A new era for autoimmune pancreatitis diagnosis: fine-needle biopsy outperforms fine-needle aspiration in endoscopic ultrasound-guided tissue acquisition
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Autoimmune pancreatitis (AIP) is a distinct form of pancreatitis driven by autoimmune mechanisms. AIP is classified into two subtypes: type 1 AIP, the pancreatic manifestation of immunoglobulin G4 (IgG4)-related disease is histologically defined by lymphoplasmacytic sclerosing pancreatitis (LPSP), whereas type 2 AIP is characterized by idiopathic duct-centric pancreatitis.
The International Consensus Diagnostic Criteria (ICDC) for AIP adopt a comprehensive diagnostic approach incorporating imaging, serology, other organ involvement, pancreatic histology, and steroid response.1 Although histological confirmation is not always necessary in cases with typical imaging features (diffuse type) or concomitant evidence from serology and other organ involvement, approximately half of patients with AIP present with indeterminate/atypical imaging features that necessitate differentiation from pancreatic malignancy. In focal-type AIP, homogeneous delayed enhancement on contrast-enhanced computed tomography can aid in distinguishing it from pancreatic cancer, with endoscopic ultrasound (EUS)-guided tissue acquisition (TA) playing a pivotal role in establishing a definitive diagnosis.2
According to the ICDC, histopathological diagnosis of type 1 AIP requires meeting at least three of four key features: periductal lymphoplasmacytic infiltration without granulocytic infiltration, obliterative phlebitis, storiform fibrosis, and abundant IgG4-positive cells. EUS-guided fine-needle aspiration (FNA) has traditionally been used with variable success for TA in patients with AIP. Recently developed fine-needle biopsy (FNB) needles offer the advantage of preserving tissue architecture for histological examination using methods including immunohistochemistry. Although EUS-FNB has shown promising results, available data remains limited.
In the current issue of Clinical Endoscopy, Yonamine et al.3 investigated the predictive factors for identifying histologic findings in 50 patients with type 1 AIP who underwent EUS-TA between 2011 and 2023. Of these, FNA needles (19-guage or 22-guage [22-G]) were used for 18 patients, whereas FNB needles (primarily 22-G), which became the preferred option after 2017, were used in 32 patients. Histopathological analysis revealed level 1 or 2 LPSP findings in 41 patients (82.0%), including level 1 and 2 in 33 patients (66%) and 11 patients (22%), respectively. Among the histological findings, lymphoplasmacytic infiltration, abundant IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis were observed in 41 (82%), 41 (82%), 33 (66.0%), and 12 (24.0%) patients, respectively. The relatively low detection rates of storiform fibrosis and obliterative phlebitis, regardless of needle type, underscore the challenges associated with their heterogeneous distribution and histological ambiguity. These findings highlight the need for optimized sampling strategies and supplementary diagnostic tools to improve detection of these key histological features.
In multivariate analysis, FNB needles were identified as the only significant predictive factor for LPSP detection (odds ratio, 15.1; 95% confidence interval, 1.62–141; p=0.017). The prevalence of good-quality specimens (specimen adequacy score ≥4) was significantly higher in the FNB needle group than in the FNA needle group (97% vs. 56%, p<0.01). Furthermore, the FNB needle group required a considerably lower number of needle passes than the FNA needle group (median number, 2 vs. 3; p<0.01).
Although macroscopic on-site evaluation (MOSE) was not an independent factor in multivariate analysis, its frequent application in the FNB group may have contributed to the elevated specimen adequacy and diagnostic yield. Future studies are warranted to investigate the additive role of MOSE in improving diagnostic accuracy. As these procedures were performed by experienced endosonographers and trainees without randomized needle allocation, operator-related factors may also have influenced outcomes. Standardizing procedural techniques and implementing structured training programs may improve consistency across institutions.
Collectively, these findings reinforce growing evidence favoring FNB over FNA for type 1 AIP diagnosis. A recent systematic review of 16 studies involving 440 patients who underwent EUS-FNA or FNB for AIP reported significantly higher accuracy of histological diagnosis using EUS-FNB than that using EUS-FNA (87.2% vs. 55.8%).4 Recent retrospective comparative studies have further highlighted the advantages of FNB over FNA. A retrospective study comparing EUS-FNB using a Franseen needle with FNA needles in type 1 AIP revealed significantly higher detection rates of level 1 and 2 histological findings in the EUS-FNB group (56.0% vs. 12.5%, p=0.001).5
Prospective studies on the diagnostic yield of FNB needles in AIP remain limited. The first prospective study to evaluate FNB needles was a randomized controlled multicenter study comparing 22-G Franseen needles with 20-G forward-beveled needles in suspected type 1 AIP.6 Level 1 histologic criteria were met in 56% of the Franseen group compared to 26% of the forward-beveled group (p=0.001). In another prospective, multicenter, single-arm study evaluating EUS-FNB with a 22G Franseen needle, level 1 histologic criteria were met in 58% of cases, whereas level 1 or 2 findings were observed in 93%.7 Notably, the detection rates for level 1 or 2 histologic findings displayed association with the length of the core tissue obtained. Few studies have evaluated fork-tip-type needles for AIP. A retrospective study comparing reverse-bevel needles (n=6) with fork-tip needles (n=18) in 24 patients with a final diagnosis of type 1 AIP found no diagnostic samples obtained with reverse-bevel needles, whereas 78% of the fork-tip samples were diagnostic (p=0.001), with 72% meeting level 1 criteria.8 These findings suggest that FNB needles, particularly Franseen or fork-tip designs, exhibit favorable detection rates for histologic diagnosis of type 1 AIP. Guideline recommendations have also evolved. A 2020 Japanese consensus guideline recommends EUS-FNA or FNB when a diagnosis cannot be established without pathology specimen collection or when malignancy cannot be excluded.9 However, a more recent 2025 European guideline suggests using end-cutting FNB needles rather than reverse-bevel FNB or FNA needles for histopathologic diagnosis of AIP.10
In conclusion, EUS-FNB exhibits superiority over FNA for histological diagnosis of AIP. Nevertheless, ongoing research is imperative to improve its reliability for detecting all level 1 histological features. Further well-designed prospective multicenter studies are warranted to establish standardized guidelines for needle selection and procedural techniques to enhance AIP diagnostic accuracy.
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Conflicts of Interest
The authors have no potential conflicts of interest.
Funding
None.
Author Contributions
Conceptualization: all authors; Supervision: TJS; Writing–original draft: GH; Writing–review & editing: all authors.