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Odontogenic tumors represent a collection of entities ranging from hamartomas to destructive benign and malignant neoplasms. Occasionally, pathologists encounter gnathic lesions which clearly exhibit an odontogenic origin but do not fit within the confines of established diagnoses. Here, we describe two such odontogenic tumors, both affecting 3-year-old males. Each case presented as a destructive, radiolucent mandibular lesion composed of mesenchymal cells, some with unique multi-lobed nuclei, frequently arranged in a reticular pattern and supported by a myxoid stroma with focal laminations. Production of odontogenic hard tissues was also seen. Because of their unique microscopic features, both cases were investigated by next-generation sequencing and found to harbor the same STRN::ALK oncogene fusion. To our knowledge, these cases represent the first report of an odontogenic tumor with a STRN::ALK gene rearrangement. We propose the possibility that this neoplasm could be separate from other known odontogenic tumors. Both patients were treated with surgical resection and reconstruction. The prognosis of patients with this entity is currently uncertain but shall become more apparent over time as more cases are identified and followed.
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Tumores Odontogênicos , Masculino , Humanos , Pré-Escolar , Tumores Odontogênicos/patologia , Fusão Oncogênica , Receptores Proteína Tirosina Quinases/genética , Proteínas de Ligação a Calmodulina/genética , Proteínas de Membrana , Proteínas do Tecido Nervoso/genéticaRESUMO
Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.
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Adenocarcinoma/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Actinas/metabolismo , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação ao Cálcio/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Proteínas S100/metabolismo , Fatores de Transcrição SOXE/metabolismo , Neoplasias das Glândulas Salivares/patologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem , CalponinasRESUMO
Paget's disease is the second most common bone disease following osteoporosis. Paget's disease is characterized by abnormal resorption and deposition of bone. The most widely used agents to treat Paget's disease are bisphosphonates. Bisphosphonates have been given much attention due to reports of osteonecrosis associated with their use. This case report demonstrates the placement of implants in a patient with Paget's disease on a six-month-course of bisphosphonate therapy. The patient had post-operative complications and a secondary placement but no signs of bisphosphonate-associated osteonecrosis of the jaw (ONJ). Although complications may exist, the placement of implants in a patient with Paget's disease taking bisphosphonates can have a positive outcome.
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Conservadores da Densidade Óssea/uso terapêutico , Implantes Dentários , Difosfonatos/uso terapêutico , Ácido Etidrônico/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Idoso , Perda do Osso Alveolar/cirurgia , Implantação Dentária Endóssea , Remoção de Dispositivo , Regeneração Tecidual Guiada Periodontal/métodos , Humanos , Masculino , Osseointegração/fisiologia , Reoperação , Infecção da Ferida Cirúrgica/etiologiaRESUMO
Black and brown pigmentation of the oral mucosa can occur due to a multitude of non-neoplastic causes. Endogenous or exogenous pigments may be responsible for oral discoloration which can range from innocuous to life-threatening in nature. Physiologic, reactive, and idiopathic melanin production seen in smoker's melanosis, drug-related discolorations, melanotic macule, melanoacanthoma and systemic diseases are presented. Exogenous sources of pigmentation such as amalgam tattoo and black hairy tongue are also discussed. Determining the significance of mucosal pigmented lesions may represent a diagnostic challenge for clinicians. Biopsy is indicated whenever the source of pigmentation cannot be definitively identified based on the clinical presentation.
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Doenças da Boca/patologia , Mucosa Bucal/patologia , Transtornos da Pigmentação/patologia , Pigmentação , HumanosRESUMO
Mycosis fungoides (MF) and Sézary syndrome are clonal T-cell proliferations that exhibit skin homing and represent the majority of cutaneous T-cell lymphomas. Early MF is a diagnostic challenge as both the clinical and microscopic features often mimic benign inflammatory conditions. Oral MF is very rare and has been associated in the past with advanced disease and a poor prognosis. Skin lesions are present for an average of > 6 years before oral involvement occurs. The clinical appearance is highly variable with tongue, palate and gingiva most often affected. We report 3 additional cases of oral MF, including one in which oral lesions are the initial disease presentation. Survival in patients presenting with oral MF is improving and can be attributed to advances in therapy.
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Neoplasias Bucais/patologia , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Squamous papillomas are exophytic proliferations of surface oral epithelium. Human papillomavirus (HPV) infection is widely accepted as the etiology of squamous papillomas however the virus cannot be detected in a significant percentage of lesions. MATERIAL AND METHODS: Using polymerase chain reaction (PCR), we tested 35 formalin-fixed paraffin-embedded (FFPE) squamous papillomas for the presence of HPV DNA. RESULTS: Six papillomas (17%) tested positive for HPV DNA; four contained HPV-6 and two contained HPV-11. Given that ß-globin DNA was only identified in half of the samples, DNA degradation appears to have significantly impacted the results. CONCLUSIONS: The results likely represent an underestimation of the true number of HPV-positive specimens in our study. Potential explanations for HPV-negative squamous papillomas include transient HPV infection, failure of the experiment to detect HPV if present, or the possibility that some lesions may not result from HPV infection. Key words:HPV, PCR, FFPE, papilloma, oral.
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PURPOSE: Cisplatin resistance remains a barrier to organ-sparing and survival of patients with advanced head and neck squamous cell carcinoma (HNSCC). Targeted therapies to overcome cisplatin-resistant HNSCC are being developed. METHODS AND MATERIALS: Cisplatin-sensitive parental HNSCC cell lines and cisplatin-resistant progeny were studied. Pretreatment HNSCC biopsies were used to construct tissue microarrays which were stained for p53 and Bcl-xL. RESULTS: HNSCC cell lines selected for cisplatin resistance had wild-type p53 and high levels of Bcl-xL. Expression of wild-type p53 in cell lines with low Bcl-xL enhanced cisplatin sensitivity. Expression of both Bcl-xL and wild-type p53 caused tumor cells to become cisplatin resistant. Patients whose tumors expressed low levels of p53 and Bcl-xL enjoyed the best organ preservation and disease-free survival whereas patients whose tumors expressed low levels of p53 and high levels of Bcl-xL had the worst outcome. Novel agents that inhibit Bcl-xL or activate p53 function may target cisplatin-resistant HNSCC. CONCLUSION: Cisplatin resistance in HNSCC is mediated, at least in part, by high Bcl-xL and functional p53.
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Carcinoma de Células Escamosas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas de Neoplasias/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína bcl-X/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Proteínas de Neoplasias/antagonistas & inibidores , Análise Serial de Tecidos/métodos , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína bcl-X/antagonistas & inibidoresRESUMO
Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile.
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Carcinoma de Células Escamosas/terapia , Receptores ErbB/metabolismo , Papillomavirus Humano 16/isolamento & purificação , Neoplasias Orofaríngeas/terapia , Fatores Sexuais , Fumar/efeitos adversos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/virologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: Acellular dermal matrix (ADM) is a cell-free dermal matrix comprised of a structurally integrated basement membrane complex and extracellular matrix in which collagen bundles and elastic fibers are the main components. There are several commercially available ADM allografts that have different processing methods. This case series reports the histologic presentation of two of the most widely used ADM allografts, referred to as ADM-A and ADM-B, in patients that had specific situations involving reentry. CASE SERIES: Two patients referred to the Louisiana State University Department of Periodontics, New Orleans, Louisiana, with 1- to 3-mm recession of at least two non-contiguous sites needing soft tissue augmentation, were treated with appropriate mucogingival procedures using ADM-A or ADM-B. After ≈6 to 8 months of healing, and due to clinical findings that necessitated further periodontal procedures, small tissue biopsies were obtained and examined microscopically. CONCLUSIONS: All samples of ADM (A and B) analyzed after staining with hematoxylin and eosin had a generally similar appearance under light microscopic examination, which suggests they are both well incorporated into native tissues after 6 to 8 months of healing. When stained with Verhoeff-Van Gieson, all samples showed elastin fibers, a finding consistent with previously published light microscopic observations of ADM. There appeared to be a more densely packed elastin pattern in the deep base of ADM-A compared with ADM-B. This might be an indication these two materials have a different healing pathway when used to augment the oral mucosa.
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BACKGROUND: Malignancies involving the bones are metastatic tumors more commonly than primary tumors. In this retrospective study, the authors review metastatic disease in the jaws. METHODS: The authors retrieved cases of metastatic disease in the jaws over a 45-year period from the pathology archives at the University of Michigan School of Dentistry, Ann Arbor, and Indiana University School of Dentistry, Indianapolis. RESULTS: The authors conducted a retrospective analysis of 114 cases of metastatic disease in the jaws and found that approximately 60 percent of subjects had no history of malignancy. The sex distribution was equivalent. Mandibular predilection was more prominent in females than in males. Metastases from the breast were significantly greater than those from the lung and prostate (P < or = .05), the second and third most frequent sites, respectively. Women exhibited twice as many jaw metastases as did men 31 to 40 years of age and significantly fewer metastases than did men 71 to 80 years of age (P < or = .05). CONCLUSION: In the majority of cases, subjects had an undiagnosed primary cancer at the time the metastatic jaw disease presented. The most common site of origin of the primary cancer was the breast, when primary sites were considered independent of sex. CLINICAL IMPLICATIONS: Patients with metastatic disease in the jaws may have innocuous dental symptoms, such as pulpal or periodontal pain; therefore, clinicians will play a significant role in diagnosing the life-threatening disease.
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Neoplasias Maxilomandibulares/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Feminino , Humanos , Neoplasias Maxilomandibulares/diagnóstico , Neoplasias Maxilomandibulares/patologia , Neoplasias Pulmonares/patologia , Masculino , Neoplasias Primárias Desconhecidas , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores SexuaisRESUMO
OBJECTIVE: This study investigated the demographic, clinicopathologic, and histopathologic findings of lesions diagnosed as peripheral giant cell granuloma (PGCG) by the Louisiana State University Oral Pathology Biopsy Service from 1974 to 2011. STUDY DESIGN: Clinical, demographic, and histopathologic evaluation was completed for 279 cases. A follow-up questionnaire was mailed to all surgeons who performed these biopsies from 1990 to 2011. RESULTS: Of the 279 lesions, 58% occurred in the mandible, 44% occurred in the anterior portion of the arches, 83% were adjacent to teeth, 14% occurred in edentulous areas, and 2% were adjacent to implants. Average duration was 10.5 months, and the average size was 12.7 mm. The recurrence rate was 17.5%. Histopathologically, 78% of lesions extended to the base of the specimen, 50% exhibited ulceration, 41% contained calcifications, and 6% exhibited features overlapping with another pathologic entity. CONCLUSIONS: PGCG is a well-defined pathologic entity among reactive gingival lesions. Recurrent lesions were more likely to contain calcifications.
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Doenças da Gengiva/patologia , Granuloma de Células Gigantes/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Feminino , Doenças da Gengiva/epidemiologia , Granuloma de Células Gigantes/epidemiologia , Humanos , Louisiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Optimal treatment for locally advanced squamous cell carcinoma of the oropharynx (SCCOP) is not well defined. Here we retrospectively compare survival and toxicities from 2 different organ preservation protocols. METHODS: The matched dataset consisted of 35 patients from each trial matched for age, stage, smoking, and tumor human papillomavirus (HPV) status. Patients in the University of Michigan Cancer Center (UMCC) trial 9921 were treated with induction chemotherapy (IC) followed by high-dose cisplatin and radiation in responders or surgery in nonresponders. Patients in the UMCC trial 0221 were treated with weekly carboplatin and paclitaxel and radiation. RESULTS: Survival was comparable for both studies and did not differ significantly across each trial after stratifying by HPV status. Grade 3 and 4 toxicities were more frequent in UMCC 9921. At 6 months posttreatment, gastrostomy tube (G-tube) dependence was not statistically different. CONCLUSION: These data suggest that survival outcomes in patients with locally advanced SCCOP are not compromised with weekly chemotherapy and radiation therapy, and such treatment is generally more tolerable.
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Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Papillomavirus Humano 6/isolamento & purificação , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Terapia Combinada , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Preservação de Órgãos , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Paclitaxel/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Pulsoterapia/métodos , Radioterapia de Alta Energia/métodos , Medição de Risco , Testes Sorológicos , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The current American Joint Committee on Cancer (AJCC) staging system may not accurately reflect survival in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to develop a system that more precisely predicts survival. METHODS: CT scans from 156 patients who underwent chemoradiation for advanced-stage oropharyngeal SCC with >2 years follow-up were reviewed. We modeled patterns of nodal metastasis associated with different survival rates. We defined HPV+ N1 as a single node <6 cm, ipsilaterally, contralaterally, or bilaterally. HPV+ N2 was defined as a single node ≥6 cm or ≥2 nodes ipsilaterally/contralaterally or ≥3 nodes bilaterally. HPV+ N3 was defined as matted nodes. RESULTS: There was no significant difference in disease-specific survival (DSS; p = .14) or overall survival (OS; p = .16) by AJCC classification. In patients grouped by HPV+ N1, HPV+ N2, and HPV+ N3 nodal classification, significant differences in DSS (100%, 92%, and 55%, respectively; p = .0001) and OS (100%, 96%, and 55%, respectively; p = .0001) were found. CONCLUSION: A staging system with reclassification of size, bilaterality, and matted nodes more accurately reflects survival differences in this cohort of patients. Review of the AJCC staging system with these criteria should be considered for HPV-positive oropharyngeal SCC.
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Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Linfonodos/patologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neoplasias Orofaríngeas/virologia , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVES/HYPOTHESIS: To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial. STUDY DESIGN: Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers, and correlations with outcome were determined. METHODS: Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers. RESULTS: Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (P = 0.0003). CONCLUSIONS: Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer.
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Biomarcadores Tumorais/análise , Neoplasias Laríngeas/química , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: Because well-documented cases of mucoepidermoid carcinomas that are of minor salivary gland origin and occur in children and adolescents have rarely been reported, little information regarding their clinical features and biologic behavior is available. This case report represents a retrospective clinical analysis of five minor salivary gland mucoepidermoid carcinomas accessioned from a 35-year period at the Louisiana State University School of Dentistry and combines the data with 15 well-documented cases from the English language literature. CASE PRESENTATION: The five mucoepidermoid carcinomas in patients from birth to 19 years of age accounted for 1.3% of the accessioned minor salivary gland neoplasms. There were an additional 15 well-documented cases in the literature. Combining the data for the 20 mucoepidermoid carcinomas resulted in a mean age of 13.5 years and a 2.3:1 female-to-male ratio. Collectively, the hard palate, soft palate, and hard palate/soft palate junction accounted for 85% of the cases. Thirty-five percent of the cases presented as a fluctuant submucosal swelling with surface color alterations. The average duration was five months, and bone involvement occurred in seven cases. A histologic grade of low to intermediate predominated (95%). Surgical removal was the treatment in all cases. Thirteen cases had adequate follow-up of three years or more, and recurrence was documented in only one case. There were no cases of death or metastasis in this series. CONCLUSIONS: In children and adolescents, mucoepidermoid carcinomas have a female predilection and occur most commonly on the hard or soft palate or both. A fluctuant submucosal lump with a bluish color is a helpful diagnostic clue. The histologic grades of most mucoepidermoid carcinomas in the first and second decades of life are low and, to a lesser degree, intermediate. Complete surgical excision is the treatment of choice and results in a recurrence rate of less than 10%.
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BACKGROUND: Despite better prognosis, there is a group of oropharyngeal squamous cell carcinoma (SCC) human papillomavirus (HPV)+ patients who experience treatment failure and succumb to distant metastasis. METHODS: Seventy-eight previously untreated patients nested in a concurrent chemoradiation protocol were reviewed to correlate patterns of local-regional tumor extent to distant metastasis. Biomarker assessment was: HPV in situ hybridization and epidermal growth factor receptor (EGFR) immunointensity. RESULTS: The 3-year disease-specific survival (DSS) for patients presenting with and without matted nodes was 69% and 94%, respectively (p = .003). Matted nodes were a poor prognostic factor independent of T classification, HPV, EGFR, and smoking status. For patients who were HPV+, 7 of 11 died of distant metastasis and 6 of 7 with distant metastasis had matted nodes. CONCLUSION: Matted nodes are a novel marker of poor prognosis in oropharyngeal SCC independent of established prognostic factors. Matted nodes may identify patients at risk for the development of distant metastasis who could benefit from systemic therapy, whereas patients without matted nodes may be candidates for de-escalation of therapy.
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Carcinoma de Células Escamosas/patologia , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/patologia , Neoplasias Orofaríngeas/patologia , Bromoexina , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/virologia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise Serial de TecidosRESUMO
OBJECTIVES/HYPOTHESIS: Human papillomavirus-16 (HPV-16)-associated carcinoma of the oropharynx has a favorable prognosis. Such patients have elevated CD8+ T-lymphocyte levels that correlate with response to chemotherapy and survival. Tumor-infiltrating lymphocyte (TIL) subpopulations were assessed in pretreatment biopsies from a prospective patient cohort to determine if TIL subsets differed by HPV status, clinical factors, or patient outcome or correlated with peripheral blood T-cell levels. STUDY DESIGN: Retrospective immunological correlative study of patients entered in a prospective Phase 2 clinical trial. METHODS: Measured were CD8, CD4, CD68, and Treg (FoxP3) lymphocytes by immunohistochemistry in a tissue microarray created from patients (n=46) with advanced oropharyngeal cancer. Correlations with peripheral blood levels, HPV status, expression of epidermal growth factor receptor (EGFR), clinical tumor, and patient characteristics and outcome were determined. Median follow-up was 6.6 years. RESULTS: HPV-16-positive patients had improved survival (P=.016). Degree of T-cell infiltration did not differ by HPV status but was significantly related to disease-specific survival (DSS) and overall survival (OS). Even after adjusting for HPV status, we found that CD8, FoxP3, and total T cells were significantly associated with DSS (P=.0236, P=.0040, and P=.0197, respectively) and OS (P=.0137, P=.0158, and P=.0115, respectively). Less T-cell infiltration (P=.0130) and CD4 cells in particular (P=.0792) were associated with higher EGFR expression. CONCLUSIONS: Improved outcomes are associated with increased TILs independent of HPV status and suggest the local immune response may be more related to factors such as tumor size, EGFR expression, or performance status than HPV status. Further study of larger numbers of patients and infiltrates combined with functional analysis of individual subsets may be necessary to detect significant differences in local immunity in HPV-16-related cancers.
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Papillomavirus Humano 16 , Linfócitos do Interstício Tumoral , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos RetrospectivosAssuntos
Eritema/patologia , Doenças Labiais/patologia , Adulto , Diagnóstico Diferencial , Feminino , HumanosRESUMO
The purpose of this work was to determine SEPT9_v1 expression levels in head and neck squamous cell carcinoma (HNSCC) and to analyze whether SEPT9_v1 expression is relevant to clinical outcomes. Recently, the SEPT9 isoform SEPT9_v1 has been implicated in oncogenesis, and methylation of the SEPT9 promoter region was reported in HNSCC. These findings led us to hypothesize that SEPT9_v1 could be differently expressed in HNSCC. To determine whether SEPT9_v1 is expressed in HNSCC, tissue microarray immunohistochemical analysis was performed using a SEPT9_v1-specific antibody. Tissue microarrays stained with a polyclonal SEPT9_v1-specific antibody was used to determine protein expression levels in HNSCC tissue samples, some with known clinical outcomes. This analysis showed that SEPT9_v1 is in fact highly expressed in HNSCC compared with normal epithelium, and high expression levels directly correlated with poor clinical outcomes. Specifically, a high SEPT9_v1 expression was associated with decreased disease-specific survival (P = .012), time to indication of surgery at primary site (P = .008), response to induction chemotherapy (P = .0002), and response to chemotherapy (P = .02), as well as advanced tumor stage (P = .012) and N stage (P = .0014). The expression of SEPT9_v1 was also strongly correlated with smoking status (P = .00094). SEPT9_v1 is highly expressed in HNSCC, and a high expression of SEPT9_v1 is associated with poor clinical outcomes. These data indicate that SEPT9_v1 warrants additional investigation as a potential biomarker for HNSCC.
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OBJECTIVE: to determine whether the favorable outcome associated with human papillomavirus (HPV) 16-positive oropharyngeal cancer is related to a patient's adaptive immunity. SETTING: academic medical center. PATIENTS: forty-seven of 66 previously untreated patients (6 of 20 patients with stage III and 41 of 46 with stage IV cancer) in a prospective clinical trial of chemoradiotherapy. INTERVENTION: all patients were treated with a single course of neoadjuvant chemotherapy followed by either surgery (for nonresponders) or chemoradiotherapy. MAIN OUTCOME MEASURES: pretreatment levels (percentages and absolute counts) of CD3, CD4, CD8, natural killer, and B cells and overall white blood cell counts were measured by flow cytometry. Correlations of subsets with HPV-16 status, tumor subsite, cancer stage, T class, N class, smoking status, performance status, sex, response to chemoradiotherapy, p53 mutation type, epidermal growth factor receptor expression, and disease-specific and overall survival were determined. RESULTS: after a median follow-up of 6.6 years, improved survival was associated with an elevated percentage of CD8 cells (P = .04), a low CD4:CD8 ratio (P = .01), low epidermal growth factor receptor expression (P = .002), and HPV status (P = .02). The percentage of CD8 cells was significantly higher (P = .04) and the CD4:CD8 ratio was significantly lower (P = .02) in HPV-16-positive patients. A higher percentage of CD8 cells was associated with response to induction chemotherapy (P = .02) and complete tumor response after chemoradiotherapy (P = .045). CONCLUSION: these findings confirm previous correlations of outcome with circulating CD8 cell levels and support the conjecture that improved adaptive immunity may play a role in the favorable prognosis of patients with HPV-16-positive cancers.