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Background and Purpose: The aims of our study are to evaluate the diagnostic performance and prognostic value of radiological lymph node (LN) characteristics in pN+ oral cavity squamous carcinoma (OSCC). Materials and Methods: pN+ OSCC treated between 2012 and 2020 were included. Preoperative imaging was reviewed by a single radiologist blinded to pathologic findings for the following nodal features: imaging‐positive LN (iN+), laterality and total number, and image‐identified extranodal extension (iENE). The sensitivity of iN+ for pN+ was calculated. The diagnostic performance of other nodal features was evaluated in the iN+ subgroup. The association of radiologic nodal features with overall survival (OS) was evaluated. Inter‐rater kappa for radiologic nodal features was assessed in 100 randomly selected cases. Results: Of 406 pN+ OSCC, 288 were iN+. The sensitivity of iN+ for pN+ was 71% overall, and improved to 89% for pN+ LN >1.5 cm. Within iN+, sensitivity/specificity for LN size (>3 cm), total LN number (>4), and ENE were 0.44/0.95, 0.57/0.84, and 0.27/0.96, respectively. Sensitivity of iENE was higher in the subset, with major (>2 mm) versus minor (≤2 mm) pENE (43% vs. 13%, p = 0.001). Reduced OS was observed in iN+ versus iN– (p = 0.006), iENE+ versus iENE– (p = 0.004), LN size >3 versus ≤3 cm (p < 0.001), and higher LN number (p < 0.001). Inter‐rater kappa for iN+, laterality, total LN number, and presence of iENE were 0.71, 0.57, 0.78, and 0.69, respectively. Conclusion: Our study shows that despite modest sensitivity of most radiological nodal features, the specificity of image‐identified nodal features is high and their prognostic values are retained in pN+ OSCC. Level of Evidence: 3 (retrospective review comparing cases and controls) Laryngoscope, 134:4947–4955, 2024 [ABSTRACT FROM AUTHOR]

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. Results: The median age of patients with HN‐NUT was 39 years (range = 17–86). It affected the sinonasal tract (43%), major salivary glands (20%), thyroid (13%), oral cavity (7%), larynx (7%), neck (7%) and nasopharynx (3%). Although most cases of HN‐NUT (63%) contained a component of primitive URC tumour, 53% showed other histological features and 37% lacked a URC component altogether. Variant histological features included basaloid (33%), differentiated squamous/squamoid (37%), clear cell changes (13%), glandular differentiation (7%) and papillary architecture (10%), which could co‐exist. While most HN‐NUT were positive for keratins, p63 and p40, occasional cases (5–9%) were entirely negative. Immunopositivity for neuroendocrine markers and thyroid transcription factor‐1 was observed in 33 and 36% of cases, respectively. The outcome of HN‐NUT was dismal, with a 3‐year disease specific survival of 38%. Conclusions: HN‐NUT can affect individuals across a wide age range and arise from various head and neck sites. It exhibits a diverse spectrum of histological features and may be positive for neuroendocrine markers, potentially leading to underdiagnosis. A low threshold to perform NUT‐specific tests is necessary to accurately diagnose HN‐NUT. [ABSTRACT FROM AUTHOR]

PurposeDespite significant improvement in locoregional control in the contemporary era of nasopharyngeal carcinoma (NPC) treatment, patients still suffer from a significant risk of distant metastasis (DM). Identifying those patients at risk of DM would aid in personalized treatment in the future. MicroRNAs (miRNAs) play many important roles in human cancers; hence, we proceeded to address the primary hypothesis that there is a miRNA expression signature capable of predicting DM for NPC patients.Methods and resultsThe expression of 734 miRNAs was measured in 125 (Training) and 121 (Validation) clinically annotated NPC diagnostic biopsy samples. A 4-miRNA expression signature associated with risk of developing DM was identified by fitting a penalized Cox Proportion Hazard regression model to the Training data set (HR 8.25; p < 0.001), and subsequently validated in an independent Validation set (HR 3.2; p = 0.01). Pathway enrichment analysis indicated that the targets of miRNAs associated with DM appear to be converging on cell-cycle pathways.ConclusionsThis 4-miRNA signature adds to the prognostic value of the current "gold standard" of TNM staging. In-depth interrogation of these 4-miRNAs will provide important biological insights that could facilitate the discovery and development of novel molecularly targeted therapies to improve outcome for future NPC patients.

Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.

The International Collaboration on Cancer Reporting was established to internationally unify and standardize the pathologic reporting of cancers based on collected evidence, as well as to allow systematic multi-institutional intercountry data collection to guide cancer care in the future. This data set has been developed by the collaborative efforts of an international multidisciplinary panel of experts involved in the care of patients with carcinomas of the nasal cavity and paranasal sinuses (sinonasal tract). The nasal cavity and paranasal sinuses (including frontal, sphenoid, ethmoid, and maxillary sinuses) comprise a very complex anatomic area of the head and neck, affected by a sometimes bewildering array of neoplasms. Management of malignancies in this anatomic region involves complex surgery because of the anatomic confines and close proximity to many vital structures. Given a multidisciplinary approach, the standardized reporting of the carcinomas that develop in this anatomic region include both required (core) and recommended (noncore) elements in pathology reporting in order to be able to identify critical prognostic factors, often requiring clinical and radiologic correlation. A summary of the International Collaboration on Cancer Reporting guidelines and clinically relevant elements, along with additional explanatory notes, are provided, based on evidentiary support from the literature, set in the context of practical application. (Arch Pathol Lab Med. 2019;143:424-431; doi: 10.5858/arpa.2018-0404-SA), Sinonasal malignancies are rare and aggressive tumors, with an incidence of less than 1 case per 100 000 population annually, representing 3% to 5% of all head and neck cancers. [...]

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. After dividing into training and validation sets, two new N‐classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM‐8‐N and two published proposals. Results: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44–2.55] and 3.21 [95% CI, 2.44–4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44–2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05–1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81–1.36]). The aHR proposal provided optimal performance with these changes to TNM‐8‐N: 1) stratification of ENE extent, 2) elimination of N2c and 6‐cm threshold, and 3) stratification of N2b by 3 cm threshold. Conclusion: A new N‐classification improved staging performance compared to TNM‐8‐N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size. There are several limitations in the most recent TNM N classification system including categories with small sample size and categories that have limited prognostic value. The authors proposed and validated a new N classification system that overcomes these limitations and outperforms the previous iteration of TNM. [ABSTRACT FROM AUTHOR]

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. Methods and results: The reviewed diagnoses of salivary gland neoplasms with HMGA2::WIF1 fusion were PA (n = four), myoepithelioma (n = one), myoepithelial carcinoma ex PA (n = two) and high‐grade carcinoma with basaloid features (n = one). Two tumours originated from the minor salivary glands. Six tumours (80%) contained areas reminiscent of CAA characterised by interconnected trabeculae/canaliculi of monotonous oncocytic or cuboidal tumour cells associated with a hypocellular, hyalinised to myxoid stroma. Areas typical of PA were seen in four (50%) cases. All tumours showed diffuse S100 and CK7 immunopositivity. Adverse events were detected in two cases, including local recurrence in a patient with PA, and local and distant recurrences and disease‐related death in a patient with a high‐grade carcinoma of the minor salivary gland of the buccal space, showing tumour necrosis and perineural invasion. Conclusion: Salivary gland neoplasms with HMGA2::WIF1 fusion are predominantly characterised by CAA/striated duct adenoma‐like histology and a S100+/CK7+ immunoprofile. These tumours are not always benign, as among all reported cases approximately 20% showed malignancy (six of 28) and adverse outcome (three of 15), including recurrence, distant metastasis and disease‐specific mortality. [ABSTRACT FROM AUTHOR]