Tumor Budding and Cell Nest Size Are Highly Prognostic in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma

Abstract

Squamous cell carcinoma (SCC) is the most common cancer of the head and neck region including—among others—laryngeal (LSCC) and hypopharyngeal (HSCC) subsites. LSCC/HSCC are heterogenous diseases with respect to patient outcome. Currently, tumor stage–based patient stratification is essential to predict prognosis and thus selection of the appropriate treatment modalities. In contrast, the prognostic impact of the current HSCC/LSCC grading system according to the WHO classification is limited. Recently, a novel grading system based on tumor budding activity (BA) and cell nest size (CNS) has been introduced for SCC in different anatomic regions of the upper aerodigestive tract. To test and transvalidate this grading scheme in LSCC and HSCC, we retrospectively correlated BA, CNS, and additional histomorphologic parameters with clinicopathologic data of 157 treatment-naive patients. In doing so, we demonstrate that a 3-tiered novel grading system (well-differentiated [nG1], intermediately [nG2], and poorly differentiated [nG3]) based on a sum score for BA and CNS is highly and independently prognostic for patient survival in LSCC/HSCC, strongly outperforming the current WHO grading scheme with a hazard ratio for disease-specific survival of 6.6 for nG2 and 13.4 for nG3 cases (P<0.001). This finding contributes to a growing body of evidence that a CNS and BA-based pan-entity grading system in SCC might be useful and seems to capture differences in underlying SCC biology crucial for survival.

Evaluating the Histologic Grade of Digital Squamous Cell Carcinomas in Dogs with Dark and Light Haircoat—A Comparative Study of the Invasive Front and Tumor Cell Budding Systems

“…Two grading systems from human (Jesinghaus et al, (2018) [7] and Boxberg et al, (2019) [9]) and veterinary (Nagamine et al, (2017) [2]) medicine were adapted for the present study. The samples were assessed by a blinded diplomat of the American College of Veterinary Pathologists (ACVP) (AC), challenging the adapted systems.…”

“…An adaptation from two similar human SCC gradings systems of Jesinghaus et al (2018) [7] and Boxberg et al (2019) [9], designed for the uterine cervix and larynx/hypopharynx, respectively, was used. Both systems focus on the invasive front.…”

“…The features evaluated within this adapted grading included tumor budding in 10 HPF (unspecified The final addition of the score values of these five morphologic features resulted in a total invasive front score value. Subsequently, the total score value was summarized into four final grades according to Nagamine [9], designed for the uterine cervix and larynx/hypopharynx, respectively, was used. Both systems focus on the invasive front.…”

A Review Study on the Prevalence of Helicobacter Pylori Infection in Laryngeal Carcinoma

“…Some viruses may alter cellular immunity and cause malignancy. Chronic infections, radiation and air pollution are other factors [3,4].…”

<p>Long noncoding RNA ZEB2-AS1 facilitates laryngeal squamous cell carcinoma progression by miR-6840-3p/PLXNB1 axis</p>

“…Laryngeal squamous cell carcinoma (LSCC) is the most common malignancy with a poor diagnosis 1,2. It has a higher incidence among the head and neck malignancies.…”