Vasaitis Lilian, Sundström Christer, Backlin Carin, Nordmark Gunnel, Baecklund Eva
a Section of Rheumatology, Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
b Department of Immunology, Genetics and Pathology, Rudbeck Laboratory , Uppsala University , Uppsala , Sweden.
Acta Oncol. 2016 Sep-Oct;55(9-10):1139-1144. doi: 10.1080/0284186X.2016.1182644. Epub 2016 May 19.
IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder, which may affect many organs, and often comes to clinical attention due to tumor-like organ swelling or is identified incidentally by specific biopsy findings. Typical histopathology of IgG4-RD is lymphoplasmacytic infiltration rich in IgG4 + plasma cells (PCs), storiform fibrosis, and obliterative phlebitis. Patients with sicca symptoms can be misdiagnosed as primary Sjögren's syndrome (pSS) instead of IgG4-RD because of clinical and histopathological similarities. Moreover, an association with lymphoma development is described in both diseases. This study investigated signs of IgG4-RD in a population-based cohort of patients diagnosed with pSS complicated by lymphoma.
Patients with pSS and lymphoma diagnoses and available lymphoma specimens were identified by linkage with the Swedish Patient Register 1964-2007 and the Cancer Register 1990-2007 (n = 79). Clinical data and lymphomas were reviewed and the diagnoses evaluated. All lymphoma tissues and available minor salivary gland biopsies (n = 11) were immunostained for IgG4 + PCs and evaluated for other histopathological signs of IgG4-RD. In a case with specific findings of IgG4-RD, other available tissue specimens of the same patient were investigated for IgG4-RD.
Only one patient of 79 (1.3%) had >10 IgG4 + PCs/high power field (HPF) in the lymphoma tissue, an unspecified low-grade B-cell lymphoma localized in the submandibular gland. This patient also had other histopathological features of IgG4-RD in the lymphoma and a surgical lung biopsy taken five years before lymphoma diagnosis and, therefore, fulfilled the criteria for IgG4-RD. Occasional IgG4 + PCs (<10/HPF) without signs of IgG4-RD were observed in another six lymphomas. No IgG4 + PCs were identified in the minor salivary gland biopsies.
Histopathological findings of IgG4-RD may co-exist with low malignant B-cell lymphoma in patients with initially suspected pSS and may be associated with an underlying IgG4-RD.
IgG4相关疾病（IgG4-RD）是一种最近才被认识的纤维炎症性疾病，可累及多个器官，常因肿瘤样器官肿大引起临床关注，或通过特异性活检结果偶然发现。IgG4-RD的典型组织病理学表现为富含IgG4+浆细胞（PCs）的淋巴细胞和浆细胞浸润、席纹状纤维化及闭塞性静脉炎。由于临床和组织病理学表现相似，干燥症状患者可能被误诊为原发性干燥综合征（pSS）而非IgG4-RD。此外，两种疾病均有与淋巴瘤发生相关的描述。本研究在一个基于人群的、诊断为pSS合并淋巴瘤的队列中调查IgG4-RD的迹象。
通过与瑞典1964 - 2007年患者登记册和1990 - 2007年癌症登记册建立联系，确定患有pSS和淋巴瘤诊断且有可用淋巴瘤标本的患者（n = 79）。回顾临床资料和淋巴瘤情况并评估诊断。对所有淋巴瘤组织和可用的小唾液腺活检标本（n = 11）进行IgG4+PCs免疫染色，并评估IgG4-RD的其他组织病理学迹象。对于有IgG4-RD特异性发现的病例，对同一患者的其他可用组织标本进行IgG4-RD调查。
79例患者中仅1例（1.3%）淋巴瘤组织中每高倍视野（HPF）有>10个IgG4+PCs，为位于下颌下腺的未指定低级别B细胞淋巴瘤。该患者淋巴瘤及淋巴瘤诊断前5年的手术肺活检中也有IgG4-RD的其他组织病理学特征，因此符合IgG4-RD标准。在另外6例淋巴瘤中观察到偶尔有IgG4+PCs（<10/HPF）但无IgG4-RD迹象。小唾液腺活检标本中未发现IgG4+PCs。
IgG4-RD的组织病理学表现可能与最初疑似pSS的患者中的低恶性B细胞淋巴瘤共存，且可能与潜在的IgG4-RD相关。
