Tumor budding - a potential biomarker in low grade salivary gland carcinomas?

Background: Low-grade salivary gland carcinoma is regularly treated with surgical therapy of the salivary gland without elective neck dissection in T1/2 carcinomas, either alone or with adjuvant radiation therapy. However, occult metastasis and locoregional recurrence influence therapy and outcome. Tumor budding is an emerging prognostic pathological factor in many carcinomas, but has not yet been adequately considered in salivary gland carcinomas. Methods: We conducted a retrospective single-center study of 64 patients diagnosed with low-grade carcinoma of the major salivary glands treated between 2003 and 2017. Pathological risk factors and TNM classification were thoroughly assessed for each case. All hematoxylin and eosin (HE)-stained histological specimens underwent careful examination, and tumor budding was identified following the guidelines set forth by the International Tumor Budding Consensus Conference in 2016. Results: Tumor budding was not statistically significant concerning 5-year survival rate (5-YSR) (p=0.969) and mean overall survival (log-rank p=0.315). Whereas 5-year disease-free survival rate (5-YDFSR) was 87% in the low tumor budding group and 61.1% in the intermediate and high tumor budding group (p=0.021). Mean disease-free survival accounted for 100.2 months (CI: 88.6;111.9) in the low budding score group and 58.7 months (CI: 42.8;74.6) in the other group (log-rank p=0.032). Notably, pT1/2 showed significantly lower tumor buds than pT3/4 stages (2.43 tumor buds/0.785 mm2 vs. 4.19 tumor buds/0.785 mm2, p=0.034). Similar findings were noted comparing nodal-positive and nodal-negative patients, as well as patients with and without lymphovascular invasion and perineural invasion (each p<0.05). Conclusions: Tumor budding might be used as an additional prognostic factor for recurrence in low-grade salivary gland carcinoma, seemingly associated with a higher nodal metastasis rate and advanced tumor stages and a worse 5-YDFSR. Consequently, the evaluation of tumor budding in resection specimens of low-grade salivary gland tumor may prove valuable in decision-making for neck dissection and follow-up strategy.

Epithelial-Myoepithelial Carcinoma of the Parotid Gland: A Report of a Rare Case and Review of Literature.

Epithelial-myoepithelial carcinoma (EMC) is a rare tumor, characterized by two different cell populations and both demonstrate a malignant nature microscopically. It constitutes less than 2% of all salivary gland malignancies. The World Health Organization (WHO) has classified this disease as a separate pathological category. The diagnosis of this tumor is arrived by biopsy. It shows slow growth and is small in size; it appears in ulcerative form of mucosa in some cases. Gland cells consist of two layers of outer myoepithelium cells and inner epithelial cells. Vimentin staining is positive. It shows calponin, muscle-specific actin, S100, smooth muscle actin, p63, and smooth muscle myosin heavy chain I. Examining different sets of data reveals that tumors exhibiting a solid growth pattern, nuclear atypia, DNA aneuploidy, and increased proliferative activity typically display a more aggressive nature, accompanied by a heightened likelihood of local recurrences and metastases. The clinical and radiological observations frequently resemble those of a benign tumor. Due to the uncommon nature of EMC, there is currently no established standard treatment protocol. It is considered a low-grade tumor where good resection holds better results. Individuals displaying histopathological indicators of aggressive disease should be evaluated for potential adjuvant radiotherapy. We present a case of a patient who had recurrence twice in a period of seven years despite surgical management, chemotherapy, and radiotherapy.

Outcome of Primary Lung Salivary Gland-Type Carcinoma: A Population-Based Study.

Introduction. Primary pulmonary salivary gland-type carcinomas are rare malignancies arising from minor salivary gland tissue in the lower respiratory tract. Given their rarity, constituting <1% of all primary lung malignancies, their epidemiological features and outcomes remain poorly documented. This study analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to identify primary pulmonary salivary gland carcinomas, including the most prevalent tumor types. Methods. All patients diagnosed with mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, with the lung designated as the primary site between 1975 and 2019, were subject to analysis. Overall and disease-specific survival were calculated using Kaplan-Meier curves and Cox proportional hazards models. Results. The study identified 323 mucoepidermoid carcinoma, 284 adenoid cystic carcinoma, and 6 epithelial-myoepithelial carcinoma diagnosed as pulmonary salivary gland-type carcinoma. An analysis of age distribution revealed a unimodal pattern for both mucoepidermoid carcinoma and adenoid cystic carcinoma, with most patients diagnosed after age 40. Most patients were Caucasians (77% for mucoepidermoid carcinoma and 83% for adenoid cystic carcinoma). Both disease-specific and overall survival were worse for patients diagnosed at the age of 60 years or above. Race or sex did not significantly impact patient survival. High-grade mucoepidermoid carcinoma demonstrated a significantly worse prognosis than low or intermediate-grade mucoepidermoid carcinoma. Conclusion. A comprehensive review of clinical and epidemiological features of pulmonary salivary gland-type carcinomas reveals that the age of diagnosis and tumor grade are the most significant factors in determining patient survival.

Diagnostic clues and pitfalls in salivary gland fine-needle aspiration cytology.

Salivary gland tumors (SGT) display morphological diversity and pose diagnostic challenges. Preoperative fine needle aspiration cytology (FNAC) is a minimally invasive and efficient diagnostic test. However, due to the limited sample size, the final diagnosis may not be established based on FNAC alone. Although cytomorphology and architecture are usually preserved on FNAC, morphologic changes specific to FNAC can complicate the diagnosis. The Milan System for Reporting Salivary Gland Cytopathology categorizes complex FNAC interpretations. Because the cytological diagnosis is closely linked to the histological diagnosis, a multidimensional approach considering the possibility of several differential diagnoses is necessary. From the standpoint of treatment, distinguishing high-grade malignancy from low-grade malignancy is more important than distinguishing malignancy from benign tumors.

Prognostic factors for development of distant metastases in surgically treated high-grade salivary gland carcinomas: results of retrospective single center study with 213 patients.

PURPOSE: Distant metastases (DM) are the primary cause of treatment failure and death of patients with salivary gland carcinomas (SGC). The purpose of present study was to evaluate factors predictive on DM development in a cohort of patients with high-grade salivary gland carcinomas. METHODS: This was a retrospective cohort study of consecutive patients surgically treated with curative intention at the authors' institution from January 1993 to December 2018. Outcomes evaluated were overall survival (OS), disease specific survival (DSS), recurrence free survival (RFS), locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS). RESULTS: A total of 213 patients, 117 males (55%) and 96 females (45%), were included in the study. Parotid gland malignancies accounted for 56% of all cases. Adenoid cystic carcinoma (119 cases; 56%) was the most common tumor type. Cumulative OS for the 5-and 10-year follow-up period was 80% and 58% respectively. DM occurred with 75 patients (35%). The most common locations for DM were lung (55 cases; 73%) and liver (12 cases; 16%). Pathological nodal status, particularly the number of metastatic nodes, was the independent prognostic factor for OS, DSS, RFS and DMFS. CONCLUSION: Number of metastatic lymph nodes, instead of extranodal extension and largest nodal diameter, was the contributing factor related to DMFS. Since the main function of staging system is to predict outcomes, the significance of extranodal extension and nodal dimension in salivary gland cancer staging system requires further clarification. The elective neck dissection could be considered therapeutic approach for high-grade SGC since occult metastases were detected in 33% of cases.

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.

Metastatic cutaneous squamous cell carcinoma accounts for nearly all squamous cell carcinomas of the parotid gland.

Primary squamous cell carcinoma of the parotid gland (pSCCP) has long been recognized as a separate entity and is included in the WHO classifications of salivary gland tumors. However, it is widely accepted among head and neck pathologists that pSCCP is exceptionally rare. Yet, there are many publications describing series of pSCCP and data from SEER and other cancer register databases indicate erroneously an increasing incidence of pSCCP. Importantly, pSCCP and metastatic (secondary) squamous cell carcinoma to the parotid gland (mSCCP) have nearly identical histological features, and the diagnosis of pSCCP should only be made after the exclusion of mSCCP. Moreover, all of the histological diagnostic criteria proposed to be in favor of pSCCP (such as, for example, dysplasia of ductal epithelium) can be encountered in unequivocal mSCCP, thereby representing secondary growth along preexistent ducts. Squamous cell differentiation has also been reported in rare genetically defined primary parotid carcinomas, either as unequivocal histological squamous features (e.g., NUT carcinoma, mucoepidermoid carcinoma), by immunohistochemistry (e.g., in NUT carcinoma, adamantinoma-like Ewing sarcoma, basal-type salivary duct carcinoma, mucoepidermoid carcinoma), or a combination of both. Another major issue in this context is that the International Classification of Diseases (ICD) coding system does not distinguish between primary or metastatic disease, resulting in a large number of patients with mSCCP being misclassified as pSCCP. Immunohistochemistry and new molecular biomarkers have significantly improved the accuracy of the diagnosis of many salivary gland neoplasms, but until recently there were no biomarkers that can accurately distinguish between mSCCP and pSCCP. However, recent genomic profiling studies have unequivocally demonstrated that almost all SCCP analyzed to date have an ultraviolet light (UV)-induced mutational signature typical of mSCCP of skin origin. Thus, mutational signature analysis can be a very useful tool in determining the cutaneous origin of these tumors. Additional molecular studies may shed new light on this old diagnostic and clinical problem. This review presents a critical view of head and neck experts on this topic.

Lymphoepithelial Carcinoma of the Sublingual Gland: A Case Report.

Lymphoepithelial carcinoma (LEC) of the salivary gland is a rare squamous cell carcinoma. LEC commonly presents in the parotid and submandibular glands and rarely in the sublingual gland. While salivary gland LEC has a predilection for Inuit-Yupik and Chinese populations, few cases have been reported in the Hispanic population and none for sublingual glands in the English language literature. Here, we present the seventh case report in the English language literature for sublingual LEC and the first case observed in a Hispanic patient.

Salivary gland carcinoma: Towards a more personalised approach.

Salivary Gland carcinomas (SGCs) are rare tumors accounting for less than 1% of all cancers with 21 histologically diverse subtypes. The rarity of the disease presents a challenge for clinicians to conduct large size randomized controlled trials. Surgery and radiotherapy remain the only curative treatment for localized disease, whereas treatments for recurrent and metastatic disease remain more challenging with very disappointing results for chemotherapy. The different histological subtypes harbor various genetic alterations, some pathognomonic with a diagnostic impact for pathologists in confirming a difficult diagnosis and others with therapeutic implications regardless of the histologic subtype. Current international guidelines urge pathologists to identify androgen receptor status, HER-2 expression that could be determined by immunohistochemistry, and TRK status in patients with non-adenoid cystic salivary gland carcinoma that are eligible to initiate a systemic treatment, in order to offer them available targeted therapies or refer them to clinical trials based on their mutational profile. A more advanced molecular profiling by next generation sequencing would offer a larger panel of molecular alterations with possible therapeutic implications such as NOTCH, PI3K, BRAF, MYB, and EGFR. In the following review, we present the most common genetic alterations in SGCs as well as actionable mutations with the latest available data on therapeutic options and upcoming clinical trials.

Adenoid cystic carcinoma of the parotid and submandibular glands in children and young adults: A population-based study.

OBJECTIVES: This study aims to analyze the behavior and treatment of adenoid cystic carcinoma (AdCC) in the pediatric and young adult population and to identify factors affecting overall survival (OS). MATERIALS AND METHODS: The study analyzed salivary gland malignancies in patients aged 0-21 with AdCC histology using the National Cancer Database from 2004 to 2018. RESULTS: A total of 72 patients (59.7% parotid, 36.1% submandibular, 1.4% sublingual, 2.8% unspecified) met criteria. Median age was 18 years [range: 0-21]. High-grade dysplasia was present in 67% of cases. Therapy consisted of primary surgery for all cases, regional lymph node dissection (LND) (74%), radiotherapy (71%), chemotherapy (8%), and chemoradiation (7%). The 5-year OS rate was 93.2% [95% confidence interval (CI): 86.9%-99.9%], respectively. Patients who underwent associated LND had improved OS (p = .0083, log-rank test) with a 5-year OS at 82.4% [95% CI: 66.1%-100%] versus 97.6% [95% CI: 93.0%-100%]. A significant difference in OS was found with unfavorable outcomes after positive marginal status: 5-year OS 84.1% [95% CI: 71.0%-99.7%] versus 100% [95% CI: 100%]; p < .001. Adjuvant therapy did not seem to impact the outcome. CONCLUSION: This study confirms that AdCC in children and young adults has an overall good prognosis despite frequent high grade. It suggests that cervical LND may be of importance, but the value of systematic adjuvant therapy is not confirmed. These findings emphasize the importance and relevance of population-based studies in shaping clinical practice and informing the design of future prospective investigations.

Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies.

BACKGROUND: HER2-expressing salivary gland carcinoma (SGC) is associated with poor prognosis. Trastuzumab deruxtecan (T-DXd, DS-8201) has shown evidence of antitumor activity for several HER2-expressing solid tumors in multiple studies. This study aimed to present the efficacy and safety of T-DXd in patients with HER2-expressing SGC from a pooled analysis. METHODS: Patients with HER2-expressing SGC were pooled from two phase I, open-label studies of T-DXd: a two-phase, multiple-dose, first-in-human study (NCT02564900) and a single-sequence crossover drug-drug interaction study (NCT03383692). Endpoints included efficacy (objective response rate [ORR], duration of response [DoR] and progression-free survival [PFS]) and safety. RESULTS: This pooled analysis included 17 patients with SGC (median age: 57 years; male: 88.2%); median (range) follow-up duration was 12.0 (2.3-|34.8) months. Among these patients, 14 had received prior HER2-targeted agents and 13 had undergone prior radiotherapy. The investigator-assessed confirmed ORR was 58.8% (95% confidence interval [CI], 32.9-|81.6). The median (95% CI) DoR and PFS were 17.6 months (4.0 to not evaluable [NE]) and 20.5 months (11.1-NE), respectively. All 17 patients reported treatment-emergent adverse events (TEAEs); 76.5% reported TEAEs of grade ≥3. The most common TEAEs were decreased appetite (94.1%), nausea (88.2%) and neutrophil count decreased (76.5%). Of the 17 patients, five (29.4%) reported adjudicated drug-related interstitial lung disease (grade 1, n = 3; grade 2, n =1; grade 3, n = 1). CONCLUSION: The results of this pooled analysis provide evidence that clinical benefit is achievable with T-DXd in patients with HER2-expressing SGC. CLINICAL TRIAL INFORMATION: FIH study, NCT02564900; DDI study, NCT03383692.

Effectiveness and risk of second primary malignancies after radiotherapy in major salivary gland carcinomas: A retrospective study using SEER database.

OBJECTIVE: To investigate the effectiveness of radiotherapy and its association with second primary malignancies (SPMs) risk in major salivary gland carcinomas (MSGCs) patients. METHODS: Cohort 1 included 7274 surgically treated MSGC patients from the Surveillance, Epidemiology, and End Results database, assessing the effectiveness of radiotherapy. Cohort 2 (n = 4213) comprised patients with ≥5-year survival in Cohort 1 to study SPMs. RESULTS: Radiotherapy decreased overall survival in MSGCs patients, but improved it in high-grade MSGCs. Cumulative SPMs incidences at 25 years were 16.5% in the radiotherapy (RT) group compared to 14.5% in the non-radiotherapy (NRT) group. For second head and neck carcinomas (SHNCs), incidences were 3.4% in RT versus 1.6% in NRT. Radiotherapy increased the relative risks of tumors, particularly SHNCs (RR = 1.78). The 10-year OS rates of SHNCs after radiotherapy were significantly lower. CONCLUSION: Radiotherapy improves survival in advanced-stage MSGCs but increases the risk of developing SPMs, particularly SHNCs.

Efficacy of Cetuximab Combined with Paclitaxel in Patients with Recurrent Salivary Gland Carcinoma: A Retrospective Observational Study.

INTRODUCTION: Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy for patients with SGC. Our study described promising results of epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel in patients with SGC. METHODS: The medical records of patients with recurrent SGC treated with weekly cetuximab combined with paclitaxel (Cmab-PTX) between December 2017 and December 2022 at our institutions were retrospectively analyzed. RESULTS: Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months (range of 2-36 months). The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response and disease control rates were 71.4% and 85.7%, respectively. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. CONCLUSION: Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC. Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy in patients with SGC. Our study described promising results of cetuximab (Cmab), epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel (PTX) in patients with SGC. Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months. The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response rate was 71.4%. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. Our study revealed a preferable objective response rate of Cmab-PTX for patients with high-grade SGC. Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC.

Development and Validation of Nomograms to Predict Risk and Prognosis in Salivary Gland Carcinoma Patient with Distant Metastases.

Background: Salivary gland carcinoma (SGC) patients with distant metastasis (DM) are rare, and understanding this disease is insufficient. Nomograms can predict the prognostic probability of patients, while few studies have examined diagnostic and prognostic factors in SGC patients with DM. The purpose of this study was to establish and validate the risk and prognostic nomograms of SGC patients with DM. Methods: Based on the SEER database, we analyzed the data of SGC patients between 2004 and 2015. Logistic regression analyses and Cox proportional hazards regression analyses were used to identify risk and prognostic factors for DM in SGC patients. Based on the Akaike information criterion (AIC) value and likelihood ratio test, the best-fitting model was selected to build risk and prognostic nomograms, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and Kaplan-Meier (K-M) survival curves. ROC curves were also used to compare the nomograms with the American Joint Committee on Cancer (AJCC) staging system. Results: 7418 SGC patients were included in the study, and 307 (4.14%) of them were diagnosed with DM. This study identified that there are variables (age ≥ 80, no-parotid gland primary site, histologic type of mucoepidermoid carcinoma and squamous cell carcinoma, T stage ≥ T2, N staged ≥ N1, histologic grade ≥ III, and tumor size ≥ 41 mm) associated with the occurrence of DM in SGC patients. Therefore, we constructed diagnostic and prognostic nomograms after incorporating these variables. ROC curves illustrated the better predictive efficacy of 2 nomograms over the AJCC staging system. DCA curves, calibration curves, and K-M survival curves showed that 2 nomograms can accurately predict the occurrence and prognosis of DM among SGC patients in training and validation sets. Conclusion: It was shown that the nomograms were highly discriminative in predicting the diagnosis and prognosis of SGC patients with DM, and could identify high-risk patients, thereby providing SGC patients with individualized treatment plans.

A Rare Case of Recurrent Carcinoma Ex Basal Cell Adenoma of the Parotid Gland.

Basal cell adenoma is encountered in the salivary glands, particularly the parotid gland; however, malignant transformation is rare, and recurrence is much rarer. We report the case of a 60-year-old man who had experienced a slow-growing mass in the parotid gland, which was suspected to be pleomorphic adenoma. Radiological and cytological examination suggested an atypical lesion in the left parotid. The final diagnosis reached on the excised specimen was that of a basal cell adenocarcinoma ex adenoma with close margins. The patient presented with a recurrence after two years. Routine histopathological examination with careful examination by the pathologist is essential for proper management of such rare malignant lesions, and recurrence is a possibility. A complete excision of the tumor with tumor-free margins from the beginning is suggested.

HRAS mutation as a diagnostic molecular analysis for epithelial-myoepithelial carcinoma of the parotid gland: A case report.

HRAS mutations are frequent genetic alterations in epithelial-myoepithelial carcinoma, and they may be useful as ancillary molecular tests and predictive molecular tests for targeted therapy with tipifarnib.

A New Era in Salivary Gland Carcinoma Treatment: A Case Report.

Salivary gland cancers are rare and heterogenous malignancies which makes it hard to standardize treatments with good evidence levels. The localized disease approach is well established, with surgery to the primary site and adjuvant radiation therapy in patients with high-risk features. Treatment of advanced disease should be multidisciplinary. Local approaches, which include radiation therapy, surgery, and thermoablation, among others, have the potential to achieve durable disease control with low toxicity. Chemotherapy has shown disappointing results, so systemic treatment should be guided by actionable genetic alterations, which in salivary gland cancers rely on the histologic type. When directed molecular tests are not useful, a multigene panel should be performed. This case is a good example of how to integrate all these possible tretaments in clinical practice, including molecular testing and target treatment.

Case Report: A case of complete response to entrectinib in NTRK fusion gene-positive parotid gland cancer.

Introduction: Expression of the NTRK gene is rare in solid tumors but is highly prevalent in salivary gland secretory carcinomas. Here, we report a case of a complete response to entrectinib in a patient with NTRK fusion gene-positive parotid carcinoma. Case description: The patient was a 44-year-old man who underwent total left parotidectomy and left cervical lymph node dissection for a left parotid tumor at 24 years of age. The histopathological diagnosis was mammary analog secretory carcinoma. Postoperatively, the patient received only radiation therapy. Sixteen years after the surgery, the patient became aware of a mass in the left parotid region. A close examination revealed local recurrence and multiple cervical lymph node metastases. S-1 monotherapy was started as chemotherapy but was discontinued 3 years later because of disease progression. As there was no standard treatment, a comprehensive genomic profiling test using a next-generation sequencer was performed, and the ETV6-NTRK3 fusion gene was identified. Entrectinib, an NTRK inhibitor, was immediately administered at a dose of 600 mg/day. The local recurrence rapidly shrank grossly from the beginning of treatment, and a complete response was observed 6 months later. However, creatinine levels exhibited an increase at week 68 of treatment; consequently, entrectinib dosage was lowered to 400 mg/day, leading to an immediate improvement in creatinine levels. Entrectinib was associated with additional side effects, including dysgeusia, fatigue, dizziness, and weight gain, all of which were also alleviated by the reduction in entrectinib dose. Thirty months after treatment initiation, the patient maintained a complete response and continued to receive entrectinib. Conclusion: The NTRK fusion gene should always be checked in the presence of salivary gland secretory carcinoma.

Combination chemotherapy with taxane and platinum in patients with salivary gland carcinoma: a retrospective study of docetaxel plus cisplatin and paclitaxel plus carboplatin.

Background: Despite advances in precision medicine, most patients with recurrent or metastatic salivary gland carcinoma still need conventional chemotherapies, such as the combination of taxane and platinum. However, evidence for these standardized regimens is limited. Methods: We retrospectively reviewed patients with salivary gland carcinoma treated with a taxane and platinum, which contained docetaxel at a dose of 60 mg/m2 plus cisplatin at a dose of 70 mg/m2 on day 1, or paclitaxel at a dose of 100 mg/m2 plus carboplatin at a dose of area under the plasma concentration-time curve = 2.5 on days 1 and 8 (both on 21-day cycles), between January 2000 and September 2021. Result: Forty patients with ten adenoid cystic carcinomas and thirty other pathologies were identified. Of these, 29 patients were treated with docetaxel plus cisplatin and 11 with paclitaxel plus carboplatin. For the total population, the objective response rate (ORR) and median progression-free survival (mPFS) were 37.5% and 5.4 months (95% confidence interval: 3.6-7.4 months), respectively. On subgroup analysis, docetaxel plus cisplatin provided favorable efficacy compared with paclitaxel plus carboplatin (ORR: 46.5% vs. 20.0%, mPFS: 7.2 vs. 2.8 months), and the findings were well retained in patients with adenoid cystic carcinoma (ORR: 60.0% vs. 0%, mPFS: 17.7 vs. 2.8 months). Grade 3/4 neutropenia was relatively frequent in the docetaxel plus cisplatin (59% vs.27%), although febrile neutropenia was uncommon (3%) in the cohort. No treatment-related death was seen in any case. Conclusion: The combination of taxane and platinum is generally effective and well-tolerated for recurrent or metastatic salivary gland carcinoma. In contrast, paclitaxel plus carboplatin appears unfavorable in terms of efficacy in certain patients, such as those with adenoid cystic carcinoma.