Cases Of Salivary Duct Carcinoma Research Articles

Salivary duct carcinoma with squamous differentiation: histomorphological and immunophenotypical analysis of six cases.

Salivary duct carcinoma (SDC) is an aggressive salivary malignancy with multiple morphological subtypes. Primary salivary squamous cell carcinoma (SCC) requires exclusion of high-grade salivary malignancies and metastatic disease and is considered exceptionally rare. We report six cases of SDC with resemblance to SCC on account of variable, but often extensive, squamous differentiation. A retrospective review (2009-2023) at two institutions of SDC with histological and immunophenotypical evidence of squamous differentiation identified six cases. Medical charts and available glass slides were reviewed. There were five males and one female with a median age of 63 years, with tumours involving the parotid (five of six) and submandibular (one of six) glands. All six tumours showed a conventional SDC component comprising < 5-90% of viable tumour. Squamous differentiation comprised 10-95%+ (> 75% in three of six cases) of total viable tumour, and demonstrated CK5/6, p63 and/or p40 immunoexpression in all cases. A sarcomatoid component, comprising 10-60% of viable tumour, was present in three of six (50%) cases. All tumours were androgen receptor (AR)-positive, but only two of six (33.3%) retained AR immunoreactivity in the squamous component. Metastatic SDC to regional lymph nodes exhibited exclusive squamous differentiation in two of six (33.3%) cases. Squamous differentiation, histologically and immunophenotypically, can be extensive in SDC. AR expression may be lost in the squamous component and metastases may demonstrate only squamous differentiation. These findings cast further doubt on the existence of primary salivary SCC. SDC should be considered whenever encountering a carcinoma with squamous differentiation in major salivary glands or within cervical lymph nodes in the setting of a salivary mass.

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.

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. 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. 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. 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.

A 22-year single institution review of 119 cases of salivary duct carcinoma.

Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p<.001), distant metastasis (p<.001), perineural invasion (p = .027), and lymphovascular invasion (p = .018) were predictive of decreased OS and DSS. Trastuzumab administration was not associated with survival in HER-2-positive patients receiving chemotherapy. Multivariate analyses demonstrated that presence of nodal disease (HR 30.337, 95% CI 2.782-330.851, p = .005) and carcinoma ex pleomorphic adenoma (HR 5.54, 95% CI 1.024-29.933, p = .047) were associated with decreased OS. Our patients had more favorable survival rates compared to prior studies, which may be due to lower incidence of nodal disease. Factors associated with worse survival included nodal and distant metastases, perineural invasion, lymphovascular invasion, and tumor size. Level 3.

Prognostic value and clinicopathological roles of the tumor immune microenvironment in salivary duct carcinoma.

Salivary duct carcinoma (SDC) is an aggressive type of salivary gland carcinoma. Recently, immunotherapies targeting immune checkpoints, including PD1, PD-L1, CTLA4, and LAG3, have had a considerable prognostic impact on various malignant tumors. The implementation of such immune checkpoint inhibitor (ICI) therapies has also been attempted in cases of salivary gland carcinoma. The tumor immune microenvironment (TIME) is implicated in tumorigenesis and tumor progression and is closely associated with the response to ICI therapies. However, the TIME in SDC has not been fully explored. We examined the immunohistochemical expression of CD8, FOXP3, PD1, PD-L1, CTLA4, LAG3, and mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (TILs), and microsatellite instability (MSI) status in 175 cases of SDC. The associations between these TIME-related markers and the clinicopathological factors and prognosis were evaluated. An elevated expression of CD8, FOXP3, PD1, CTLA4, and LAG3 was associated with more aggressive histological features and an advanced N and/or M classification, elevated Ki-67 index, and poor prognosis. Furthermore, cases with a high PD-L1 expression exhibited more aggressive histological features and adverse clinical outcomes than those with a low expression. Alternatively, there was no significant correlation between TILs and clinicopathological factors. No SDC cases with an MSI-high status or MMR deficiency were found. The coexistence of both an immunostimulatory and immunosuppressive TIME in aggressive SDC might play a role in the presence of T-cell exhaustion. The contribution of multiple immune escape pathways, including regulatory T cells and immune checkpoints, may provide a rationale for ICI therapy, including combined PD1/CTLA4 blockade therapy.

Immunohistochemical Expression Of Human Epidermal Growth Factor Receptor-2 (Her-2) In Common Salivary Gland Carcinomas.

Carcinomas of the salivary gland are known to be aggressive in nature, making them difficult to manage. The therapeutic options offered include excision of the gland (maxillectomy in cases of palatal tumours), with or without lymph node dissection, proceeded with radiotherapy. Chemotherapy has not produced promising outcomes and has a minimal impact as a therapeutic alternative. Targeted therapy against human epidermal growth factor receptor 2 (HER-2), which is a commonly used treatment modality for their mammary analogues, is not being offered to these patients since scant literature is available showing its usefulness and no promising evidence is present regarding their efficacy and efficiency in such cases. The study aimed to evaluate and quantify the immunohistochemical expression of HER-2 in cases of adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC) and salivary duct carcinoma (SDC), which are analogues of similar tumours arising in breast tissue. A retrospective, cross-sectional study was carried out in the department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, duration of which was six months. A total of 45 cases (15 of each tumour) were taken, and sampled using non-probability convenience technique. The immunohistochemical marker, monoclonal HER-2 antibody (Leica microsystem Germany) was applied on appropriate blocks of all included cases. The staining pattern and intensity were recorded after visualizing the slides under a light microscope. Seven cases of salivary duct carcinoma and a single case of mucoepidermoid carcinoma expressed positivity for HER-2, while no expression could be seen in the case of adenoid cystic carcinoma. A statistically significant difference was seen when HER-2 expression was compared among the aforementioned tumours. The use of targeted therapy against HER-2 is limited to patients of salivary duct carcinoma and a fraction of patients suffering from mucoepidermoid carcinoma.

Clinical analysis of 61 cases of salivary duct carcinoma

The clinical data of 61 patients of salivary duct carcinoma admitted to the First Medical Centre of Chinese PLA General Hospital from January 2010 to December 2020 were retrospectively reviewed. A total of 55 patients (90.2%) were male and 6 (9.8%) were female. There were 51 patients (83.6%) aged≥50 years. The primary tumor of 45 patients (73.8%) were from the parotid gland. There were 35 patients (57.4%) who had cervical lymph node metastasis and 25 patients (41.0%) had distant metastasis. All patients underwent surgery and 50 of them (82.0%) received adjuvant radiotherapy. The 3-year and 5-year survival rates were 58.0% and 43.3%, respectively. Compared with the patients who had undergone surgery only, the survival rates of those who had postoperative adjuvant radiotherapy and chemoradiotherapy were higher. It can be seen that radical surgical treatment is necessary, and postoperative radiotherapy can reduce the recurrence rate and increase the survival rate to a certain extent.

The implicated clinical factors for outcomes in 304 patients with salivary duct carcinoma: Multi-institutional retrospective analysis in Japan.

BackgroundSalivary duct carcinoma (SDC) is a high‐grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC.MethodsWe selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes.ResultsThe median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0–III cases.ConclusionsThe absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC.

Demography, patterns of care, and survival outcomes in patients with salivary duct carcinoma: an individual patient data analysis of 857 patients.

Aim:Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. The optimal treatment protocols are debated.Methodology:A systematic search and individual patient data analysis of published cases of SDC was performed. SPSS v21 was used for statistical analysis.Results:Data of 857 patients available. Median overall survival (OS) and progression-free survival (PFS) of the entire cohort 42 months and 24 months. Nodal involvement, males, primary size >5 cm, androgen receptor (AR) negativity significantly worse OS. Patients with surgery had a favorable median PFS (p = 0.000) and OS (p = 0.077). Patients with adjuvant radiation had better PFS (30 vs 18 months; p = 0.077).Conclusion:SDC has modest survival. Surgery and adjuvant radiation should be advocated for all patients. AR expression appears prognostic for survival.

Three cases of salivary duct carcinoma arising from accessory parotid gland

Three cases of salivary duct carcinoma arising from accessory parotid gland

PAX-8 Expression in Salivary Duct Carcinoma.

Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma resembling breast ductal carcinoma. It accounts for ~10% of malignant tumors of the salivary glands. Most cases show expression of CK7 and androgen receptor. PAX-8 is a transcription factor, with expression reported in renal, Müllerian, and thyroid carcinomas. Previous studies have described an absence of PAX-8 immunostaining in most primary salivary gland neoplasms, including SDCs. However, PAX-8 expression is frequently found in neoplasms that can metastasize to salivary glands, suggesting the possibility that this protein can be used to differentiate SDC from secondary neoplastic involvement of the salivary gland. We evaluated the expression of PAX-8 in 14 cases of SDC from our institution. One case showed diffuse moderate to strong PAX-8 positivity, while 2 tumors showed focal weak staining. Therefore, we conclude that although the majority of SDC are negative for PAX-8, rare diffuse positivity can be seen in these primary salivary gland tumors. This could potentially pose difficulty in ruling out metastatic disease from another PAX-8-positive primary neoplasm.

The radiologic (CT/MRI)-pathological correlations of the salivary duct carcinoma (SDC) with hyaline degeneration and peripheral nerve invasion.

Salivary duct carcinoma is an aggressive tumour commonly showing local invasion and/or nerve palsy. However, their CT/MRI findings, especially, regarding T2WI, and the diffusion-weighted-image (DWI), were not well known. In this study, we correlated the CT/MRI appearance and the pathological findings containing the nerve invasion cases such as a facial nerve. We reviewed 14 cases of SDC (parotid = 11, submandibular = 2, minor salivary gland = 1) pathologically proven peripheral nerve involvement. Their CT findings of all patient including dynamic contrast-enhancement study､MRI (n = 9) and DWI (n = 6) were also analyzed with histopathological correlation. On contrast-enhanced CT, the solid component was moderately enhanced. On MRI, T2WI central low signal core (n = 6) with peripheral high intensity rim (n = 5) was frequently observed except heterogeneous low and high (n = 1), diffuse low (n = 1), and high (n = 1) signal cases. The hyaline degenerative area located in the tumour core was poorly enhanced. Eleven tumours had an ill-defined margin, reflecting invasive tumour growth. On DWI, they showed high signal [the central low and peripherally high (n = 4), and diffuse (n = 1), heterogeneously high signal (n = 1)]. The mean ADC value was 1.148 ~ 0.961 x 10-3 mm2/s. With pathological correlation, the central low signal area on T2WI reflected hyaline degeneration. The sites of gross nerve involvement were revealed as tubular or branching structures on CE-CT (n = 3), and MRI (n = 1). (1) We frequently observed a central low signal area on T2WI/DWI in SDC. With histopathological correlation, it corresponded to the central hyaline degeneration with the peripheral viable tumour. 2) The gross nerve involvement might be detected as a strongly enhancement structure.

Primary and Secondary/ Metastatic Salivary Duct Carcinoma Presenting within the Sinonasal Tract

Traditionally, sinonasal adenocarcinomas have been subdivided into intestinal (ITAC) and non-intestinal (non-ITAC) categories. The latter encompasses salivary-type adenocarcinomas originating from the seromucinous glands of the sinonasal mucosa and non-salivary adenocarcinomas. The non-salivary adenocarcinoma category is further subdivided into low-and high-grade variants. Among salivary-type sinonasal adenocarcinomas, tumors recapitulating salivary duct carcinoma (SDC) are exceedingly rare, but some might have been lumped into the high-grade non-ITAC category. To date, only three primary SDCs originating in the sinonasal tract have been reported. We herein describe 7 cases of SDC including one previously reported case (4 primary sinonasal, 3 metastatic/ extension from parotid gland SDC). The primary tumors affected 3 males and one female aged 60 – 75. Different sites were involved by the primary tumors while the secondary tumors affected the sphenoidal (2) and the frontal + maxillary (1) sinuses. Three primary tumors were de novo high-grade SDC and one was confined to contours of a pre-existing pleomorphic adenoma. All 3 secondary tumors were SDC ex pleomorphic adenoma of the parotid with a long history of recurrences, ultimately involving the sinonasal tract. Androgen receptor was positive in 7/7 cases. Four of 6 cases were strongly HER2/neu + (either score 3 + or with verified amplification). This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies.

Immunohistochemical Reactivity of Prostate-Specific Markers for Salivary Duct Carcinoma

Objectives: NKX3.1, a transcription factor related to androgen expression, has recently been introduced as a diagnostic marker of prostate adenocarcinoma. Salivary duct carcinoma (SDC) is typically positive for androgen receptor (AR). Therefore, we hypothesized that NKX3.1 is a new immunohistochemical marker for SDC and aimed to investigate whether NKX3.1 staining in combination with other immunomarkers of prostate carcinoma could have a diagnostic or prognostic value in SDC. Methods: Materials obtained from 42 resected SDCs were examined by immunohistochemistry using antibodies against AR, NKX3.1, α-methylacyl-CoA racemase (AMACR), prostatic acid phosphatase (PAP), and prostate-specific antigen (PSA). Results: In immunoreactivity among SDC cases, 81.0, 35.7, 58.5, 33.3, and 0% were positive for AR, NKX3.1, AMACR, PAP, and PSA, respectively. AMACR and PAP immunoreactivity rates were higher in recurrence cases than in cases with no recurrence. Conclusions: NKX3.1 expression is useful for SDC diagnosis, but decreased NKX3.1 expression was not correlated with SDC progression. The immunoreactivity of AMACR and PAP could be useful for assessing prognosis in SDC, but immunohistochemical staining of prostate-specific markers should be interpreted with caution when determining whether a metastatic tumor is of prostate origin, especially when patients have a history of SDC.

Prognostic Implication of Histopathologic Indicators in Salivary Duct Carcinoma: Proposal of a Novel Histologic Risk Stratification Model.

Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling.

Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage. A proportion of SDC are characterized by HER2 amplification and/or overexpression of androgen receptor (AR), which could be targeted in a subset of patients, but the presence of AR splice variant‐7 (AR‐V7) in some SDC cases could result in resistance to anti‐androgen therapy. We evaluated a cohort of 28 cases of SDC for potentially targetable biomarkers and pathways using immunohistochemistry (IHC) and next‐generation sequencing (DNA and RNA) assays. Pathogenic genetic aberrations were found in all but 1 case and affected TP53 (n = 19), HRAS (n = 7), PIK3CA, ERBB2 (HER2), and NF1 (n = 5 each); KMT2C (MLL3) and PTEN (n = 3 each); BRAF (p.V600E), KDM5C and NOTCH1 (n = 2 each). Androgen receptor was expressed in all cases and 13 of 27 harbored the AR‐V7 splice variant (including a case without any other detectable genetic alteration). HER2 IHC was expressed in 11 of 28 cases. The majority of SDC cases had no biomarkers predictive of immunotherapy response: 5 cases exhibited low (1%‐8%) programmed death ligand 1 (PD‐L1) expression in tumor cells, 2 cases exhibited elevated TMB, and no samples exhibited microsatellite instability. Notably, the pre‐treatment biopsies from 2 patients with metastatic disease, who demonstrated clinical responses to anti‐androgen therapy, showed AR expression and no AR splice variants. We conclude that comprehensive molecular profiling of SDCs can guide the selection of patients for targeted therapies involving AR, HER2, PD‐L1, mitogen‐activated protein kinase, and PIK3CA pathways.

NCOA4-RET and TRIM27-RET Are Characteristic Gene Fusions in Salivary Intraductal Carcinoma, Including Invasive and Metastatic Tumors: Is "Intraductal" Correct?

Intraductal carcinoma (IC) is the new WHO designation for tumors previously encompassed by "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma." The relationship of IC to salivary duct carcinoma (SDC) is controversial, even though they are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with histopathological features reminiscent of atypical ductal hyperplasia or ductal carcinoma in situ of the breast, showing diffuse S100 protein and mammaglobin positivity, while it is partially defined genetically. Recently, RET rearrangements including NCOA4-RET and TRIM27-RET have been described in IC. Here, we genetically characterize the largest cohort of IC to date (33 cases) including 8 cases with focal or widespread invasive growth and 1 case with lymph node metastasis. Thirty-three cases of IC were analyzed by next-generation sequencing (NGS) using the FusionPlex Solid Tumor kit (ArcherDX). Identified gene fusions were confirmed using fluorescence in situ hybridization break-apart and fusion probes and an reverse transcription polymerase chain reaction designed specifically for the detected breakpoints. Ten cases of SDC were analyzed for comparison using NGS panels that detect mutations and fusion transcripts. NGS analysis detected an NCOA4-RET fusion transcript in 11 cases of intercalated duct-type IC joining exon 7 or 8 of NCOA4 gene and exon 12 of the RET gene. Eight cases of IC had an invasive growth pattern, including one with widespread invasion and lymph node metastasis. Three invasive ICs harbored an NCOA4-RET fusion transcript, while 1 case was negative, and 2 cases were not analyzable. In addition, a novel TRIM27-RET fusion transcript between exon 3 of TRIM27 and exon 12 of RET was identified in 2 cases of IC with apocrine features, and one of them displayed invasive growth. Two IC cases with invasive growth harbored novel fusions TUT1-ETV5 and KIAA1217-RET, respectively. A total of 42.4% of the cases in this series of IC harbored fusions involving RET. Such fusion transcripts were not detected in any of the 10 SDC cases. We have confirmed NCOA4-RET as a predominant fusion in intercalated duct-type IC, including 3 cases with invasive growth pattern. A novel finding in our series was a case of widely invasive intercalated duct-type IC, with a single lymph node metastasis that revealed an NCOA4-RET fusion transcript. We also demonstrated that a subset of apocrine ICs harbored a TRIM27-RET gene fusion, including one case with invasive growth. In contrast, neither NCOA4-RET nor TRIM27-RET fusions were detected in any tested SDCs. Thus, the distinct molecular findings in IC and SDC support that the tumors are separate malignant salivary tumor entities. The presence of tumor-type-specific NCOA4-RET or TRIM27-RET translocations in a subset of widely invasive carcinomas with intercalated duct-like immunoprofiles suggests that a recharacterization of IC including its redesignation as "intercalated duct carcinoma, invasive or noninvasive" may be appropriate.

Biomarker immunoprofile and molecular characteristics in salivary duct carcinoma: clinicopathological and prognostic implications

Salivary duct carcinoma (SDC) is one of the most aggressive salivary gland tumors, and prognosis remains poor for most patients. The aim of this study was to investigate the prognostic implications of biomarker immunoprofile in a cohort of SDC and to identify molecular characteristics through next-generation sequencing (NGS) in a subset of cases. Clinicopathological and follow-up information of 25 cases diagnosed as SDC was collected. Immunoexpression of AR, HER-2/neu, GATA3, CK5/6, and MIB1 was analyzed, and ERBB2 (HER-2/Neu) gene amplification was investigated by fluorescence in situ hybridization. Cases were classified under the "SDC revised classification system." Eight SDC cases were analyzed by targeted NGS for detection of gene fusions and variants. Overall survival and disease-free survival were analyzed with Kaplan-Meier curves and Cox regression. Most cases expressed AR (100%), GATA3 (73%), and CK5/6 (76.5%), and 42% expressed HER-2/neu. ERBB2 gene amplification was proven by fluorescence in situ hybridization in 7 of 15 (46%) cases. Apocrine HER2 (AR+/HER2+) subtype was significantly associated with lower overall survival (P = .05). NGS analysis revealed 9 pathogenic mutations in 7 SDC cases, and the most frequently mutated gene was HRAS (4/9) followed by PIK3CA (2/9) and TP53 (2/9). One case (1/9) presented homozygous deletion of locus 9p21 (CDKN2A), and another case (1/9) showed MDM2 amplification. In conclusion, we demonstrated that Apocrine HER2 (AR+/HER2+) is a potential biomarker of poor outcome in SDC. Furthermore, NGS analysis revealed recurrent mutations in SDC.

Clinicopathological analysis of 40 cases of salivary duct carcinoma

Objective: To investigate the clinical manifestations and pathological changes of salivary duct carcinoma (SDC) and the relationship between them, so as to provide reference for the diagnosis of SDC. Methods: In this retrospective analysis 40 cases of SDC diagnosed from January 2012 to August 2018 in the Department of Pathology of the First Affiliated Hospital of Zhengzhou University were enrolled and the clinical and pathological characteristics were analyzed, 29 were male and 11 were female, the ratio of male to female was 2.64∶1, the median age was 59.0 years, the average course of disease was 3.5 years. The reported cases of SDC were reviewed and compared with patients of this study. Results: Among the 40 patients, 24 cases occurred in parotid gland, 9 cases in submandibular gland and 7 cases in small salivary glands; 24 cases had cancer cell infiltration and invasion of adjacent tissues, 11 cases had lymph node metastasis and 9 cases had distant metastasis at the time of diagnosis. Pathological results showed that 27 cases belonged to primary salivary duct carcinoma, 13 cases belonged to malignant transformation of pleomorphic adenoma; 10 cases invaded local nerve, 22 cases invaded glandular lobules and ducts. Immunohistochemical results showed that 33 cases were positive for androgen receptor, 27 cases were positive for cytokeratin-7, 22 cases were positive for human epidermal growth factor receptor-2, 8 cases were positive for gross cyst disease fluid protein 15. The proliferation index of nuclear antigen Ki-67 ranged from 10% to 90%. Among them 18 cases were over 50% and 22 cases were below 50%. Conclusions: Salivary duct carcinoma is a rare and highly malignant tumor of the salivary gland. Accurate pathological diagnosis is helpful to inhibit the early local recurrence, distant metastasis and improve survival rate of salivary duct carcinoma.

The expression of programed death ligand‐1 could be related with unfavorable prognosis in salivary duct carcinoma

Salivary duct carcinoma (SDC) is a rare tumor occurring in the salivary gland. SDC is a highly aggressive tumor and its prognosis is extremely poor. Effective treatments in advanced SDC have not yet been established. Recently, immune checkpoint inhibitors have paved the way for the treatment of various malignancies. We examined the expressions of programed death ligand (PD-L) 1/PD-L2 and programed death (PD-1), and the correlation of clinicopathological findings. We examined 18 cases of SDC and conducted immunohistochemical staining using formalin-fixed paraffin-embedded full-face sections. The expression of PD-L1 and PD-L2 in tumor cells was observed in nine cases (50%) and 14 cases (78%), respectively. Cases with a high expression of PD-L1 and PD-L2 were found in four (22%) and seven cases (39%), respectively. The cases with a high expression of PD-L1 showed significantly shorter overall survival compared to those with low PD-L1 expression and null expression. We also examined the expression of PD-L1/PD-L2 and PD-1 of tumor-infiltrating mononuclear cells (TIMC) in stroma. The expressions of PD-L1 in tumor cells and stroma had a significant correlation. Association between the expressions of PD-L1 in tumor cells and those of PD-1 in stroma was significant. However, PD-L2 expression in the tumor had no significant correlation with expression in TIMCs. PD-L1, PD-L2 and PD-1 expressions in stroma were not associated with patient prognosis. High PD-L1 expression in SDC was strongly associated with unfavorable prognosis, indicating that PD-1/PD-L1 inhibitors could be effective in SDC.

The implications of TrkA and MET aberrations in de novo salivary duct carcinoma

Salivary duct carcinoma (SDC) is an aggressive carcinoma with poor prognosis. Although anti-HER2 therapy is a potential treatment option for HER2-positive SDC, other potential therapeutic targets are not known, in particular for HER2-negative cases. In this study, the recently identified receptors tyrosine kinases MET and tropomyosin-receptor kinase (Trk) were investigated as potential therapeutic targets. A total of 28 consecutive, surgically resected, de novo SDC cases were selected after evaluating histology and immunohistochemical expression of androgen receptor. Immunohistochemical expression of c-erb2, TrkA, TrkB, TrkC, and c-MET was analyzed, and the genetic status of the HER2 and MET genes was investigated through dual-color silver in situ hybridization. High expression of c-MET or Trk was defined as that above the median value. Among the 28 SDC cases, 64.3% (18/28) were HER2-positive. c-MET expression varied, with a median H-score of 65 (range, 0 to 200). Copy number gain and amplification of MET were noted in 57.1% (16/28) and 10.7% (3/28) of cases, respectively. TrkA was variably expressed, with a median H-score of 100 (range, 0 to250). High TrkA expression was significantly related to an inferior overall survival rate in HER2-negative SDC. High expression of TrkA and c-MET and MET copy number gain/amplification were frequent events in SDC, and high expression of TrkA revealed the tendency to be related to poor prognosis in HER2-negative SDC. TrkA and MET may be possible therapeutic targets in SDC, especially in HER2-negative SDC.