Cribriform adenocarcinoma of the salivary gland (CASG) is an entity that is currently classified under polymorphous adenocarcinoma (PAC), cribriform subtype per the 2022 WHO classification of head and neck tumours. There is debate about whether CASG should be considered a separate diagnostic entity, as CASG differs from conventional PAC in anatomic site, clinical behaviors, and molecular patterns. Herein we describe a challenging and unique case which shares histologic and behavioral features between CASG and conventional PAC with a YLPM1::PRKD1 rearrangement not previously reported in the literature.

Extranodal extension (ENE) is a pattern of cancer growth from within the lymph node (LN) outward into perinodal tissues, critically defined by disruption and penetration of the tumor through the entire thickness of the LN capsule. The presence of ENE is often associated with an aggressive cancer phenotype in various malignancies including head and neck squamous cell carcinoma (HNSCC). In HNSCC, ENE is associated with increased risk of distant metastasis and lower rates of locoregional control. ENE detected on histopathology (pathologic ENE; pENE) is now incorporated as a risk-stratification factor in human papillomavirus (HPV)-negative HNSCC in the eighth edition of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) TNM classification. Although ENE was first described almost a century ago, several issues remain unresolved, including lack of consensus on definitions, terminology, and widely accepted assessment criteria and grading systems for both pENE and ENE detected on radiological imaging (imaging-detected ENE; iENE). Moreover, there is conflicting data on the prognostic significance of iENE and pENE, particularly in the context of HPV-associated HNSCC. Herein, we review the existing literature on ENE in HNSCC, highlighting areas of controversy and identifying critical gaps requiring concerted research efforts.

Polymorphous adenocarcinoma (PAC) is a common, usually low-grade salivary gland carcinoma. While conventional PACs are most associated with PRKD1 p.E710D hotspot mutations, the cribriform subtype is often associated with gene fusions in PRKD1, PRKD2, or PRKD3. These fusions have been primarily identified by fluorescence in situ hybridization (FISH) analysis, with a minority evaluated by next-generation sequencing (NGS). Many of the reported fusions were detected by break-apart FISH probes and therefore have unknown partners or were negative by FISH altogether. In this study, we aimed to further characterize the fusions associated with PAC with NGS. Fifty-four PACs (exclusively cribriform and mixed/intermediate types to enrich the study for fusion-positive cases) were identified and subjected to NGS. Fifty-one cases were successfully sequenced, 28 of which demonstrated gene fusions involving PRKD1, PRKD2, or PRKD3. There were 10 cases with the PRKD1 p.E710D mutation. We identified a diverse group of fusion partners, including 13 novel partners, 3 of which were recurrent. The most common partners for the PRKD genes were ARID1A and ARID1B. The wide variety of involved genes is unlike in other salivary gland malignancies and warrants a broader strategy of sequencing for molecular confirmation for particularly challenging cases, as our NGS study shows.

COVID-19 caused by SARS-CoV2 has reached pandemic proportions. The fear of Covid-19 has deterred many to abandon efforts for seeking timely medical help. In this setting, Obstructive sleep apnea (OSA)-like covid/non-covid cohorts have presented. Atypical pathologies can present like OSA and take the clinician unawares. With this series of misfits suffering silently, it would be unwise to underestimate its impact on quality-of-life (QOL). To determine the effect on quality-of-life by pathologies mimicking OSA and assess Covid-19 as a cause for delayed presentation. This was a prospective cross-sectional study. 127(N). Recent onset of symptoms of OSA. Study duration March 2020 to September 2021. Pittsburgh Sleep Quality Index (PSQI) screening done. Study criteria defined. Sleep parameters calculated. Primary surgical intervention given. Non-responders were put on CPAP therapy. QOL assessment done with sf-36 and SAQLI. Fear of Covid-19 scale (FCV-19S) quantified to study cause for temporal delay. Correlations computed. Level of Evidence-Level 3. 97 candidates completed study. Demographic and anthropometric details noted. Mean range was 43.85 ± 11.39 years. Male predominance. Overall AHI-19.73 ± 8.72. Moderate impact on QOL by sf-36/SAQLI. 78n Primary surgical candidates fared well. Polysomnography (PSG) and Continuous positive airway pressure (CPAP) titration/trial characteristics for 19n available. Statistically significant improvement in QOL after treatment completion. Correlations were meaningful. Body Mass Index (BMI) as a single factor was not influential on OSA-mimickers. Fear of Covid-19 significantly impacted emergency medical aid acquisition. OSA mimicking atypical airway pathologies may need emergent treatment not only from a surgical point-of-view but also from the QOL of the patient. On the contrary, these also unmask sub-clinical OSA, especially in patients with low/normal BMI. This category of recent onset OSA, if fortunately picked up at the earliest possible presentation, may hopefully not go through the significant QOL impact suffered by chronic OSA candidates.

Sinonasal teratocarcinosarcoma (SNTCS) is a rare, aggressive malignancy that displays a heterogeneous combination of malignant blastema-like, epithelial and mesenchymal components. Its exact histogenesis is unknown with hypotheses ranging from true germ cell derivation to origin from pluripotent stem cells. However, despite this tumor\'s multiphenotypic histology, which includes frequent glandular, squamous, and neuroectodermal differentiation similar to adnexal germ cell tumors, SNTCS appears to have some differences from adnexal teratomas. For example, unlike adnexal teratomas, SNTCS has never been described as a component in a mixed germ cell tumor. Accurate recognition of SNTCS is difficult due to its rarity and histologic overlap with other sinonasal tumors. It is even more problematic on biopsy, since not all elements may be present in small samples. SNTCS can also share similar staining patterns with other neoplasms in the differential diagnosis. A recent study found nuclear β-catenin expression in a single TCS, but this has yet to be confirmed in additional cases. SALL-4, a marker of germ cell tumors, has not been examined. We performed β-catenin and SALL-4 immunohistochemistry on whole sections of 7 SNTCS and 19 other sinonasal neoplasms to assess whether β-catenin and SALL-4 are of utility in establishing a diagnosis of SNTCS. Intensity of expression and percentage of staining was noted for each tumor. For SNTCS, distribution of staining within each histologic component (immature neuroectodermal, epithelial, and mesenchymal) was also documented. Nuclear β-catenin expression was not identified in any SNTCS, with all cases demonstrating membranous expression (6 cases) or cytoplasmic and membranous expression (1 case). SALL-4 immunohistochemistry, however, was relatively sensitive (85.7%) and specific (89.5%) for SNTCS. SALL-4 expression was also identified in one poorly differentiated neuroendocrine carcinoma and one case of sinonasal undifferentiated carcinoma. SALL-4 appears to have utility in distinguishing SNTCS from other high grade sinonasal tumors.

Peripheral giant cell granulomas (PGCG) associated with hyperparathyroidism (HPT) are rare clinical entities. The aim of this study is to report on 21 PGCGs of the oral cavity as the first clinical sign of unknown primary HPT (PHPT) referred to the Complex Operating Unit of Odontostomatology of Aldo Moro University of Bari from 2009 to 2019. Surgical treatment consisted in conservative enucleation of the lesion, if possible, with contextual bone rim osteoplasty with piezosurgical tools and following histological examination. After histological diagnosis of PGCG, PHPT screening was performed dosing parathyroid hormone and serum calcium. In all the patients haematological investigation demonstrated elevated values of parathyroid hormone and serum calcium ruling out an unknown PHPT. Specifically, after endocrinological evaluation, patients showed PHPT related to: parathyroid adenoma (13), parathyroid hyperplasia (two, one of which occurred in a intra-thyroidal parathyroid), and parathyroid carcinoma (1) and were scheduled for surgical treatment. Considering that PGCGs could represent the first clinical sign of an undiagnosed PHPT and the screening of PHPT is a non-invasive and cheap exam, in case of histological diagnosis of a giant cell lesion, both central and peripheral, especially in patients with synchronous or history of methacronous giant cell lesions, parathyroidal screening should be mandatory.

Salivary gland tumors (SGT) represent an uncommon heterogeneous group of tumors with complex clinical and pathological characteristics. The prevalence of these lesions varies between studies but has been estimated between 3 and 6% of all tumors in the head and neck region. The present study aimed to evaluate the distribution and demographic findings of salivary gland tumors diagnosed in an oral pathology service in Mexico. A retrospective descriptive cross-sectional study was performed. A total of 164 cases of SGT from a private oral pathology service were diagnosed between 2000 and 2019 in Mexico City. All cases were reviewed histologically, and demographic data and histopathological diagnoses were collected. A total of 110 (67.1%) tumors were benign, and 54 (32.9%) were malignant. The majority of patients were female (n = 100, 61.0%) with an overall female:male ratio of 1.6:1. The minor salivary glands were affected more than the major salivary glands (68.9% vs. 25.6%). The palate (n = 67, 40.9%) was the most commonly affected site, followed by the parotid gland (n = 37, 22.6%), lips (n = 16, 9.8%), and buccal mucosa (n = 14, 8.5%). Pleomorphic adenoma (n = 88; 80.0%) and mucoepidermoid carcinoma (n = 16, 29.6%) were the most frequent benign and malignant tumors, respectively. The general features of SGT from the studied Mexican population shared some similarities and differences compared to previously reported series from various parts of the world.

Cystic salivary gland lesions present diagnostic challenges on fine-needle aspiration (FNA) specimens that are related to sampling limitations and a broad differential diagnosis. This study evaluated the benefit of applying the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) to a series of cystic salivary gland lesions.
The pathology archives at the Johns Hopkins Hospital were searched to identify cystic salivary gland FNA specimens over a 19-year period (2000-2018). Patient demographics, cytomorphologic features, and clinical and surgical follow-up were recorded. The MSRSGC was applied to the cases. The risk of malignancy (ROM) and the risk of neoplasia (RON) were calculated for each category.
One hundred seventy-eight cases were identified (96 males and 82 females) with a mean age of 53 years (range, 4-90 years). After the MSRSGC was applied, there were 52 nondiagnostic cases (29.2%), 80 nonneoplastic cases (44.9%), 35 cases of atypia of undetermined significance (AUS; 19.7%), 3 benign neoplasms (1.7%), 3 salivary gland neoplasms of uncertain malignant potential (SUMP; 1.7%), 4 cases suspicious for malignancy (SFM; 2.2%), and 1 malignant case (0.6%). One hundred fifty-six of the 178 patients (87.6%) had follow-up data available. The RON and ROM values for cases with surgical follow-up were 33.3% (3 of 9) and 22.2% (2 of 9) for the nondiagnostic category, 42.9% (9 of 21) and 19% (4 of 21) for the nonneoplastic category, 76.5% (13 of 17) and 29.4% (5 of 17) for the AUS category, 100.0% (2 of 2) and 50.0% (1 of 2) for the SUMP category, and 100% (2 of 2) and 100% (2 of 2) for the SFM category, respectively.
Applying the MSRSGC to cystic salivary gland lesions improves patient management by preventing unnecessary surgery for nonneoplastic conditions. The ROM was highest in the SFM category (100%), which was followed by the SUMP, AUS, nondiagnostic, and nonneoplastic categories. Less than adequate specimens may increase the diagnosis of AUS.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has established distinct diagnostic categories for reporting cytopathological findings, and each is associated with a defined risk of malignancy (ROM). However, the ROM is applied at the overall category level and is not specific for particular morphological entities within a category. Here, the diagnostic performance of the MSRSGC for pleomorphic adenoma (PA) and Warthin tumor (WT) is reported.
The pathology archives of 11 institutions from 4 countries were retrospectively searched to identify all salivary gland fine-needle aspiration (FNA) biopsies with a differential or definitive diagnosis of PA or WT and all resection specimens with a diagnosis of PA or WT; only paired cases were included. All FNA diagnoses were retrospectively classified according to the MSRSGC.
A total of 1250 cases met the inclusion criteria, and they included 898 PA cases and 352 WT cases. The ROM in the benign neoplasm category was 3.0% and 1.3% for cases with a differential or definitive diagnosis of PA and WT, respectively. The ROM in the salivary gland neoplasm with uncertain malignant potential (SUMP) category was 2.7% and 18.8% for PA and WT, respectively (P = .0277). The diagnostic accuracy for PA and WT was 95.1% and 96.1%, respectively.
The diagnostic accuracy for PA and WT on FNA is high. Furthermore, these findings highlight the difference in the ROMs associated with 2 specific differential diagnoses in the SUMP category: basaloid neoplasms and oncocytoid neoplasms.

Simultaneous primary cancers are rare in the oropharynx. This report describes the first reported case of a collision tumor of squamous cell and adenoid cystic carcinoma in the soft palate. The patient was immunosuppressed with a history of liver transplantation, smoking and heavy alcohol drinking. He was treated with wide local excision followed by adjuvant radiotherapy with surface acrylic mold brachytherapy. This technique was used instead of external beam radiotherapy in order to minimize toxicity. The patient tolerated the treatment well and with the only acute grade two mucositis at the soft palate and minimal late toxicity. There is no evidence of disease recurrence and the patient continues to maintain excellent quality of speech and swallowing 14 months after treatment completion.