OBJECTIVES To describe a novel subtype of autoimmune myopathy, immune-mediated megaconial myopathy (IMMM), myopathologically characterized by giant mitochondria (megaconia). METHODS In this case series, we reviewed the Mayo Clinic Muscle Pathology database, between 2018 and 2023, to identify patients with megaconial pathology, subacute progressive weakness, and hyperCKemia, clinically resembling myositis. We recruited 1 patient from another institute, who had similar clinicopathologic features. RESULTS Five patients were identified. Age at onset of weakness ranged from 19 to 45.5 years. All patients had proximal weakness, elevated creatine kinase levels (1,214 to 5,920 U/L), negative myositis antibodies, necrotizing myopathology, and nonnecrotic myofibers harboring giant mitochondria. Immunohistochemical studies conducted in 4 patients showed sarcolemmal MHC-1 and C5b9 immunoreactivities. Megaconial pathology was considered pathognomonic of congenital muscular dystrophy due to biallelic pathogenic variants in CHKB. Sequencing of CHKB in 4/5 patients was unrevealing. Immunomodulatory therapy improved weakness and hyperCKemia in 4 treated patients. Of interest, all patients had coexisting pancreatic diseases (3 cystic fibrosis-related exocrine pancreatic insufficiency, 1 pancreatic cancer, and 1 pancreatitis). DISCUSSION In addition to incurable CHKB-congenital muscular dystrophy, giant mitochondria can also occur in this new subtype of treatable autoimmune myopathy, IMMM. The association between IMMM and pancreatic disorders remains to be elucidated.

中文翻译：

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免疫介导的巨圆锥肌病：自身免疫性肌病的一种新亚型。


目的 描述自身免疫性肌病的一种新亚型，免疫介导的巨圆锥肌病 （IMMM），肌病理学特征为巨大线粒体 （megaconia）。方法 在本病例系列中，我们回顾了 2018 年至 2023 年间的梅奥诊所肌肉病理学数据库，以确定临床上类似于肌炎的巨圆锥病变、亚急性进行性无力和高 CK血症患者。我们从另一个研究所招募了 1 例患者，他们具有相似的临床病理特征。结果 确定 5 例患者。肌无力发作的年龄为 19 至 45.5 岁。所有患者均存在近端无力、肌酸激酶水平升高 （1,214 至 5,920 U/L）、肌炎抗体阴性、坏死性肌病理学和携带巨大线粒体的非坏死性肌纤维。对 4 例患者进行的免疫组织化学研究显示肌膜 MHC-1 和 C5b9 免疫反应。由于 CHKB 中的双等位基因致病性变异，巨圆锥病变被认为是先天性肌营养不良症的特异性病理学。4/5 患者的 CHKB 测序未显示。免疫调节疗法改善了 4 例接受治疗的患者的虚弱和高 CK血症。有趣的是，所有患者都同时患有胰腺疾病 （3 例囊性纤维化相关胰腺外分泌功能不全，1 例胰腺癌和 1 例胰腺炎）。讨论 除了无法治愈的 CHKB 先天性肌营养不良症外，巨大线粒体也可见于这种可治疗的自身免疫性肌病 IMMM 的新亚型中。IMMM 与胰腺疾病之间的关联仍有待阐明。