Search

Grading of squamous cell carcinomas (SCCs) based on tumour budding and cell nest size has been termed cellular dissociation grading (CDG) and was suggested as a robust outcome predictor when assessed in biopsies and resections of various extrapulmonary SCCs. In pulmonary SCC (pSCC), this has so far been shown only for resected cancers. As most lung cancers are inoperable, it is of utmost importance to clarify whether the prognostic impact of CDG is retained in the biopsy setting. Two independent pSCC biopsy cohorts from Munich (n = 134, non‐resected) and Heidelberg (n = 135, resected) were assessed. Tumour budding and cell nest size measures were assembled into the three‐tiered CDG system (G1–G3). Data were correlated with clinicopathological parameters and overall‐ (OS), disease‐specific‐ (DSS), and disease‐free survival (DFS). Interobserver variability and concordance between biopsy and resection specimen were also investigated. CDG was highly congruent between biopsy and resection specimens (κ = 0.77, p < 0.001). In both pSCC cohorts, biopsy‐derived CDG strongly impacted on OS, DSS, and DFS (e.g. DFS: p < 0.001). In multivariate survival analyses, CDG remained a stage independent predictor of survival in both cohorts (DFS: p < 0.001 respectively; hazard ratio Munich cohort: CDG‐G2: 4.31, CDG‐G3; 5.14; Heidelberg cohort: CDG‐G2: 5.87, CDG‐G3: 9.07). Interobserver agreement for CDG was almost perfect (κ = 0.84, p < 0.001). We conclude that assessment of CDG based on tumour budding and cell nest size is feasible on pSCC biopsies and harbours stage independent prognostic information in resectable as well as non‐resectable pSCC. Integration of this grading approach into clinicopathological routine should be considered. [ABSTRACT FROM AUTHOR]

Abstract: Cervical cancer is one of the commonest cancers worldwide, especially in developing countries. In early stage disease, a variety of pathological parameters are of prognostic value but currently this does not include tumour grade which, for a number of reasons, is of limited or no value in cervical squamous cell carcinomas. In a recent article in this journal, Jesinghaus and colleagues investigated a novel histopathological grading system based on tumour budding and cell nest size, which has been shown to outperform conventional grading systems for squamous cell carcinoma at several other sites such as lung, oral cavity, and oesophagus in terms of patient prognostication. They tested the prognostic value of this grading system in two independent cohorts of cervical squamous cell carcinoma. The grading system proved to be a highly effective, stage‐independent prognosticator in both cohorts with small cell nest size and high tumour budding indicative of a poor prognosis. It is hoped that the results of this study will be validated in additional independent larger cohorts and will act as an impetus for the development of a meaningful and easy‐to‐implement grading system for cervical squamous cell carcinoma. As comparable tumour budding/cell nest size‐based grading systems have been shown to be of prognostic value for squamous cell carcinomas at other sites, this shows the potential of these parameters to serve as the basis for a common grading system applicable to squamous cell carcinomas of different anatomic sites. [ABSTRACT FROM AUTHOR]

Abstract: A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO‐based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology‐based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e.g., keratinization, nuclear size, mitotic activity) in a test cohort (n = 125) and an independent validation cohort (n = 122) of cervical SCC. All parameters were correlated with clinicopathological factors and patient outcome. Small cell nest size and high tumour budding activity were strongly associated with a dismal patient prognosis (p < 0.001 for overall survival [OS], disease‐specific survival, and disease‐free survival; test cohort) in both cohorts of cervical SCC. A novel grading algorithm combining these two parameters proved to be a highly effective, stage‐independent prognosticator in both cohorts (OS: p < 0.001, test cohort; p = 0.001, validation cohort). In the test cohort, multivariate statistical analysis of the novel grade revealed that the hazard ratio (HR) for OS was 2.3 for G2 and 5.1 for G3 tumours compared to G1 neoplasms (p = 0.010). In the validation cohort, HR for OS was 3.0 for G2 and 7.2 for G3 tumours (p = 0.012). In conclusion, our novel grading algorithm incorporating cell nest size and tumour budding allows strongly prognostic histopathological grading of cervical SCC superior to WHO‐based grading. Therefore, our data can be regarded as a cross‐organ validation of previous results demonstrated for oesophageal, lung, and oral SCC. We suggest this grading algorithm as an additional morphology‐based parameter for the routine diagnostic assessment of this tumour entity. [ABSTRACT FROM AUTHOR]