Wolf in sheep's clothing - Oral proliferative verrucous leukoplakia: Progression with longitudinal molecular insights.

BACKGROUND: Oral proliferative verrucous leukoplakia (OPVL) is a chronic form of oral leukoplakia that progresses to a multifocal disease with confluent, exophytic and proliferative features. The clinical differential diagnosis for OPVL includes frictional keratosis, leukoplakia, chronic hyperplastic candidiasis, squamous papilloma, verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma. In this study, we aimed to delineate the dynamic changes in molecular signature during OPVL progression. We compare to a cohort of oral cavity keratinizing squamous cell carcinoma (OSCC) patients covering the spectrum of verrucous carcinoma to invasive squamous cell carcinoma including cytologically bland cuniculatum variant. METHODS: Samples from a large OPVL lesion that exhibited a histopathologic continuum of OPVL progression. RESULTS: Canonical hotspot TERT promoter mutations were identified in all patients. TERT C228T was dominant and mutually exclusive with TERT C250T. In patients with TERT C250T, there was concurrent PI3 point mutation. TP53 mutations were also consistently found (8/10). At the protein level, p53 was abnormal, with loss of function and gain of function. CONCLUSIONS: OPVL is a pathology that shows proximity to the gene expression profile of OSCC, highlighting signatures in common that can be important targets for drug treatment, as well as in the development of diagnostic and prognostic strategies for this disease.

NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

Heterotopic SMARCB1-deficient high-grade transformed/dedifferentiated acinic cell carcinoma and sine-qua-non radiology- pathology with TNM challenge.

Heterotopic salivary tissue (HSGT) is found where salivary glands are not normally placed. HSGT manifests as accessory salivary glands, salivary tissue associated with branchial cleft anomalies, and true heterotopic salivary gland tissue. Benign and malignant salivary heterotopias have been described in the literature, with the most common reported neoplasm being Warthin tumor. In the malignant group, the most frequent tumors are mucoepidermoid carcinomas (MEC) and acinic cell carcinomas (AciCC). For the treating physician, this condition presents a diagnostic dilemma, whether these salivary heterotopias represent metastasis from orthotopic salivary origin or primary of heterotopic origin. We report a unique case of heterotopic high-grade/dedifferentiated SWI/SNF (SMARC-B1) deficient AciCC. A 48 yo male presented for evaluation of a persistently enlarged right sided lymph node for the past 6 months. A biopsy was performed, and initial interpretation was squamous cell carcinoma- p16 negative. Diffuse adenopathy and lack of an obvious primary source prompted a modified right neck dissection. Final pathological diagnosis was heterotopic SWI/SNF (SMARCB1)-deficient high-grade/dedifferentiated salivary AciCC. This case is an example of meticulous pathological investigation and multidisciplinary decision-making process of a heterotopic SMARCB1-deficient dedifferentiated AciCC. Heterotopic dedifferentiated AciCC are extremely rare (two cases reported so far), necessitating definitive surgery with neck dissection and adjuvant therapy. Long term outcomes are not known, and an adequate follow up is mandatory.

Prognostic Impact of Histologic Grade for Papillary Thyroid Carcinoma.

BACKGROUND: While numerous factors affect prognosis in papillary thyroid carcinoma (PTC), the comparative impact of histologic grade has not been well described. Moreover, indications for external beam radiation therapy (EBRT) remain imprecise. We evaluate clinicopathologic characteristics and outcomes for PTC stratified by grade. METHODS: We profiled histologic grade for PTC (well differentiated, moderately differentiated, poorly differentiated) via hospital (National Cancer Database) and population-based (Surveillance, Epidemiology, and End Results) registries. Cox regression was used to adjust for clinicopathologic covariates. Statistical interactions between subtypes and the effect of EBRT on survival were assessed. RESULTS: Collectively, worsening clinicopathologic factors (age, tumor size, extrathyroidal extension, nodal spread, M1 disease) and outcomes (disease-free survival, overall survival) correlated with less differentiated state, across all histologic grades (p < 0.001). Multivariable analysis showed escalating hazard with loss of differentiation relative to well-differentiated PTC (moderately differentiated hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.41, p = 0.02; poorly differentiated HR 2.62, 95% CI 2.23-3.08, p < 0.001). Correspondingly, greater survival benefit was associated with EBRT for poorly differentiated cases (HR 0.36, 95% CI 0.18-0.72, p = 0.004). This finding was upheld after landmark analysis to address potential immortal time bias (HR 0.37, 95% CI 0.17-0.80, p = 0.01). CONCLUSIONS: Worsening histologic grade in PTC is independently associated with parallel escalation in mortality risk, on a scale approximating or surpassing established thyroid cancer risk factors. On preliminary analysis, EBRT was associated with improved survival in the most aggressive or least differentiated subvariants. Further investigation is warranted to examine the efficacy of EBRT for select poorly differentiated thyroid carcinomas.

Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

Oral complications of cancer and cancer therapy: from cancer treatment to survivorship.

Answer questions and earn CME/CNE Oral complications resulting from cancer and cancer therapies cause acute and late toxicities that may be underreported, underrecognized, and undertreated. Recent advances in cancer treatment have led to changes in the incidence, nature, and severity of oral complications. As the number of survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long-term oral health and general well-being. Advances in care have had an impact on previously recognized oral complications and are leading to newly recognized adverse effects. Here, the authors briefly review advances in cancer therapy, including recent advances in surgery, oral care, radiation therapy, hematopoietic cell transplantation, and medical oncology; describe how these advances affect oral health; and discuss the frequent and/or severe oral health complications associated with cancer and cancer treatment and their effect upon long-term health. Although some of the acute oral toxicities of cancer therapies may be reduced, they remain essentially unavoidable. The significant impact of long-term complications requires increased awareness and recognition to promote prevention and appropriate intervention. It is therefore important for the primary oncologist to be aware of these complications so that appropriate measures can be implemented in a timely manner. Prevention and management is best provided via multidisciplinary health care teams, which must be integrated and communicate effectively in order to provide the best patient care in a coordinated manner at the appropriate time.

NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018.

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

Surgical Perspectives in Head and Neck Cancer.

Head and neck cancer treatment is a complex multidisciplinary undertaking. Cancer cure and survival is a primary goal, yet safe-guarding appearance and function to preserve the quality of life are similarly critical. The head and neck surgeon remains central to multidisciplinary cancer care, with deep knowledge of operative technique and an even deeper understanding of cancer biology. The surgeon models practice based on the highest levels of scientific evidence, but also takes into consideration the approaches that may best suit an individual patient. The surgeon's role moreover spans the life history of a head and neck cancer patient, from diagnosis to surveillance. The intimacy of this role makes the surgeon a trusted and frequent frame of reference for the patient. In this chapter, we provide an overview of the surgeon's role in head and neck cancer management. We discuss surgical perspectives within the multidisciplinary care team and selectively highlight some of the more provocative clinical scenarios in the field.

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

Head and Neck Cancers, Version 1.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

The New Face of Head and Neck Cancer: The HPV Epidemic.

There has been a significant increase in the incidence of human papillomavirus (HPV)-mediated oropharyngeal cancer in the United States. This entity is most commonly diagnosed in nonsmoking middle-aged white males. The majority of the patients present with asymptomatic, persistent neck masses despite antibiotic therapy. An awareness of this condition and a high degree of suspicion is necessary for timely diagnosis. HPV-mediated oropharyngeal squamous cell carcinomas (HPV-OPSCCs) are unique biologically and clinically, and affected patients enjoy better outcomes with existing standard therapies than do patients with OPSCC mediated by tobacco exposure. The p16 protein is usually overexpressed in HPV-OPSCC, and its detection on immunohistochemistry is a reliable surrogate marker for this disease. In this review, we discuss current paradigms in the diagnosis and management of HPV-OPSCC, and we emphasize pertinent research questions to investigate going forward, including whether to deintensify treatment in these patients.

Comparison of the efficacy and safety of ultrasound-guided core needle biopsy versus fine-needle aspiration for evaluating thyroid nodules.

OBJECTIVE: Ultrasound-guided core needle biopsy (UG-CNB) is a procedure that is often performed either after repeated inadequate or nondiagnostic ultrasound-guided fine-needle aspiration (UG-FNA) or in combination with UG-FNA in the evaluation of thyroid nodules. The purpose of this study was to compare the efficacy and safety of UG-CNB and UG-FNA for evaluating thyroid nodules. METHODS: This was a retrospective study of 350 consecutive patients who had thyroid nodules biopsied by UG-CNB or UG-FNA from January 2007 until November 2011 at our institution. Biopsy results were compared to the surgical specimen pathology reports for the 105 patients who subsequently underwent hemi- or total thyroidectomy in order to determine whether UG-CNB has advantages over UG-FNA for diagnosing thyroid malignancy and neoplasia. RESULTS: Out of 461 thyroid nodules biopsied from 350 patients, 365 (79%) involved UG-CNB and 96 (21%) involved UG-FNA. The UG-FNA biopsy group had a significantly higher rate of inadequate sampling than the UG-CNB group (P<.0001; Fisher's exact test). Out of 365 UG-CNB samples, 6 (2%) were deemed inadequate for histologic diagnosis, whereas 26 (27%) of the 96 UG-FNA samples were considered inadequate for cellularity. Comparison of biopsy results with the surgical specimen pathology reports revealed that the diagnostic accuracy of UG-CNB and UG-FNA for detecting malignancy was similar, at 89 and 94%, respectively (not significant by Fisher's exact test). However, the UG-CNB group had a higher detection rate for benign follicular lesions compared to the UG-FNA group (65% versus 48% for UG-FNA; P = .002). Although UG-FNA detected neoplasia with high sensitivity (100%), the specificity was poor (30%). Neither biopsy group had any significant immediate or delayed procedure-related complications. CONCLUSION: Our study demonstrated that UG-CNB is safe and is less likely to result in a nondiagnostic biopsy. The accuracy of the UG-CNB technique is similar to that of UG-FNA for detecting thyroid malignancy.

Head and neck cancers, Version 2.2014. Clinical practice guidelines in oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."

ETV6::NTRK3-associated papillary adenocarcinoma: let us play it by ear.

Ceruminous glands are modified apocrine glands, situated in the external auditory canal (EAC) that, together with sebaceous glands, produce cerumen. The neoplastic transformation of these structures is exceedingly rare. We encounter two cases of EAC adenocarcinoma with ETV6::NTRK3 fusion. Despite this genetic overlap, the morphology and immunophenotype delineate its clear separation from secretory carcinoma. These cases demonstrate novel primary EAC adenocarcinoma with papillary morphology, which expands the ever-increasing list of ETV6::NTRK3-positive malignancies and which we would like to term ETV6::NTRK3-translocation associated papillary adenocarcinoma. We also advocate the use of molecular techniques in rare tumors of uncertain type or differentiation, to increase understanding and possibilities of reproducible classification of these rare neoplasms. Pathologists and oncologists should recognize this entity, which leads to a direct approach for detecting NTRK fusion for appropriate treatment.

The impact of pretreatment symptom burden on long-term quality of life following head and neck radiation: A prospective longitudinal study.

BACKGROUND: This study characterized the impact of baseline symptom burden on long-term quality-of-life in patients receiving head and neck radiation therapy (RT). METHODS: The Vanderbilt Head and Neck Symptom Survey was collected prior to head and neck RT and at follow-up visits. Responses were divided into symptom clusters of toxicities and scored from 0 (asymptomatic) to 10 (severe). Patients with responses at baseline and 1-year or 2-year follow-up were stratified by scores ≤1 or >1 and compared using the Mann-Whitney U-test. RESULTS: At 1-year follow-up (n = 75), patients with higher baseline scores had greater symptom burden for every cluster except in taste/smell. At 2-year follow-up (n = 47), patients with higher baseline scores had greater symptom burden for every cluster except in nutrition, dry mouth, trismus, neck tightness, and hearing. CONCLUSION: The Vanderbilt Head and Neck Symptom Survey demonstrated a relationship between baseline symptom burden and long-term quality-of-life and might be useful as a screening tool.

Patient perceptions underlying ctDNA molecular surveillance for HPV(+) oropharyngeal squamous cell carcinoma.

OBJECTIVE: Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC). METHODS: Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay. RESULTS: Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety. CONCLUSION: ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines.

Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines.

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).

Implications of updated staging system for p16+ oropharyngeal squamous cell carcinoma: Is valuable prognostic information being omitted?

BACKGROUND: This study characterized whether the updated AJCC 8th edition nodal staging system for p16+ oropharyngeal squamous cell carcinoma (OPSCC) resulted in the loss of prognostic value. METHODS: The NCDB was queried for patients with node-positive p16+ OPSCC. The prognostic impact of nodal size, nodal quantity, nodal laterality, and extracapsular extension (ECE) on overall survival (OS) was assessed. RESULTS: In the clinical cohort, inferior 5-year OS was observed in patients with more than one positive lymph node (p < 0.001; 82% vs. 86%), ECE (p < 0.001; 82% vs. 75%), or nodal size >6 cm (p < 0.001; 66% vs. 82%). In the pathologic cohort, inferior 5-year OS was observed in patients with > four positive lymph nodes (p < 0.001; 76% vs. 90%), ECE (p < 0.001; 83% vs. 92%), or largest nodal size >6 cm (p < 0.001; 81% vs. 89%). CONCLUSIONS: Simplifications in the current p16+ OPSCC staging system led to loss of prognostic information in nodal staging.

Prognostic Impact of Primary Tumor Extent and Postoperative Radiation Facility Location in Major Salivary Gland Malignancies.

Introduction The treatment of primary salivary malignancies often requires a multimodality approach. The purpose of this analysis was to evaluate the interaction between primary tumor extent and the treatment location of postoperative radiotherapy (PORT) in patients with primary salivary malignancies with respect to survival outcomes. Methods Patients with primary salivary malignancies who underwent upfront surgery followed by radiation were queried in the National Cancer Database (NCDB). Patients were stratified by pathologic T stage and whether PORT was performed at the same or different facility as the definitive surgery. Survival outcomes were compared using the Kaplan-Meier method and Cox proportional hazards regression. Results A total of 5,553 patients were selected, of which 1,159 had pathologic T4 (pT4) tumors. Patients who received PORT at the same facility compared with a different facility demonstrated superior overall survival (OS) on log-rank analysis (p=0.003). On subgroup analysis, patients with pT4 tumors had superior OS (p=0.015), whereas patients with smaller T1-3 tumors did not. PORT receipt at the same surgical facility was not a significant predictor of OS on multivariable analysis when all patients were included (p=0.057). However, among patients with pT4 tumors, OS was improved in patients who got PORT at the same facility as their surgery (p=0.015), with 10-year survival rates of 38.3 (95% confidence interval (CI): 33%-44%) versus 31% (95%CI: 24%-38%). Conclusion OS was improved in patients with primary salivary malignancies who received PORT at the same facility as their surgery, but the difference appears to be primarily driven by patients with pT4 primary tumors.

Prolonged response to checkpoint inhibitor therapy in two metastatic mucoepidermoid salivary gland carcinoma cases: a research report.

Salivary gland tumors (SGTs) are heterogeneous tumors that range from benign masses to aggressive high-grade carcinomas with distant metastatic potential and limited response to chemotherapy. Mucoepidermoid carcinoma (MEC) accounts for 10% of SGTs and has a poor prognosis. In this research report, we describe two cases of metastatic high-grade MECs with prolonged response to immune checkpoint inhibitor pembrolizumab. Case 1 presented with a left neck mass, and biopsy of the parotid mass revealed MEC. The patient underwent surgical resection and adjuvant chemoradiation therapy for stage IVB disease. Post-treatment, she was found to have brain and spinal metastases and was placed on pembrolizumab. Case 2 presented with a left neck mass, and biopsy of the right parotid gland revealed MEC. Further staging demonstrated metastatic disease in the lungs, and he was placed on pembrolizumab. Both cases of MEC demonstrated prolonged extracranial responses to pembrolizumab. Although both cases reported little to no PD-L1 expression, these results demonstrate immunotherapy efficacy in advanced/metastatic MEC.