RESUMO
Loss of LKB1 is associated with increased metastasis and poor prognosis in lung cancer, but the development of targeted agents is in its infancy. Here we report that a glutaminolytic enzyme, glutamate dehydrogenase 1 (GDH1), upregulated upon detachment via pleomorphic adenoma gene 1 (PLAG1), provides anti-anoikis and pro-metastatic signals in LKB1-deficient lung cancer. Mechanistically, the GDH1 product α-KG activates CamKK2 by enhancing its substrate AMPK binding, which contributes to energy production that confers anoikis resistance. The effect of GDH1 on AMPK is evident in LKB1-deficient lung cancer, where AMPK activation predominantly depends on CamKK2. Targeting GDH1 with R162 attenuated tumor metastasis in patient-derived xenograft model and correlation studies in lung cancer patients further validated the clinical relevance of our finding. Our study provides insight into the molecular mechanism by which GDH1-mediated metabolic reprogramming of glutaminolysis mediates lung cancer metastasis and offers a therapeutic strategy for patients with LKB1-deficient lung cancer.
Assuntos
Anoikis/fisiologia , Proteínas de Ligação a DNA/metabolismo , Glutamato Desidrogenase/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Células A549 , Quinases Proteína-Quinases Ativadas por AMP , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática/fisiologia , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Metástase Neoplásica/patologia , Transplante de Neoplasias , Transplante HeterólogoRESUMO
Although recent studies demonstrate active mitochondrial metabolism in cancers, the precise mechanisms through which mitochondrial factors contribute to cancer metastasis remain elusive. Through a customized mitochondrion RNAi screen, we identified succinyl-CoA ligase ADP-forming subunit beta (SUCLA2) as a critical anoikis resistance and metastasis driver in human cancers. Mechanistically, SUCLA2, but not the alpha subunit of its enzyme complex, relocates from mitochondria to the cytosol upon cell detachment where SUCLA2 then binds to and promotes the formation of stress granules. SUCLA2-mediated stress granules facilitate the protein translation of antioxidant enzymes including catalase, which mitigates oxidative stress and renders cancer cells resistant to anoikis. We provide clinical evidence that SUCLA2 expression correlates with catalase levels as well as metastatic potential in lung and breast cancer patients. These findings not only implicate SUCLA2 as an anticancer target, but also provide insight into a unique, noncanonical function of SUCLA2 that cancer cells co-opt to metastasize.
Assuntos
Neoplasias , Succinato-CoA Ligases , Humanos , Catalase/metabolismo , Grânulos de Estresse , Succinato-CoA Ligases/metabolismo , OxirreduçãoRESUMO
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/patologiaRESUMO
OBJECTIVES: The aim of the study was to investigate the association of surgical margin conditions, including positive specimen margins revised to negative relative to local recurrence, disease-free survival, and overall survival (OS) within a cohort of HPV-mediated oropharyngeal squamous cell carcinoma (OPSCC) who underwent en bloc resection via transoral robotic surgery (TORS). MATERIALS AND METHODS: Retrospective cohort of patients with untreated HPV-mediated OPSCC cT1 or T2 undergoing TORS resection between October 2014 and March 2020. The methodologic description of our interdisciplinary institutional approach, number of cut-through margins (CTMs) during intraoperative consultation, percentage of final positive margin cases, and disease-free survival and OS stratified by margin status and margin tumor-free distance is identified. RESULTS: 135 patients with primary cT1/T2 HPV-mediated OPSCC met inclusion criteria. Twenty-eight of 135 (20.7%) specimens revealed CTM and were revised during the same operative setting. Three of 135 (2.2%) surgical cases had positive final margin status. Local control rate was 97%. On univariate analysis, margin distance did not impact OS. CTM and final positive margins had lower OS than initially negative margins (p = 0.044). Pathologic N-stage significantly impacted OS (p < 0.001). CONCLUSIONS: High local control rate and low final positive margin status confound the study of specimen margin-based techniques in HPV-mediated OPSCC resected en bloc with TORS. Pathologic N-stage may impact OS more than margin status. Larger numbers are needed to confirm differences.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Procedimentos Cirúrgicos Robóticos , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Margens de Excisão , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/patologia , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/cirurgiaRESUMO
The DNA cytosine deaminase APOBEC3B (A3B) is a newly recognized endogenous source of mutations in a range of human tumors, including head/neck cancer. A3B inflicts C-to-T and C-to-G base substitutions in 5'-TCA/T trinucleotide motifs, contributes to accelerated rates of tumor development, and affects clinical outcomes in a variety of cancer types. High-risk human papillomavirus (HPV) infection causes A3B overexpression, and HPV-positive cervical and head/neck cancers are among tumor types with the highest degree of APOBEC signature mutations. A3B overexpression in HPV-positive tumor types is caused by the viral E6/E7 oncoproteins and may be an early off-to-on switch in tumorigenesis. In comparison, less is known about the molecular mechanisms responsible for A3B overexpression in HPV-negative head/neck cancers. Here, we utilize an immunohistochemical approach to determine whether A3B is turned from off-to-on or if it undergoes a more gradual transition to overexpression in HPV-negative head/neck cancers. As positive controls, almost all HPV-positive oral epithelial dysplasias and oropharyngeal cancers showed high levels of nuclear A3B staining regardless of diagnosis. As negative controls, A3B levels were low in phenotypically normal epithelium adjacent to cancer and oral epithelial hyperplasias. Interestingly, HPV-negative and low-grade oral epithelial dysplasias showed intermediate A3B levels, while high-grade oral dysplasias showed high A3B levels similar to oral squamous cell carcinomas. A3B levels were highest in grade 2 and grade 3 oral squamous cell carcinomas. In addition, a strong positive association was found between nuclear A3B and Ki67 scores suggesting a linkage to the cell cycle. Overall, these results support a model in which gradual activation of A3B expression occurs during HPV-negative tumor development and suggest that A3B overexpression may provide a marker for advanced grade oral dysplasia and cancer.
Assuntos
Citidina Desaminase/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/virologia , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologiaRESUMO
BACKGROUND: With an expectation of excellent locoregional control, ongoing efforts to de-intensify therapy for patients with human papillomavirus-associated squamous cell oropharyngeal cancer necessitate a better understanding of the metastatic risk for patients with this disease. The objective of this study was to determine what factors affect the risk of metastases in patients with squamous cell cancers of the oropharynx. METHODS: Under a shared use agreement, 547 patients from Radiation Therapy Oncology Group 0129 and 0522 with nonmetastatic oropharyngeal squamous cell cancers who had a known p16 status and smoking status were analyzed to assess the association of clinical features with the development of distant metastases. The analyzed factors included the p16 status, sex, T stage, N stage, age, and smoking history. RESULTS: A multivariate analysis of 547 patients with a median follow-up of 4.8 years revealed that an age ≥ 50 years (hazard ratio [HR], 3.28; P = .003), smoking for more than 0 pack-years (HR, 3.09; P < .001), N3 disease (HR, 2.64; P < .001), T4 disease (HR, 1.63; P = .030), and a negative p16 status (HR, 1.60; P = .044) were all factors associated with an increased risk of distant disease. CONCLUSIONS: Age, smoking, N3 disease, T4 disease, and a negative p16 status were associated with the development of distant metastases in patients with squamous cell cancers of the oropharynx treated definitively with concurrent chemoradiation.
Assuntos
Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Fumar Tabaco/epidemiologia , Adulto , Fatores Etários , Idoso , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/patologia , Estudos Prospectivos , Medição de RiscoRESUMO
BACKGROUND: Radiographic concern for lymphatic extranodal extension (ENE) impacts upfront management decisions for patients with human papilloma virus (HPV) oropharyngeal squamous cell carcinoma (OPSCC). Therefore, we set out to evaluate the accuracy of preoperative contrast-enhanced computed tomography (CECT) to predict major ENE (> 2 mm). METHODS: Twenty-seven consecutive patients with HPV-associated OPSCC who presented at our institutional multidisciplinary tumor board were staged radiographically with positron emission tomography (PET/CT) and CECT, and underwent primary transoral robotic resection and neck dissection. CECT imaging results were correlated with pathologic ENE (pENE). RESULTS: CECT specificity for all pENE was 69 and 75% for radiologist 1 and 2, respectively. For pENE > 2 mm, the sensitivities were 88 and 100%, but specificities were 52.6 and 63.2%. Positive predictive values (PPV) were 43.8 and 53.3%; negative predictive values were 90.9 and 100%. On logistic regression analysis, only size ≥3 cm (OR 4.7-5.4, p < 0.02, 95% CI 1.3-44.0) demonstrated significant correlation with major ENE > 2 mm. CONCLUSIONS: Preoperative imaging for HPV-associated OPSCC had a PPV for pENE > 2 mm of 44-55%, based on any interruption in the capsule or invasion into the perinodal fat. The PPV is low and equipoise in treatment decision making for patients with HPV-associated OPSCC may require other imaging characteristics.
Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Invasividade Neoplásica/diagnóstico por imagem , Neoplasias Orofaríngeas/diagnóstico por imagem , Infecções por Papillomavirus/complicações , Tomografia Computadorizada por Raios X , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Meios de Contraste , Humanos , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Cuidados Pré-Operatórios , Prognóstico , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodosRESUMO
Laryngeal chondrosarcoma is an uncommon malignancy with a predilection for the cricoid cartilage of adult male patients. Although rare, identification of aggressive chondrosarcoma variants, such as dedifferentiated chondrosarcoma (DDCS) may influence preoperative patient counseling, definitive surgical management, potential implementation of post-operative adjuvant therapy and prognosis. Herein we describe clinical and imaging features of laryngeal DDCS, the unique perspective of fresh and formalin fixed macroscopic examination, a spectrum of histopathologic findings, and detail the full course of the patient's disease.
Assuntos
Condrossarcoma/diagnóstico por imagem , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Idoso , Condrossarcoma/patologia , Condrossarcoma/radioterapia , Evolução Fatal , Feminino , Humanos , Neoplasias Laríngeas/radioterapia , Laringe/diagnóstico por imagem , Laringe/patologia , Metástase Neoplásica , Tomografia por Emissão de PósitronsRESUMO
An estimated 200,000 deaths each year worldwide are due to cancer of the head and neck, mostly mucosal squamous cell carcinoma and nonmelanoma skin cancer. The status of surgical margins is important for prognosis and need for adjuvant therapy. We will discuss how margin status impacts outcomes and therapy, and the conundrum of determining margin status.
Assuntos
Carcinoma de Células Escamosas/prevenção & controle , Carcinoma de Células Escamosas/cirurgia , Secções Congeladas , Neoplasias de Cabeça e Pescoço/prevenção & controle , Neoplasias de Cabeça e Pescoço/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Procedimentos Cirúrgicos Operatórios/normas , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Período Intraoperatório , Terapia Neoadjuvante/métodos , Neoplasia Residual/prevenção & controle , Prognóstico , Radioterapia Adjuvante , Mucosa Respiratória/patologia , Mucosa Respiratória/cirurgia , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/cirurgia , Taxa de SobrevidaRESUMO
OBJECTIVE: The objective of our study was to report head and neck deep fibromatosis as part of the differential diagnosis of a firm painful neck mass after cervical fusion and diskectomy. CONCLUSION: Although they are rare tumors, fibromatosis tumors or desmoid tumors should be considered in a patient with a painful neck mass; a history of cervical spine surgery; and MRI findings showing a large, avidly enhancing, heterogeneous mass adjacent to surgical hardware that is hyperintense on T2-weighted imaging.
Assuntos
Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Fibroma/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Fusão Vertebral/efeitos adversos , Adulto , Fibroma/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Assessment of benign and malignant lesions of the parotid gland, including metastatic lesions, is challenging with current imaging methods. Fluorine-18 FDG PET/CT is a noninvasive imaging modality that provides both anatomic and metabolic information. Semiquantitative data obtained from PET/CT, also known as PET/CT parameters, are maximum, mean, or peak standardized uptake values (SUVs); metabolic tumor volume; total lesion glycolysis; standardized added metabolic activity; and normalized standardized added metabolic activity. Our aim was to determine whether FDG PET/CT parameters can differentiate benign, malignant, and metastatic parotid tumors. MATERIALS AND METHODS: Thirty-four patients with parotid neoplasms underwent PET/CT before parotidectomy; maximum SUV, mean SUV, peak SUV, total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity were calculated on a dedicated workstation. Univariate analyses were performed. A ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven benign, malignant, and metastatic parotid gland neoplasms. RESULTS: Fourteen patients had a benign or malignant primary parotid tumor. Twenty had metastases to the parotid gland. When the specificity was set to at least 85% for each parameter to identify cut points, the corresponding sensitivities ranged from 15% to 40%. Assessment of benign versus malignant lesions of parotid tumors, as well as metastasis from squamous cell carcinoma versus other metastatic causes, revealed that none of the PET/CT parameters has enough power to differentiate among these groups. CONCLUSION: PET/CT parameters, including total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity, are not able to differentiate benign from malignant parotid tumors, primary parotid tumors from metastasis, or metastasis from squamous cell carcinoma and nonsquamous cell carcinoma metastasis.
Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Parotídeas/metabolismo , Neoplasias Parotídeas/cirurgia , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade , Carga TumoralRESUMO
Metastasis is the leading cause of death in patients with breast, lung, and head and neck cancers. However, the molecular mechanisms underlying metastases in these cancers remain unclear. We found that the p90 ribosomal S6 kinase 2 (RSK2)-cAMP response element-binding protein (CREB) pathway is commonly activated in diverse metastatic human cancer cells, leading to up-regulation of a CREB transcription target Fascin-1. We also observed that the protein expression patterns of RSK2 and Fascin-1 correlate in primary human tumor tissue samples from head and neck squamous cell carcinoma patients. Moreover, knockdown of RSK2 disrupts filopodia formation and bundling in highly invasive cancer cells, leading to attenuated cancer cell invasion in vitro and tumor metastasis in vivo, whereas expression of Fascin-1 significantly rescues these phenotypes. Furthermore, targeting RSK2 with the small molecule RSK inhibitor FMK-MEA effectively attenuated the invasive and metastatic potential of cancer cells in vitro and in vivo, respectively. Taken together, our findings for the first time link RSK2-CREB signaling to filopodia formation and bundling through the up-regulation of Fascin-1, providing a proinvasive and prometastatic advantage to human cancers. Therefore, protein effectors of the RSK2-CREB-Fascin-1 pathway represent promising biomarkers and therapeutic targets in the clinical prognosis and treatment of metastatic human cancers.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteína de Ligação a CREB/metabolismo , Proteínas de Transporte/biossíntese , Regulação Neoplásica da Expressão Gênica , Proteínas dos Microfilamentos/biossíntese , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Transdução de Sinais , Animais , Biomarcadores Tumorais/genética , Proteína de Ligação a CREB/genética , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Nus , Proteínas dos Microfilamentos/genética , Metástase Neoplásica , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patologia , Pseudópodes/genética , Pseudópodes/metabolismo , Pseudópodes/patologia , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Regulação para Cima/genéticaRESUMO
BACKGROUND: Lymph node extracapsular extension (ECE) is a known adverse prognostic factor in head and neck cancer and is an indication for adjuvant chemoradiation (CRT). However, the extent of ECE may provide additional prognostic information in the setting of adjuvant CRT. METHODS: This study included 350 patients with oral cavity cancer (72.6%) or bulky/nonfunctional laryngeal cancer (27.4%) who underwent initial surgical resection. Extent of ECE was graded from 0 to 4 based on the scale established by Lewis and colleagues. Multivariable analyses (MVA) were adjusted for primary site, pathologic risk factors, and adjuvant therapy. RESULTS: In univariate failure-free survival (FFS) analysis, there was no significant difference in FFS for patients with lymph node-positive disease and no ECE (grade 0) versus patients with ECE grades 1 through 3. However, patients with ECE grade 4 had significantly worse FFS. In MVA for FFS, differences between ECE grades 0 through 3 and grade 4 did not remain significant. In MVA of overall survival, ECE grade 4 was significantly associated with higher risk of death compared with ECE grade 0 (hazard ratio, 0.46; P = .02) and ECE grades 1 through 3 (HR, 0.41; P = .01). CONCLUSIONS: Dichotomous evaluation of ECE is useful for determining appropriate adjuvant therapy but has limited additional prognostic value in the setting of adjuvant CRT. The detrimental effect of ECE grades 1 through 3 relative to no ECE is effectively mitigated with adjuvant CRT, but ECE grade 4 retains a poorer prognosis despite CRT with regard to overall survival. Patients with ECE grade 4 may be candidates for trials investigating novel methods of adjuvant therapy intensification.
Assuntos
Quimiorradioterapia Adjuvante , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Análise Multivariada , Esvaziamento Cervical , Gradação de Tumores , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: Tyrosine-rich or tyrosine-like crystalloids (TC) were initially described in salivary gland pleomorphic adenoma. The presence of TC in non-neoplastic tissues is rare, and it has been reported exclusively in the larynx. This study aims to characterize the frequency and anatomical localization of TC in total laryngectomy specimens. METHODS: Review of consecutive laryngectomy specimens in which the cassette summary documented parasagittal section sampling of the right and left vocal folds and the anterior commissure. Data collected included patient demographics, underlying diagnoses, history of radiation therapy, presence, and location of TC. RESULTS: Of 86 laryngectomy specimens, 16 (19%) contained amphophilic to eosinophilic TC. The study cohort included 11 males and 5 females, aged 37 to 85 years (mean 62, median 63). Laryngectomy surgery was performed for advanced untreated squamous cell carcinoma (SCCa) (7/16, 43.75%), recurrent post-treatment SCCa (7/16, 43.75%), previously untreated laryngeal large cell neuroendocrine carcinoma (1/16, 6.25%), and non-functional larynx post-chemoradiation (1/16, 6.25%). According to the macroscopic cassette summary, TC were predominantly found in the anterior commissure Sect. (13/16, 81.25%), with fewer cases in sections containing the left (2/16, 12.5%) or the right (1/16, 6.25%) vocal folds. Microscopically, TC localized to the anterior macula flava and/or adjacent vocal ligament (12/16, 75%) and the anterior commissure tendon (4/16, 25%). CONCLUSIONS: TCs are predominantly reported as admixed with a neoplasm, however this study confirms that TC can also occur in non-neoplastic tissues of the larynx. There was no clear relationship between the presence of TC and prior radiation therapy. TC in the specialized connective tissues of the macula flava and true cord tendinous insertions distinct from tumor may form in response to alterations in mechanical stress, though an age-related change within the spectrum of normal laryngeal microanatomy also remains a possibility.
Assuntos
Prega Vocal , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Adulto , Idoso de 80 Anos ou mais , Prega Vocal/patologia , Laringectomia , Tirosina , Neoplasias Laríngeas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0238497.].
RESUMO
Systemic complications of levamisole-adulterated cocaine (LAC) use have recently been described. The objective of this review is to increase awareness of these manifestations among oral and maxillofacial surgeons. LAC exposure through inhalation, nasal insufflation, or injection can induce cutaneous vasculopathy and hematologic abnormalities such as neutropenia or agranulocytosis. Unlike other vasculopathies involving the skin, LAC-induced vascular injury frequently manifests with purpuric and necrotic lesions that involve the face and ears. Oral manifestations have also been reported but are not yet well characterized. The aforementioned hematologic manifestations are not uncommon, and patients exposed to LAC are potentially at higher risk for infectious complications. When manifestations of LAC affect the head, neck, and oral cavity, oral and maxillofacial surgeons may be the first providers to encounter the patient. Early recognition of the clinical signs and laboratory abnormalities will better allow for distinguishing LAC-related effects from various clinical mimics, will facilitate appropriate patient management, and may further contribute to the understanding of the biological effects of LAC.
Assuntos
Agranulocitose/induzido quimicamente , Transtornos Relacionados ao Uso de Cocaína/complicações , Contaminação de Medicamentos , Levamisol/efeitos adversos , Púrpura/induzido quimicamente , Artralgia/induzido quimicamente , Autoanticorpos , Cocaína/química , Transtornos Relacionados ao Uso de Cocaína/patologia , Orelha Externa/irrigação sanguínea , Face/irrigação sanguínea , Humanos , Doenças da Boca/induzido quimicamente , Pescoço/irrigação sanguínea , Doenças Nasais/induzido quimicamente , Fístula Bucal/induzido quimicamenteRESUMO
BACKGROUND: The World Health Organization's (WHO) chapter on odontogenic and maxillofacial bone tumors provides a global reference for diagnosis of these tumors. In the fifth edition, the inclusion of consensus definitions and development of essential and desirable diagnostic criteria help improve recognition of distinct entities. These are key enhancements since the diagnosis of odontogenic tumors is largely based on histomorphology which is taken in combination with clinical and radiographic appearances. METHODS: Review. RESULTS: Despite delineation of diagnostic criteria for ameloblastoma, adenoid ameloblastoma, and dentinogenic ghost cell tumor, a subset of these tumors continues to show overlapping histological features that can potentially lead to misdiagnosis. Accurate classification may be challenging on small biopsies, but potentially enhanced by refining existing diagnostic criteria and utilization of immunohistochemistry and/or molecular techniques in a specific cases. It has become clear that the clinical and histologic features of the non-calcifying Langerhans cell-rich subtype of calcifying epithelial odontogenic tumor and the amyloid-rich variant of odontogenic fibroma converge into a single tumor description. In addition, this tumor shows remarkable clinical, histological overlap with a subset of sclerosing odontogenic carcinoma located in the maxilla. Benign perineural involvement vs perineural invasion is an underexplored concept in odontogenic neoplasia and warrants clarification to reduce diagnostic confusion with sclerosing odontogenic carcinoma. CONCLUSION: While controversial issues surrounding classification and discrete tumor entities are addressed in the WHO chapter, ambiguities inevitably remain. This review will examine several groups of odontogenic tumors to highlight persistent knowledge gaps, unmet needs and unresolved controversies.
Assuntos
Ameloblastoma , Carcinoma , Neoplasias Bucais , Tumores Odontogênicos , Humanos , Ameloblastoma/patologia , Nova Orleans , Tumores Odontogênicos/diagnóstico , Tumores Odontogênicos/patologiaRESUMO
BACKGROUND: Verruciform xanthoma (VX) is an uncommon, benign epithelial lesion of the oral mucosa. While this entity can also present extraorally, including on the skin and in anogenital areas, the variation in its histologic features in extraoral sites is not yet well defined. Differences in the demographics and morphologic features of oral versus extraoral VX were assessed to help facilitate the accurate diagnosis and management of this lesion. METHODS: After obtaining IRB approval, 110 cases of diagnosed VX were retrospectively collected from our institutional archives spanning from 2000 to 2022. Patient age, gender, available medical history, lesion appearance, and duration were obtained for each case. RESULTS: The median age was 55 years (range 13-86) with a male-to-female ratio of 1.2:1. The most common oral sites, in descending order, were the palate (n = 24, 22%), buccal mucosa (n = 18, 16%), gingiva (n = 16, 15%), and tongue (n = 13, 12%). Extraoral sites comprised 9% of all lesions, including the scrotum (9), vulva (2), cheek (1), wrist (1), gluteal region (1), and abdominal wall (1). The median size for all lesions was 6.0 mm, and extraoral lesions were associated with a 6.7 mm larger size compared to oral lesions (B ± SE: 6.7 ± 2.5 cm, p = 0.01). The lesions were most frequently pink or white in color and often described as papillary, pedunculated, verrucous, and/or exophytic. Microscopically, the presence of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated inflammation significantly differed between oral and extraoral lesions. Prominent wedge-shaped parakeratosis (p = 0.04) and keratin projections above the epithelium/epidermis (p < 0.001) were more prevalent in extraoral lesions. There was no significant link between keratin projections and epithelial atypia (p = 0.44). CONCLUSIONS: Familiarity with the broad morphological spectrum of VX, including the presence and degree of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated underlying inflammation, will be helpful in diagnosing it in unusual locations.
Assuntos
Doenças da Boca , Paraceratose , Xantomatose , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Doenças da Boca/patologia , Xantomatose/patologia , Queratinas , Genitália/patologiaRESUMO
BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated. RESULTS: A review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms.
Assuntos
Infecções Fúngicas Invasivas , Sinusite , Humanos , Estudos Prospectivos , Infecções Fúngicas Invasivas/diagnóstico , Doença Aguda , Prognóstico , Sinusite/diagnóstico , Sinusite/terapia , Sinusite/microbiologiaRESUMO
Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon lesion with remarkably consistent histopathologic features that arises primarily in the pediatric population. We describe a MNTI arising in the anterior maxilla of a 6-month-old boy.