Fingertip cutaneous metastasis of salivary duct carcinoma secondary to scald: A unique case report and a brief review of literature (following CARE guidelines).

RATIONALE: Salivary duct carcinoma (SDC) is an aggressive form of cancer, with cutaneous metastasis being a rare occurrence. Furthermore, cutaneous metastasis of SDC secondary to a scald is even rarer, and to the best of our knowledge, our case represents the first such instance. Considering the involvement of the fingers in the metastatic site, which may affect limb function and quality of life, we present this case to explore the reason why scald could lead to distant recurrence and better treatment options. PATIENT CONCERNS: An 85-year-old man diagnosed with SDC in the parotid gland found enlarged masses at the fingertips as a consequence of a burn, 6 years after his initial treatment. DIAGNOSES: Cutaneous metastasis of SDC in the parotid gland and left thumb loss due to surgery. INTERVENTIONS: Radiotherapy was offered, targeting at the masses on the fingers, with dose at 15 Gy in 3 fractions, 12 Gy in 3 fractions, 15 Gy in 3 fractions for both hands and additional 21 Gy in 7 fractions only for left hand. OUTCOMES: The tumors shrank after 2 months of radiotherapy and the patient recovered well. Side effects included nail hyperplasia and paronychia. LESSONS: Connections between scald and distant metastasis of malignant tumors in this case needed further investigation. Considering reserving function of the fingers while dealing with metastasis, radiotherapy is recommended rather than surgery.

Comparative analysis of approaches to the Wharton's duct during surgery of the submandibular gland: A retrospective case-control study.

INTRODUCTION: We investigated complications and recurrence rates after surgical techniques for sialolith removal with intact and resected Wharton's duct of the submandibular gland. METHODS: The retrospective case-control analysis of a series analysed 271 surgical operations (2003-2022) for sialolithiasis performed at a hospital department of Otolaryngology-Head and Neck Surgery. The study compared two approaches: (1) pure endoscopic technique or pinpoint stone removal with Wharton's duct left intact and (2) transoral duct dissection or pinpoint stone removal technique, after which the duct was shortened. While choosing the surgical option, the size of the stone, the location of the stone, and the presence of multiple stones were taken into account. The rates of complications (lingual nerve paraesthesia, duct stenosis, drooling, and sialoadenitis), the incidence of foreign bodies, and the rate of recurrence during follow-up of ≥18 months were compared. RESULTS: 323 sialoliths were removed from 271 patients. Of these 323 calculi, 150 were removed by the first approach and 173 by the second approach. The calculi varied in diameter from 2 to 38 mm with an average diameter of 8.2 mm. For all 271 patients, the rate of recurrence was 4.8%, but 11 recurrent cases (8.7%) appeared after the first approach surgeries and 2 cases (1.4%) after the second approach surgeries (p = .03). Other variables did not show statistically significant differences. CONCLUSIONS: Surgical removal of the submandibular calculi, ending with shortening of Wharton's duct, reduces the recurrence rate for sialolithiasis but does not affect the rate of postsurgical complications.

The extent of androgen receptor and HER2 expression allows for targeted therapy in most cases of salivary duct carcinoma: analysis of clinical and histopathological data in a tertiary care center.

PURPOSE: The incidence of salivary duct carcinoma (SDC) seems to be underestimated due to inaccurate classification. Further, the frequency of SDC patients with targeted therapy options according to current guidelines is unclear. Therefore, this study aimed at (a) describing the proportion of SDC among salivary gland carcinoma (SGC) before and after reclassification of cases initially classified as adenocarcinoma, not otherwise specified (ANOS); and (b) quantifying the frequency of SDC patients with targeted therapy options. METHODS: All patients with SDC or ANOS treated in a tertiary care center between 1996 and 2023 were identified. Histopathological diagnosis was verified for patients primarily diagnosed with SDC and reviewed for patients initially diagnosed with ANOS. Clinical data for SDC patients were retrieved from clinical charts. Immunohistochemical (IHC) androgen receptor (AR) and HER2 staining was performed. RESULTS: Among 46 SDC, 34 were primarily diagnosed as SDC and 12 had initially been classified as ANOS. The proportion of SDC among SGC was 12.1% and was rising when comparing the time periods 2000-2015 (7.1-11.5%) versus 2016-2023 (15.4-18.1%). Nuclear AR staining in > 70% of tumor cells was found in 56.8% and HER2 positivity (IHC 3 +) in 36.4% of cases. 70.5% of patients showed AR staining in > 70% of tumor cells and/or HER2 positivity and therefore at least one molecular target. 5-year overall and disease-free survival (DFS) were 62.8% and 41.0%. Multivariate Cox regression revealed positive resection margins (HR = 4.0, p = 0.03) as independent negative predictor for DFS. CONCLUSIONS: The results suggest a rising SDC incidence and show that the extent of the AR and HER2 expression allows for targeted therapy in most SDC cases.

Differential expression of TRKB tyrosine kinase in the two histological types of parotid salivary duct carcinoma with cancer aggressiveness.

Parotid salivary duct carcinoma (SDC) is a rare and aggressive parotid gland carcinoma (PGC). SDC has two origins: de novo and ex pleomorphic adenoma (SDC ex PA); however, because of its rarity, the clinical and molecular features of the two types of SDC are not sufficiently understood. Here, we studied the differences in their clinicopathological and molecular features using clinical specimens while comparing them to those of adenoid cystic carcinoma (AdCC), an intermediate-grade PGC. Clinicopathological analysis of tissues from patients with PGC revealed significant associations between histological types and malignant phenotypes, including nodal metastasis, recurrence, vascular invasion, and neural invasion, and revealed more malignant phenotypes of de novo SDC than of SDC ex PA. The de novo SDC showed a significantly higher frequency of intra-neural invasion (intra-NI) and vascular invasion than AdCC and SDC ex PA. PGCs with high intra-NI were significantly correlated with malignant phenotypes and survival rates. Recently, we observed the overexpression of tropomyosin receptor kinase B (TRKB), a receptor tyrosine kinase, in PGC cells. Here, immunohistochemical and clinicopathological analyses showed that TRKB was highly expressed in SDC cells, particularly de novo SDC cells, and was significantly associated with poor survival and highly malignant phenotypes, including intra-NI and vascular invasion. Collectively, these data show that TRKB expression is significantly elevated in PGC, particularly in de novo SDC, and can be one of the biomarkers of their aggressiveness.

Brain metastases in patients with salivary duct carcinoma: A retrospective study.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with a 5-year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses. METHODS: We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC-graded prognostic assessment (GPA) score for disease prognostication. RESULTS: Sixty-five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2-negative status, and locoregional uncontrolled disease were associated with poor OS. SDC-GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p < 0.001). CONCLUSION: The SDC-GPA score emerged as a useful prognostication tool for patients with BM.

MR sialographic assessment of the masseter muscle and the ductal kinking in patients with recurrent parotitis.

Dysfunction of the masseter muscle may cause pathological kinking of the parotid duct leading to parotitis; MR sialography is a non-invasive radiological examination that allows to evaluate dynamically the ductal system of the parotid glands. In the present study we aimed to assess the relationships between Stensen's duct and masseter muscle and their implications in the aetiopathogenesis of recurrent parotitis secondary to masseter muscle dysfunction. Forty-one patients with recurrent unilateral parotitis and nine with bilateral recurrent parotitis, all with a clinical suspicious of masseter muscle hypertrophy due to bruxism were enrolled. They underwent ultrasonography as a first line examination and then MR sialography and sialendoscopy. Different anatomical features were studied. Involved parotid glands had a wider duct compared to contralateral unaffected parotid glands of patients with recurrent parotitis (p = 0.00134); male subjects with parotitis had a longer duct compared to the salivary glands of healthy patients (p = 0.00943 for affected glands and p = 0.00629 for the contralateral). A concordance between the evidence of an acute duct angle during sialendoscopy and a wider duct in patients with parotitis was observed although not statistically significant. These initial findings suggest that the masticatory muscle dysfunction related to bruxism seems to condition alteration of parotid duct course and anatomy thus favouring the occurrence of recurrent parotitis. A specific diagnostic iter based on clinical evaluation, dynamic ultrasonography and MR sialography, is therefore, mandatory to confirm the relationship between masseter muscle anatomy and parotid duct anomalies; this is the premise for an adequate therapeutic approach to underlying masticatory muscle disorder.

The anterior lobe of the parotid gland: a CT sialographic study.

OBJECTIVES: To investigate the imaging and anatomic features of the anterior lobe (AL) of the superficial parotid gland (SPG). METHODS: Computed tomographic sialography examinations were undertaken for 142 parotid glands in 77 patients. Whole computer tomography (CT) data were analyzed using multi-planar reformation and maximum intensity projection to generate sialographic CT images. The tributary ducts of the SPG were analyzed to classify the parotid morphology. Three-dimensional analyses were used to investigate the AL and its relationship with adjacent anatomic landmarks. RESULTS: Four major types (I-IV) and 2 minor types (V-VI) of the AL and the superficial parotid gland were observed. Type I AL (83/142) was contiguous and not separated from the retromandibular parotid gland. Type II AL (16/142) was detached from the retromandibular parotid gland with 1-4 tributary ducts. Type III AL (12/142) showed a small isolated lobe above the Stensen duct around the anterior edge of the masseter. Type IV (28/142) showed the absence of the AL. Type V (3/142) shows the absence of the retromandibular parotid gland. Type VI (3/142) showed the presence of ectopic salivary gland beneath the Stensen duct anterior to the retromandibular parotid gland. CONCLUSIONS: The AL gives rise to the morphological variations of the superficial parotid gland. AL also gives rise to the accessory parotid gland when it is detached from the retromandibular parotid gland.

Specific localization of fibroblasts at the intercalated duct in the major salivary glands of rats.

OBJECTIVES: Immunohistochemical methods were employed to investigate the morphological heterogeneity and localization of fibroblasts associated with the function of major salivary glands in rats. METHODS: Histochemical and electron microscopic observations were made in rat parotid, submandibular, and sublingual glands and pancreas. Fibroblasts were immunostained using their specific marker, 47 kDa heat shock protein (Hsp47). RESULTS: Hsp47-immunopositive fibroblasts within the intralobular connective tissue exhibited a notably smaller size compared with the interlobular connective tissue. They were loosely distributed throughout the connective tissue. However, fibroblasts with elongated long processes were explicitly identified at the intercalated ducts in parotid, sublingual, and submandibular glands. Fibroblastic bodies and processes were tightly approximated with the basement membrane of the duct. Electron microscopy confirmed these findings, revealing a thin layer consisting of collagen fibers was found between the fibroblasts and the basement membrane. Double staining of Hsp47 and α-smooth muscle actin (αSMA) in parotid glands indicating that Hsp47-positive fibroblasts enveloped both the duct and αSMA-positive myoepithelial cells. Additionally, They projected long and thin processes longitudinally at the straight portion or circularly at the bifurcated portion of the duct. The three-dimensional reconstruction showed a frame-like structure of fibroblasts surrounding the intercalated duct with longitudinal myoepithelial cells. However, such specific localization of fibroblasts was not detected in the exocrine pancreas lacking myoepithelium. CONCLUSIONS: Small fibroblasts with long processes connecting or overwrapping each other and thin collagen layers surround the intercalated ducts in rat major salivary glands, presumably contributing to protecting the ducts from salivary flow and myoepithelial contraction.

Muscarinic acetylcholine receptor-mediated phosphorylation of extracellular signal-regulated kinase in HSY salivary ductal cells involves distinct signaling pathways.

OBJECTIVES: Typical agonists of G protein-coupled receptors (GPCRs), including muscarinic acetylcholine receptors (mAChRs), activate both G-protein and ß-arrestin signaling systems, and are termed balanced agonists. In contrast, biased agonists selectively activate a single pathway, thereby offering therapeutic potential for the specific activation of that pathway. The mAChR agonists carbachol and pilocarpine are known to induce phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2) via G-protein-dependent and -independent pathways, respectively. We investigated the involvement of ß-arrestin and its downstream mechanisms in the ERK1/2 phosphorylation induced by carbachol and pilocarpine in the human salivary ductal cell line, HSY cells. METHODS: HSY cells were stimulated with pilocarpine or carbachol, with or without various inhibitors. The cell lysates were analyzed by western blotting using the antibodies p44/p42MAPK and phosphor-p44/p42MAPK. RESULTS: Western blot analysis revealed that carbachol elicited greater stimulation of ERK1/2 phosphorylation compared to pilocarpine. ERK1/2 phosphorylation was inhibited by atropine and gefitinib, suggesting that mAChR activation induces transactivation of epidermal growth factor receptors (EGFR). Moreover, inhibition of carbachol-mediated ERK1/2 phosphorylation was achieved by GF-109203X (a PKC inhibitor), a ßARK1/GRK2 inhibitor, barbadin (a ß-arrestin inhibitor), pitstop 2 (a clathrin inhibitor), and dynole 34-2 (a dynamin inhibitor). In contrast, pilocarpine-mediated ERK1/2 phosphorylation was only inhibited by barbadin (a ß-arrestin inhibitor) and PP2 (a Src inhibitor). CONCLUSION: Carbachol activates both G-protein and ß-arrestin pathways, whereas pilocarpine exclusively activates the ß-arrestin pathway. Additionally, downstream of ß-arrestin, carbachol activates clathrin-dependent internalization, while pilocarpine activates Src.

Gastric Metastasis from Salivary Duct Carcinoma Mimicking Scirrhous Gastric Cancer.

A 59-year-old man underwent submandibular gland excision for salivary duct carcinoma (SDC). One year later, esophagogastroduodenoscopy indicated gastric diffuse mucosal thickening with luminal contraction, mimicking scirrhous gastric carcinoma. Biopsy specimens showed dense proliferation of neoplastic cells expressing androgen receptor and human epidermal growth factor 2, indicating SDC. Gastric diffuse infiltrative metastasis is generally characteristic of gastric metastasis from invasive ductal carcinoma, which shows histologic features similar to SDC. This is the first known report of gastric diffusely infiltrating metastasis in an SDC patient. Rapidly progressing, diffuse gastric wall thickening should also be considered indicative of salivary tumor-associated gastric metastasis.

Comparing botulinum toxin and 4-duct ligation for Sialorrhea in children - A systematic review.

INTRODUCTION: Sialorrhea or drooling can result in physical and psychosocial complications, such as aspiration and social isolation. Treatment options include botulinum toxin into the salivary glands and 4-duct ligation (i.e., simultaneous ligation of the bilateral parotid and submandibular ducts). This systematic review aimed to compare the efficacy and complication rates of botulinum toxin and 4-duct ligation for the treatment of drooling in children. METHODS: Following PRISMA guidelines, PubMed, Embase, Web of Science, and Cochrane Library were searched from inception through June 17, 2021 for studies examining the efficacy of botulinum toxin or 4-duct ligation for drooling in children. Data were summarized by pooled counts, percentages, and means. Complication rates were compared by a chi-squared test. RESULTS: A total of 22 studies (n = 606) examining botulinum toxin and 5 studies (n = 124) examining 4-duct ligation were included. From 12 botulinum toxin studies (n = 211), mean drooling frequency and severity scores was 7.5 at baseline. Mean difference from baseline was -2.6 (n = 92) at 4 weeks follow-up, -2.1 at 8 weeks (n = 41), -2.1 at 12 weeks (n = 56), and - 2.1 at 16 weeks (n = 58). From 4 4-duct ligation studies (n = 103), mean baseline drooling frequency and severity score was 8.4. Mean difference was -3.7 at mean follow-up of 35.6 months (n = 103). Eighteen botulinum studies (n = 343) recorded 53 (15.5 %) complications, including thickened saliva (n = 9), dysphagia (n = 4), and cheek abscesses (n = 4). Four 4-duct ligation studies (n = 108) recorded 25 (23.1 %) complications, including parotid gland swelling (n = 4), aspiration pneumonia (n = 3), and oxygen desaturation (n = 3). There was no statistically significant difference in complication rates between botulinum toxin and four-duct ligation (p = 0.065). CONCLUSION: Botulinum toxin injection and 4-duct ligation are both effective in improving sialorrhea in children and have comparable complication rates.

Removal of intraglandular calculi in Wharton's duct: clinical outcome and treatment algorithm.

The aim of this study was to propose a treatment strategy for intraglandular submandibular calculi based on calculus site. Seventy-three consecutive patients with impalpable intraglandular submandibular calculi were enrolled retrospectively. The calculi were classified as either post-hilar type, central type, or superficial type. Treatment approaches included transoral duct slitting (TDS), interventional basket retrieval (IBR), intraductal laser lithotripsy (ILL), and transcervical lithotomy (TCL). Complete calculus removal with gland preservation was achieved in 64 patients (87.7%). The success rate for post-hilar, central, and superficial calculi was 86.4% (51/59), 90.9% (10/11), and 100% (3/3), respectively. The treatment approach applied in patients with treatment success was TDS in 32 cases, IBR in 20, ILL in nine, and TCL in three. During follow-up (median 17.3 months), one patient experienced gland atrophy and three had ductal stenosis; the remaining 60 patients (93.8%, 60/64) had good clinical outcomes. In the eight failure cases operated by TDS, the deeply situated calculi could not be detached despite the parenchymal incision in five cases, while the procedure was ceased due to the patient's inability to cooperate in the other three cases. In the remaining failure case, the submandibular gland was sacrificed after calculus extraction via TCL. Application of the proposed treatment algorithm might help preserve gland function in patients with intraglandular submandibular calculi.

Comparative Efficacy and Side Effect Profiles of Interventions for Pediatric Saliva Control: A Cohort Study.

OBJECTIVE: To compare efficacy and side effect profile data on conservative, behavioral, pharmacological, and surgical treatments used for pediatric saliva control. STUDY DESIGN: A cohort study of children (n = 483) referred to a specialty Saliva Control service between May 2014 and November 2019 was performed, using quantitative data from pretreatment and post-treatment questionnaires (the Drooling Impact Scale [DIS], Drooling Rating Scale [DRS]) and recording of side effects. Overall, 483 children were included; treatment choices were based on published international guidelines. RESULTS: The greatest improvement was seen after intraglandular botulinum toxin A (BTX-A) injections (n = 207; 551 courses; mean DIS change, 34.7; 95% CI = 29.2-35.7) or duct transpositional surgery (n = 31; mean change in DIS, 29.0; 95% CI, 22.3-35.7). Oral anticholinergics were associated with good outcomes, with no significant statistical difference between glycopyrronium bromide (n = 150; mean DIS change, 21.5; 95% CI, 19.1-24.0) or trihexyphenidyl (n = 87; mean DIS change, 22.4; 95% CI, 18.9-25.8). Inhaled ipratropium bromide was not as efficacious (n = 80; mean DIS change, 11.1; 95% CI, 8.9-13.3). Oromotor programs were used in a selected group with reliable outcomes (n = 9; mean DIS change, 13.0). Side effects were consistent with previous studies. Overall, in cases of milder severity, enterally administered therapies provided a good first-line option. With more severe problems, BTX-A injections or saliva duct transpositional surgery were more effective and well tolerated. CONCLUSIONS: We describe a large, single-center pediatric saliva control cohort, providing direct comparison of the efficacy and side effect profiles for all available interventions and inform clinical practice for specialists when considering different options. BTX-A injections or saliva duct transpositional surgery seem to be more effective for saliva control that is more severe.

Near-infrared photoimmunotherapy for salivary duct carcinoma.

In Japan, near-infrared photoimmunotherapy (NIR-PIT) was introduced in 2021 as a treatment option for unresectable recurrent head and neck cancer. The treatment targets the epidermal growth factor receptor (EGFR), which is overexpressed in 80-90 % of head and neck squamous cell carcinoma (HNSCC). NIR-PIT should theoretically show therapeutic efficacy if EGFR is expressed, even in nonsquamous cell carcinomas (non-SCC). To the best of our knowledge, there are no case reports of NIR-PIT for non-SCC. We performed NIR-PIT in a patient with non-SCC of the head and neck region. After performing two NIR-PIT treatments, small free clusters of residual tumor cells were observed. Immunostaining in this specimen revealed EGFR expression in residual tumor cells. The residual tumor cells had been irradiated sufficiently to achieve necrosis. It is suggested that not only laser irradiation and expression of EGFR but also other factors are involved in the efficacy of this treatment. Further investigation for these other factors is warranted.

Pulmonary and Clinical Outcomes After Bilateral Submandibular Gland Excision and Parotid Duct Ligation for Refractory Sialorrhea.

Importance: Refractory sialorrhea in children can result in pulmonary aspiration and irreversible lung damage. Despite many studies devoted to the surgical treatment of sialorrhea, there is a paucity of objective outcome measures after surgery, especially with regard to pulmonary health. Objectives: To assess whether bilateral submandibular gland excision and bilateral parotid duct ligation ("DROOL" procedure) is associated with reduced pulmonary inflammation in bronchoalveolar lavage (BAL) samples after surgery and to assess patient factors associated with improvement after surgery. Design, Setting, and Participants: This retrospective case series included all 112 patients undergoing the DROOL procedure at a single tertiary care pediatric children's hospital from January 1, 2012, to December 31, 2021. Statistical analysis was performed from March 30 to June 10, 2023, and August 20 to September 23, 2023. Exposure: DROOL procedure for refractory sialorrhea. Main Outcomes and Measures: Degree of pulmonary inflammation (neutrophil percentage) according to BAL cytologic findings and overall bronchoscopy findings up to 12 months before and after the DROOL procedure. Secondary outcomes included number of annual hospitalizations, caregiver report of function before and after the procedure, and need for revision procedures and/or additional operations for secretion management. Results: A total of 112 patients (median age, 3.4 years [IQR, 2.0-7.1 years]; 65 boys [58.0%]) underwent DROOL procedures and had both preoperative and postoperative BAL samples during the study period. Patients demonstrated objective improvement in pulmonary inflammation after surgery, with the median polymorphonuclear neutrophil percentage decreasing from 65.0% (IQR, 14.0%-86.0%) before the surgery to 32.5% (IQR, 3.0%-76.5%) after the surgery (median difference in percentage points, -9.0 [95% CI, -20.0 to 0.0]). Prior to the DROOL procedure, 34 patients (30.4%; 95% CI, 21.8%-38.9%) were hospitalized 2 or more times annually for respiratory illness, which decreased to 10.1% (11 of 109; 95% CI, 4.4%-15.7%) after surgery (3 patients did not have hospitalization data available following surgery). Most caretakers (73 [65.2%]) reported improved secretion management after the procedure. Conclusions and Relevance: This study suggests that patients with impaired secretion management who underwent a DROOL procedure demonstrated improvement in pulmonary inflammation and a reduction in hospitalizations after surgery. Caretakers were also likely to report subjective improvement in secretion management and quality of life. Additional research is necessary to guide optimal timing and patient selection for this procedure.

Idiopathic dilatation of the submandibular gland duct.

Lithiasis and stenosis may cause salivary duct dilatation due to the increased pressure in the duct upstream of the obstruction. Idiopathic dilatations, also called megaducts, with no associated increase in pressure, have only been described in the parotid gland. The aim of this study was to describe the characteristics of submandibular duct dilatation unrelated to lithiasis, stenosis, or an imperforate duct, to report the existence of submandibular megaducts. This retrospective single-centre study included patients treated at La Conception University Hospital, Marseille, France, between 2007 and 2019. Patients with submandibular duct dilatation of ≥4 mm confirmed by magnetic resonance imaging sialography (sialo-MRI), who also underwent sialendoscopy to identify any associated stenosis, were included. Patients with lithiasis, stenosis, an imperforate ostium, or a history of trauma or surgery to the floor of the mouth were excluded. Five patients (three female, two male) aged 30-76 years with idiopathic duct dilatations in nine submandibular glands were included. The most commonly reported symptoms were submandibular swelling, pruritus, and discomfort, mostly outside mealtimes. Recurrence of symptoms after treatment was frequent. This study is novel in describing submandibular megaducts as opposed to dilatation caused by high pressure associated with stenosis, with confirmation by sialo-MRI and sialendoscopy.