High-Grade Follicular Cell-Derived Non-Anaplastic Thyroid Carcinoma: Correlating Extent of Invasion and Mutation Profile with Oncologic Outcome.

The 2022 World Health Organization classification introduced the term high-grade follicular cell-derived nonanaplastic thyroid carcinoma (HGFCTC) to define invasive/infiltrative nonanaplastic thyroid carcinoma with high-grade features, including poorly differentiated thyroid carcinoma and high-grade differentiated thyroid carcinoma. Our objectives were to compare clinicopathological characteristics, oncologic outcomes, and mutation profiles among HGFCTC subgroups to better inform prognostication and treatment. In this single-center, retrospective cohort study of 252 patients who had surgery for HGFCTC from 1986 to 2020, we categorized HGFCTC and its related entity, "encapsulated noninvasive neoplasms of follicular cells with high-grade features," into five subgroups: (A) encapsulated noninvasive, (B) encapsulated with capsular invasion only (minimally invasive), (C) encapsulated angioinvasive with focal vascular invasion (VI), (D) encapsulated angioinvasive with extensive VI, and (E) infiltrative tumors.

Targeted RNA sequencing in diagnostically challenging head and neck carcinomas identifies novel MON2::STAT6, NFATC2::NUTM2B, POC5::RAF1, and NSD3::NCOA2 gene fusions.

Aims: Although molecular tests developed for a growing list of oncogenic alterations have significantly aided in the classification of head and neck carcinomas, tumours in which prototypical histologic and immunophenotypic features are lacking or only partially developed continue to pose diagnostic challenges. Searching for known diagnostic and therapeutic targets by clinical next-generation sequencing (NGS) assays can often lead to new discoveries.

Methods And Results: We present our institutional experience in applying targeted RNA NGS in 36 head and neck carcinomas that were morphologically difficult to classify between 2016 and 2023.

Analysis of ASCL1/NEUROD1/POU2F3/YAP1 Yields Novel Insights for the Diagnosis of Olfactory Neuroblastoma and Identifies Sinonasal Tuft Cell-Like Carcinoma.

The diagnosis and treatment of sinonasal small round epithelial/neuroepithelial malignancies depend on the expression of conventional neuroendocrine markers (NEMs), such as synaptophysin, chromogranin A, INSM1, and CD56/NCAM1. However, these tumors remain diagnostically challenging because of overlapping histologic and immunohistochemical features. The transcriptional regulators ASCL1, NEUROD1, POU2F3, and YAP1 are novel NEM (nNEM) used for the subtyping of small-cell lung cancer (SCLC).

The Utility of BSND Immunohistochemistry in the Differential Diagnosis of Oncocytic and Warthin-like Mucoepidermoid Carcinoma of Salivary Gland.

Purpose: BSND is a chloride channel subunit that is expressed in the normal salivary gland. We aimed to validate the utility of BSND immunohistochemistry in the differential diagnosis of oncocytic salivary gland neoplasms.

Methods: BSND immunohistochemistry was performed in a retrospective cohort of 93 salivary gland lesions, enriched with tumors with oncocytic features and histologic variants of mucoepidermoid carcinoma (MEC).

Defining angioinvasion and lymphatic invasion in papillary thyroid carcinoma: morphological criteria, utility of D2-40/CD31/ERG immunohistochemistry and correlation with clinicopathological characteristics.

Aims: While CAP and ICCR protocols mandate the separation of angioinvasion (AI) and lymphatic invasion (LI) in thyroid carcinoma, distinction between them can be difficult. Because the presence of AI is used to stratify patients with papillary thyroid carcinoma (PTC), there is a need to accurately diagnose AI and LI.

Methods And Results: AI and LI were evaluated in 162 cases of PTC (n = 155) and high-grade differentiated thyroid carcinoma, papillary phenotype (HGDTCp, n = seven) using haematoxylin and eosin (H&E), D2-40 and CD31/ERG.

RBM10 loss induces aberrant splicing of cytoskeletal and extracellular matrix mRNAs and promotes metastatic fitness.

RBM10 modulates transcriptome-wide cassette exon splicing. Loss-of-function mutations are enriched in thyroid cancers with distant metastases. Analysis of transcriptomes and genes mis-spliced by RBM10 loss showed pro-migratory and RHO/RAC signaling signatures.

DNA Mutational and Copy Number Variation Profiling of Primary Craniofacial Osteosarcomas by Next-Generation Sequencing.

Background: Craniofacial osteosarcomas (CFOS) are uncommon malignant neoplasms of the head and neck with different clinical presentation, biological behavior and prognosis from conventional osteosarcomas of long bones. Very limited genetic data have been published on CFOS.

Methods: In the current study, we performed comprehensive genomic studies in 15 cases of high-grade CFOS by SNP array and targeted next generation sequencing.

Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions.

Background: Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets.

The histological spectrum and immunoprofile of head and neck NUT carcinoma: A multicentre series of 30 cases.

Background And Aim: Head and neck nuclear protein of testis carcinoma (HN-NUT) is a rare form of carcinoma diagnosed by NUT immunohistochemistry positivity and/or NUTM1 translocation. Although the prototype of HN-NUT is a primitive undifferentiated round cell tumour (URC) with immunopositivity for squamous markers, it is our observation that it may assume variant histology or immunoprofile.

Methods: We conducted a detailed clinicopathological review of a large retrospective cohort of 30 HN-NUT, aiming to expand its histological and immunohistochemical spectrum.

Papillary thyroid carcinoma tall cell subtype (PTC-TC) and high-grade differentiated thyroid carcinoma tall cell phenotype (HGDTC-TC) have different clinical behaviour: a retrospective study of 1456 patients.

Aims: Papillary thyroid carcinoma, tall cell subtype (PTC-TC) is a potentially aggressive histotype. The latest World Health Organisation (WHO) classification introduced a novel class of tumours; namely, high-grade differentiated thyroid carcinoma (HGDTC), characterised by elevated mitotic count and/or necrosis, which can exhibit a tall cell phenotype (HGDTC-TC).

Methods And Results: We analysed the clinical outcomes in a large retrospective cohort of 1456 consecutive thyroid carcinomas with a tall cell phenotype, including PTC-TC and HGDTC-TC.

A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer.

Purpose: We investigated reflectance confocal microscopy (RCM) as a possible noninvasive approach for the diagnosis of cancer and real-time assessment of surgical margins.

Experimental Design: In a phase I study on 20 patients, we established the RCM imaging morphologic features that distinguish oral squamous cell carcinoma (OSCC) from normal tissue with a newly developed intraoral RCM probe. Our subsequent phase II prospective double-blinded study in 60 patients tested the diagnostic accuracy of RCM against histopathology.

-Mutated Cytologically Indeterminate Thyroid Nodules: Prevalence of Malignancy and Behavior Under Active Surveillance.

Genomic profiling is now available for risk stratification of cytologically indeterminate thyroid nodules (ITNs). Mutations in genes (, , ) are found in both benign and malignant thyroid nodules, although isolated mutations are rarely associated with aggressive tumors. Because the long-term behavior of -mutant ITNs is not well understood, most undergo immediate surgery.

Novel prognostic nomogram for predicting recurrence-free survival in medullary thyroid carcinoma.

Aims: Recently, there have been attempts to improve prognostication and therefore better guide treatment for patients with medullary thyroid carcinoma (MTC). In 2022, the International MTC Grading System (IMTCGS) was developed and validated using a multi-institutional cohort of 327 patients. The aim of the current study was to build upon the findings of the IMTCGS to develop and validate a prognostic nomogram to predict recurrence-free survival (RFS) in MTC.

FGFR1/2/3-rearranged carcinoma of the head and neck: expanded histological spectrum crossing path with high-risk HPV in the sinonasal tract.

Aims: Oncogenic FGFR1/2/3 rearrangements are found in various cancers. Reported cases in head and neck (HN) are mainly squamous cell carcinomas (SCCs) with FGFR3::TACC3 fusions, a subset of which also harbour high-risk human papillomavirus (HPV). However, the knowledge of the clinicopathological spectrum of FGFR-rearranged head and neck carcinomas (FHNC) is limited.

Expanding the histological spectrum of salivary gland neoplasms with HMGA2::WIF1 fusion emphasising their malignant potential: a report of eight cases.

Aims: Recently, HMGA2::WIF1 fusion has been reported in pleomorphic adenoma (PAs) originating from the parotid gland with a characteristic canalicular adenoma (CAA)-like pattern. However, it is unclear whether HMGA2::WIF1 fusion may occur in salivary gland carcinoma or tumours originating from the minor salivary glands. We herein conducted a detailed clinicopathological review of eight salivary gland tumours harbouring HMGA2::WIF1 fusions.

Association of the Genomic Profile of Medullary Thyroid Carcinoma with Tumor Characteristics and Clinical Outcomes in an International Multicenter Study.

The prognostic importance of and mutations and their relationship to clinicopathologic parameters and outcomes in medullary thyroid carcinoma (MTC) need to be clarified. A multicenter retrospective cohort study was performed utilizing data from 290 patients with MTC. The molecular profile was determined and associations were examined with clinicopathologic data and outcomes.

Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma.

Background: For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N).

Methods: Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established.

Ki67 proliferation index in medullary thyroid carcinoma: a comparative study of multiple counting methods and validation of image analysis and deep learning platforms.

Aims: The International Medullary Thyroid Carcinoma Grading System, introduced in 2022, mandates evaluation of the Ki67 proliferation index to assign a histological grade for medullary thyroid carcinoma. However, manual counting remains a tedious and time-consuming task.

Methods And Results: We aimed to evaluate the performance of three other counting techniques for the Ki67 index, eyeballing by a trained experienced investigator, a machine learning-based deep learning algorithm (DeepLIIF) and an image analysis software with internal thresholding compared to the gold standard manual counting in a large cohort of 260 primarily resected medullary thyroid carcinoma.