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Purpose: The purpose of this study is to clarify whether the image analysis using contrast enhanced CT, contrast enhanced T1‐weighted MR imaging and ultrasonography (US), is related with the cellular dissociation grade (CDG) based on tumor budding grade and cell nest size in stage I and II tongue oral squamous cell carcinoma (OSCC). Method: Seventeen cases of T1N0M0 and T2N0M0 tongue OSCC with the completion of more than 1‐year follow‐up were retrospectively enrolled. The satisfactory data, including contrast enhanced CT images, contrast enhanced T1‐weighted MR images, and US images as well as histopathological specimens could be taken from 16 cases and analyzed by the specialists of oral pathologist, oral radiologist, and oral and maxillofacial surgeon. Results: The differences between tumor thickness (TT) on US images and TT on contrast enhanced CT images or contrast enhanced T1‐weighted MR images were larger in the lower tumor budding grade cases rather than in the higher budding grade. Likely, such image‐measured TT differences were larger in the bigger nest cases than in the smaller nest cases. The occurrence of delayed nodal metastasis was related to the small TT differences of CT–US or MRI–US and the higher CDG score (≧5 points). All the cases with delayed nodal metastasis were CDG score ≧5 points. Conclusions: TT differences between on contrast enhanced CT/MR imaging, and US imaging may predict the cell dissociation activity and nodal metastasis. [ABSTRACT FROM AUTHOR]

Abstract 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

Background: Laryngeal squamous cell carcinoma (SCC) which is the most common carcinoma of the respiratory system after lung carcinomas is graded by the World Health Organization (WHO) into three groups as grades 1, 2, and 3. This system does not correlate with the prognosis and has a low reproducibility among the pathologists. Searching for a new grading system, in this study, we investigated the relationship between tumor budding and histomorphological parameters and survival status. We examined the new grading system based on cell nest size and tumor budding. Methods: Partial and total laryngectomy materials of 130 patients diagnosed as laryngeal SCC between 2012 and 2018 in our clinic were evaluated retrospectively by two pathologists. Tumor budding activity and cell nests were scored and a new score was obtained by summing the scores. According to the scores obtained, a new grading system was created. Results: There was a statistically significant difference between the tumor budding activity and the overall and disease-free survival times of the groups. The overall and disease-free survival time of the patients with high tumor budding significantly reduced. Tumor budding was found to be low in the presence of an intense lymphocytic host response (P < 0.05). There was no relationship between the new grade system and cell nest size and life expectancy (P > 0.05). Conclusions: Tumor budding provides significant clues in predicting the life expectancy of the patients. Therefore, tumor budding might be a component of new grading systems and should take place in pathology reports.

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]

Simple Summary: The pathological status of regional lymph nodes (pN) is the most important predictor of survival in patients with invasive squamous cell carcinoma of the penis. However, staging strategies have limited prediction, which results in false-negative findings or unnecessary lymphadenectomies. Therefore, additional criteria should be identified to improve the prediction of lymph node involvement. The "Cellular Dissociation Grade" (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the CDG was examined in 109 cases of invasive penile squamous cell carcinoma that were treated at the University Medicine Rostock between 2014 and 2022. Furthermore, its correlation with the pathologic status of regional lymph nodes (pN) as the main prognostic factor was verified. Finally, cellular dissociation grading was compared with classic WHO grading. The results showed that pN in penile squamous cell carcinoma showed a highly significant association with the CDG and no statistically significant association with WHO grading. These results support the notion that cellular dissociation grading is an important prognostic factor for squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Aims: Tumour budding (TB) activity, cell nest size (CNS), and desmoplastic reaction (DR) have been confirmed to be significantly correlated with prognosis in oesophageal squamous cell cancer (ESCC) recently. However, there are limited data on the prognostic significance of combined assessment of cellular dissociation and tumour stroma in ESCC. Methods: In all, 265 cases with resected ESCCs diagnosed between January 2018 and August 2019 were retrospectively reviewed. All slides were reviewed for assessing TB, CNS, and DR. The Cellular Dissociation Grading and our Combined CNS and DR (CNS/DR) Grading systems were adopted to re‐grade ESCCs. Results: High TB activity, small CNS, and immature DR had a strong association with shorter overall survival (OS) and progression‐free survival (PFS) (P < 0.001, respectively) in ESCC. Combined assessment of CNS and DR in a 4‐tiered grading system displayed a prognostic excellence for survival (P < 0.001), and outperformed the Cellular Dissociation Grading for both OS (area under the curve [AUC], 0.728 versus 0.644, P = 0.043) and PFS (AUC, 0.763 versus 0.667, P = 0.018) by receiver operator characteristic curves. Also, Combined CNS/DR Grading showed superiority in recognizing a G4 subgroup with the worst outcome in our cohort, to whom the most urgent attention needs to be called. Conclusions: This is the first study to propose a novel Combined Grading system based on CNS and DR in ESCC, which has been demonstrated to be relatively superior to Cellular Dissociation Grading in predicting prognosis. The findings shed new light on the histopathological grading of ESCC and facilitates identifying biologically aggressive ESCCs. [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]

Background: Laryngeal squamous cell carcinoma (SCC) which is the most common carcinoma of the respiratory system after lung carcinomas is graded by the World Health Organization (WHO) into three groups as grades 1, 2, and 3. This system does not correlate with the prognosis and has a low reproducibility among the pathologists. Searching for a new grading system, in this study, we investigated the relationship between tumor budding and histomorphological parameters and survival status. We examined the new grading system based on cell nest size and tumor budding., Methods: Partial and total laryngectomy materials of 130 patients diagnosed as laryngeal SCC between 2012 and 2018 in our clinic were evaluated retrospectively by two pathologists. Tumor budding activity and cell nests were scored and a new score was obtained by summing the scores. According to the scores obtained, a new grading system was created., Results: There was a statistically significant difference between the tumor budding activity and the overall and disease-free survival times of the groups. The overall and disease-free survival time of the patients with high tumor budding significantly reduced. Tumor budding was found to be low in the presence of an intense lymphocytic host response (P < 0.05). There was no relationship between the new grade system and cell nest size and life expectancy (P > 0.05)., Conclusions: Tumor budding provides significant clues in predicting the life expectancy of the patients. Therefore, tumor budding might be a component of new grading systems and should take place in pathology reports., Competing Interests: None

Aims: Squamous 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., Methods: 108 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., Results: The 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., Conclusions: In 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)