCAs arise from bile duct epithelium. Intrahepatic ducts have far greater surface area than the common bile duct. Thus, most arise within the liver.

Involvement of intra- or extrahepatic bile ducts may be seen with resultant biliary ductal dilatation and associating filling defects on MRCP and/or ERCP images.

BCA: Bile Duct Involvement● On ERCP note the BCA causing biliary ductal dilatation and bulging into and

causing a filling defect extending down to cystic duct insertion (blue arrows)● On CT, MRI, and MRCP see the cyst bulging into the common bile duct

(yellow arrows)

ERCP ERCP CT with contrast MRCP

T2W

Management

● Complete surgical resection with negative margins is necessary for BCTs. If appropriately resected, there is ~5-10% rate of recurrence

● If a cyst is aspirated for a presumed simple cyst and rapidly recurs, then it was likely a BCA and misdiagnosed

● Fine needle aspiration or core needle biopsy of a suspected BCA should be avoided due to possible pleural and peritoneal dissemination if it is a BCAC

Incomplete Resection = Recurrence

BCAs need to be completed resected, not drained or marsupialized, to prevent recurrence. Above is chronological depiction of what happens if a BCA is not completed removed. CT, MRI, and ERCP images exemplify characteristic ‘cyst-in-cyst’ appearance of a BCA, inappropriately treated initially with drainage. Subsequently it recurred and was treated correctly with complete resection.

2007 1/2008

11/2008 11/201411/2015

found bigger

recurred recurred biggerdrained

drained

Prognosis● Overall survival for BCA is > 90% at 18 yrs● Prognosis of BCAC is worse than BCA with a 5 yr survival rate of ~65-70% after complete

resection. For incomplete resection, the 5 yr survival rate was ~36%

Polygon cysts

CTs (left and right) and T2W (middle) images of BCAs. Note the characteristic germinal centers (yellow arrows) and polygonal (non-circular) cysts (green arrows)

PresenterPresentation NotesWhat do these pictures do on this page ?? This is PROGNOSIS and the SLIDE is diagnostic Great MURAL NODULES (or ARE they compressed ducts left image) ARE THESE Cancers Picture folder: from PRE RSNA fascicle

LEFT is good for germinal center mural noduleMiddle is good IF it is a BCA. Maybe a Tiny BCA has round cysts. Right is good to show GERMINAL CENTER and POLYGONAL Cysts created by pseudomembranes

Biliary Cystadenocarcinoma (BCAC) BCAC are thought to arise either de novo or from malignant transformation of a BCA. BCACs are more likely to have mural or septal nodularity or papillary components. However, imaging cannot reliably differentiate between the two.

An example of pathologically proven BCAC is seen below and to the right with enhancing mural nodularity, multiple septations with scattered calcifications, and fluorodeoxyglucose (FDG) avid mural nodules.

T1W FS pre-contrast T1W FS post-contrast

T2W FS FDG PET-CT

CT pre-contrast CT post-contrast

Potential Differentials

● IPNB● Hydatid Cysts● Cystic or necrotic neoplasms

○ Embryonal sarcoma● Liver Abscesses● Atypical simple cyst

● Post traumatic cyst● Hemorrhagic cyst

Intraductal papillary neoplasms of the Bile Ducts (IPNBs)

To the right is a suspected IPNB with dilated bile ducts that were filled with mucin. Mucin drained from the T-tube with a T-tube study shown at the upper right.

Notice the dilated bile ducts on the CT (lower right) with a cystic lesion within the right hepatic lobe with an internal punctuate calcification (yellow arrow). The mucin production and presumed bile duct communication is suggestive of an IPNB.

Case courtesy of Ellen Wolf from Montefiore

PresenterPresentation NotesCase courtesy of Ellen Wolf from Montefiore

Liver Abscess

Gallbladder

Clue:Air bubble

The clinical presentation (including abdominal pain, fevers, chills, weight loss, and fatigue) are helpful at differentiating liver abscesses from BCAs.

Imaging findings that are more predictive of a liver abscess include peripheral hyperemia and foci of air.

To the right are images from the same patient with a liver abscess causing mass effect including near complete effacement of the gallbladder.

PresenterPresentation Notes2302218 Liver abscess bulging liver and compressing GB 761-2100-MOR-2303218

Epithelioid Hemangioendothelioma

Rare hepatic vascular tumor often multifocal and occasionally contain calcifications. Often are peripheral in location with subcapsular retraction due to tumor related fibrosis and hypertrophy of uninvolved surrounding parenchyma.

Ultrasound typically shows hypoechoic lesions but can be heterogeneous or hyperechoic.

CT often demonstrates scattered hypodense lesions, some of which may coalesce, with peripheral predominate distribution, capsular retraction, and peripheral enhancement like in this example on the right.

MRI will show T1 weighted hypointense lesions with heterogeneous to hyperintense T2 signal and peripheral enhancement.

PresenterPresentation NotesCT image does not show ccapsular retraction

Hydatid Cyst

Differentiating an hydatid cyst from BCTs may be difficult due to similar ‘cyst-in-cyst’ appearances.

Features that may help differentiate a hydatid cyst from BCAs include: right hepatic lobe preference, history of exposure in an endemic area, serology markers, serpiginous linear components from broken daughter cyst membranes, round morphology of the cysts rather than polygonal shape, multiplicity, lack of septa, and may contain internal debris.

Hydatid Cyst

Big single cyst without septa

Amorphous density

Multiple

Summary● BCA are multi-loculated, cystic tumors without biliary tree communication that has a female

predilection if it has ovarian-like stroma○ Cystic lesions with biliary tree communication that lack ovarian-like stroma are now

preferentially called IPNB● Entire resection of a BCA is necessary to lower the rate of recurrence● BCAs may undergo malignant transformation into BCAC. However, BCACs may also occur de

novo○ Imaging cannot reliably differentiate BCA from BCAC

ReferencesAhmad Z, Uddin N, Memon W, Abdul-Ghafar J, Ahmed A. Intrahepatic biliary cystadenoma mimicking hydatid cyst of liver: a

clinicopathologic study of six cases. J Med Case Rep. 2017;11(1):317.Katabathina VS, Flaherty EM, Dasyam AK, Menias CO, Riddle ND, Lath N, Kozaka K, Nakanuma Y, Prasad SR. “Biliary

disease with pancreatic counterparts”: cross-sectional imaging findings. Radiographics. March-April 2016;36(2):374-392.Lim JH, Yoon KH, Kim SH, Kim HY, Lim HK, Song SY, Nam KJ. Intraductal papillary muscinous tumor of the bile ducts.

Radiographics. January-February 2004;24(1):53-66.Park HJ, Kim SY, Kim HJ, Hong GS, Byun JH, Hong S, Lee M. Intraductal papillary neoplasm of the bile duct: clinical, imaging,

and pathologic features. AJR. July 2018; 211:67-75.Soares KC, Arnaoutakis DJ, Kamel I, Anders R, Adams RB, Bauer TW, Pawlik TM. Cystic neoplasms of the liver: biliary

cystadenoma and cystadenocarcinoma. J Am Coll Surg. January 2014; 218(1):119-128.Tholomier C, Wang Y, Aleynikova O, Vanounou T, Pelletier J. Biliary mucinous cystic neoplasm mimicking a hydatid cyst: a

case report and literature review. BMC Gastroenterol. 2019;19:103.

The Biliary Cystadenoma: Evolving and UpdatedDisclosuresBiliary Cystadenoma (BCA) – How common?BCA – What is it?BCA – Mostly FemalesBCA – New classificationIntraductal papillary neoplasms of the Bile Ducts (IPNBs)BCA�Plain film – US – CT – MRIBCA�Plain film – US – CT – MRIBCA �Plain film – US – CT – MRIBCA�Plain film – US – CT – MRI‘Cysts-in-cyst’ Appearance: Rad + Path Correlate�BCA - ‘Cyst-in-cyst’BCA: Bile Duct InvolvementBCA: Bile Duct InvolvementManagementIncomplete Resection = RecurrencePrognosisBiliary Cystadenocarcinoma (BCAC) Potential DifferentialsIntraductal papillary neoplasms of the Bile Ducts (IPNBs)Liver AbscessEpithelioid HemangioendotheliomaHydatid Cyst�Hydatid CystSummaryReferences