Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 223
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Mod Pathol ; 37(1): 100371, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38015043

RESUMO

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.


Assuntos
Neoplasias da Mama , Carcinoma de Células Acinares , Carcinoma Adenoide Cístico , Carcinoma Mucoepidermoide , Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Feminino , Carcinoma Adenoide Cístico/patologia , Prognóstico , Carcinoma de Células Acinares/patologia , Neoplasias das Glândulas Salivares/patologia , Carcinoma Mucoepidermoide/patologia , Carcinoma/patologia , Glândulas Salivares/química , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Biomarcadores Tumorais/análise
2.
Histopathology ; 85(4): 590-597, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38828680

RESUMO

BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Imunofenotipagem , Neoplasias das Glândulas Salivares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/patologia , Idoso , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal/patologia , Carcinoma Ductal/diagnóstico , Ductos Salivares/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
3.
BMC Cancer ; 24(1): 1174, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304797

RESUMO

BACKGROUND: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer, frequently associated with incurable recurrences and distant metastases (R/M). Proliferation of SDC relies on androgen receptor (AR) signalling, prompting the use of combined androgen blockade (CAB, i.e., luteinizing hormone-releasing hormone agonist and/or AR antagonists) to R/M SDC patients. However, only a subset of patients benefits from such treatments. We have shown that response to CAB is associated with steroid 5α-reductase 1 (SRD5A1) mRNA expression. SRD5A1 catalyses the intracellular conversion of testosterone into the more potent AR-agonist dihydrotestosterone. This conversion can be inhibited by dutasteride, a potent SRD5A1-inhibitor, which is currently prescribed for benign prostatic hyperplasia. We hypothesize that repurposing dutasteride to target AR signalling in SDC could enhance therapeutic response and clinical outcome in SDC patients. METHODS: This prospective, open-label, randomized controlled phase II clinical trial, is designed to investigate whether dutasteride as an adjunct drug to CAB improves response rate and clinical outcome in patients with AR-positive R/M SDC. Patients are divided in two cohorts based on their prior systemic treatments. In cohort A, CAB-naïve patients (n = 74) will be randomly assigned to either a control arm (Arm 1) receiving CAB (goserelin 10.8 mg/3m and bicalutamide 50 mg/OD) or an experimental arm (Arm 2) where dutasteride (0.5 mg/OD) is added to the CAB regimen. In cohort B, patients with disease progression after adjuvant or first-line palliative CAB therapy (max. n = 24) will receive goserelin, bicalutamide, and dutasteride to assess whether the addition of dutasteride can overcome therapy resistance. The primary endpoints are the objective response rate and duration of response. Secondary endpoints are progression-free survival, overall survival, clinical benefit rate, quality of life, and safety. Translational research will be performed to explore molecular target expression differences and their correlation with clinical outcome. DISCUSSION: The DUCT study addresses an unmet medical need by investigating the repurposing of dutasteride to enhance treatment response and improve clinical outcome for patients with R/M SDC, especially those with limited alternative treatment options, such as HER2-negative cases. By repurposing a registered low-cost drug, this trial's findings could be readily applied into clinical practice. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05513365. Date of registration: August 24, 2022. PROTOCOL VERSION: Current protocol version 4.0, February 21, 2024.


Assuntos
Antagonistas de Androgênios , Protocolos de Quimioterapia Combinada Antineoplásica , Dutasterida , Neoplasias das Glândulas Salivares , Compostos de Tosil , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de 5-alfa Redutase/uso terapêutico , Inibidores de 5-alfa Redutase/administração & dosagem , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Androgênios/administração & dosagem , Anilidas/administração & dosagem , Anilidas/uso terapêutico , Anilidas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dutasterida/uso terapêutico , Dutasterida/administração & dosagem , Nitrilas/uso terapêutico , Nitrilas/administração & dosagem , Estudos Prospectivos , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/genética , Compostos de Tosil/uso terapêutico , Compostos de Tosil/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase II como Assunto
4.
Semin Diagn Pathol ; 41(4): 165-172, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38853124

RESUMO

Salivary gland neoplasms characterized by abundant mucin production are rare but have long been recognized. Due to their scarcity, precise classification has long eluded these mucin-rich tumors. Recent molecular discoveries, however, have shed considerable light on the genetic underpinnings of mucin-rich salivary gland neoplasms. This manuscript will review the most up-to-date information on this fascinating group of salivary gland neoplasms.


Assuntos
Mucinas , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/genética , Mucinas/metabolismo , Biomarcadores Tumorais/genética
5.
Semin Diagn Pathol ; 41(4): 197-206, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38658249

RESUMO

High-grade carcinomas of the salivary glands are a group of several tumor entities with highly malignant histologic appearances, and have an aggressive biological behavior accompanied by poor a prognosis. In general, they require more intensive treatment than low- or intermediate-grade carcinomas. High-grade salivary carcinomas are rare and the microscopic features often overlap between different tumor types, making an appropriate diagnosis challenging in daily practice settings. However, with recent rapid advances in molecular pathology and molecular-targeted therapy in this field, there is a growing need to properly classify tumors, rather than just diagnosing the cases as "high-grade carcinomas". This leads to specific treatment strategies. In this article, we review representative high-grade salivary gland carcinomas, including salivary duct carcinoma and its histologic subtypes, high-grade mucoepidermoid carcinoma, solid-type adenoid cystic carcinoma, and high-grade transformation of low- or intermediate-grade carcinomas, and discuss their differential diagnoses and clinical implications. Other rare entities, such as neuroendocrine carcinoma, NUT carcinoma, and metastatic carcinoma, should also be considered before diagnosing high-grade carcinoma, NOS. Of these tumors, salivary duct carcinoma has received the most attention because of its strong association with androgen deprivation and anti-HER2 therapies. Other tumor-type-specific treatments include anti-TRK therapy for high-grade transformation of secretory carcinoma, but further therapeutic options are expected to be developed in the future. It should be emphasized that detailed histological evaluation with adequate sampling, in addition to the effective use of molecular ancillary tests, is of the utmost importance for a suitable diagnosis.


Assuntos
Tomada de Decisão Clínica , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/terapia , Gradação de Tumores , Carcinoma/patologia , Carcinoma/diagnóstico , Carcinoma/terapia , Diagnóstico Diferencial
6.
Eur Arch Otorhinolaryngol ; 281(7): 3779-3789, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38587651

RESUMO

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.


Assuntos
Receptor ErbB-2 , Receptores Androgênicos , Ductos Salivares , Neoplasias das Glândulas Salivares , Centros de Atenção Terciária , Humanos , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/terapia , Receptores Androgênicos/metabolismo , Receptor ErbB-2/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Ductos Salivares/patologia , Adulto , Estudos Retrospectivos , Carcinoma Ductal/patologia , Carcinoma Ductal/metabolismo , Carcinoma Ductal/terapia , Carcinoma Ductal/tratamento farmacológico , Idoso de 80 Anos ou mais , Terapia de Alvo Molecular , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia
7.
Artigo em Inglês | MEDLINE | ID: mdl-38091970

RESUMO

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.


Assuntos
Carcinoma , Neutropenia , Neoplasias das Glândulas Salivares , Humanos , Idoso , Cetuximab/uso terapêutico , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias das Glândulas Salivares/tratamento farmacológico , Receptores ErbB/metabolismo , Glândulas Salivares/metabolismo
8.
Cancer ; 129(19): 2966-2974, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37246414

RESUMO

BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab. METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC. PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.


Assuntos
Neoplasias da Mama , Carcinoma Ductal , Humanos , Feminino , Docetaxel/uso terapêutico , Micelas , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trastuzumab/uso terapêutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Glândulas Salivares/metabolismo , Neoplasias da Mama/tratamento farmacológico
9.
Mod Pathol ; 36(10): 100273, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37423585

RESUMO

Salivary duct carcinoma (SDC) is aggressive with limited therapeutic options. A subset of SDC display human epidermal growth factor receptor 2 (HER2) protein overexpression by immunohistochemistry, and some show ERBB2 gene amplification. Guidelines for HER2 scoring are not firmly established. Recent advances in breast carcinoma have established a role for anti-HER2 therapies in lesions with low HER2 expression lacking ERBB2 amplification. Delineating HER2 staining patterns in SDC is critical for evaluating anti-HER2 treatments. In total, 53 cases of SDC resected at our institution between 2004 and 2020 were identified. Androgen receptor (AR) and HER2 immunohistochemistry and ERBB2 fluorescence in situ hybridization were performed in all cases. AR expression was scored for percentage positive cells and categorized as positive (>10% of cells), low positive (1%-10%), or negative (<1%). HER2 staining levels and patterns were recorded, scored using 2018 ASCO/CAP guidelines, and categorized into HER2-positive (3+ or 2+ with ERBB2 amplification), HER2-low (1+ or 2+ without ERBB2 amplification), HER2-very low (faint staining in <10% of cells), or HER2-absent types. Clinical parameters and vital status were recorded. Median age was 70 years, with a male predominance. ERBB2-amplified tumors (11/53; 20.8%) presented at lower pT stages (pTis/pT1/pT2; P = .005, Fisher exact test) and more frequently had perineural invasion (P = .007, Fisher exact test) compared with ERBB2 nonamplified tumors; no other pathologic features differed significantly by gene amplification status. In addition, 2+ HER2 staining by 2018 ASCO/CAP criteria was most common (26/53; 49%); only 4 cases (8%) were HER2-absent status; 3+ HER2 staining was found in 9 tumors, and all were ERBB2 amplified. Six patients with HER2-expressing tumors received trastuzumab therapy, including 2 with ERBB2-amplified tumors. Overall survival and recurrence-free survival did not differ significantly based on ERBB2 status. This work suggests that 2018 ASCO/CAP guidelines for HER2 evaluation in breast carcinoma could be applied to SDC. Our findings also show broad overexpression of HER2 in SDC raising the possibility that more patients may benefit from anti-HER2-directed therapies.

10.
Eur Arch Otorhinolaryngol ; 280(1): 409-417, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36036273

RESUMO

PURPOSE: To explore the clinical characteristics, prognostic factors, and value of adjuvant therapy for major salivary duct carcinoma (SDC). METHODS: Data of SDC patients who received surgery was obtained from Surveillance, Epidemiology, and End Results (SEER) database (2004-2016). Kaplan-Meier and Cox regression analyses were performed to assess prognostic factors. Propensity score matching (PSM) was done to evaluate the clinical value of adjuvant therapy. RESULTS: A total of 287 patients were enrolled. The 5-year overall survival (OS) and disease-specific survival (DSS) rates were 53.8% and 70.8%, respectively. In the univariate analysis, tumor size, T, N, TNM staging, SEER combined staging, number of regional lymph nodes examined, and number of positive lymph nodes were associated with OS and DSS. Age and primary surgical methods were also related to OS. Among patients with negative lymph nodes, patients with tumor size > 4 cm had significantly worse prognosis (P = 0.009). Multivariate analysis showed that age > 75 years, T3-4, and positive lymph nodes were independent risk factors for SDC. After PSM, the prognostic factors were age, tumor site, and T and N stage. Postoperative radiotherapy could improve OS in patients with tumor size > 4 cm (P = 0.049). CONCLUSIONS: Advanced age, submandibular gland lesions, T3-4 stage, and lymph node involvement were independent prognostic factors for SDC. In patients with tumors > 4 cm, adjuvant radiotherapy improved the OS of SDC patients.


Assuntos
Carcinoma Ductal , Neoplasias das Glândulas Salivares , Humanos , Idoso , Estudos de Coortes , Prognóstico , Glândulas Salivares/patologia , Terapia Combinada , Neoplasias das Glândulas Salivares/patologia , Estadiamento de Neoplasias , Carcinoma Ductal/terapia , Carcinoma Ductal/patologia , Radioterapia Adjuvante , Programa de SEER
11.
Eur Arch Otorhinolaryngol ; 280(4): 1939-1954, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36422671

RESUMO

PURPOSE: In a large salivary duct carcinoma (SDC) cohort, we aimed to investigate the clinical factors influencing their survival outcomes and to further establish prognostic models. METHODS: Data of patients with SDC were extracted from the Surveillance, Epidemiology, and End Results database (1975-2019). A retrospective analysis was conducted to explore the prognostic factors on overall survival (OS) and disease-specific survival (DSS), and corresponding nomograms were established. RESULTS: A steady upward trend in the incidence of SDC was observed over the past four decades. Totally, 399 patients (280 in the training set and 199 in the testing set) were enrolled. Advanced T stage, lymph node metastasis, distant metastasis, and surgery were associated with favorable OS and DSS. Besides, age > 80 years exhibited worse OS. The selected variables above were used to construct nomograms and online web calculators that could accurately predict patient survival. In addition, risk stratification systems were generated to identify low- and high-risk patients. As the risk level increased, the risk of both patient mortality and disease-specific mortality increased. CONCLUSIONS: The SDC incidence was low, but steadily increasing. The proposed prognostic models provided a robust and efficient approach to predict survival and risk stratification in SDC patients.


Assuntos
Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Idoso de 80 Anos ou mais , Prognóstico , Estudos Retrospectivos , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/patologia , Carcinoma/patologia , Programa de SEER
12.
BMC Neurol ; 22(1): 165, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501715

RESUMO

BACKGROUND: As a debilitating syndrome, paraneoplastic cerebellar degeneration (PCD) remains challenging to treat. Further, anti-Yo antibody (directed against human cerebellar degeneration-related protein 2) detection in patients with PCD is associated with unsatisfactory responses to existing therapies. Here, we present the case of a 60-year-old woman who developed PCD with anti-Yo antibodies and a submandibular gland tumor. CASE PRESENTATION: A 60-year-old woman presented with a 5-day history of unsteadiness of gait and inadequate coordination of her extremities, along with truncal instability. Although walking without aid was possible, dysmetria of all four limbs, trunk, and gait ataxia was observed. While routine biochemical and hematological examinations were normal, the patient's blood was positive for anti-Yo antibodies. When the neurological symptoms deteriorated despite administration of intravenous methylprednisolone, fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) images with contrast enhancement were performed, which showed a tumor in the left submaxillary gland. She underwent total left submandibular gland resection, including the tumor; histological and immunohistochemical results revealed a salivary duct carcinoma. She was administered intravenous methylprednisolone, followed by 10 plasma exchange sessions, intravenous immunoglobulins, and cyclophosphamide therapy. Following treatment, her symptoms were not alleviated, even after the reduction of anti-Yo titers. CONCLUSIONS: Although tumor detection was delayed, early tumor detection, diagnosis, and PCD treatment are essential because any delay can result in the progression of the disorder and irreversible neurological damage. Therefore, we recommend that the possibility of a salivary gland tumor should be considered, and whole-body dual-modality CT, including the head and neck, and FDG-PET should be performed at the earliest for patients with well-characterized paraneoplastic antibodies when conventional imaging fails to identify a tumor.


Assuntos
Degeneração Paraneoplásica Cerebelar , Neoplasias da Glândula Submandibular , Anticorpos Antineoplásicos , Autoanticorpos , Feminino , Fluordesoxiglucose F18 , Humanos , Metilprednisolona , Pessoa de Meia-Idade , Degeneração Paraneoplásica Cerebelar/complicações , Degeneração Paraneoplásica Cerebelar/diagnóstico , Neoplasias da Glândula Submandibular/complicações
13.
Immunol Invest ; 51(5): 1498-1514, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34486463

RESUMO

Although immune checkpoint inhibitors (ICIs) have emerged as new therapeutic options for refractory cancer, they are only effective in select patients. Tumor antigen-pulsed dendritic cell (DC) vaccine therapy activates tumor-specific cytotoxic T lymphocytes, making it an important immunotherapeutic strategy. Salivary ductal carcinoma (SDC) carries a poor prognosis, including poor long-term survival after metastasis or recurrence. In this study, we reported a case of refractory metastatic SDC that was treated with a tumor lysate-pulsed DC vaccine followed by a single injection of low-dose nivolumab, and a durable complete response was achieved. We retrospectively analyzed the immunological factors that contributed to these long-lasting clinical effects. First, we performed neoantigen analysis using resected metastatic tumor specimens obtained before treatment. We found that the tumor had 256 non-synonymous mutations and 669 class I high-affinity binding neoantigen peptides. Using synthetic neoantigen peptides and ELISpot analysis, we found that peripheral blood mononuclear leukocytes cryopreserved before treatment contained pre-existing neoantigen-specific T cells, and the cells obtained after treatment exhibited greater reactivity to neoantigens than those obtained before treatment. Our results collectively suggest that the rapid and long-lasting effect of this combination therapy in our patient may have resulted from the presence of pre-existing neoantigen-specific T cells and stimulation and expansion of those cells following tumor lysate-pulsed DC vaccine and ICI therapy.


Assuntos
Vacinas Anticâncer , Carcinoma Ductal , Carcinoma , Antígenos de Neoplasias , Vacinas Anticâncer/uso terapêutico , Carcinoma Ductal/terapia , Células Dendríticas , Humanos , Leucócitos Mononucleares , Nivolumabe/uso terapêutico , Peptídeos , Estudos Retrospectivos , Ductos Salivares/metabolismo
14.
Ann Diagn Pathol ; 50: 151673, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33248386

RESUMO

Salivary duct carcinoma (SDC) is a high-grade salivary gland neoplasm. It may occur de novo or secondarily from pleomorphic adenoma (ex-PA), with secondary development accounting for more than 50% of the cases. In recent years, the expression of tyrosine kinase receptor B (TrkB), which is in the same family as HER2, has been confirmed in various types of carcinomas. However, there are a few studies on SDC. In order to examine the expression and role of TrkB in SDC, we investigated it. Immunohistochemistry was used to detect the expression of TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) in 20 patients with SDC. The mRNA levels of TrkB, BDNF, and NT-4 were analyzed using quantitative polymerase chain reaction. TrkB was negative in 10 cases and positive in 10 cases, BDNF was negative in 11 cases and positive in 9 cases, and NT-4 was positive in all cases. There was a high number of TrkB-positive cases in the pT4 group and The H-score of TrkB was also significantly higher in the stage III and IV groups. There was a high number of BDNF-positive cases in the ex-PA group and Histo-score of BDNF had a trend of high expression in ex-PA. There were no significant differences or correlations in mRNA expression. Our results suggest that TrkB may be involved in SDC tumor growth.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carcinoma Ductal/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptor trkB/metabolismo , Ductos Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Adenoma Pleomorfo/complicações , Adenoma Pleomorfo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma Ductal/diagnóstico , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Fatores de Crescimento Neural/metabolismo , RNA Mensageiro/genética , Ductos Salivares/patologia
15.
Int J Cancer ; 146(11): 3196-3206, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31745978

RESUMO

Androgen deprivation therapy (ADT) is first-line palliative treatment in androgen receptor-positive (AR+) salivary duct carcinoma (SDC), and response rates are 17.6-50.0%. We investigated potential primary ADT resistance mechanisms for their predictive value of clinical benefit from ADT in a cohort of recurrent/metastatic SDC patients receiving palliative ADT (n = 30). We examined mRNA expression of androgen receptor (AR), AR splice variant-7, intratumoral androgen synthesis enzyme-encoding genes AKR1C3, CYP17A1, SRD5A1 and SRD5A2, AR protein expression, ERBB2 (HER2) gene amplification and DNA mutations in driver genes. Furthermore, functional AR pathway activity was determined using a previously reported Bayesian model which infers pathway activity from AR target gene expression levels. SRD5A1 expression levels and AR pathway activity scores were significantly higher in patients with clinical benefit from ADT compared to those without benefit. Survival analysis showed a trend toward a longer median progression-free survival for patients with high SRD5A1 expression levels and high AR pathway activity scores. The AR pathway activity analysis, and not SRD5A1 expression, also showed a trend toward better disease-free survival in an independent cohort of locally advanced SDC patients receiving adjuvant ADT (n = 14) after surgical tumor resection, and in most cases a neck dissection (13/14 patients) and postoperative radiotherapy (13/14 patients). In conclusion, we are the first to describe that AR pathway activity may predict clinical benefit from ADT in SDC patients, but validation in a prospective study is needed.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Receptores Androgênicos/deficiência , Receptores Androgênicos/metabolismo , Neoplasias das Glândulas Salivares/tratamento farmacológico , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Adulto , Idoso , Membro C3 da Família 1 de alfa-Ceto Redutase/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores Androgênicos/genética , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/patologia , Esteroide 17-alfa-Hidroxilase/genética
16.
Pathobiology ; 87(1): 30-36, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31865345

RESUMO

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.


Assuntos
Proteínas de Homeodomínio/genética , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Fatores de Transcrição/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Neoplasias das Glândulas Salivares/secundário
17.
Cytopathology ; 31(3): 185-192, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31749241

RESUMO

OBJECTIVE: Intraductal carcinomas (IDCs) are rare, poorly characterised salivary gland tumours. The cytological features of IDCs are even less known. In this paper, a systematic literature review of pure IDCs (without stromal invasion, not associated with other histotypes) of low-grade (LG-IDCs) and high-grade (HG-IDCs) was performed. METHODS: The bibliographic research included multiple databases (PubMed, Scopus, Web of Science). Mild-moderate nuclear atypia favoured LG-IDCs, severe atypia favoured HG-IDCs. RESULTS: Preoperative fine-needle aspiration cytology (FNAC) was performed in 13/94 published cases (14%): 10 parotid; two oral; one submandibular. All the cases were histologically LG-IDCs, except two parotid IDCs. FNAC results included: negative for malignancy (three of 13 cases, 23%); tumour of uncertain malignant potential (seven of 13, 54%); malignancy (three of 13, 23%). The ductal component was identified in two cases; mucoepidermoid carcinoma was suggested in two additional cases. The grade was underestimated on FNAC evaluation in one HG-IDC as focal high-grade features were present on subsequent histological examination. The cases diagnosed as malignant tumours or describing intermediate atypia resulted in LG-IDCs on subsequent histology. Occasional mitoses were described only in one HG-IDC; this feature may have not been considered in the remaining published cases. CONCLUSIONS: FNAC and clinico-pathological correlation are important aids for clinicians and pathologists. FNAC could assist surgery even if an accurate diagnosis is sometimes impossible. Discrepancy in grading the nuclear atypia between the FNAC material and the resected specimen can occur, sometimes being unavoidable. Further studies are needed to better characterise this rare tumour.


Assuntos
Carcinoma Intraductal não Infiltrante/patologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Adulto , Idoso , Biópsia por Agulha Fina/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Histopathology ; 75(5): 672-682, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31237963

RESUMO

AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary malignancy that results in high mortality rates and is often resistant to chemotherapy. Anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint inhibitors have led to dramatic improvements in patients with various cancers. Other immunotherapeutic approaches, e.g. cancer vaccines, have shown promising results. Cancer testis antigens, e.g. preferentially expressed antigen in melanoma (PRAME), are regarded as promising vaccine targets because of their tumour-specific expression pattern. METHODS AND RESULTS: We analysed the immunoexpression of PD-L1, PD-1, major histocompatibility complex class I (MHC I) and PRAME in 53 SDCs. The immunoexpression levels of PD-L1 in tumour cells (TCs) and immune cells (ICs), PD-1 in ICs, PRAME in TCs and MHC I in TCs were analysed, and were correlated with outcome. PRAME expression was seen in 83% of SDCs. No PRAME staining was present in normal salivary gland tissue. With the three established diagnostic algorithms proposed for head and neck squamous cell carcinoma, the criteria being a combined positive score of ≥1, TC% ≥1%, and TC% ≥25%, 35 (66%), 17 (32%) and three cases (6%), respectively, were deemed to be positive for PD-L1. PD-1-positive ICs were seen in 35 (66%) cases. MHC I down-regulation was seen in 82% of SDCs. There was a significant correlation among PD-L1 expression in ICs, PD-1 expression in ICs, and PRAME expression in TCs. PD-L1 expression in TCs and lack of PD-1 expression in ICs were associated with decreased disease-specific survival in SDC patients. CONCLUSIONS: Alterations of the tumour immune microenvironment are common in SDCs, including expression of PD-1/PD-L1 and PRAME, which opens the way to potential novel immune therapies, such as cancer vaccination and PD-1/PD-L1 blockade, in these tumours.


Assuntos
Antígenos de Neoplasias/metabolismo , Antígeno B7-H1/metabolismo , Carcinoma Ductal/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral/imunologia , Carcinoma Ductal/metabolismo , Histocitoquímica , Humanos , Neoplasias das Glândulas Salivares
19.
Tohoku J Exp Med ; 249(4): 285-290, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31875582

RESUMO

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease, characterized by high serum IgG4 concentrations and IgG4-producing plasma cell expansion with fibrotic or sclerotic changes in affected organs. Recent work has focused on the relationship between IgG4-RD and malignancies, but there is no report of malignancies associated with IgG4-RD in head and neck regions. The aim of this study was to analyze the clinicopathological characteristics of malignancies in patients with IgG4-RD in head and neck regions. We retrospectively analyzed 26 patients with IgG4-RD (12 men and 14 women aged 60.6 ± 11.6 years). The mean follow-up period was 26.6 months (from 12 to 96 months). These patients were divided into single-lesion group (n = 12) with IgG4-RD only in head and neck regions and multiple-lesion group (n = 14) with IgG4-RD in other regions. There was no significant difference in serum IgG4 concentrations between the single-lesion group (459.4 ± 336.4 mg/dL) and the multiple-lesion group (908.0 ± 739.2 mg/dL) (P = 0.07), whereas the IgG4/IgG ratio was significantly lower in the single-lesion group (22.8 ± 11.0%; n = 11) compared with the multiple-lesion group (31.7 ± 15.0%; n = 11, P = 0.02). Among the 26 patients, two patients (7.7%), both in the multiple-lesion group, developed life-threatening malignancies (salivary duct carcinoma in the submandibular gland and lymphoma in the orbital tissue). All physicians need to keep in mind the possible coexistence of malignancies in patients with IgG4-RD with high IgG4/IgG ratio and multiple lesions at the time of diagnosis.


Assuntos
Neoplasias de Cabeça e Pescoço/complicações , Doença Relacionada a Imunoglobulina G4/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Doença Relacionada a Imunoglobulina G4/patologia , Masculino , Pessoa de Meia-Idade
20.
Eur Arch Otorhinolaryngol ; 276(7): 2031-2038, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31062093

RESUMO

PURPOSE: The aim of the study was to assess the treatment results of the parotid gland salivary duct carcinoma (SDC). MATERIAL AND METHODS: A retrospective clinicopathological analysis of 40 patients treated for parotid SDC in 1996-2015 was performed. The impact of following factors on 5-year disease-free survival (DFS) and overall survival (OS) was studied: age, sex, preoperative 7th nerve palsy, skin infiltration, pT, pN, surgical margin, type of parotidectomy and neck dissection, histology (SDC de novo vs. SDC ex pleomorphic adenoma, SDCexPA), intra/periparotid lymph nodes metastases, perineural invasion (PNI), extraparenchymal extension (EPE), and overexpression HER2. RESULTS: The average age of the patients was 62 years (ranged from 39 to 81). Males predominated (57.5%). Patients with the clinical stage IV predominated (82.5%). In 1/3 of patients preoperative, 7th nerve palsy occurred. All patients were treated surgically, and all but one had supplementary radiotherapy. In 28 patients (70%), total radical parotidectomy was performed. A neck dissection was performed in all patients. In 19 cases (47.5%), SDCexPA was diagnosed. Negative microscopic surgical margin was obtained in 60% of patients. The follow-up for the whole analyzed group ranged from 2 to 22 years, average was 11.6 years. In 23 patients (57.5%), the disease recurred. Local recurrence was observed in 10 (25%) and distant metastases in 15 (37.5%) cases. 20 patients (50%) died of cancer. 5-year DSF and OS were 42.5% and 41%, respectively. Univariate analysis proved that the significant influence on the survival had 7th nerve palsy (p = 0.024 and p = 0.017, respectively), higher pT-stage (p < 0.001), radical parotidectomy (p = 0.024 and p = 0.022), radical treatment of the neck (p = 0.001 and p = 0.002), EPE (p = 0.040 and p = 0.028), and histology SDCexPA and PNI (p = 0.036 and 0.048). Multivariate analysis showed that independent prognostic factors were the 7th nerve palsy and the histology SDCexPA, which worsened 5-year DFS, respectively, 3.61 and 3.94 times (p = 0.033 and p = 0.026). On the other hand, on 5-year OS, only 7th nerve palsy had an influence (3.86 times worse prognosis, p = 0.033). CONCLUSIONS: SDC is a clinically aggressive cancer with high risk of local recurrence and distant metastases, however, with a chance of curing of around 40%. In the majority of patients, a radical surgical treatment is necessary due to the high clinical stage of disease. Worse prognosis have patients with preoperative 7th nerve palsy and in whom SDC develops in pleomorphic adenoma.


Assuntos
Carcinoma , Esvaziamento Cervical , Neoplasias Parotídeas , Neoplasias das Glândulas Salivares , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Esvaziamento Cervical/métodos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/mortalidade , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia , Polônia/epidemiologia , Prognóstico , Estudos Retrospectivos , Ductos Salivares/patologia , Ductos Salivares/cirurgia , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA