bims-netuvo 2023-03-05 papers

Issue of 2023‒03‒05
three papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

J Oral Pathol Med. 2023 Feb 27.

Prognostic significance of the neural invasion in oral squamous cell carcinoma.

Eder da Silva Dolens, Everton Freitas de Morais, Lívia Máris Ribeiro Paranaíba, Ana Lúcia Carrinho Ayroza Rangel, Alhadi Almangush, Tuula Salo, Peter A Brennan, Ricardo D Coletta.

BACKGROUND: Although nerve involvement can predict recurrence and prognosis in oral squamous cell carcinomas (OSCC), there still have controversies and limitations regarding the standardization for its detection. In this study we explore the impact of neural invasion in OSCC prognosis, comparing intraneural invasion (INI, tumor cells inside nerve structure) and perineural invasion (PNI, cells involving the nerve, but not invading its sheath).METHODS: Surgical slides stained with hematoxylin and eosin from 235 patients with OSCC were carefully verified for the presence of INI and PNI. The location in the tumor (intratumoral versus peritumoral) and number of foci (unifocal or multifocal) were also explored. Survival analyses for cancer-specific survival (CSS) and disease-free survival (DFS) were performed with Cox proportional model.
RESULTS: Neural invasion was identified in 74 cases, 64.9% displayed INI and 35.1% displayed PNI. Univariate analysis revealed a significantly poorer CSS, but not DFS, in patients with INI, in contrast to cases with PNI that did not achieve significant association with both CSS and DFS. Further analyses revealed that the location in the tumor and number of foci had little impact on discriminatory ability of INI. Multivariate analysis confirmed that INI is significantly and independently associated with poor CSS (HR: 2.50, 95% CI: 1.31-3.79, p=0.003).
CONCLUSION: This study provides evidence that INI, but not PNI, is a relevant predictor of survival in patients with OSCC, suggesting that its association with other clinical and pathological prognostic factors should be consider in determining the optimal treatment protocol and prognosis of these patients.

Keywords: histopathological features; oral cancer; perineural invasion; prognosis

DOI: https://doi.org/10.1111/jop.13423

Mod Pathol. 2023 Feb;pii: S0893-3952(22)00006-0. [Epub ahead of print]36(2): 100006

Clinicopathologic Predictors of Clinical Outcomes in Mammary Adenoid Cystic Carcinoma: A Multi-institutional Study.

Thaer Khoury, Marilin Rosa, Anupma Nayak, Rouzan Karabakhtsian, Oluwole Fadare, Zaibo Li, Bradley Turner, Yisheng Fang, Asangi Kumarapeli, Xiaoxian Li, Numbereye Numbere, Tatiana Villatoro, Ji-Gang Wang, Saed Sadeghi, Kristopher Attwood, Anthony George, Rohit Bhargava.

Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome. Clinical, radiological, and pathologic variables were recorded for 76 AdCC cases from 11 institutions. The following histologic characteristics were evaluated by the breast pathologist in each respective institution, including Nottingham grade (NG), percentages of various growth patterns (solid, cribriform, trabecular-tubular), percentage of basaloid component, tumor borders (pushing, infiltrative), perineural invasion, lymphovascular invasion, necrosis, and distance from the closest margin. Various grading systems were evaluated, including NG, salivary gland-type grading systems, and a new proposed grading system. The new grading system incorporated the growth pattern (percent solid, percent cribriform), percent basaloid morphology, and mitotic count using the Youden index criterion. All variables were correlated with recurrence-free survival. Nineteen (25%) women developed local and/or distant recurrence. Basaloid morphology (≥25% of the tumor) was identified in 20 (26.3%) cases and a solid growth pattern (using ≥60% cutoff) in 22 (28.9%) cases. In the univariate analysis, the following variables were significantly correlated with worse recurrence-free survival: solid growth pattern, basaloid morphology, lymphovascular invasion, necrosis, perineural invasion, and pN-stage. In the multivariate analysis including basaloid morphology, pN-stage, lymphovascular invasion, and perineural invasion, basaloid morphology was statistically significant, with a hazard ratio of 3.872 (95% CI, 1.077; 13.924; P =.038). The NG and the new grading system both correlated with recurrence-free survival. However, grade 2 had a similar risk as grade 3 in the NG system and a similar risk as grade 1 in the new grading system. For solid growth patterns and basaloid morphology, using a 2-tier system with 1 cutoff was better than a 3-tier system with 2 cutoffs. Basaloid morphology and solid growth pattern have prognostic values for AdCC, with a 2-tier grading system performing better than a 3-tier system.

Keywords: adenoid cystic carcinoma; basaloid; breast; grading; solid; survival

DOI: https://doi.org/10.1016/j.modpat.2022.100006

Neuro Oncol. 2023 Mar 02. pii: noad053. [Epub ahead of print]

Atypical Neurofibromas reveal distinct epigenetic features with proximity to benign peripheral nerve sheath tumor entities.

BACKGROUND: Plexiform neurofibromas can transform into atypical neurofibromas (ANF) and then further progress to aggressive malignant peripheral nerve sheath tumors (MPNST). ANF have been described to harbor distinct histological features and frequent loss of CDKN2A/B. However, histological evaluation may be rater-dependent, and detailed knowledge about the molecular mechanisms of malignant transformation is scarce. In general, malignant transformation can be accompanied by significant epigenetic changes, and global DNA methylation profiling is able to differentiate relevant tumor subgroups. Therefore, epigenetic profiling might provide a valuable tool to distinguish and characterize ANF with differing extent of histopathological atypia from neurofibromas and MPNST.METHODS: We investigated 40 tumors histologically diagnosed as ANF and compared their global methylation profile to other peripheral nerve sheath tumors.
RESULTS: Unsupervised class discovery and t-SNE analysis indicated that 36/40 ANF cluster with benign peripheral nerve sheet tumors with clear separation from MPNST. 21 ANF formed a molecularly distinct cluster in proximity to schwannomas. Tumors in this cluster had frequent heterozygous or homozygous loss of CDKN2A/B and significantly more lymphocyte infiltration than MPNST, schwannomas, and NF. Few ANF clustered closely with neurofibromas, schwannomas, or MPNST, raising the question, whether diagnosis based on histological features alone might pose a risk to both over- and underestimate the aggressiveness of these lesions.
CONCLUSIONS: Our data suggest that ANF with varying histological morphology show distinct epigenetic similarities and cluster in proximity to benign peripheral nerve sheath tumor entities. Future investigations should pay special respect to correlating this methylation pattern to clinical outcome.

Keywords: Atypical neurofibroma; DNA methylation; classification; diagnostic marker; peripheral nerve sheath tumors

DOI: https://doi.org/10.1093/neuonc/noad053