Obstructive Jaundice in Polycystic Liver Disease Related to Coexisting Cholangiocarcinoma

Although jaundice rarely complicates polycystic liver disease (PLD), secondary benign or malignant causes cannot be excluded. In a 72-year-old female who presented with increased abdominal girth, dyspnea, weight loss and jaundice, ultrasound and computed tomography confirmed the diagnosis of PLD by demonstrating large liver cysts causing extrahepatic bile duct compression. Percutaneous cyst aspiration failed to relief jaundice due to distal bile duct cholangiocarcinoma, suspected by magnetic resonance cholangiopancreatography (MRCP) and confirmed by endoscopic retrograde cholangiopancreatography (ERCP). Coexistence of PLD with distal common bile duct cholangiocarcinoma has not been reported so far

Polycystic liver in two adult llamas

Polycystic liver is usually considered an incidental finding in human and veterinary medicine. Two unrelated adult llamas ( Lama glama) with a history of marked anorexia and weight loss were received for autopsy and diagnostic workup. The main gross change in the liver of both animals was multiple variably sized cysts randomly distributed throughout the parenchyma. Histologically, the cysts compressed the adjacent parenchyma and were lined by a single layer of cuboidal-to-columnar epithelium, surrounded by a fibrous collagen capsule. The lumen of the cysts contained finely granular-to-homogeneous basophilic material. The lining epithelium displayed strong immunoreactivity for pancytokeratin AE1/AE3 and cytokeratins 7, 8, 8/18, and 19, and was negative for vimentin, confirming the biliary epithelial origin of the cysts. No parasitic or infectious agents, or neoplastic changes, were detected. All other laboratory tests performed in both llamas were negative or non-diagnostic, suggesting that the congenital hepatic cysts described may have been at least partly responsible for clinical disease in both animals

Chromosomal abnormalities in hepatic cysts point to novel polycystic liver disease genes

Autosomal dominant polycystic liver disease (ADPLD) is caused by variants in PRKCSH, SEC63, and LRP5, whereas autosomal dominant polycystic kidney disease is caused by variants in PKD1 and PKD2. Liver cyst development in these disorders is explained by somatic loss-of-heterozygosity (LOH) of the wild-type allele in the developing cyst. We hypothesize that we can use this mechanism to identify novel disease genes that reside in LOH regions. In this study, we aim to map abnormal genomic regions using high-density SNP microarrays to find novel PLD genes. We collected 46 cysts from 23 patients with polycystic or sporadic hepatic cysts, and analyzed DNA from those cysts using high-resolution microarray (n=24) or Sanger sequencing (n=22). We here focused on regions of homozygosity on the autosomes (>3.0 Mb) and large CNVs (>1.0 Mb). We found frequent LOH in PRKCSH (22/29) and PKD1/PKD2 (2/3) cysts of patients with known heterozygous germline variants in the respective genes. In the total cohort, 12/23 patients harbored abnormalities outside of familiar areas. In individual ADPLD cases, we identified germline events: a 2q13 complex rearrangement resulting in BUB1 haploinsufficiency, a 47XXX karyotype, chromosome 9q copy-number loss, and LOH on chromosome 3p. The latter region was overlapping with an LOH region identified in two other cysts. Unique germline and somatic abnormalities occur frequently in and outside of known genes underlying cysts. Each liver cyst has a unique genetic makeup. LOH driver gene BUB1 may imply germline causes of genetic instability in PLD