The molecular pathogenesis of salivary gland acinic cell carcinoma (AciCC) is poorly understood. The secretory Ca-binding phosphoprotein (SCPP) gene cluster at 4q13 encodes structurally related ...phosphoproteins of which some are specifically expressed at high levels in the salivary glands and constitute major components of saliva. Here we report on recurrent rearrangements t(4;9)(q13;q31) in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. We show that NR4A3 is specifically upregulated in AciCCs, and that active chromatin regions and gene expression signatures in AciCCs are highly correlated with the NR4A3 transcription factor binding motif. Overexpression of NR4A3 in mouse salivary gland cells increases expression of known NR4A3 target genes and has a stimulatory functional effect on cell proliferation. We conclude that NR4A3 is upregulated through enhancer hijacking and has important oncogenic functions in AciCC.
Objective/Hypothesis
The ideal extent of surgical intervention for benign parotid tumors remains a matter of controversy. The aim of the study was to trace the development of surgical therapy in a ...large cohort, explore its changes in a single institution specializing in salivary gland pathologies over the last 12 years, and determine the extent to which a possible shift in the surgical therapy of parotid benign tumors toward less radical methods was correlated with a change in the incidence of facial palsy and Frey's syndrome.
Study Design
Retrospective clinical study.
Methods
A retrospective evaluation of the records for all patients treated for benign parotid tumors between 2000 and 2012 at a tertiary referral center was carried out. Surgical methods were classified into four groups: extracapsular dissection, partial superficial parotidectomy, superficial parotidectomy, and complete parotidectomy.
Results
A total of 1,624 patients were included in the study. Our analysis demonstrated an increase in the total number of parotidectomies for benign lesions from 71 (2000) to 184 (2012), mostly due to the increase in extracapsular dissections (from 9 to 123). Increased performance of less radical surgery was associated with a significantly decreased incidence of temporary and permanent facial palsies (from 22.8% to 9% and 9.8% to 5.9%, respectively) and Frey's syndrome (from 11.3% to 1.6%).
Conclusions
One of the most controversial issues in the treatment of benign parotid tumors is the best therapeutic approach to be taken in such patients. Our study showed that increased performance of less radical surgery was associated with better functional outcomes.
Level of Evidence
2b. Laryngoscope, 125:122–127, 2015
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives/Hypothesis
To assess long‐term results after the treatment of parotid pleomorphic adenomas (PPAs) using different surgical techniques and focusing on recurrence rates and the risk of ...adverse effects.
Study Design
Retrospective analysis.
Methods
Retrospective analysis of 182 patients treated exclusively for PPAs at a tertiary referral center between 2000 and 2004. Thorough follow‐up examinations over a mean period of 13 years were possible in 53.8% (n = 98/182). Tumors were categorized according to the European Salivary Gland Society (ESGS) system to improve the comparison of outcomes. After different surgical resection strategies, recurrence rates, postoperative facial nerve paresis (FNP), and incidence of Frey's syndrome were assessed. The follow‐up period included clinical examinations and imaging of every patient in the treating department.
Results
Of 182 patients, extracapsular dissection (ED) was performed in 29.7%, and other surgical modalities (OSMs), including facial nerve dissection, in 70.3%. After the long‐term follow‐up, 98% of all the patients (n = 96/98) were recurrence free. When recurrence rates were compared, no significant differences were noted (P < .331). ED resulted in significantly lower FNP rates compared to OSMs (P < .001). FNP rates significantly increased with size and location of the tumors according to ESGS categories (temporary and permanent FNP, P = .04). Surgical invasiveness corresponded to a significant increase in the incidence of Frey's syndrome (P < .001).
Conclusions
ED was associated with the lowest complication rates, but not with a higher risk of recurrence, when compared with OSM in the long‐term course. As ED can be performed in the majority of PPAs, it can be regarded as the treatment of choice whenever possible.
Level of Evidence
4 Laryngoscope, 131:E445–E451, 2021
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Hearing loss is one of the most common disorders worldwide. It affects communicative abilities in all age groups. However, it is well known that elderly people suffer more frequently from hearing ...loss. Two different model approaches were employed: A generalised linear model and a random forest regression model were used to quantify the relationship between pure-tone hearing loss, age, and speech perception. Both models were applied to a large clinical data set of 19,801 ears, covering all degrees of hearing loss. They allow the estimation of age-related decline in speech recognition for different types of audiograms. Our results show that speech scores depend on the specific type of hearing loss and life decade. We found age effects for all degrees of hearing loss. A deterioration in speech recognition of up to 25 percentage points across the whole life span was observed for constant pure-tone thresholds. The largest decrease was 10 percentage points per life decade. This age-related decline in speech recognition cannot be explained by elevated hearing thresholds as measured by pure-tone audiometry.
Objectives/Hypothesis
To investigate epidemiological features and symptoms of sialolithiasis and their implications for diagnosis and management.
Study Design
Retrospective cohort study.
Methods
...Retrospective analysis on 2,322 patients with sialolithiasis, between 1987 and 2009. The statistical significance between two sample distributions was computed using analysis of variance Student t test for two‐tailed distribution.
Results
A total of 2,959 calculi were identified by means of ultrasound. Of those, 80.4% were located in the submandibular duct system (53% hilar/proximal, 37% distal, 10% intraparenchymal) and 19.6% were parotid stones (83% in Stensen's duct, 17% intraparenchymal). Sialoliths had been discovered beforehand in the submandibular gland (P = 0.00024; t test). Symptoms, measured from first visit, lasted on average 26 months (range: 1 day–30 years). The main group suffered from swelling (50.3%), followed by painful swelling (41.6%) and pain (3.1%). Multiple stones were found in 16.9% of patients (18.1% in the submandibular gland; 14.3% in the parotid). Average stone diameter in the submandibular gland was 8.3 mm (range 1–35 mm), and the stones were in Lustmann group II (46%). In the parotid gland, the average diameter was 6.4 mm (range 1–31 mm), and 51% were in Lustmann group I.
Conclusion
Nowadays, epidemiologic features and clinical manifestations of sialolithiasis play an important role, assisting not only in diagnosis but also in determining appropriate treatment. Due to their location and smaller diameter, parotid stones in some cases can only be treated using a mini‐invasive endoscopic technique. Submandibular stones more often require a combined approach.
Level of Evidence
4 Laryngoscope, 125:1879–1882, 2015
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives/Hypothesis
The aim of this study was to identify potential associations between epidemiologic, morphologic, and histopathologic features in pleomorphic adenomas (PAs) of the parotid gland ...in order to extract information about the natural course and biologic behavior of these lesions on the basis of a single‐center series of 845 cases within a period of 15 years.
Study Design
Retrospective study in a tertiary academic center.
Methods
For this study, an experienced head and neck pathologist critically re‐evaluated the histological slides of the pathological specimens of all patients who underwent a parotidectomy for PA of the parotid gland between 2006 and 2020.
Results
A total of 845 cases made up our study sample. Our analysis showed a statistically significant association of the histologic subtype with younger age (P = .001) and maximal diameter (P = .044), with the hypocellular type being encountered more often in younger patients and in smaller lesions. The same subtype was significantly associated with an incomplete capsule (P = .001), pseudopodia (P = .006), and satellite nodules (P = .001). An incomplete capsule was associated with the presence of pseudopodia (P = .001) and satellite nodules (P = .001).
Conclusion
It seems that various histologic subtypes have different capsule‐producing properties. Apparently, over the course of time, tumor material builds a finger‐like projection still inside the capsule, separates itself from the parenchyma with fibrous tissue still remaining enclosed within the capsule (pseudopodium), slowly penetrates the capsule (incomplete capsule), and leaves the main lesion taking a part of the capsule with it (satellite nodules). Laryngoscope, 132:73–77, 2022
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recently, we discovered the recurrent genomic rearrangement t(4;9)(q13;q31) enabling upregulation of the transcription factor Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) through enhancer ...hijacking as the oncogenic driver event in acinic cell carcinoma (AciCC) of the salivary glands. In the current study, we evaluated the usefulness of NR4A3 immunostaining and NR4A3 fluorescence in situ hybridization (FISH) in the differential diagnosis of AciCC, comparing a total of 64 AciCCs including 17% cases with high-grade transformation, 29 secretory (mammary analog) carcinomas (MASC), and 70 other salivary gland carcinomas. Nuclear NR4A3 immunostaining was a highly specific (100%) and sensitive (98%) marker for AciCC with only 1 negative case, whereas NR4A3 FISH was less sensitive (84%). None of the MASCs or other salivary gland carcinomas displayed any nuclear NR4A3 immunostaining. The recently described HTN3-MSANTD3 gene fusion was observed in 4 of 49 (8%) evaluable AciCCs, all with nuclear NR4A3 immunostaining. In summary, NR4A3 immunostaining is a highly specific and sensitive marker for AciCC, which may be especially valuable in cases with high-grade transformation and in “zymogen granule”-poor examples within the differential diagnostic spectrum of AciCC and MASC.
Objectives/Hypothesis:
To determine the incidence of major and minor complications and their impact on patients' comfort after parotid surgery in benign disease.
Study Design:
Retrospective.
Methods:
...Four hundred ninety‐two patients were included. Total parotidectomy (TP) was performed in 65.8%, superficial parotidectomy (SP) in 27.2%, and partial superficial parotidectomy (PSP) in 7.0%. Patients were interviewed using a self‐designed questionnaire. Incidence of complications was evaluated depending on the extent of surgery and intensity of complaints. To ascertain the impact of morbidity on their daily lives, patients were asked to estimate it according to a visual analog scale.
Results:
Frey's syndrome occurred in 63.4%, and temporary facial nerve palsy in 32.7% of all cases. Both rates were significantly reduced after PSP. Permanent facial nerve paresis was observed in 2.3% of the cases, but in no case after PSP. Perception of patients and their scores reflected these results. Scores regarding Frey's syndrome and facial nerve paresis showed a significant positive correlation with extent of surgery. The recurrence rate was 2.2%; no recurrences were noted after PSP. Scores of perceived general condition indicated an excellent state.
Conclusions:
The incidence of complications was reduced after PSP compared to SP or TP. Patient scores, which represent their perception of these complications, reflected these data and may be an additional instrument to measure outcome. These data suggest that less invasive operative techniques should be considered in case of a benign disease. Laryngoscope, 2010
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
The aim of this study was to investigate and compare the histopathological findings in pleomorphic adenomas (PA) of the parotid and submandibular gland with emphasis on the histological ...subtype and capsular characteristics.
Materials and Methods
The histopathological specimens of all patients with PAs of the parotid and submandibular gland between 2000 and 2020 were re‐examined by an experienced head and neck pathologist. Patients without representative slides allowing evaluation of the whole periphery of the PA were excluded from our study sample.
Results
Nine hundred and thirty‐four patients formed our study sample (327 men, 607 women, male‐to‐female ratio: 0.53:1). Eight hundred and forty‐four cases had a PA in the parotid gland and the remaining 90 in the submandibular gland. Our comparative analysis showed that submandibular PAs are characterized by the consistent presence of an intact anatomical capsule, infrequent occurrence of pseudopodia and satellite nodules, and a low proportion of the high‐risk myxoid subtype.
Conclusion
Our study highlights significant differences between PAs of the parotid and submandibular glands in their histopathological characteristics. Their differences likely underlie the favorable surgical outcome observed in PAs of the submandibular glands and may explain the propensity of PAs of the parotid glands for local recurrences.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To evaluate the oncologic and functional outcome in cases in which a false preoperative working hypothesis "benign parotid tumor" led to a primary extracapsular dissection being performed rather than ...a traditional, more radical surgical modality.
Case series with chart review.
Academic tertiary referral center.
The records of all patients treated for malignant tumors of the parotid gland between 2006 and 2012 were retrospectively studied. Patients were excluded from our study sample for insufficient data or if their histories indicated manifestation of malignant tumors without primary parotid origin (squamous cell carcinomas, lymphomas, melanomas), revision surgery, as well as concomitant or past malignant tumors. Consequently, a total of 29 patients with 30 primary malignant tumors of the parotid gland formed our study sample (14 men, 15 women; male:female ratio, 0.93:1; mean age, 55.4 years; range, 14-85 years).
Of 30 cases, 22 had low-grade tumors. Further tumor cells were detected in only the histology specimens of the parotid in 3 of the 25 cases treated subsequently with completion parotidectomy. Five patients received adjuvant radiation. Five-year disease-specific survival was 100%; local disease control was 96.6%. Of 30 cases, 28 had House-Brackmann I after tumor treatment; the other 2 cases had a slight paralysis (House-Brackmann II).
Beginning with the "false" working hypothesis and performing an extracapsular dissection in unsuspected cases seems to have no adverse impact on patients' survival and postoperative quality of life in cases in which definitive histology reveals malignancy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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