Liver histology in short telomere syndrome: A case report and review of the literature

Introduction/Objective Short telomere syndrome (STS) is a genetically inherited syndrome resulting in premature telomere shortening. STS encompasses a spectrum of clinical manifestations, including dyskeratosis congenita, premature hair graying, bone marrow failure, immunodeficiency, pulmonary fibrosis and liver disease. Liver histopathologic features in STS patients have not been well characterized. Methods/Case Report A 46-year-old man presented for dyspnea and cryptogenic cirrhosis. He had a complicated medical history significant for immune thrombocytopenic purpura and splenectomy, recurrent respiratory tract infections, pneumonia, sepsis, primary immunodeficiency, pulmonary mucosa-associated lymphoid tissue lymphoma, and severe hepatopulmonary syndrome. He and his brother had gray hair in their late 20s. He also had a long history of intermittently elevated liver enzymes starting at age 33. A liver biopsy performed 12 years before showed chronic portal inflammation with hepatocellular damage without significant fibrosis. These clinical manifestations prompted an evaluation for a possible telomere biology disorder, which revealed the telomere length was critically short and fell at or below the first percentile for age, supportive of the diagnosis. The most recent liver biopsy showed marked portal lymphocytic inflammation with interface hepatitis, bile ductular reaction and frequent foci of lobular inflammation with focal hepatocyte dropout. Some hepatocytes around the portal tracts were swollen with feathery degeneration and occasional Mallory-Denk bodies. A Rhodanine stain highlighted copper granules in the periportal hepatocytes, suggesting chronic cholestasis. Trichrome and reticulin stains demonstrated portal/periportal/pericellular/perisinusoidal fibrosis and focal bridging fibrosis. Results (if a Case Study enter NA) NA Conclusion Partly due to the rarity of STS and the risk of bleeding associated with biopsies, liver histology was described in only few limited studies with small samples of STS patients, including inflammation, nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, cirrhosis, and large cell change of hepatocytes. Our case and others suggest liver disease associated with STS demonstrates a spectrum of histopathology. Being aware of these histomorphologic features in STS is important for establishing the correct diagnosis.

Congenital hepatic fibrosis and its mimics: a clinicopathologic study of 19 cases at a single institution

Background Congenital hepatic fibrosis (CHF) is a rare inherited form of ductal plate malformation associated with polycystic kidney disease. The diagnosis requires histopathologic confirmation, but can be challenging to distinguish from other undefined fibrocystic liver diseases. We aimed to describe the clinicopathologic features of congenital hepatic fibrosis (CHF), with comparisons to other entities that may clinically and/or histologically mimic CHF. Methods Nineteen cases that carried a clinical and/or histologic impression of CHF were identified at our institution, of which the histology was reassessed and reappraised into two categories: CHF (n=13) and mimics (n=6). The clinicopathologic features between the two groups were analyzed and compared. Results The CHF group was further sub-classified into those with clinical suspicion (CHF-c, n=8) and those as incidental histology findings (CHF-i, n=5). Patients of CHF-i were much older than CHF-c or mimics (P<0.05). Male and female were equally affected. Six of 8 CHF-c (66.7%) had concurrent kidney diseases, including 5 polycystic kidney diseases. Five of 6 mimics (83.3%) had various kidney diseases, including nephronophthisis, Alport syndrome, renal agenesis, and nephrolithiasis. None of the CHF-i patients had kidney disease, but 3 were associated with hepatic carcinomas. Histology analysis demonstrated characteristic triads (bile duct abnormalities, portal vein hypoplasia, and fibrosis) in all CHF cases. One mimic had paucity of intrahepatic bile ducts, while the other 5 mimics showed abnormal portal veins and nodular regenerative hyperplasia consistent with hepatoportal sclerosis (HPS). Conclusions Our study demonstrates classic histology triad of CHF despite a wide spectrum of clinical presentations. HPS is unexpectedly a clinical mimicker of CHF, which can be distinguished histologically.

Portal hypertension after prolonged use of trastuzumab emtansine: nodular regenerative hyperplasia with autoimmune features

We report a rare complication associated with prolonged use of trastuzumab emtansine (T-DM1) – a composed therapy for HER2+ breast cancer – presenting with laboratorial autoimmune features that could have delayed the diagnosis or led to misdiagnosis. A 55-year-old female was referred to the hepatologist with a computed tomography suggestive of portal hypertension for etiological investigation. History of invasive ductal carcinoma in the right breast undergoing treatment for 5 years. She had already undergone neoadjuvant chemotherapy, mastectomy, radiotherapy and adjuvant chemotherapy. By the time of metastatic diagnosis, she was in monotherapy with T-DM1 for 2.5 years. Upper endoscopy showed esophageal varices and portal hypertension gastropathy. Laboratorial tests revealed increased transaminases, hypergammaglobulinemia and positive antinuclear antibody. Liver biopsy was performed for autoimmune hepatitis differential diagnosis but revealed nodular regenerative hyperplasia. T-DM1 was discontinued. After a 2-year follow-up, the patient did not present any complications of portal hypertension, although persisted with esophageal varices.