Rationale for Increasing Oncological Vigilance in Relation to Clinical Findings in Accessory Parotid Gland-Observations Based on 2192 Cases of the Polish Salivary Network Database.

The accessory parotid gland (APG, Vth level) differs in histological structure from main parotid tissue. This gives rise to the hypothesis, mirrored in clinical observations, that the representation of tumours is different than in the rest of the gland. The aim of the study was to analyse the epidemiological and histological differences of parotid tumours located in regions I-V, with particular emphasis on the distinctiveness of region V. To define the epidemiological factors that will indicate the risk of histological malignancy from clinically benign appearance, multicentre prospective studies conducted between 2017-2021 by five Head and Neck Surgery University Departments, cooperating within the Polish Salivary Network Database 1929 patients (1048 women and 881 men), were included. The age, gender, patient occupation, place of inhabitation, tumour size, clinical features of malignancy, histology, and facial nerve (FN) paresis were analysed for superficial (I_II) and deep (III_IV) lobes and with special regard to the tumours affecting region V. Twenty eight tumours were located exclusively in region V (1.45% total) and seventy-two tumours were found in region V exhibiting extensions to neighbouring regions (3.7% total), characterised as significantly younger and less frequent in retirees. In I-IV regions, approximately 90% of tumours were benign, with pleomorphic adenoma (PA) and Whartin tumour (WT) predominance. In region V, PA exceeded 75% but WT were casuistic (2/28). Incidences of malignancies in region V was 40% but clinical signs of malignancy were evident only in tumours > 4 cm or in the presence of FN paresis. In 19% of patients with a benign appearance, imaging revealed malignancy; however, 38% of patients showed false negative results both in terms of clinical and radiological features of malignancy. Logistic regression models in 28 patients with tumours located exclusively in region V vs. 1901 other patients and in 100 patients with V extension vs. 1829 other patients showed no clinical symptoms of malignancy binding with final malignant tumour histology as a single variable or in combination with other variables. The logistic regression models obtained in this study show strong linkage between tumour location and predictors (age, male gender, and tumour diameter) and also aimed to function as a good classifier. Our conclusion is that, despite the very clear image of the mid-cheek tumour which is easily accessible in palpation and ultrasound examination, it is necessary to improve oncological vigilance and preoperative patient preparation.

Hemoptysis during pregnancy: a comprehensive review of literature and an unprecedented case report of oropharyngeal carcinoma.

OBJECTIVES: Hemoptysis in pregnancy is a very rare finding causing diagnostic and therapeutic difficulties. The case report of hemoptysis by a 29 years old patient in the 31st week of pregnancy is presented and discussed along with the diagnostic process and treatment provided.Upon pharyngeal cancer occurrence in a pregnant patient a multidisciplinary medical team performed appropriate treatment along with delivery of a healthy newborn at term. Patients and fetal conditions and outcomes were analyzed and compared to available literature in this newly created literature review. MATERIAL AND METHODS: After MEDLINE database analysis using formula "hemoptysis" AND "pregnancy" more than 125 results were found published during the period 2002-2022. Almost 30 papers about hemoptysis were found and included for full analysis. CONCLUSIONS: The literature review offers a detailed description of previously reported incidents of hemoptysis in pregnancy to gain understanding of the etiology, differential diagnosis, available treatment and predicted future outcomes for both patient and fetus.

Effect of Glucocorticoid Administration in Intravenous Pulses on Selected Parameters of the Coagulation System.

Background: Changes of the coagulation system are promoted by serious infectious or noninfectious diseases, surgical procedures, and exogenous substances, including drugs. This study aimed to assess the effect of methylprednisolone pulses on selected parameters of the coagulation system. Methods: The study group consisted of patients suffering from multiple sclerosis, thyroid orbitopathy, or sudden sensorineural hearing loss. 48 patients and 20 healthy volunteers were examined. The hemostatic parameters: activity of coagulation factors (VIII, IX, and XI), antithrombin activity, protein C and S activity, and concentration of soluble tissue factor were analyzed at baseline and after 3 g and 5 g of methylprednisolone administration. Results: A statistically significant increase was noted in the activity of all the studied plasma coagulation factors, plasma coagulation inhibitors (except protein S activity), and the concentration of soluble tissue factor after methylprednisolone administration. Conclusion: The glucocorticoids administered in the intravenous pulses of methylprednisolone shift the balance toward thromboembolic complications.

Intrasalivary Thymic Carcinoma: A Case Report and Literature Review.

Ectopic thymic carcinomas are rarely diagnosed in the thyroid gland, let alone in extrathyroid tissues. In the currently available literature, only five cases of extrathyroidal malignancies with thymic differentiation have been reported as arising in the major salivary glands. A 69-year-old female presented with a slow-growing palpable mass in the left parotid gland. Fine needle aspiration biopsy suggested metastatic cancer, whereas core needle biopsy revealed high-grade squamous cell carcinoma. The patient underwent left radical parotidectomy with selective ipsilateral lymph node dissection and subsequent radiation therapy. The surgical specimen was taken for histopathological examination. Microscopically, the tumor resembled thymic carcinoma. It was composed of large nests of squamoid cells with smooth contours, focally with a syncytial growth pattern, and accompanied by abundant lymphocytes with reactive lymphoid follicles. This appearance resembled a micronodular thymic carcinoma with lymphoid hyperplasia. Moreover, the tumor displayed expression of squamous markers (p40 and p63) and markers of thymic carcinoma (CD5 and CD117). Therefore, the final diagnosis of intrasalivary thymic carcinoma was rendered. The molecular analysis including next-generation sequencing demonstrated no variants of the strong, potential, or unknown clinical significance. The patient remains disease-free at 1-year follow-up. In the current case, we comprehensively present a clinical, microscopic, molecular, and radiological picture of CD5-positive squamous cell carcinoma of the parotid. We postulate that similar cases should be designated as intrasalivary thymic carcinoma analogically to similar thyroid tumors. Our case and the limited literature data indicate they should be distinguished from conventional squamous cell carcinoma of major salivary glands due to their rather favorable prognosis.

Adjuvant radiotherapy in parotid gland pleomorphic adenoma - recommendations.

<b>Introduction:</b> Standard treatment for pleomorhic adenoma (PA) of the parotid gland is complete surgical excision. Radiotherapy (RT) as a primary treatment method is controversial and generally is not applied. However, RT might be considered as an adjuvant therapy in some selected cases. </br></br> <b>Aim:</b> The aim of this work was to define recommendations for RT in patients with parotid gland PA after primary surgical treatment.</br></br> <b>Material and methods:</b> Based on the results currently published in the literature and the authors' own experiences from leading Polish laryngological and oncological clinical centers dealing with the treatment of salivary gland tumors, the indications for irradia- tion and its methods in patients with PA of the salivary glands were discussed. </br></br> <b>Results and discussion:</b> Authors recommend personalized treatment based on multidisciplinary panel decisions in each patient. Adjuvant RT should be considered in cases of suboptimal resection of primary PA (close margin, intraoperative tumor spillage, risk of recurrence based on clinical factors and histological features), and in cases of PA recurrence. Doses/ fractions and techniques of irradiation are recommended depending on the clinical extension of the primary or recurrent tumor. </br></br> <b> Conclusions:</b> Adjuvant RT in PA treatment should be a result of a personalized multidisciplinary decision after considering all possible risks of irradiation consequences. Recommendations for this treatment should be taken into consideration.

Trial Proteomic Qualitative and Quantitative Analysis of the Protein Matrix of Submandibular Sialoliths.

Our studies aimed to explore the protein components of the matrix of human submandibular gland sialoliths. A qualitative analysis was carried out based on the filter aided sample preparation (FASP) methodology. In the protein extraction process, we evaluated the applicability of the standard demineralization step and the use of a lysis buffer containing sodium dodecyl sulfate (SDS) and dithiothreitol (DTT). The analysis of fragmentation spectra based on the human database allowed for the identification of 254 human proteins present in the deposits. In addition, the use of multi-round search in the PEAKS Studio program against the bacterial base allowed for the identification of 393 proteins of bacterial origin present in the extract obtained from sialolith, which so far has not been carried out for this biological material. Furthermore, we successfully applied the SWATH methodology, allowing for a relative quantitative analysis of human proteins present in deposits. The obtained results correlate with the classification of sialoliths proposed by Tretiakow. The performed functional analysis allowed for the first time the selection of proteins, the levels of which differ between the tested samples, which may suggest the role of these proteins in the calcification process in different types of sialoliths. These are preliminary studies, and drawing specific conclusions requires research on a larger group, but it provides us the basis for the continuation of the work that has already begun.

Value of dynamic contrast enhanced MRI in differential diagnostics of Warthin tumors and parotid malignancies.

To define an algorithm for differential diagnostics of parotid malignancies and Warthin tumors (WTs) based on dynamic contrast enhanced MRI (DCE-MRI). 55 patients with parotid tumors treated surgically were analyzed. Of which, 19 had parotid malignancy and 36 had WTs confirmed with postoperative histopathological examination. Accuracy of DCE-MRI parameters (Tpeak and WR) was compared with the histopathological diagnosis. ROC analysis was performed to determine sensitivity and specificity of DCE-MRI with various Tpeak and WR cut-off values. WT showed significantly lower median Tpeak and higher median WR than malignant lesions. The cut-off values for Tpeak and WR providing maximum sensitivity (84.2%) and specificity (86.1%) for malignant tumors were Tpeak > 60 s and WR ≤ 30%. Different diagnostic algorithm, i.e., lower cut-off value for Tpeak (Tpeak = 60 s), increases sensitivity of DCE-MRI in differentiating parotid malignancies from WTs. However, WR > 30% seems to be a key diagnostic criterion for benign lesions. Precise and reliable preoperative diagnostics of parotid tumors aids in careful surgical planning, thereby assisting in achieving sufficient surgical resection margins and facial nerve preservation.

ALK alterations in salivary gland carcinomas.

Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture-based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.

Clinical and demographic data improve diagnostic accuracy of dynamic contrast-enhanced and diffusion-weighted MRI in differential diagnostics of parotid gland tumors.

PURPOSE: To verify if differential diagnostic algorithms based on selected parameters of dynamic and diffusion-weighted MRI, clinical and demographic variables are accurate enough to differentiate between parotid malignancies, pleomorphic adenomas and Warthin tumors. MATERIALS AND METHODS: The study included 84 patients, among them 19 (23%) with postoperative diagnosis of a parotid malignancy, 37 (44%) with Warthin tumors and 28 (33%) with pleomorphic adenomas. Accuracy of dynamic and diffusion-weighted MRI parameters (Tpeak, Tmax, WR and ADC), clinical parameters of the tumor (location in the superficial or deep parotid lobe, single vs. multiple lesion, concomitant lymphadenopathy) and demographic characteristics of the patient (age, sex) was determined on ROC analysis. RESULTS: Compared to Warthin tumors, parotid malignancies showed higher Tpeak, Tmax and ADC, lower WR, were more often located in the deep lobe of the parotid and presented as single lesions with concomitant lymphadenopathy. Consideration of all these variables provided 100% sensitivity and 89.2% specificity of the differential diagnostic algorithm. Compared to pleomorphic adenomas, parotid malignancies presented with lower ADC and Tpeak, higher Tmax, were more often located in the deep lobe of the parotid, associated with concomitant lymphadenopathy, diagnosed in men and individuals older than 66 years. Consideration of all these variables provided 100% sensitivity and 96.4% specificity of the differential diagnostic algorithm. CONCLUSION: Combined analysis of clinical data and results of dynamic and diffusion-weighted MRI may provide nearly ideal accuracy in differential diagnostics of parotid malignancies and the two most common histological types of benign tumors.

Parotid salivary duct carcinoma: a single institution's 20-year experience.

PURPOSE: The aim of the study was to assess the treatment results of the parotid gland salivary duct carcinoma (SDC). MATERIAL AND METHODS: A retrospective clinicopathological analysis of 40 patients treated for parotid SDC in 1996-2015 was performed. The impact of following factors on 5-year disease-free survival (DFS) and overall survival (OS) was studied: age, sex, preoperative 7th nerve palsy, skin infiltration, pT, pN, surgical margin, type of parotidectomy and neck dissection, histology (SDC de novo vs. SDC ex pleomorphic adenoma, SDCexPA), intra/periparotid lymph nodes metastases, perineural invasion (PNI), extraparenchymal extension (EPE), and overexpression HER2. RESULTS: The average age of the patients was 62 years (ranged from 39 to 81). Males predominated (57.5%). Patients with the clinical stage IV predominated (82.5%). In 1/3 of patients preoperative, 7th nerve palsy occurred. All patients were treated surgically, and all but one had supplementary radiotherapy. In 28 patients (70%), total radical parotidectomy was performed. A neck dissection was performed in all patients. In 19 cases (47.5%), SDCexPA was diagnosed. Negative microscopic surgical margin was obtained in 60% of patients. The follow-up for the whole analyzed group ranged from 2 to 22 years, average was 11.6 years. In 23 patients (57.5%), the disease recurred. Local recurrence was observed in 10 (25%) and distant metastases in 15 (37.5%) cases. 20 patients (50%) died of cancer. 5-year DSF and OS were 42.5% and 41%, respectively. Univariate analysis proved that the significant influence on the survival had 7th nerve palsy (p = 0.024 and p = 0.017, respectively), higher pT-stage (p < 0.001), radical parotidectomy (p = 0.024 and p = 0.022), radical treatment of the neck (p = 0.001 and p = 0.002), EPE (p = 0.040 and p = 0.028), and histology SDCexPA and PNI (p = 0.036 and 0.048). Multivariate analysis showed that independent prognostic factors were the 7th nerve palsy and the histology SDCexPA, which worsened 5-year DFS, respectively, 3.61 and 3.94 times (p = 0.033 and p = 0.026). On the other hand, on 5-year OS, only 7th nerve palsy had an influence (3.86 times worse prognosis, p = 0.033). CONCLUSIONS: SDC is a clinically aggressive cancer with high risk of local recurrence and distant metastases, however, with a chance of curing of around 40%. In the majority of patients, a radical surgical treatment is necessary due to the high clinical stage of disease. Worse prognosis have patients with preoperative 7th nerve palsy and in whom SDC develops in pleomorphic adenoma.

Bilateral Tolosa-Hunt syndrome mimicking pituitary adenoma.

The authors report a rare case of bilateral Tolosa-Hunt syndrome, which occurred in a 80-year-old female and remitted spontaneously. Inflammatory lesions were found not only in typical locations, i.e. superior orbital fissures and cavernous sinuses, but also in the pituitary; these imitated gland's macroadenoma in imaging studies.

Diffusion-weighted MRI in the differential diagnosis of parotid malignancies and pleomorphic adenomas: can the accuracy of dynamic MRI be enhanced?

OBJECTIVES: (1) To verify whether appropriate selection of cutoff values for dynamic and diffusion-weighted magnetic resonance imaging (MRI) parameters optimizes the accuracy of preoperative differential diagnosis of parotid malignancies and pleomorphic adenomas. (2) To define the role of preoperative MRI in the differential diagnosis of parotid tumors. STUDY DESIGN: The retrospective analysis included 221 surgical patients with parotid tumors. Aside from ultrasonography-guided fine-needle biopsy, the preoperative protocol included dynamic and diffusion-weighted MRI. Final diagnoses were based on histopathologic examination of surgical specimens. Receiver operating characteristic analysis was conducted to determine the sensitivity and specificity of preoperative MRI with various combinations of cutoff values. RESULTS: Twenty-four patients with parotid malignancies (10.8%) and 57 with pleomorphic adenomas (25.8%) were identified. Parotid malignancies had significantly lower values of apparent diffusion coefficient and Tpeak, as well as significantly higher values of Tmax and washout rate. An apparent diffusion coefficient ≤1.267 × 103 mm/s2 yielded optimum accuracy in identification of parotid malignancies (95.8% sensitivity and 93% specificity). CONCLUSION: Diffusion-weighted MRI is effective in differential diagnosis of parotid malignancies. Optimization of preoperative diagnosis of parotid tumors should include preselection identification of Warthin tumors on the basis of dynamic MRI, followed by identification of pleomorphic adenomas based on diffusion-weighted MRI and cytologic examination of the remaining lesions.

Close surgical margin after conservative parotidectomy in early stage low-/intermediate-grade parotid carcinoma: Outcome of watch and wait policy.

AIM: The aim of the study was to assess the watch&wait strategy for management of patients with close surgical margin after conservative parotidectomy due to early low/intermediate grade parotid carcinoma. PATIENTS AND METHODS: Out of 78 patients operated on due to primary parotid gland cancer we selected 32 patients with a history of parotidectomy, and preservation of 7th nerve, with negative (≥1mm), but close (≤5mm) surgical margin and who did not receive supplementary radiotherapy due to other indications. Margins ranged from 1 to 3mm (in 27 cases it was 1mm, in 3 cases - 2mm and in 2 cases - 3mm), average 1.2mm. The patients underwent further clinical-histological analysis. RESULTS: 3 of 32 (9.38%) patients experienced a local recurrence 36, 53 and 56months post-surgery. The 5-year disease-free survival (DFS) was 90.6%. Recurrences were treated surgically, followed by radiotherapy, which resulted in an overall survival of 107, 104 and 104months. One patient died 72months after surgery due to non-oncological causes. The 10-year disease-free survival (DFS) was 96.3%. The 3 patients with recurrence of cancer had histological diagnosis of epithelial-myoepithelial carcinoma LG, with a margin of 2, 1 and 3mm, respectively. There were no other distinctive features. CONCLUSION: The watch&wait strategy with intensive follow-up seems justified in cases of close margin after excision of I/LG T1/T2 parotid tumors. EMC should be considered as a neoplasm associated with higher risk of recurrence.

Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging-An Alternative to Fine Needle Biopsy or Only an Adjunct Test in Preoperative Differential Diagnostics of Malignant and Benign Parotid Tumors?

PURPOSE: The role of dynamic magnetic resonance imaging (MRI) in the preoperative differential diagnostics of parotid tumors is unclear. The aim of this study was to compare the accuracy of dynamic MRI and routinely used fine needle biopsy examination in the preoperative differentiation of malignant and benign parotid tumors. MATERIALS AND METHODS: The study included 100 consecutive patients with parotid tumors treated surgically at the authors' center. Accuracy of dynamic MRI and fine needle biopsy examinations in the differential diagnostics of malignant and benign lesions was verified against the gold standard (ie, final histologic diagnosis). RESULTS: Based on histopathologic examination of surgical specimens, 19 tumors were eventually diagnosed as malignant lesions and 81 were diagnosed as benign. Preoperative fine needle biopsy examination yielded 9 true positive, 70 true negative, 11 false positive, and 10 false negative results, which corresponded to 47.4 and 86.4% sensitivity and specificity, respectively. The most commonly established preoperative diagnosis for 10 tumors that were misdiagnosed as benign based on examination of biopsy specimens was pleomorphic adenoma (n = 10). Dynamic MRI examination yielded 17 true positive, 81 true negative, 2 false negative, and 0 false positive results, which corresponded to 89.5% sensitivity and 100% specificity. CONCLUSIONS: These results suggest that dynamic MRI is highly accurate in the detection of malignant parotid tumors. However, taking into account the high cost and limited availability of this examination, its logical application seems to be verification of preoperative diagnoses in patients whose fine needle biopsy examination turned out to be nondiagnostic or showed pleomorphic adenoma.

Probability and pattern of occult cervical lymph node metastases in primary parotid carcinoma.

The present study was undertaken to evaluate real probability and pattern of cervical occult lymph node metastases (OLNM) in primary parotid carcinoma (PPC). We carried out a retrospective analysis of 66 patients treated in years 1992-2010 due to PPC, who underwent elective neck dissection (END). In search of risk factors for OLNM, we analysed the following parameters: age, sex, pT-Status, tumour size, skin invasion, facial nerve palsy, tumour fixation, extraparotid extension, localization, grade, histology, intra/periparotid LN metastases (IPLNM). OLNM was observed in 30.3% of patients. In a univariate analysis statistical significance was found for IPLNM, extraparotid extension and high risk histology. A multivariate analysis showed statistical significance only for the first variable. The most common location of cervical OLNM was level II (80%), then III (45%) and V (30%). In a compilation of our own material with data from the literature (5 series), we obtained a group of 80 patients with OLNM, selected out of 650 patients with cN0 (12.3%). The proportion of metastases to particular levels was the following: 69%-II, 22.5%-III, 20%-I,16%-V, 7.5%-IV. END should be carried out in case of all T3/T4a carcinomas with minimal range of levels II and III. Removal of levels Ib and Va is recommended as well. In the T1/T2 carcinomas with high grade/high risk histology, END should be performed including levels II and III.

Parotid malignancies are not homogenous in terms of their presentation on dynamic MRI - a preliminary report.

CONCLUSION: At least two groups of parotid malignancies exist, including one whose parameters of dynamic MRI closely resemble those of pleomorphic adenomas. Also tumors with long time to peak enhancement after administration of a contrast agent (Tpeak) and low washout rate (WR) should be considered malignant, especially single masses with concomitant lymphadenopathy located within the deep parotid lobe. OBJECTIVE: To verify if malignant tumors of the parotid are homogeneous in terms of parameters of preoperative dynamic MRI: Tpeak and WR. METHODS: The retrospective analysis included 221 surgical patients with parotid tumors. Aside from fine needle biopsy, pre-operative examination included dynamic and diffusion-weighted MRI. Final diagnosis was based on histopathological examination of the surgical specimen. RESULTS: Twenty-four of 221 (10.8%) malignant lesions were identified. Using k-means clustering based on Tpeak and WR values, two distinct clusters of parotid malignancies were identified. The cut-off value for Tpeak optimally differentiating between the clusters was 140 s; the cut-off value for WR could not be identified. The two clusters did not differ in terms of dynamic and diffusion-weighted MRI parameters, patient age, sex and prevalence of lymphadenopathy. Significant inter-cluster differences were found in the prevalence of deep parotid lobe involvement and presence of a single mass.