Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts, often resulting in end-stage renal disease (ESRD). This disorder is genetically heterogeneous with ∼7% of families genetically unresolved. We performed whole-exome sequencing (WES) in two multiplex ADPKD-like pedigrees, and we analyzed a further 591 genetically unresolved, phenotypically similar families by targeted next-generation sequencing of 65 candidate genes. WES identified a DNAJB11 missense variant (p.Pro54Arg) in two family members presenting with non-enlarged polycystic kidneys and a frameshifting change (c.166_167insTT) in a second family with small renal and liver cysts. DNAJB11 is a co-factor of BiP, a key chaperone in the endoplasmic reticulum controlling folding, trafficking, and degradation of secreted and membrane proteins. Five additional multigenerational families carrying DNAJB11 mutations were identified by the targeted analysis. The clinical phenotype was consistent in the 23 affected members, with non-enlarged cystic kidneys that often evolved to kidney atrophy; 7 subjects reached ESRD from 59 to 89 years. The lack of kidney enlargement, histologically evident interstitial fibrosis in non-cystic parenchyma, and recurring episodes of gout (one family) suggested partial phenotypic overlap with autosomal-dominant tubulointerstitial diseases (ADTKD). Characterization of DNAJB11-null cells and kidney samples from affected individuals revealed a pathogenesis associated with maturation and trafficking defects involving the ADPKD protein, PC1, and ADTKD proteins, such as UMOD. DNAJB11-associated disease is a phenotypic hybrid of ADPKD and ADTKD, characterized by normal-sized cystic kidneys and progressive interstitial fibrosis resulting in late-onset ESRD.

HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.

Gastrointestinal lymphoma is an uncommon disease but is the most frequently occurring extranodal lymphoma and is almost exclusively of non-Hodgkin type. Primary gastrointestinal lymphoma most commonly involves the stomach but can involve any part of the gastrointestinal tract from the esophagus to the rectum. Risk factors for the development of gastrointestinal lymphoma include Helicobacter pylori infection, immunosuppression after solid organ transplantation, celiac disease, inflammatory bowel disease, and human immunodeficiency virus infection. Although gastrointestinal lymphoma has a wide variety of imaging appearances and definitive diagnosis relies on histopathologic analysis, certain findings (eg, a bulky mass or diffuse infiltration with preservation of fat planes and no obstruction, multiple site involvement, associated bulky lymphadenopathy) can strongly suggest the diagnosis. Imaging also plays an important role in the detection of complications such as perforation, obstruction, and fistulization. The most commonly used imaging modalities are barium examination and computed tomography (CT). These modalities are complementary, although CT provides a better overall assessment of the disease stage.

Autoimmune pancreatitis is the pancreatic manifestation of IgG4-related sclerosing disease, which recently was recognized as a distinct disease entity. Numerous extrapancreatic organs, such as the bile ducts, gallbladder, kidneys, retroperitoneum, thyroid, salivary glands, lung, mediastinum, lymph nodes, and prostate may be involved, either synchronously or metachronously. Most cases of autoimmune pancreatitis are associated with elevated serum IgG4 levels; extensive IgG4-positive plasma cells; and infiltration of lymphocytes into various organs, which leads to fibrosis. There are several established diagnostic criteria systems that are used to diagnose autoimmune pancreatitis and that rely on a combination of imaging findings of the pancreas and other organs, serologic findings, pancreatic histologic findings, and response to corticosteroid therapy. It is important to recognize multiorgan involvement of IgG4-related sclerosing disease and be familiar with its clinical and imaging features because it demonstrates a favorable response to treatment.