5 years ago

Overinterpretation is common in pathological diagnosis of appendix cancer during patient referral for oncologic care

Irene Thung, Ann P. Tipps, Mojgan V. Hosseini, Joel M. Baumgartner, Grace Y. Lin, Alexey A. Hodkoff, Esha Gollapalle, Mark A. Valasek, Vera Vavinskaya, Andrew M. Lowy, Kaitlyn J. Kelly

by Mark A. Valasek, Irene Thung, Esha Gollapalle, Alexey A. Hodkoff, Kaitlyn J. Kelly, Joel M. Baumgartner, Vera Vavinskaya, Grace Y. Lin, Ann P. Tipps, Mojgan V. Hosseini, Andrew M. Lowy


Low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma are known to cause the majority of pseudomyxoma peritonei (PMP, i.e. mucinous ascites); however, recognition and proper classification of these neoplasms can be difficult despite established diagnostic criteria.


To determine the pathological diagnostic concordance for appendix neoplasia and related lesions during patient referral to an academic medical center specialized in treating patients with PMP.


The anatomic pathology laboratory information system was searched to identify cases over a two-year period containing appendix specimens with mucinous neoplasia evaluated by an outside pathology group and by in-house slide review at a single large academic medical center during patient referral.


161 cases containing appendix specimens were identified over this period. Forty-six of 161 cases (28.6%) contained appendiceal primary neoplasia or lesions. Of these, the originating pathologist diagnosed 23 cases (50%) as adenocarcinoma and 23 cases (50%) as LAMN; however, the reference pathologist diagnosed 29 cases (63.0%) as LAMN, 13 cases (28.3%) as adenocarcinoma, and 4 cases (8.7%) as ruptured simple mucocele. Importantly, for cases in which the originating pathologist rendered a diagnosis of adenocarcinoma, the reference pathologist rendered a diagnosis of adenocarcinoma (56.5%, 13 of 23), LAMN (39.1%, 9 of 23), or simple mucocele (4.3%, 1 of 23). The overall diagnostic concordance rate for these major classifications was 71.7% (33 of 46) with an unweighted observed kappa value of 0.48 (95% CI, 0.27–0.69), consistent with moderate interobserver agreement. All of the observed discordance (28.3%) for major classifications could be attributed to over-interpretation. In addition, the majority of LAMN cases (65.5%) had potential diagnostic deficiencies including over-interpretation as adenocarcinoma and lacking or discordant risk stratification (i.e. documentation of extra-appendiceal neoplastic epithelium).


Appendiceal mucinous lesions remain a difficult area for appropriate pathological classification with substantial discordance due to over-interpretation in this study. The findings highlight the critical need for recognition and application of diagnostic criteria regarding these tumors. Recently published consensus guidelines and a checklist provided herein may help facilitate improvement of diagnostic concordance and thereby reduce over-interpretation and potential overtreatment. Further studies are needed to determine the extent of this phenomenon and its potential clinical impact.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.pone.0179216

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