For a long time prior to the popularization of serum IgG4 measurement and EUS-FNA, we occasionally encountered patients with TFCP among them undergoing resection for suspected pancreatic malignancy [12–14]. When we received pathological reports of benignancy in patients with suspected malignancy, we reviewed the clinical images and surgical indications and examined the pathological etiology of the tumor-forming lesions. Since the emergence of new concepts such as AIP [8, 15, 16], it has been clarified that some patients with AIP have been included among those with TFCP. We therefore focused on determining how many patients with AIP were included among those with TFCPs prior to the practical use of IgG4 immunostaining in our institution. Because retrospective histological reviews were rarely performed [11], we also investigated tissue blocks of TFCP obtained during the 30 years before 2009. IgG4 immunostaining revealed 14 (43.8%) cases of AIP among 32 cases of TFCP without ACP, which is similar to the findings reported by Kobayashi et al. [17] [i.e., 6 (66.7%) cases of AIP among 9 cases of TFCP]. This suggests that nearly half of TFCP cases are AIP. Moreover, IgG4 immunostaining of non-neoplastic diseases (i.e., false-positive specimens) in patients with ACP and stenosis of the larger pancreatic duct during the same time period revealed 14 (27.5%) cases of AIP among 51 non-neoplasms, which is almost identical to the findings in four surgical series in which AIP was present in 31/159 (19.5%), 11/47 (23.4%), 6/23 (26.1%), and 10/33 (30.3%) patients who underwent resection non-neoplastic pancreatic disease, respectively [13, 14, 18, 19]. Consequently, it seems likely that nearly 30% of false-positive cases are AIP.
The emergence of serum IgG4 measurement and EUS-FNA for the diagnosis of AIP has surely reduced the incidence of non-neoplastic pancreatic resection. This was clearly demonstrated in our series: 32 (4.7%) cases of TFCP (excluding ACP) were present among 675 pancreatic resections during the 30 years before 2009, whereas 11 (0.9%) cases of TFCP were present among 1289 pancreatic resections during the 10 years after 2009. Moreover, it is evident that the increased use of the ICDC for AIP [6] and greater precision of diagnostic imaging (i.e., CT, US, and magnetic resonance imaging) have contributed to a marked decrease in TFCP resection during the last decade. Interestingly, the ratio of AIP/unknown etiology among cases of TFCP during the two periods in the present study was very similar at 0.78 (14/18) in the former 30 years and 0.83 (5/6) in the latter 10 years.
We found no reports of the anatomical distribution of lesions in non-neoplastic pancreatic resection. Moreover, the relationship between the anatomical distribution and AIP has rarely been reported [17]. We found AIP in 7 (58.3%) of 12 diffuse (head-to-body or body-to-tail) lesions and in 12 (30.8%) of 39 focal/segmental lesions. The percentage of patients with AIP was higher among those with diffuse lesions; thus, it is likely that AIP is more often observed in larger lesions. Although these larger lesions are generally easy to diagnose by serum IgG4 measurement or EUS-FNA, how to diagnose focal, small lesions remains controversial [20–22]. Small lesions do not always show remarkable elevation of the serum IgG4 concentration, and it may be anatomically difficult to obtain a specimen by EUS-FNA. In previous studies involving such cases, the diagnostic performance was significantly higher when both cytological and Tru-Cut biopsy [23] and cell-block examination [24] were carried out than when only cytological examination was performed. During the latter 10 years of the present study, popularization of EUS-FNA for differential diagnosis of pancreatic tumors advanced remarkably, and this is certain to facilitate further reduction in the performance of non-neoplastic pancreatic resection in the near future.
In conclusion, retrospective IgG4 immunostaining of TFCP tissue blocks obtained during the 30 years before 2009 revealed 14 (43.8%) cases of AIP among 32 cases of TFCP, whereas 5 (45.5%) cases of AIP were found among 11 cases of TFCP during the 10 years after 2009 (i.e., the period during which serum IgG4 measurement and EUS-FNA were implemented). The TFCP ratio was 6.7% in the former 30 years and only 0.9% in the latter 10 years. The findings of the present study indicate that serum IgG4 measurement and EUS-FNA are imperative for the diagnosis of TFCP.