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1.
Gland Surg ; 10(6): 2054-2061, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34268090

RESUMO

Giant cell tumor of soft tissue (GCT-ST) is a rare benign tumor of low malignant potential. It is thought to be the soft tissue counterpart of giant cell tumors of the bone due to its pathological resemblances. GCT-ST is most commonly found in superficial soft tissue of thigh, trunk and upper extremities. The head and neck region is rarely affected. Here for the first time, we describe a case of GCT-ST in the thyroid region. A 70-year-old female patient presented with a painless swelling in her left neck for the previous three weeks. The condition was initially diagnosed as thyroid goiter and left lobectomy was arranged. Intraoperative findings showed an irregular mass invading the strap muscles and trachea. Complete tumor resection was difficult, and part of the tumor was left in the thyroid bed. Histopathology of the resected specimen showed a mixture of mononuclear round to oval cells and multinucleated osteoclast-like giant cells. The giant cells were CD 68 positive. The patient received a revision surgery 3 months after the first operation to achieve complete resection. There was no recurrence in the first 3-month follow-up. However, 6 months after the revision surgery, the tumor recurred on both sides of the neck. The patient suffered from dysphagia and breathlessness. As further surgery and radiation therapy were not considered, denosumab was used as a novel agent After three months of treatment, the patient showed symptom-relief and tumor-regression. The patient continued to have tumor-regression after 1 year of the denosumab treatment. GCT-ST is a benign tumor, although in this case, it was showing features of malignancy. A review of the literature was conducted to identify previous studies on GCT-ST in the head and neck. We present this case for its rare location and novel treatment with denosumab.

2.
J Clin Endocrinol Metab ; 106(1): 120-132, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000173

RESUMO

CONTEXT: Programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin and ITIM domain (TIGIT) are considered major immune co-inhibitory receptors (CIRs) and the most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in medullary thyroid carcinoma (MTC). OBJECTIVE: We aimed to provide the first evidence regarding the expression profiles and clinical significance of CIRs in a large cohort of MTC patients. DESIGN AND PATIENTS: In total, 200 MTC patients who received initial surgery in our hospital were included. Immunohistochemistry was performed to evaluate CIR expressions in tissue microarrays (TMAs). Combined with the results of our previous programmed cell death ligand-1 (PD-L1) study, clinicopathologic and prognostic correlations of these proteins were retrospectively analyzed. RESULTS: TIM-3, PD-1, CTLA-4, LAG-3, and TIGIT positivity was detected in 96 (48.0%), 27 (13.5%), 25 (12.5%), 6 (3.0%), and 6 (3.0%) patients, respectively, in whom TIM-3, PD-1, and CTLA-4 expressions were positively correlated. Log-rank tests and multivariate Cox analyses both indicated that TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression were associated with worse structural recurrence-free survival. In addition, among 20 patients who developed advanced disease during follow-up, 12 (60%) showed TIM-3 positivity, among whom 6 cases also had concurrent moderate to strong PD-1, PD-L1, or CTLA-4 expression. CONCLUSIONS: Using the currently largest TMA cohort of this rare cancer, we delineated the CIR expression profiles in MTC, and identified TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression as promising biomarkers for tumor recurrence. Furthermore, a subset of advanced MTCs are probably immunogenic, for which single or combined immunotherapy including TIM-3, PD-1, PD-L1, or CTLA-4 blockade may be potential therapeutic approaches in the future.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Neuroendócrino/metabolismo , Proteínas de Checkpoint Imunológico/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos CD/metabolismo , Biomarcadores Tumorais/análise , Antígeno CTLA-4/análise , Antígeno CTLA-4/metabolismo , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Criança , China/epidemiologia , Estudos de Coortes , Progressão da Doença , Feminino , Receptor Celular 2 do Vírus da Hepatite A/análise , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Proteínas de Checkpoint Imunológico/análise , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/análise , Receptor de Morte Celular Programada 1/metabolismo , Receptores Imunológicos/análise , Receptores Imunológicos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Análise Serial de Tecidos , Adulto Jovem , Proteína do Gene 3 de Ativação de Linfócitos
3.
Oral Oncol ; 115: 105092, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33189578

RESUMO

Mammary analog secretory carcinoma (MASC), or secretory carcinoma of the thyroid is an extremely rare disease harboring ETV6-NTRK3 gene fusion with TRK activation. Here we report the twelfth case of MASC of the thyroid worldwide. A 36-year-old female was diagnosed with poor-differentiated thyroid carcinoma (PDTC). Pathology consultant and immunochemical workups showed the tumor cells were negative for TTF1, TG, PAX8, positive for S100, Vimentin, GATA-3, and focally positive for mammaglobin. Fluorescence in situ hybridization (FISH) assay using a dual-color break-apart probe showed ETV6 translocation t(12p13) (ETV6) was present and established the diagnosis of MASC. Next-generation sequencing (NGS) of a 47-gene panel identified exon 1-5 of ETV6 gene were fused with exons 15-19 of NTRK3 gene. The patient experienced three loco-regional recurrences within 12 months and eventually developed inoperable local disease as well as bilateral lung metastasis. She is currently receiving anti-TRK treatment with a follow-up time of 33 months. A literature review of MASC in the thyroid was also conducted.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Feminino , Humanos , Carcinoma Secretor Análogo ao Mamário/diagnóstico , Carcinoma Secretor Análogo ao Mamário/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
4.
Thyroid ; 29(9): 1269-1278, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31328653

RESUMO

Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.


Assuntos
Antígeno B7-H1/análise , Carcinoma Neuroendócrino/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Neuroendócrino/química , Carcinoma Neuroendócrino/tratamento farmacológico , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto Jovem
5.
Laryngoscope ; 122(7): 1497-506, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22539053

RESUMO

OBJECTIVES/HYPOTHESIS: To find the risk factors of lymph node (LN) metastasis of salivary gland cancer and draw a scheme for LN management. STUDY DESIGN: Hospital-based retrospective study. METHODS: The records of salivary gland cancer patients treated at the Department of Head and Neck Surgery, Cancer Hospital, Fudan University, were entered in a database, and 219 consecutive patients with carcinomas of major salivary glands primarily operated on between January 1998 and January 2011 were chosen for univariate and multivariate analysis to identify risk factors for LN involvement. RESULTS: Fifty-eight (26.5%) patients had LN involvement. Factors associated with cervical LN involvement on univariate analysis included pathologic type, male sex, shorter duration of preoperative course, facial paralysis, advanced T stage, and major nerve, soft tissue, lymphatic/vascular (L/V), neural/perineural, and extracapsular invasion. Multivariate analysis identified major nerve invasion, histologic type, L/V invasion, and extracapsular invasion as significant factors for LN involvement. The proportion of patients with LN involvement with low (105), middle (61), high (34), and super high (19) predictive index scores based on the four risk factors were 3.8%, 27.9%, 55.9%, and 94.7%, respectively. CONCLUSIONS: A predictive index using the clinicopathologic factors described in this report can effectively stratify patients into risk groups for nodal metastasis. Comprehensive management based on this risk index should improve treatment outcomes for patients with salivary gland cancer.


Assuntos
Neoplasias das Glândulas Salivares/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias das Glândulas Salivares/cirurgia
6.
Acta Otolaryngol ; 132(8): 879-86, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22497626

RESUMO

CONCLUSION: Chinese patients have a higher rate of lymphoepithelial carcinoma (LEC) and salivary duct carcinoma (SDC). Comprehensive use of diagnostic modalities, neck dissection, and postoperative radiation will improve the treatment results for salivary gland tumors (SGTs). OBJECTIVES: To study the clinicopathological characteristics of SGTs in a Chinese population. METHODS: The records of SGT patients operated in a tertiary cancer hospital of China were retrieved. RESULTS: From December 1997 to December 2007, 289 malignant and 887 benign SGTs were operated at Cancer Hospital, Shanghai, China. Pleomorphic adenoma and Warthin's tumor were the most common types of SGT. Mucoepidermoid carcinoma (24.6% of malignant cases) and adenoid cystic carcinoma (18.0%) were the most frequent malignant cases, followed by acinic cell carcinoma (12.1%), LEC (9.7%), and SDC (9.3%). The sensitivity and specificity of ultrasound scan, fine needle aspiration biopsy, and frozen section were 58.3 and 88.6%, 87.2 and 96.7%, 86.9 and 99.6%, respectively. Neck dissections and postoperative radiation were carried out for 48.6 and 48.0% of carcinomas, respectively. The percentage of tumors by pathologic TNM stage were 23.7% for stage I, 32.9% for stage II, 17.3% for stage III, and 26.1% for stage IV. The 5-year overall survival rate was 88.0%.


Assuntos
Estadiamento de Neoplasias , Neoplasias das Glândulas Salivares/patologia , Centros de Atenção Terciária/estatística & dados numéricos , Biópsia por Agulha Fina , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/epidemiologia , Taxa de Sobrevida
7.
Zhonghua Bing Li Xue Za Zhi ; 33(3): 229-32, 2004 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-15256114

RESUMO

OBJECTIVE: To investigate 30 bp deletion of latent membrane protein (LMP)-1 gene in lymphoepithelial carcinoma (LEC) of the salivary glands and to determine the frequency of this deletion. METHODS: Forty-six cases of salivary gland LEC were investigated by PCR to explore the site specific, 30 bp deletion in the 3' terminal region of LMP-1 gene. To guarantee amplifiable DNA extracted from paraffin-embedded tissue sections, PCR amplification of a house-keeping gene (beta-actin) was performed simultaneously. In addition, DNA sequencing of the PCR product was performed in representative cases. RESULTS: Although amplifiable DNA was obtained in 42 of the 46 specimens, as indicated by beta-actin gene amplification, successful amplification of LMP-1 gene was achieved in 35/42 (83.3%) cases. Two types of PCR products of LMP-1 gene were observed and confirmed by DNA sequencing. A wild-type PCR product (316 bp) was present in 31 cases (88.6%) and only 4 cases (11.4%) showed an aberrant 286 bp PCR product, corresponding to the 3' terminal 30 bp deletion of the gene. CONCLUSION: Site-specific 30 bp deletion of LMP-1 gene is not a common feature of salivary gland LEC.


Assuntos
Carcinoma/patologia , Herpesvirus Humano 4/genética , Neoplasias das Glândulas Salivares/patologia , Deleção de Sequência , Proteínas da Matriz Viral/genética , Sequência de Bases , Carcinoma/genética , Carcinoma/virologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/virologia , Deleção de Genes , Humanos , Dados de Sequência Molecular , Proteínas Oncogênicas Virais/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/virologia
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