ciliated hepatic foregut cysts ( chfc ) are rare , typically benign liver lesions of congenital origin . during embryologic development , the primitive foregut gives rise to the tracheobronchial tree , and it is speculated that the common origin of the esophagus and liver accounts for the histological findings in ciliated hepatic foregut cysts . despite first being described in 1857 by friedreich , a literature review reveals only about 100 reported cases of chfc . while this number may not reflect the prevalence of these cysts due to their benign , asymptomatic nature , it is agreed that chfc are an uncommon finding . while the previous belief was that chfc were benign lesions with rare morbidity , there have been four recent reports of malignant transformation of chfc into primary squamous cell carcinoma ( scc ) of the liver . primary scc of the liver is itself a very rare entity with approximately 25 reported cases in the literature . pathogenesis of primary scc of the liver is not entirely clear but previous cases have been associated with various diseases including non - parasitic cysts , hepatic cirrhosis , hepatolithiasis , hepatic teratoma , and caroli 's disease . hepatic primary scc is highly malignant with high rates of recurrence and poor overall prognosis . the disease state is typically advanced upon diagnosis and presents clinically as right upper quadrant pain , vague fullness , jaundice , weight loss , nausea , and/or vomiting . the outcomes of cases in the literature suggest a prognosis of less than 1 year survival with only isolated cases achieving 5 year survival . there is no current treatment standard , but most commonly , tace , surgical resection , and radiation therapy have been utilized . herein , this report identifies a fifth case of primary scc of the liver arising from a chfc . this case is unique in that the liver lesion was asymptomatic and was found incidentally on computed tomography ( ct ) . in addition , successful management with sequential transcatheter arterial chemoembolization ( tace ) and portal vein embolization ( pve ) allowed for a therapeutic surgical intervention . a 34-year - old man with a past medical history remarkable for ulcerative colitis underwent a ct scan due to an elevated c - reactive protein ( crp ) and erythrocyte sedimentation rate ( esr ) , in addition to anemia on his routine blood work . unexpectedly , the ct revealed a 10  cm hypoenhancing lesion in the right anterior sector plus left medial section of the liver ( fig . laboratory studies revealed anemia suggestive of iron deficiency , normal serological tumor markers ( cea , ca 19 - 9 , and afp ) , viral hepatitis panel was negative , and crp / esr were elevated at 3.0  mg / dl and 74  mm / hr respectively . a dedicated liver magnetic resonance imaging ( mri ) was performed and revealed a heterogeneous hepatic lesion in segments 4 , 5 , and 8 . 2 ) . computer generated volume assessment of the liver was performed at this time and it was found that segments 1 , 2 , and 3 comprised only 18% of the total liver volume . the patient underwent lipiodol - based transarterial chemoebolization ( tace ) of the right hepatic artery and segment 4 branches . six weeks after pve , cross sectional imaging demonstrated that segments 1,2 , and 3 had hypertrophied from 18% to 33% of total liver volume , providing an adequate liver remnant for right trisectionectomy ( fig . the patient tolerated the procedure well and had an uncomplicated recovery . at 6 months , surveillance imaging demonstrated evidence of extrahepatic recurrence ( lung and abdominal ) . the liver specimen demonstrated a smooth mottled capsule with a 13  cm    7  cm rough white  gray nodular area exhibiting overlying fibrous adhesions . a well - circumscribed yellow gray mass measuring 14  cm    12.5  cm    10.5  cm and a cyst , central within the mass measuring 5.5  cm    5  cm    4.5  cm , were revealed by sectioning . the cyst wall exhibited a smooth to focally granular surface and was filled with a soft tan  gray tumor material . immunohistochemical staining demonstrated tumor cells positive for ck 5/6 and p40 , but negative for p16 . the cyst was lined with pseudostratified ciliated columnar epithelium and had regions of wall - thickening ( fig . the tumor showed sheets of neoplastic cells with eosinophilic cytoplasm and round - to - oval nuclei . malignant transformation of ciliated hepatic foregut cysts is exceedingly rare . since chfc were first described in 1857 , only five such cases , including this one , have been reported ( table 1 ) . due to their normally asymptomatic nature , chfc are usually found incidentally during surgery ( 6% ) , via imaging studies ( 40% ) , or post mortem at autopsy ( 26% ) . the remainder present with abdominal symptoms . diagnosis of chfc preoperatively is difficult because radiographic studies can not differentiate chfc from other cysts and thus , biopsy is typically required . malignant transformation of chfc is even more difficult to diagnose preoperatively due to the sampling error associated with aspiration cytology , and the difficulty associated with distinguishing benign and neoplastic cysts with imaging studies . in addition , serological tumor markers such as ca 19 - 9 seem to lack efficacy for diagnosis as they have been demonstrated to be elevated in benign chfc and may be normal in malignancy , as in this case . which presented with multiple small cysts ( 35  mm ) , the remaining chfc that have undergone malignant transformation have been larger than 5  cm in diameter . it is difficult to definitively say that primary scc of the liver is a result of malignant transformation of the chfc wall . however , after establishing no extrahepatic disease , a primary hepatic cancer should be suspected . in addition , given that the cyst was adjacent to and focally connected with the squamous cell carcinoma in this case , it was felt that the cyst wall was the origin of pathogenesis . squamous cell metaplasia , dysplasia , and malignant transformation of the ciliated columnar epithelium is the proposed mechanism of pathogenesis . chfc have historically been considered non - neoplastic lesions . however , with the recent publication of now five cases of squamous cell carcinoma arising from chfc , approximately 5% of reported chfc have demonstrated malignant transformation , suggesting the need for serious clinical consideration . due to the aggressive nature of these malignant lesions , it is mandatory that thorough pathological and radiological studies be conducted in order to differentiate cysts upon discovery . differential diagnoses of large hepatic cysts include : parasitic cyst , simple hepatic cyst , and biliary cyst , as well as non - cystic lesions if cysts are filled with dense fluid or demonstrate metastatic change . the ciliated epithelium of chfc is unique and can serve as a differentiating histological marker . our case and the existing literature suggest that primary scc of the liver is an aggressive disease with poor prognosis . only isolated cases have been reported in which 5 year survival has been achieved and zhao et al . reports that survival does not usually exceed 1 year . in part due to the rarity of these lesions reported a case of primary hepatic scc that responded very well to chemotherapeutics ( cis - diaminedichloro - platinum ( cddp ) and 5-fluorouracil ) administered via hepatic arterial injection . in addition , recent studies have demonstrated the efficacy of sequential tace and pve in management of hepatocellular carcinoma . this approach has demonstrated significant increases in the future liver remnant ( flr ) and longer recurrence - free and overall survival versus pve alone . in this case , sequential tace and pve was well tolerated and was successful in inducing sufficient flr hypertrophy for surgical intervention . the possibility of malignant transformation of chfc and aggressive nature of primary hepatic scc necessitates accurate diagnosis of hepatic cysts . given this review of cases , we recommend surgical excision of chfc . also , in cases of otherwise unresectable primary scc of the liver , sequential tace and pve may induce optimal flr hypertrophy to allow for surgical resection . written informed consent was obtained from the patient for publication of this case report and case series and accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal on request . r. groeschl wrote and edited the manuscript , concept / design development , data collection / analysis . patel wrote and edited the manuscript , concept / design development , data collection / analysis . gamblin wrote and edited the manuscript , concept / design development , data collection / analysis .
introductionciliated hepatic foregut cysts ( chfc ) are rare , typically benign liver lesions . 
 primary squamous cell carcinoma ( scc ) of the liver is also a rare entity with only approximately 25 reported cases in the literature . 
 recently , there have been four reports of malignant transformation of chfc into primary squamous cell carcinoma of the liver . 
 here we report a fifth with unique presentation and review the literature.presentation of casea 34 year - old man , with a history of ulcerative colitis , was incidentally found to have a 10  cm lesion in the right anterior sector plus left medial section of the liver on computerized tomography ( ct ) scan . 
 the patient was asymptomatic at presentation and neoplastic markers were not elevated . sequential transarterial chemoembolization ( tace ) and portal vein embolization ( pve ) allowed for left lateral section plus segment 1 hypertrophy and subsequent resection . 
 histology later revealed the cyst to be a chfc and showed its malignant transformation . at 6 month follow - up , 
 the patient has lung and abdominal recurrence.discussionwith now the fifth case of malignant transformation of chfc being reported , approximately 5% of all reported chfc have undergone malignant transformation . 
 this frequency , taken together with the aggressive disease course and poor prognosis , suggests that chfc must not be presumed benign and should be regarded with clinical suspicion.conclusionaccurate diagnosis of chfc is mandatory given its potential malignant transformation . even in asymptomatic chfc , surgical excision is recommended . 
 in addition , in cases of otherwise unresectable lesions , sequential tace and pve may provide optimal hypertrophy of future liver remnant .