Clinicopathological features of immunoglobulin G4‐related pleural lesions and diagnostic utility of pleural effusion cytology

Abstract

Objective Immunoglobulin (Ig)G4‐related disease is a recently described systemic immune‐mediated fibro‐inflammatory disease that frequently occurs in tumorous form. Herein, we elucidated the clinicopathological and cytological characteristics of IgG4‐related pleural lesions (PLs). Patients and methods Among 22 patients with fibro‐inflammatory PLs of idiopathic aetiology, eight cases were diagnosed as IgG4‐PL and the remaining 14 as non‐IgG4‐PL according to comprehensive diagnostic criteria for IgG4‐related disease. Cell block examination of pleural effusion (CBPE) was performed in five patients with IgG4‐PL and in six with non‐IgG4‐PL. Both groups were compared in terms of clinical presentation, laboratory data, histopathological features of resected pleura, and cytological features of pleural effusion (PE). Results PE was the most common (six patients, 75%) clinical presentation of IgG4‐PL. IgG4‐PL comparatively showed significantly more frequent concomitant allergic disease (P = .021), higher serum IgE levels (P = .012), higher adenosine deaminase levels in pleural fluid (P = .005), and rare spontaneous recovery without treatment (P = .046). The IgG4‐PL group was histologically characterised by thicker fibrous pleura, storiform fibrosis, and infiltration of regulatory T cells, eosinophils and basophils. Using CBPE, IgG4‐PL was cytologically distinct with numerous IgG4+ cells and eosinophils. The cytology of CBPE positively correlated with the histology of pleural tissue in the number of IgG4+ cells and eosinophils (R = .769 and .803, respectively). Conclusion IgG4‐PL frequently presents with PE and is histologically and cytologically characterised by abundant infiltration of IgG4+ cells and eosinophils. We believe that CBPE with immunohistochemistry/special staining could assist in the auxiliary diagnosis of IgG4‐PL.

Pleural effusion related to IgG4

“…This study was the first to estimate the frequency of the IgG4-associated cause in idiopathic pleural effusions. Consistently, Kasashima et al [30 ▪▪ ] reported that 8/22 (36%) of patients with fibroinflammatory pleural lesions of idiopathic cause met defined diagnostic criteria for IgG4-RD. In this study, 6/8 (75%) patients with IgG4-related pleural lesion had pleural effusions, which was the most common manifestation of IgG4-related pleural lesion.…”

“…The pleural manifestations of IgG4-RD include pleural mass, pleuritis with fibrosis (nodular or diffuse pleural thickening), and pleural effusion [23]. Although thoracic involvement in IgG4-RD is frequently observed in association with other organ disease such as pancreatitis and sialadenitis [21,22 ▪ ,24], it should be emphasized that pleural effusions in IgG4-RD without other organ involvement are also increasingly recognized [25 ▪ ,26–28,29 ▪ ,30 ▪▪ ]. Pleural effusions in IgG4-RD are exudative with cellular constituents rich in lymphocytes and plasma cells.…”

“…Two independent studies have recently reported the association of IgG4 with pleural effusions of idiopathic cause [29 ▪ ,30 ▪▪ ]. Murata et al [29 ▪ ] reported that 12 of 35 (34%) patients with pleural effusions undiagnosed during follow-up (median, 5 years; range, 1–10 years) were found to have marked IgG4-positive plasma cell infiltration in the pleura by IgG4 immunostaining along with elevated effusion IgG4 concentrations (Figs.…”

“…Therefore, relying on IgG4 levels alone may result in under-diagnosis or over-diagnosis, and the lack of elevated IgG4 level does not exclude this diagnosis. Inflammatory markers such as C-reactive protein and LDH levels are often within normal limits in IgG4-RD [30 ▪▪ ,35] although LDH levels were elevated in some cases [25 ▪ ,36]. In general, IgG4-RD tends to show relatively weak inflammation signs [37].…”

A case of isolated IgG4-related lung disease in a teenager

“…[11] выделили 4 основных рентгенологических паттерна IgG4-связанных поражений легких (IgG4-СЗЛ): 1) солидное узловое образование; 2) округлые тени по типу «матового стекла»; 3) альвеолярно-интерстициальный тип; 4) бронховаскулярный тип. Позднее были описаны и другие изменения, такие как формирование полостей в легком и вовлечение плевры по типу плеврита или, чаще, утолщения плевральных листков, а также практически патогномоничное для IgG4-СЗ поражение по типу формирования мягкотканных образований, вытянутых вдоль позвоночника по типу ленты [10,12,13]. Различные паттерны могут сочетаться у одного и того же пациента, что дополнительно усложняет оценку результатов компьютерной томографии (КТ) [14].…”