Parotid squamous cell carcinoma metastases: Application of human papillomavirus -DNA test on liquid-based cytology to recognize oropharyngeal origin of the neoplasm.

Malignancies of the parotid gland are relatively uncommon and in most cases are primary neoplasms; intraparotid metastases are rare. Oral and oropharyngeal squamous cell carcinoma (O- and OP-SCC) can potentially metastasize to the parotid gland or intraparotid lymph nodes. Fine-needle aspiration cytology (FNAC) serves as the initial diagnostic approach for this purpose. HPV status in FNAC specimens is relevant and can guide the diagnostic workup, indicating a potential oropharyngeal origin of the primary tumor. A small series of occult SCC metastases is presented below, in which HPV-DNA testing of FNAC specimens helped identify primary neoplasms located in the oropharynx. US-guided FNAC of parotid nodules was conducted by an experienced interventional cytopathologist in three cases. Each patient underwent assessment of direct smears, cell blocks, and liquid-based samples for HPV testing. The morphological and immunocytochemical features of SCC were documented, and real-time PCR was employed for the detection and genotyping of HPV. The role of HPV testing on FNAC specimens in pinpointing the primary neoplasms in the oropharynx is highlighted. Consequently, FNAC samples emerge as valuable diagnostic and prognostic tools in this context, providing essential insights for patient management.

The Role of Sentinel Node Biopsy in the Era of Adjuvant Therapy for Melanoma.

Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients. First, pT1b and pT2a patients with negative SLNB (stages IA and IB) and those with positive SLNB (stage IIIA) would all not benefit from adjuvant treatment. Therefore, SLNB might be avoided in these categories of patients. Second, in IIB and IIC, melanoma patients are already candidates for adjuvant treatment; therefore, SLNB in patients with T3b, T4a, or T4b melanoma would not change treatment decisions. On the other end of the spectrum, patients with pT2b and pT3a melanomas (clinical stage IIA) represent the only two groups whose management would be significantly affected by the SLNB status, being adjuvant therapy only indicated for SLN-positive patients. Further studies are needed to investigate which melanoma patient deserves SLNB.

Safety and Aesthetics of Autologous Dermis-Fat Graft after Parotidectomy: A Multidisciplinary Retrospective Study.

(1) Background: In surgical procedures for maxillofacial tumours, it is challenging to preserve functional and cosmetic properties in the affected patients. The use of fat grafting is considered as a valuable alternative to overcome postoperative aesthetic asymmetry problems. (2) Methods: In this study, we enrolled thirty patients with parotid gland tumours in which a partial or complete parotidectomy was performed with positioning in the parotid bed of autologous dermis-fat grafts. We evaluated the satisfaction rate of the patients and the objective efficacy in solving the deformity by comparing MRI data before and after surgery. (3) Results: Twenty-six patients showed a satisfying cosmetic result with proper facial symmetry between the affected side and the healthy one. Two patients presented mild postsurgical complications such as haematomas, and two patients reported temporary weakness of the facial nerve related to the parotidectomy. (4) Conclusions: Based on the imaging data obtained via MRI before and after surgery, we can assess that the employment of fat grafts in parotidectomy surgical procedures gives good cosmetic results and does not affect the post operative management and follow up of oncologic patients.

Medication-Related Osteonecrosis of the Jaws: A Comparison of SICMF-SIPMO and AAOMS Guidelines.

(1) Background: Medication-related osteonecrosis of the jaws (MRONJ) is an adverse drug reaction characterized by progressive bone disruption and necrosis in the mandibular and/or maxillary bones. It occurs in individuals who have received antiresorptive drugs without prior radiotherapy. Since its first reported cases in the USA in 2003, extensive literature has emerged worldwide, leading to significant advancements in understanding MRONJ's pathogenesis and management. (2) Results: This article aims to compare the current national recommendations provided by the Italian Society of Maxillofacial Surgery (SICMF)/Italian Society of Oral Pathology and Medicine (SIPMO) and the American Association of Oral and Maxillofacial Surgeons (AAOMS). (3) Conclusions: Historically, the AAOMS advocated for a more conservative approach compared to the Italian guidelines. However, in their 2022 update, the AAOMS adopted a different perspective based on reported evidence, highlighting the advantages of early surgical treatment. Despite resolving some initial controversies, differences still exist between the two sets of recommendations, particularly regarding diagnosis and staging.

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO.

OBJECTIVES: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. METHODS: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. RESULTS: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). CONCLUSIONS: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. CLINICAL RELEVANCE: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

Metastatic Lung Cancer to the Head and Neck: A Clinico-Pathological Study on 21 Cases with Narrative Review of the Literature.

Metastases from lung cancer to the oral cavity and to the head and neck generally are very infrequent and usually manifest in advanced stages of the disease. Even more rarely, they are the first sign of an unknown metastatic disease. Nevertheless, their occurrence always represents a challenging situation both for clinicians, in the management of very unusual lesions, and for pathologists, in the recognition of the primary site. We retrospectively studied 21 cases of metastases to the head and neck from lung cancer (sixteen males and five females, age range 43-80 years; eight cases localized to the gingiva [two of these to the peri-implant gingiva], seven to the sub-mandibular lymph nodes, two to the mandible, three to the tongue, one case to the parotid gland; in eight patients, metastasis was the first clinical manifestation of an occult lung cancer) and proposed a wide immunohistochemical panel for a proper identification of the primary tumor histotype, including CK5/6, CK8/18, CK7, CK20, p40, p63, TTF-1, CDX2, Chromogranin A, Synaptophysin, GATA-3, Estrogen Receptors, PAX8, PSA. Furthermore, we collected data from previously published studies and narratively reviewed the relevant literature.

Interventions for the Prevention of Oral Mucositis in Patients Receiving Cancer Treatment: Evidence from Randomised Controlled Trials.

Oral mucositis is a common and most debilitating complication associated with cancer therapy. Despite the significant clinical and economic impact of this condition, there is little to offer to patients with oral mucositis, and the medications used in its management are generally only palliative. Given that mucositis is ultimately a predictable and, therefore, potentially preventable condition, in this study we appraised the scientific literature to evaluate effective methods of prevention that have been tested in randomised controlled trials (RCTs). Published high-level evidence shows that multiple preventative methods are potentially effective in the prevention of oral mucositis induced by radiotherapy, chemotherapy, or both. Anti-inflammatory medications (including benzydamine), growth factors and cytokines (including palifermin), cryotherapy, laser-and-light therapy, herbal medicines and supplements, and mucoprotective agents (including oral pilocarpine) showed some degree of efficacy in preventing/reducing the severity of mucositis with most anticancer treatments. Allopurinol was potentially effective in the prevention of radiotherapy-induced oral mucositis; antimicrobial mouthwash and erythropoietin mouthwash were associated with a lower risk of development of severe oral mucositis induced by chemotherapy. The results of our review may assist in highlighting the efficacy and testing the effectiveness of low-cost, safe preventative measures for oral mucositis in cancer patients.

Increased Delay in Diagnosis, but Not Treatment, Among Patients With Oral Cancer During the COVID-19 Pandemic.

This retrospective cohort study assesses delays in diagnosis and treatment for patients with oral squamous cell carcinoma in a tertiary care university hospital in Naples, Italy.

Solitary Extrapleural Fibrous Tumor in Salivary Glands: Our Experience-Case Series and Literature Review.

(1) Background: Extrapleural solitary fibrous tumors (ESFTs) are rare oncological entities occurring in the head and neck, and even more so in the salivary glands. The clinical presentation and histologic features are usually unspecific, resulting in frequent misclassification. As an unusual tumor, ESTFs have an unpredictable clinical behavior. (2) Methods: We present two clinical cases referred to our Maxillofacial Surgery Unit for the onset of a symptomless mass involving, in one case, the parotid gland, and in the other case, the sublingual gland. (3) Results: Solitary fibrous tumors could be considered as neoplasms with intermediate biological behavior that are not entirely predictable on the basis of morphological features, as these are mostly still unknown. However, a few histologic, immunohistochemical, and imaging features, such as a hypodense signal at the T1 sequence in an MRI, or positivity for CD34, bcl2, and CD99, and the NAB2-STATS6 fusion gene, could be useful for an early differential diagnosis of ESTFs. (4) Conclusions: All patients were alive at follow-up with no evidence of disease. Surgical management should always be considered as the first choice for oncological radicality, and clinical behavior should always be defined with the help of the study of radiological and anatomopathological features.

Patients with post-COVID-19 vaccination facial palsy: To boost or not to boost?

A possible association between Bell's palsy and COVID-19 vaccination has been suggested. While it is likely that COVID-19 vaccine recipients from the general population do have a slightly increased risk of developing Bell's palsy, there are little data regarding this risk in individuals with a history of disease. Gaining a better understanding of this association is particularly important for informing evidence-based recommendations regarding future booster shots in subjects who developed Bell's palsy as a side effect of vaccination, or as a result of SARS-CoV-2 infection. We previously described the first case of COVID-19 vaccine-related Bell's palsy; here we report an 18-month clinical and electromyographic follow-up and discuss the implications of receiving further vaccine doses in patients with positive disease history.

Where do you live? North versus Central-South differences in relation to Italian patients with oral lichen planus: a cross-sectional study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: Oral lichen planus (OLP) is an immune-mediated inflammatory chronic disease of the oral mucosa, with different patterns of clinical manifestations which range from keratotic manifestations (K-OLP) to predominantly non-keratotic lesions (nK-OLP). The aim of the study was to analyze the differences in the clinical, psychological profile and symptoms between Italian patients of the North and Central-South with K-OLP and nK-OLP. METHODS: 270 K-OLP and 270 nK-OLP patients were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The Central-South K-OLP (CS-K-OLP) patients reported a higher frequency of pain/burning compared with the K-OLP patients of the North (N-K-OLP) with higher scores in the NRS and T-PRI (p value < 0.001**). The CS-K-OLP and the CS-nK-OLP patients showed higher scores in the HAM-D, HAM-A, PSQI and ESS compared with the Northern patients (p value < 0.001**). Multivariate logistic regression revealed that the NRS and T-PRI showed the greatest increase in the R2 value for the CS-K-OLP (DR2 = 9.6%; p value < 0.001**; DR2 = 9.7% p value < 0.001**; respectively) and that the oral symptoms (globus, itching and intraoral foreign body sensation) and PSQI showed the greatest increase in the R2 value for the CS-nK-OLP (DR2 = 5.6%; p value < 0.001**; DR2 = 4.5% p value < 0.001** respectively). CONCLUSIONS: Pain and mood disorders are predominant in patients with OLP in the Central-South of Italy. Clinicians should consider that the geographical living area may explain the differences in oral symptoms and psychological profile in OLP.

Kabat Rehabilitation in Facial Nerve Palsy after Parotid Gland Tumor Surgery: A Case-Control Study.

Temporary facial nerve palsy after parotid tumor surgery ranges from 14 to 65%, depending on surgery, tumor type, and subsite. The study aimed to evaluate the role of Kabat physical rehabilitation in the outcomes of patients affected by severe facial nerve palsy following parotid gland surgery. The results and clinical data of two groups, Kabat and non-Kabat (control), were statistically compared. Descriptive statistics, the multiple linear regression model, difference in difference approach, and the generalized linear model were used. F-Test, Chi-square test, McFadden R-squared, and adjusted R-squared were used to assess the significance. The results showed that the House-Brackmann (HB) stage of patients who had physiotherapy performed were lower than the control group. The decrease of HB staging in the Kabat group at 3 months was -0.71 on average, thus the probability of having a high HB stage decreased by about 13% using Kabat therapy. The results are statistically significant, and indicated that when the Kabat rehabilitation protocol is performed, mainly in the cases of a high-grade HB score, the patients showed a better and faster improvement in postoperative facial nerve palsy.

TLR4 Expression in Ex-Lichenoid Lesions-Oral Squamous Cell Carcinomas and Its Surrounding Epithelium: The Role of Tumor Inflammatory Microenvironment.

Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment. This study included 150 human samples: 30 normal oral control (NOC), 38 non-lichenoid epithelium surrounding OSCC (NLE-OSCC), 28 lichenoid epithelium surrounding OSCC (LE-OSCC), 30 OSCC ex-non oral lichenoid lesion (OSCC Ex-NOLL), and 24 OSCC ex-oral lichenoid lesion (OSCC Ex-OLL). TLR4 expression was investigated by immunohistochemistry and the percentage of positive cells was quantified. In addition, a semiquantitative analysis of staining intensity was performed. Immunohistochemical analysis revealed that TLR4 is strongly upregulated in LE-OSCC as compared to normal control epithelium and NLE-OSCC. TLR4 expression was associated with the inflammatory environment, since the percentage of positive cells increases from NOC and NLE-OSCC to LE-OSCC, reaching the highest value in OSCC Ex-OLL. TLR4 was detected in the basal third of the epithelium in NLE-OSCC, while in LE-OSCC, TLR4 expression reached the intermediate layer. These results demonstrated that an inflammatory microenvironment can upregulate TLR4, which may boost tumor development.

High-Definition Ultrasound Characterization of Squamous Carcinoma of the Tongue: A Descriptive Observational Study.

High-definition ultrasonography is a diagnostic tool that uses sound echoes to produce images of tissues and organs. In the head and neck region, ultrasounds have been used to diagnose different types of lesions. The intraoral approach was shown to be a real-time, non-invasive way to characterize oral lesions. The tongue is the most often examined region because of its accessibility. This observational study aimed to describe the qualitative characteristics of tongue squamous cell carcinoma images obtained with high-definition intraoral ultrasound by comparing them with the corresponding histopathological sample. Twenty patients were enrolled in this study. The scans of the lesions were carried out with an 18 MHz linear ultrasound probe following the long axis of the lesion. For each lesion, five frames were selected, on which descriptive analysis was performed. A histological sample was taken and then compared to the ultrasonographic acquisition. The sonographic appearance of the tissue layers has a good correlation between ultrasound and histological morphology, and it was easy to distinguish the tumor from the homogenous composition of the tongue tissues. Furthermore, a correlation between the structure by section and pattern of tumor margin features by ultrasound was obtained. Intraoral ultrasonography appears to be a promising technique in the non-invasive characterization of tongue squamous cell carcinoma. Further studies will be needed to improve the technique in terms of ergonomics and repeatability.

Assessment of sleep disturbance in oral lichen planus and validation of PSQI: A case-control multicenter study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. METHODS: Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. RESULTS: Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values < 0.001**). Moreover, OLPs had higher scores in the HAM-D, HAM-A, NRS, and T-PRI (p-values < 0.001**). No differences in the PSQI sub-items' scores were found between the K-OLPs and nK-OLPs, although nK-OLPs suffered from higher levels of anxiety, depression, and pain (p-values: HAM-A, 0.007**, HAM-D, 0.009**, NRS, <0.001**, T-PRI, <0.001**). The female gender, anxiety, depression (p-value: 0.007**, 0.001**, 0.020*) and the intensity of pain, anxiety, and depression (p-value: 0.006**, <0.001**, 0.014*) were independent predictors of poor sleep (PSQI > 5) in K-OLPs and nK-OLPs, respectively. The PSQI's validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. CONCLUSIONS: The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.

Health-Related Quality of Life in Oral Cancer Patients: Scoping Review and Critical Appraisal of Investigated Determinants.

BACKGROUND: health-related quality of life (HRQOL) represents a secondary endpoint of medical interventions in oncological patients. Our aim was to highlight potential sources of bias that could be encountered when evaluating HRQOL in oral cancer patients. METHODS: this review followed PRISMA-ScR recommendations. PARTICIPANTS: patients treated for oral cancer. CONCEPT: HRQOL assessed by EORTC QLQ-C30 and QLQ-H&N35/QLQ-H&N43. A critical appraisal of included studies was performed to evaluate the accuracy of data stratification with respect to HRQOL determinants. RESULTS: overall, 30 studies met the inclusion criteria, totaling 1833 patients. In total, 8 sociodemographic (SDG) and 15 disease/treatment-specific (DT) HRQOL determinants (independent variables) were identified. The mean number of the independent variables was 6.1 (SD, 4.3)-5.0 (SD, 4.0) DT-related and 1.1 (SD, 1.8) SDG-related variables per article. None of the included papers considered all the identified determinants simultaneously. CONCLUSIONS: a substantial lack of evidence regarding HRQOL determinants was demonstrated. This strongly weakens the reliability of the reported findings due to the challenging presence of baseline confounding, selection, and omitted variable biases. The proposed approach recommends the use of further evaluation tools that gather more variables in a single score together with a selection of more homogeneous, reproducible, and comparable cohorts based on the identified baseline confounding.

Elbasvir/Grazoprevir combination therapy in a B-NHL patient with HCV genotype 1 infection.

Patients with indolent non-Hodgkin lymphomas (NHL) may often be followed up only with observation, reserving chemotherapy in case of spread. Patients with chronic HCV infection and B cell NHL frequently undergo regression of lymphoproliferative disease once HCV infection is eradicated by treatment. Interferon (IFN)-based therapy has been the treatment of choice for years, remaining unclear whether it is effective in B cell NHL directly or through HCV eradication, since IFN is effective in both HCV infection and B cell NHL. IFN therapy for HCV infection became obsolete with the advent of the well tolerated direct-acting antiviral agents (DAAs), whose excellent efficacy in treating patients with chronic HCV infection and B cell NHL has been recently highlighted. We treated a 53-year-old woman with chronic HCV infection and marginal zone lymphoma (MZL) with elbasvir plus grazoprevir in 2018, with complete remission and persisting excellent results: sustained virological response 24 weeks after treatment (SVR24). The exclusive role of HCV eradication in B cell NHL regression is also underlined.

Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy.

Head and neck cancers (HNC) represent the seventh most frequent cancer worldwide, with squamous cell carcinomas as the most frequent histologic subtype. Standard treatment for early stage diseases is represented by single modality surgery or radiotherapy, whereas in the locally advanced and recurrent or metastatic settings a more aggressive multi-modal approach is needed with locoregional intervention and/or systemic therapies. Epidermal Growth Factor Receptor (EGFR) plays an important role in HNC biology and has been studied extensively in preclinical and clinical settings. In this scenario, anti-EGFR targeted agent cetuximab, introduced in clinical practice a decade ago, represents the only approved targeted therapy to date, while the development of immune-checkpoint inhibitors has recently changed the available treatment options. In this review, we focus on the current role of anti-EGFR therapies in HNCs, underlying available clinical data and mechanisms of resistance, and highlight future perspectives regarding their role in the era of immunotherapy.