UNASSIGNED: Radiotherapy following primary operation is strongly recommended for salivary gland carcinomas (SGCs) with adverse features. The interval between surgery and the initiation of radiotherapy (SRT) varied and a prolonged SRT may cause failure of cancer treatment. However, the association of SRT with survival is unclear in major SGCs.
UNASSIGNED: This retrospective study included a total of 346 patients who underwent radiotherapy after the primary operation from Fudan University Shanghai Cancer Center from 2005 to 2020. The best cutoff value of the SRT was determined by the maximum log-rank statistic method. The primary endpoint of the study was overall survival (OS). Correlations between variables and OS were conducted by the univariable analysis using the Log-rank method, and a multivariate Cox proportional hazards regression was performed to identify the independent prognostic factors associated with OS. The estimated survival rates were captured using the Kaplan-Meier method.
UNASSIGNED: With a median follow-up time of 70.31 months, the estimated 5-year OS, LRFS, and DMFS were 83.3%, 80.1%, and 75.9%, respectively. The cutoff value for SRT was 8.5 weeks, while age, T stage, N stage, perineural invasion (PNI), pathological aggression, chemotherapy, and SRT were associated with OS in the univariable analysis. The Cox regression analysis demonstrated that older age (P < 0.001), T3-4 tumors (P = 0.007), positive N stage (P < 0.001), pathological aggression (P = 0.014), and longer SRT (P = 0.009) were independent prognostic factors for major SGCs. Using the stratification model, we observed that delay in the SRT was associated with worse OS (P = 0.006) in the high-risk group, whereas no significant difference was observed in the low-risk subgroup (P = 0.61).
UNASSIGNED: The delay in the initiation of postoperative radiotherapy may be a prognostic factor for patients with major SGCs. It was suggested that radiotherapy should be delivered within 8.5 weeks following the operation, especially for patients with ≥2 risk factors, including older age, high pathological aggression, T3-4 tumors, and positive N stage.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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 (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.

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.

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.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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.

OBJECTIVE: 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.

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.

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