5228University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Int J Surg Pathol. 2022 May;30(3):350-355. doi: 10.1177/10668969211054102. Epub 2021 Oct 29.
Short telomere syndrome (STS) encompasses a broad family of genetically inherited conditions caused by various mutations in telomerase and other telomere maintenance genes, resulting in premature telomere shortening. STS involves a variety of clinical manifestations, including dyskeratosis congenita, premature achromotrichia, bone marrow failure, immunodeficiency, pulmonary fibrosis and liver disease. Liver histopathologic features in STS patients have not been well characterized. We report a 46-year-old male patient who presented for dyspnea. The patient had a complicated medical history significant for immune thrombocytopenic purpura and splenectomy, recurrent respiratory tract infections, pneumonia, primary immunodeficiency, and severe hepatopulmonary syndrome. He and his brother both developed gray hair by their late 20s. He had a long history of intermittently elevated liver enzymes starting at age 33. 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, supporting the diagnosis. The liver biopsy showed marked portal inflammation with interface hepatitis, ductular reaction and frequent foci of lobular inflammation with focal hepatocyte dropout. Hepatocytes around the portal tracts demonstrated ballooning degeneration and occasional Mallory-Denk bodies. A trichrome stain highlighted bridging fibrosis. A literature review shows liver histology is available in only a small number of STS patients, demonstrating a variety of morphologic features. Our case and others suggest liver disease associated with STS exhibits a spectrum of histopathology. Being aware of these features is important for establishing the correct diagnosis of STS which is under recognized.
短端粒综合征（STS）包含一组广泛的遗传性疾病，由端粒酶和其他端粒维持基因的各种突变引起，导致端粒过早缩短。STS 涉及多种临床表现，包括先天性角化不良、过早的色素减退、骨髓衰竭、免疫缺陷、肺纤维化和肝病。STS 患者的肝脏组织病理学特征尚未得到很好的描述。我们报告了一名 46 岁的男性患者，因呼吸困难就诊。该患者有复杂的病史，包括免疫性血小板减少性紫癜和脾切除术、复发性呼吸道感染、肺炎、原发性免疫缺陷和严重的肝肺综合征。他和他的哥哥在 20 多岁时都出现了灰发。他从 33 岁开始就有间歇性肝酶升高的长期病史。这些临床表现促使我们对可能的端粒生物学紊乱进行评估，结果显示端粒长度严重缩短，处于或低于年龄的第一百分位，支持诊断。肝脏活检显示明显的门脉炎症伴界面肝炎、胆管反应和频繁的小叶炎症伴局灶性肝细胞丢失。门脉周围的肝细胞表现为气球样变性和偶尔的 Mallory-Denk 小体。三色染色突出了桥接纤维化。文献复习显示，只有少数 STS 患者的肝脏组织学可供研究，表现出多种形态特征。我们的病例和其他病例表明，与 STS 相关的肝病表现出一系列组织病理学特征。了解这些特征对于正确诊断 STS 非常重要，因为 STS 常常被漏诊。
