Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system

Boxberg, Melanie; Jesinghaus, Moritz; Dorfner, Christiane; Mogler, Carolin; Drecoll, Enken; Warth, Arne; Steiger, Katja; Bollwein, Christine; Meyer, Petra; Wolff, Klaus; Kolk, Andreas; Weichert, Wilko

doi:10.1111/his.13173

Cited by 90 publications

(162 citation statements)

References 47 publications

(71 reference statements)

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“…Our recently proposed histopathological grading scheme for OSCC15 consists of the morphological patterns ‘cell nest size’—scored from 1 (large cell nests>15 cells) to up to 4 (single cell invasion)—and ‘tumour budding activity’—scored from 1 (no budding activity) to up to 3 (>15 budding nests/10HPF). Both criteria, cell nest size and budding activity, have previously been described as surrogate parameters for tumour aggressiveness in head and neck SCC40–44 and in a variety of other solid cancers 15 18 19 21 22.…”

Section: Discussionmentioning

confidence: 99%

“…15 This novel grading scheme is strongly linked to and cross validated by comparable grading algorithms recently developed for SCC of the larynx (unpublished data), lung, oesophagus and uterine cervix 16–19. Major prognostic impact of the feature tumour budding has furthermore been reported for other cancers such as breast, gastric and colorectal adenocarcinoma 20–24…”

Section: Introductionmentioning

confidence: 88%

“…Total 108 cases of a previously characterised cohort of n=157 OSCC15 were evaluated. To focus our evaluation on prototypical oral squamous cell carcinomas, cases which exceeded the oral cavity as well as those with p16 expression on immunohistochemistry15 were excluded from our study as were cases in which tumour area covered below 20% of the H&E stained slide.…”

Section: Methodsmentioning

confidence: 99%

“…To focus our evaluation on prototypical oral squamous cell carcinomas, cases which exceeded the oral cavity as well as those with p16 expression on immunohistochemistry15 were excluded from our study as were cases in which tumour area covered below 20% of the H&E stained slide. All carcinomas were surgically resected in the department of Oral and Maxillofacial Surgery of the Klinikum Rechts der Isar, University Hospital of the Technical University Munich between 2007 and 2012 according to a standard protocol derived from the German guidelines for treatment of OSCC 38.…”

Section: Methodsmentioning

confidence: 99%

“…Histopathological evaluation of tumour budding activity in 10 high power fields (HPF) and cell nest size was carried out as previously described15 (Field diameter 0.55 mm). Tumour budding was defined as branching of small tumour nests harbouring <5 tumour cells into the surrounding parenchyma/stroma with low budding activity defined as 1–14 and high budding activity ≥15 budding nests per 10 HPF.…”

Section: Methodsmentioning

confidence: 99%

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Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance

et al. 2018

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AimsSquamous cell carcinoma of the oral cavity (OSCC) is a common tumour entity with a variable, partially highly aggressive clinical course. Recently, we proposed a novel (three-tiered) clinically useful grading scheme strongly associated with patient outcome in OSCC, consisting of a sum score of the histomorphological patterns tumour budding and cell nest size which outperforms WHO based grading algorithms currently in use. The aim of our study was to probe for interobserver and intraobserver reliability of this novel grading system.Methods108 OSCC were retrospectively scored according to the proposed grading scheme by three independent pathologists—two experienced head and neck pathologists and one pathologist in training—blinded to each other’s scoring results.ResultsThe Cohen’s Kappa (κ) values for concordance rates between experienced pathologists were κ=0.97 for the overall grade, κ=0.97 for budding activity and κ=0.91 for cell nest size, indicating a strong interobserver reliability of our proposed grading system. Initial interobserver agreement was markedly lower with the pathologist in training (κ=0.55 for overall grade) but improved significantly after a training session (κ=0.87 for overall grade). Intraobserver concordance was high (κ=0.95 for overall grade), indicating a high reproducibility of the algorithm.ConclusionsIn conclusion, our study indicates that OSCC grading based on our proposed novel scheme yields an excellent inter-reader and intrareader agreement, further supporting the suitability of this grading system for routine pathological practice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance

et al. 2018

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Poor tumor differentiation is an independent adverse prognostic variable in patients with locally advanced oral cavity cancer––Comparison with pathological risk factors according to the NCCN guidelines

et al. 2021

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Methods We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p < 0.001), distant metastases (DM, 6%/18%/40%, p < 0.001), disease‐free survival (DFS, 78%/63%/46%, p < 0.001), disease‐specific survival (DSS, 85%/71%/49%, p < 0.001), and overall survival (OS, 68%/55%/39%, p < 0.001). Multivariable analysis identified the following variables as independent prognosticators for 5‐year outcomes: ENE (LC/NC/DM/DFS/DSS/OS), poorly differentiated tumors (NC/DM/DFS/DSS/OS), positive margins (LC/DFS), lymphatic invasion (DFS/DSS/OS), perineural invasion (DM), and age ≥65 years (OS). Conclusions In addition to ENE, poor tumor differentiation was identified as the second most relevant adverse RF for patients with pT3–4 OCSCC. We suggest that the NCCN guidelines should include poor tumor differentiation as an adverse RF to refine and tailor clinical management.

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Post‐neoadjuvant assessment of tumour budding according to ITBCC subgroups delivers stage‐ and regression‐grade independent prognostic information in intestinal‐type gastric adenocarcinoma

Jesinghaus

Herz

Kohlruss

et al. 2022

The Journal of Pathology CR

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Tumour budding (TB) has been associated with adverse clinicopathological factors and poor survival in a plethora of therapy‐naïve carcinoma entities including gastric adenocarcinoma (GC). As conventional histopathological grading is usually omitted in the post‐neoadjuvant setting of GC, our study aimed to investigate the prognostic impact of TB in GCs resected after neoadjuvant therapy. We evaluated TB according to the criteria from the International Tumour Budding Consensus Conference (ITBCC) in 167 post‐neoadjuvant resections of intestinal‐type GC and correlated the results with overall survival (OS) and clinicopathological parameters. GCs were categorised into Bd1 (0–4 buds, low TB), Bd2 (5–9 buds, intermediate TB), and Bd3 (≥10 buds, high TB). Carcinomas with intermediate and high TB were significantly enriched in higher ypTNM stages and strongly associated with reduced 5‐year OS in univariable analyses ( p < 0.001). In multivariable analyses including sex, age, resection status, UICC stage, and tumour regression grading, TB remained a stage‐independent predictor of survival ( p < 0.001, hazard ratio Bd2: 2.60, Bd3: 4.74). The assessment of TB according to the ITBCC criteria provides valuable prognostic information in the post‐neoadjuvant setting of intestinal‐type GC and may be a considerable substitute for the conventional grading system in GCs after neoadjuvant therapy.

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Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system

Cited by 90 publications

References 47 publications

Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance

Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance

Poor tumor differentiation is an independent adverse prognostic variable in patients with locally advanced oral cavity cancer––Comparison with pathological risk factors according to the NCCN guidelines

Post‐neoadjuvant assessment of tumour budding according to ITBCC subgroups delivers stage‐ and regression‐grade independent prognostic information in intestinal‐type gastric adenocarcinoma

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