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

PLoS One. 2017 Jun 7;12(6):e0179216. doi: 10.1371/journal.pone.0179216. eCollection 2017.


Context: 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.

Objective: 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.

Design: 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.

Results: 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).

Conclusions: 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.

MeSH terms

  • Adenocarcinoma, Mucinous / classification
  • Adenocarcinoma, Mucinous / diagnosis*
  • Adenocarcinoma, Mucinous / physiopathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Appendiceal Neoplasms / classification
  • Appendiceal Neoplasms / diagnosis*
  • Appendiceal Neoplasms / physiopathology
  • Appendix / pathology
  • Clinical Laboratory Information Systems
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Pseudomyxoma Peritonei / classification
  • Pseudomyxoma Peritonei / diagnosis*
  • Pseudomyxoma Peritonei / physiopathology
  • Referral and Consultation

Grant support

The authors received no specific funding for this work.