Inter- and intra-observer variability in the classification of extracapsular extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases

Abstract

Objective: Discern inter- and intra-observer variability in the classification of extracapsular extension (ECE) in p16+ oropharyngeal (OP) SCC comparing pathologists' own criteria versus those of a well-defined classification system.

Methods: Five pathologists reviewed 50 digitally scanned nodal metastasis slides in three Rounds. Round One was by their own criteria as ECE present or absent, and Rounds Two and Three were with a defined ECE system: Grade 0 (no ECE), 0c (no ECE - thick capsule; no infiltration), 1 (ECE - cells beyond capsule), and 2 (soft tissue metastasis - cells in soft tissue without residual node). Round Three assessed intra-observer variability after an 8 month washout period.

Results: In Round One, all five agreed on only 48% of cases (n=24). Fleiss's Kappa value was 0.508 (95% CI: 0.357-0.644). For Rounds Two and Three, Grades 0 and 0c and Grades 1 and 2 were separately grouped as ECE absent or present. In Round Two, all five agreed on 68% of cases (n=34). Fleiss' Kappa was 0.635 (95% CI: 0.472-0.783), indicating statistically significantly better agreement. In Round Three, all five agreed on 64% of cases (n=32) giving a Fleiss's Kappa of 0.639. Pathologists agreed with their prior reads in approximately 90% of cases (average n=45.4, range n=42-49), an average intra-observer Cohen's Kappa of 0.8 (range: 0.68-0.95). Inter- and intra-observer variability rates for classification of soft tissue metastasis (ECE2) were substantially worse.

Conclusion: There is substantial inter-, and modest intra-, observer variability among head and neck pathologists for ECE in p16+ OPSCC, which is modestly improved by a defined system.

Keywords: Extracapsular extension; Inter-observer variability; Lymph node metastasis; Oropharyngeal squamous cell carcinoma; Soft tissue metastasis; p16.

Figure 1

Defined classification system for extracapsular extension in nodal metastases. Grade 0 and 0c are considered to represent no extracapsular extension, while Grade 1 represents simple extracapsular extension with tumor cells invading perinodal soft tissue in the background of an at least partially preserved lymph node and Grade 2 represents nodal metastases where tumor cells have obliterated all nodal tissue and are just growing in irregular collections (so-called “soft tissue metastasis”).

Figure 2

Histopathologic examples of extracapsular extension Grades from the defined classification system. A) Tumor cells limited to lymph node parenchyma without alteration of the capsule or nodal architecture (Grade 0). B) Tumor cells limited to lymph node but with expansion of the node and development of a thickened capsule/pseudocapsule (designated by dashed line) around them (Grade 0c). C) Tumor cells invading into perinodal soft tissue (beyond dashed line and indicated by “ECE”) but with at least partial preservation of the lymph node (Grade 1). D) Tumor cells growing as irregular collections in the neck soft tissues without any histologic evidence of residual nodal parenchyma (Grade 2 or “soft tissue metastasis”) (all images hematoxylin and eosin stained; 15× magnification). ECE = extracapsular extension