Proposed method of histological separation between connective tissue disease-associated interstitial pneumonia and idiopathic interstitial pneumonias

Abstract

ObjectivesIdiopathic interstitial pneumonia (IIP) and connective tissue disease -associated interstitial pneumonia (CTD-IP) are the two most common types of interstitial pneumonia. IIP and CTD-IP share common histological features, yet their clinical management is different. Separation of the two conditions based solely on histology can be challenging, and there are no established criteria.Materials and methodsWe selected 105 consecutive cases of IIP (79 usual interstitial pneumonia and 26 non-specific interstitial pneumonia) and 49 cases of CTD-IP for derivation and 32 cases of IIP and 10 cases of CTD-IP for validation. Fourteen histological parameters were evaluated independently by two pathologists for derivation group and graded into 0 to 3. The association between the score for each marker and a diagnosis of CTD was investigated using Fisher’s exact test and stepwise logistic regression analysis. A formula for calculating the probability of IIP and CTD-IP was constructed by the markers identified in the regression test with coefficients for each finding. The formula was confirmed using validation case group.ResultsStepwise logistic regression analysis showed that plasmacytosis, lymphoid follicle with germinal center, and airspace fibrin were suggestive of CTD-IP and that fibroblastic foci, smooth muscle hyperplasia, cellular IP, dense perivascular collagen, and fat metaplasia were suggestive of IIP. The formula used to calculate the probabilities based on estimated values for each finding was created, and user-friendly web based app was composed at www.ctdip.com.On the validation study, 30 out of 32 IIP and eight out of 10 CTD-IPs were distinguished correctly by the app (Specificity: 93%, Sensitivity: 80%).ConclusionsWe identified histological markers and derived a practical formula and user-friendly app to distinguish CTD-IPs from IIP.

Histologic features suggesting connective tissue disease in idiopathic pulmonary fibrosis

“…*Cytotoxic agents included azathioprine, cyclophosphamide, cyclosporine, and mycophenolate mofetil. www.nature.com/scientificreports/ with idiopathic interstitial pneumonia (IIP; 79 with UIP and 26 with NSIP) and 49 with CTD-ILD and showed that plasma cell infiltration, lymphoid follicle with germinal centres, and airspace fibrin were predictive of CTD-ILD 21 . On the basis of these results, lymphoplasmacytic infiltration and interstitial lymphoid aggregates with germinal centres were suggested as histopathologic patterns of the morphologic domain in IPAF 6 .…”

“…Some histologic features, such as lymphoplasmacytic infiltration and lymphoid aggregates with or without germinal centres, have been reported to suggest CTD 7 , 21 . A previous study on 100 patients with a UIP pattern diagnosed via surgical lung biopsy (39 with CTD and 61 with IPF) reported that patients with CTD-UIP had higher total inflammation and germinal centre scores than those with IPF/UIP 7 .…”

“…A previous study on 100 patients with a UIP pattern diagnosed via surgical lung biopsy (39 with CTD and 61 with IPF) reported that patients with CTD-UIP had higher total inflammation and germinal centre scores than those with IPF/UIP 7 . Ozasa et al studied 105 patients with idiopathic interstitial pneumonia (IIP; 79 with UIP and 26 with NSIP) and 49 with CTD-ILD and showed that plasma cell infiltration, lymphoid follicle with germinal centres, and airspace fibrin were predictive of CTD-ILD 21 . On the basis of these results, lymphoplasmacytic infiltration and interstitial lymphoid aggregates with germinal centres were suggested as histopathologic patterns of the morphologic domain in IPAF 6 .…”

Interstitial lung disease pathology in systemic sclerosis

“…The profusion of plasma cells and lymphoid aggregates with germinal centers is variable, but tends to be greater in patients with underlying connective tissue disease, including systemic sclerosis, compared with patients with idiopathic NSIP. 16 Fibroblast foci are rare and the fibrosis tends to consist of dense collagen deposition. Although most cases comprise a mixture of inflammation and fibrosis, one component may predominate, resulting in what is referred to as cellular or fibrotic NSIP ( Figure 1a,b ).…”

Recognition of Connective Tissue Disease-Related Interstitial Pneumonia Based on Histological Score—A Validation Study of an Online Diagnostic Decision Support Tool

“…In view of this, a detailed histopathological scoring of 154 cases of IP was conducted to identify the parameters that reliably differentiated CTD-IPs and IIPs. Furthermore, a CTD-IP index capable of distinguishing these two disease groups was formulated; the formula was used to create a user-friendly application (www.CTDIP.com accessed on 17 September 2020), in which the user could enter a histological score for the parameter, and the application would yield the calculated result [16].…”