PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

Prognosis of primary breast salivary gland-type carcinoma: a propensity score-matching analysis with invasive carcinoma of no special type based on the SEER database for years 2010-2020.

BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST). METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST. RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p < 0.05). Nonetheless, tumor grade 3 and higher AJCC stage groups remained as significant independent prognostic factors in multivariate analysis (p < 0.05). The apparent better breast cancer-specific survival of salivary gland-type carcinoma as compared to that of invasive carcinoma, NST, was diminished following adjustment for differences in baseline clinicopathological features and treatment-related variables. CONCLUSIONS: This study suggests that when managing primary breast salivary gland-type carcinoma, greater emphasis should be given to the tumor grade and AJCC stage group in addition to acinic cell carcinoma histological type and HER2 overexpression. Conventional prognostic factors are important as salivary gland-type carcinoma had similar prognosis as invasive carcinoma, NST, following adjustment for confounding variables.

Oncocytoid Salivary Tumors: Differential Diagnosis and Utility of Newly Described Immunohistochemistry.

BACKGROUND: Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma (AciCC), oncocytic mucoepidermoid carcinoma (OMEC), intraductal carcinoma, and epithelial myoepithelial carcinoma (EMC). This review investigates the differential diagnosis of oncocytoid salivary tumors and explore the role of newly described immunostains as valuable tools for their diagnosing and potentially guiding treatment options. METHODS: We assess the utility of incorporating new immunohistochemical markers in routine practice to aid in diagnosing oncocytoid salivary tumors and potentially provide treatment options. RESULTS: In SDC, AR and Her2 immunostains are utilized as diagnostic tools and biomarkers for selecting patients who might benefit from Androgen-deprivation therapy (ADT) and HER2-targeted therapy. Furthermore, nuclear Pan-Trk immunostaining can aid in diagnosing SC. Additionally, NR4A3 immunostaining has been shown high sensitivity and specificity in identifying AciCC in both surgical and cytologic specimens. Similarly, RAS Q61R mutant-specific immunostaining, detected in EMC, may offer a cost-effective diagnostic marker for this tumor. Although further studies are required to evaluate the role of BSND, this marker has been reported to be positive in Warthin tumor and oncocytoma, aiding in differentiating them from other oncocytoid tumors, particularly OMEC. In addition, BRAFV600E mutant-specific immunostaining can serve as a diagnostic and potentially therapeutic marker for oncocytic intraductal carcinoma in mutation positive cases. CONCLUSION: Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.

Ductal Adenocarcinoma of the Prostate with Novel Genetic Alterations Characterized by Next-Generation Sequencing.

Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy. Herein, we report a case of DAP with novel genetic alterations (BCOR P1153S, ERG M219I, KDR A750E, POLE S1896P, and RAD21 T461del).

Successful endotracheal intervention for primary tracheal acinic cell carcinoma: A case report and literature review.

INTRODUCTION: Primary tracheal acinic cell carcinoma (ACC) is an exceptionally rare malignancy, posing challenges in understanding its clinical behavior and optimal management. Surgical resection has traditionally been the primary treatment modality, but we present a compelling case of tracheal ACC managed with endotracheal intervention, challenging conventional approaches. PATIENT CONCERNS: A 53-year-old woman presented with shortness of breath, cough, and hemoptysis. Enhanced computed tomography revealed an obstructive tracheal lesion, leading to her referral for further assessment. DIAGNOSIS: Microscopic evaluation, immunohistochemistry, and clinical assessments confirmed primary tracheal ACC, an exceedingly rare condition with limited clinical insights. INTERVENTIONS: We utilized rigid bronchoscopy to perform endotracheal intervention, successfully resecting the tumor and restoring tracheal patency. Postoperatively, the patient received no radiotherapy or chemotherapy. OUTCOMES: The patient achieved complete recovery, with 24-month follow-up examinations indicating no recurrence or metastatic disease. Only minimal scar tissue remained at the resection site. CONCLUSION: This case demonstrates the potential of endotracheal intervention as a curative approach for primary tracheal ACC, minimizing invasiveness and preserving tracheal function. Collaborative research efforts and extensive case reporting are crucial for advancing our understanding of this rare malignancy and optimizing treatment strategies for improved patient outcomes.

Analysis of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance.

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.

Recent developments in the pathology of primary pulmonary salivary gland-type tumours.

Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland-type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland-type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland-type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type-tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high-grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland-type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland-type tumours of the lung and those primary to other sites.

Primary synovial sarcoma and acinar adenocarcinoma of prostate rarely occur simultaneously: A case report.

RATIONALE: Primary synovial sarcoma of the prostate is an extremely rare mesenchymal malignant soft tissue tumor with unique morphological features. Synovial sarcoma often occurs in the pararticular tissues of limbs in young people, but rarely occurs in prostate. Because it is very rare, it is easily misdiagnosed as benign prostatic hyperplasia or prostate cancer clinically. A case of synchronous acinar adenocarcinoma of the prostate has not been reported. In this article, we report a unique case of primary prostatic synovial sarcoma with acinar adenocarcinoma. PATIENT CONCERNS: A 58-year-old male patient was found to have a prostate mass during physical examination. Prostate ultrasound examination showed an increase in prostate volume of 5.2 × 3.3 × 3.3 cm, mixed echo mass can be seen on the left side of the prostate, with a size of approximately 4.9 × 4.3 cm, left seminal vesicle compressed. DIAGNOSES: Prostatic synovial sarcoma (biphasic type) combined with prostatic acinar adenocarcinoma (Gleason 3 + 3). INTERVENTION: The patient received radical prostatectomy, followed by adjuvant chemotherapy and radiotherapy. OUTCOME: After 2 months of follow-up, at the time of writing this article, the patient received a comprehensive treatment plan of adjuvant chemotherapy and radiotherapy for 2 months, and no recurrence or metastasis was found. LESSONS: Primary prostatic synovial sarcoma (biphasic type) combined with prostatic acinar adenocarcinoma is a very unique and rare case, and effective treatment guidelines are not yet clear, posing new challenges to clinical treatment. Making full use of pathological and imaging examinations, early diagnosis and radical surgery combined with multidisciplinary treatment seem to be still a positive method.

Utility of MUC4 in the diagnosis of secretory carcinoma of salivary glands.

Salivary gland tumors are diverse in morphology and both benign and malignant tumors may pose diagnostic challenges especially in small biopsies. Secretory carcinoma (SC) is histologically characterized by microcysts, follicles, solid growth pattern and occasional papillary structures, and absence of zymogen granules. SC is molecularly defined by the presence of novel gene fusion ETV6::NTRK3. Among the positive stains (S100 and mammaglobin), MUC4 is now another promising marker for the diagnosis of SC, that would enable the pathologists to exclude other morphologically close simulators. Aim of this study was to report clinicopathological features and assess utility of MUC4 in the diagnosis of SC. MUC4 was performed on 22 cases of SC. Glass slides were reviewed to record morphological patterns and staining of S100, mammaglobin, DOG1 and MUC4. Age ranged from 9 to 63 years with mean age of 34.41 ± 16.28 years. The male: female ratio was 72.7 %:27.3 %. The majority occurred in major salivary glands. A combination of patterns was seen; microfollicles were the most prevalent (90 %) followed by papillary-cystic and macrofollicles. MUC4 was positive in 19/21 (90 %) cases with almost equal number of 2+ and 3+ staining. MUC4 was negative in all cases of acinic cell carcinoma, polymorphous adenocarcinoma, adenoid cystic carcinoma, salivary duct carcinoma, myopepithelioma and myoeithelial carcinoma, cystadenoma and cribriform adenocarcinoma and all except 3 cases of mucoepidermoid carcinoma tested. Overall sensitivity of MUC4 was 95.4 %, specificity 90 %, p-value being <0.01, positive predictive value 87.5 % and negative predictive value 96.4 %. A characteristic cytoplasmic granular pattern was observed in 76.1 % tumors. S100 and mammaglobin were positive in all the performed cases. DOG1 was positive in 6/11 (28.5 %) tumors. In conclusion, MUC4 is a useful addition to a diagnostic immunohistochemical panel for SC, and to distinguish it from close potential mimickers such as acinic cell carcinoma, especially in practice settings where molecular testing is unavailable.

[Differential expression of LLGL2 in prostate ductal adenocarcinoma and acinar adenocarcinoma and its significance].

Objective: To investigate the expression differences of LLGL2 between prostatic ductal adenocarcinoma (PDA) and prostatic acinar adenocarcinoma, and its potential clinical significance. Methods: Eighteen patients diagnosed of PDA or prostatic acinar adenocarcinoma with PDA component by histopathology during January 2015 and December 2019 in the Beijing Hospital, China were retrospectively studied. The transcriptome analysis was conducted using the tissue of PDA and prostatic acinar adenocarcinoma. Differentially expressed genes and the differences in expression profiles were identified. Further, differentially expressed proteins were verified by immunohistochemistry. Results: The tissue from 8 of the 18 patients were used for transcriptome analysis, the results of which were compared with data from public databases. 129 differentially expressed genes were identified. 45 of them were upregulated while 84 were downregulated. The results of gene enrichment analysis and gene oncology (GO) analysis revealed that the differentially expressed genes were mostly enriched in the hypertrophic cardiomyopathy and interleukin-17 related pathways. GPAT2, LLGL2, MAMDC4, PCSK9 and SMIM6 were differentially expressed between PDA and prostatic acinar adenocarcinoma. Moreover, LLGL2 was more likely expressed in the cytoplasm (P=0.04) than the nucleus (P<0.01) in PDA, compared with prostatic acinar adenocarcinoma. Conclusions: The gene expression profiling indicates that PDA are very similar to prostatic acinar adenocarcinoma. Among the differentially expressed proteins screened and verified in this study, the expression of GPAT2, LLGL2, MAMDC4 and PCSK9 is increased in PDA, while that of SMIM6 is reduced in PDA. The expression of LLGL2 shows significantly different patterns between PDA and prostatic acinar carcinoma, and thus may help differentiate PDA from prostatic acinar adenocarcinoma in clinical practice.

True Oncocytic Acinic Cell Carcinoma: A Case Image.

A 67-year-old female with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) presented with right sided otalgia and a 2-3 cm firm, tender right posterior parotid mass. Fine needle aspiration biopsy (FNAB) established a diagnosis of acinic cell carcinoma (AciCC). Further workup demonstrated lung nodules which were confirmed by FNAB to represent metastatic AciCC. A right radical parotidectomy with sacrifice of the facial nerve, segmental mandibulectomy, and selective neck dissection (levels II-IV) was performed. Microscopically, the tumor displayed an infiltrative border with a solid multinodular growth pattern and fibrosclerotic septation. The tumor was composed mainly of uniform cells with abundant eosinophilic granular cytoplasm with round nuclei with prominent nucleoli. Nuclei were fairly monomorphic, mitotic counts were 3-4 per 2mm2 and there was no necrosis despite the aggressive growth pattern. An anti-mitochondrial immunohistochemical stain showed strong reactivity in the tumor cells, with an internal positive control of adjacent striated ducts. An immunohistochemical stain for NR4A3 demonstrated strong nuclear reactivity in the tumor cells. Electron microscopy highlighted the tumor cells with numerous mitochondria and distinctive electron dense intramitochondrial inclusions. Concurrent CLL/SLL was identified on histologic examination of the lymph nodes, but they were free of AciCC. After eight weeks of follow-up, she tolerated the surgery well and is currently receiving radiation therapy to the parotid and neck. In this illustrative case, we justify the oncocytic designation of AciCC by morphology, immunohistochemistry, and electron microscopy.

Exploring the Epidemiology and Survival Trends in Pediatric Major Salivary Gland Malignancies: Insights from the National Cancer Database.

OBJECTIVE: To investigate the clinicopathological, therapeutic, and survival data on pediatric major salivary gland cancers. MATERIALS AND METHODS: National Cancer Database (NCDB) query from 2004 to 2018. RESULTS: In total, 967 cases of individuals under the age of 21 were identified. Most cancers affected the parotid gland (86%). Mucoepidermoid carcinoma (41.3%) and acinic cell adenocarcinoma (33.6%) were the most common. Tumors occurred more often from age 11 to 21, and females were more affected. Histology varied by age, gender, and race. In the 0-5 age group, mucoepidermoid carcinoma and myoepithelial carcinoma/sarcoma/rhabdomyosarcoma were the most common pathologies. In patients over 5 years old, mucoepidermoid carcinoma was the most frequent tumor in boys, while acinic cell adenocarcinoma was more common in girls. African American patients had a higher incidence of mucoepidermoid carcinoma, while White patients in the 0-5 age group had a higher incidence of myoepithelial carcinoma/sarcoma/rhabdomyosarcoma tumors. Low-grade tumors were commonly diagnosed at stage I, but the 0-5 age group had a high frequency of stage IV tumors. The overall 5-year survival rate was 94.9%, with 90% for the 0-5 years age group and 96% for the 11-15 years age group. Negative margins were associated with higher 5-year survival rates in high-stage tumors (93%) compared to positive margins (80%). Submandibular malignancies had worse 5-year survival rates across all age groups. CONCLUSIONS: Major salivary gland malignancies in pediatric patients exhibit variations in histopathologic characteristics by age, gender, and race. Negative margins impact 5-year survival rates, especially in high-stage tumors.

Cytomorphologic, immunophenotypical and molecular features of pancreatic acinar cell carcinoma.

OBJECTIVES: As a rare tumor in pancreas, pancreatic acinar cell carcinoma (PACC) possesses a distinct molecular feature from pancreatic ductal carcinoma (PDAC). Though the diagnosis of PACC is often established based on cytology specimens, its cytologic diagnosis can be challenging. Furthermore, the correlation between PACC cytomorphology and its unique different molecular alterations have not been fully explored. METHODS: Cytology features were analyzed in 8 histologically proven PACC and cytohistological correlation was performed. Immunocytochemistry for trypsin, chymotrypsin, BCL10, synaptophysin, chromogranin A, INSM1, ß-catenin, and Ki-67 was assessed. Comprehensive molecular profiling and additional targetable treatment biomarker assessment were also performed. RESULTS: The cohort included 4 mixed acinar-neuroendocrine carcinomas, 3 pure PACCs, and 1 mixed acinar-ductal carcinoma. Immunophenotypical features are consistent with diagnoses of PACC or PACC with neuroendocrine features. Identified genetic alterations included somatic mutations of CTNNB1, TP53, MAP2K1, PTEN, RAC1, germline mutations of NBN and BRAC2, and gene fusion of CCDC6-RET. CONCLUSIONS: The current study is the first attempt to explore the correlation between the cytomorphology characteristics and molecular features of PACC and a few intriguing findings were observed. Further validation in larger cohorts is warranted.

Prostate-Specific Membrane Antigen Uptake Heterogeneity in Mixed Ductal-Acinar Adenocarcinoma of the Prostate.

ABSTRACT: Prostate-specific membrane antigen (PSMA) PET findings of mixed ductal-acinar adenocarcinoma of the prostate are rarely reported. We describe 18 F-PSMA-1007 PET/CT and delayed pelvic 18 F-PSMA-1007 PET/MRI findings in a case of prostatic mixed ductal-acinar adenocarcinoma with multiple lymph node and bone metastases. The primary tumor showed heterogeneous PSMA uptake. The metastases in the right ilium and acetabulum showed intense PSMA uptake, but the pelvic lymph node and left iliac bone metastases showed no significant PSMA uptake. Knowledge of the intraprimary and intermetastatic heterogeneity of PSMA uptake in mixed ductal-acinar adenocarcinoma of the prostate may be helpful for accurate interpretation.

Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC) Unveils New Actionable Genomic Aberrations in PACC.

PURPOSE: Pure pancreatic acinar cell carcinomas (PACC) are rare malignancies with no established treatment. PACC demonstrates significant genetic intertumoral heterogeneity with multiple pathways involved, suggesting using targeted cancer therapeutics to treat this disease. We aggregated one of the largest datasets of pure PACC to examine the genomic variability and explore patient-specific therapeutic targets. EXPERIMENTAL DESIGN: PACC specimens (n = 51) underwent next-generation sequencing of DNA (n = 29) or whole exome (n = 22) and RNA (whole transcriptome, n = 29) at a commercial laboratory. We performed comparative analyses of a genomic cohort of pancreatic ductal adenocarcinomas (PDAC; n = 4,205). In parallel, we conducted a retrospective review of patients with PACC treated at Huntsman Cancer Institute (HCI). RESULTS: The real-world dataset included samples from 51 patients with PACC. We found key molecular differences between pure PACC and PDAC, highlighting the unique characteristics of pure PACC. Major differences in PACC include lower MAPK signaling and less stromal cell abundance compared with PDAC. Pure PACC showed genomic loss-of-heterozygosity to largely coincide with mutations in BRCA1, BRCA2, and PALB2. Of the 7 patients treated at HCI, one had a tumor that harbored a BRAF-V600E mutation. Leveraging precision oncology, this patient is being treated with encorafenib plus binimetinib, achieving an exceptionally durable and ongoing complete response of more than 3 years. CONCLUSIONS: There are major differences between PACC and PDAC, including downregulation of the MAPK signaling pathway, and less stromal cell abundance. In addition, genomic characterization of pure PACC revealed frequent targetable alterations, which can guide patient treatment.

Role of Adjuvant Radiotherapy in Acinic Cell Carcinoma of the Salivary Glands: A Systematic Review.

A systematic review was carried out to evaluate if adjuvant radiotherapy for acinic cell carcinomas (ACCs) of salivary glands improves survival. Twelve retrospective studies published between 2000 and 2020 that analysed the effect of radiotherapy on salivary gland neoplasms and ACCs of salivary glands and met the inclusion criteria were included in the review. The overall quality of the studies was moderate to low. There was no high-quality evidence for improved survival with radiotherapy for ACCs of the salivary gland. Some evidence suggests that there may be an advantage for patients with high-grade tumours, but these data should be interpreted with caution due to the small number of patients and low-quality evidence. Good quality of evidence is lacking. Recommendation for adjuvant radiotherapy for tumours with poor prognostic factors will require discussion and shared decision-making with the patients.

Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system.

BACKGROUND: The comparative impact of histologic variants and grade has not been well described. METHODS: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival. RESULTS: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). CONCLUSION: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.