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1.
J Low Genit Tract Dis ; 26(2): 156-163, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35067584

RESUMEN

OBJECTIVE: The aim of this second article was to complete part 1 review of nonsquamous lesions of the vulvar skin and subcutaneous tissue (Journal of Lower Genital Tract Disease, 2021), clinically and pathologically, based on the fifth edition of the World Health Organization tumor classification. MATERIALS AND METHODS: A database search of PubMed and Google Scholar was performed between 1970 and 2021, using the search terms "vulva," "lower genital tract," and "non-squamous lesions." The search was limited to "human gynecological pathology." Full article texts were reviewed, and reference lists were screened for additional articles. We excluded abstracts and articles written in the non-English language. RESULTS: An initial list of 400 articles was identified. Thirty-seven articles discussed clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue. CONCLUSIONS: Clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue as categorized by the updated World Health Organization classification are presented.


Asunto(s)
Tejido Subcutáneo , Neoplasias de la Vulva , Femenino , Humanos , Tejido Subcutáneo/patología , Vulva/patología , Neoplasias de la Vulva/patología
2.
Genes Dev ; 27(13): 1447-61, 2013 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-23824538

RESUMEN

Macroautophagy (autophagy hereafter) degrades and recycles proteins and organelles to support metabolism and survival in starvation. Oncogenic Ras up-regulates autophagy, and Ras-transformed cell lines require autophagy for mitochondrial function, stress survival, and engrafted tumor growth. Here, the essential autophagy gene autophagy-related-7 (atg7) was deleted concurrently with K-ras(G12D) activation in mouse models for non-small-cell lung cancer (NSCLC). atg7-deficient tumors accumulated dysfunctional mitochondria and prematurely induced p53 and proliferative arrest, which reduced tumor burden that was partly relieved by p53 deletion. atg7 loss altered tumor fate from adenomas and carcinomas to oncocytomas-rare, predominantly benign tumors characterized by the accumulation of defective mitochondria. Surprisingly, lipid accumulation occurred in atg7-deficient tumors only when p53 was deleted. atg7- and p53-deficient tumor-derived cell lines (TDCLs) had compromised starvation survival and formed lipidic cysts instead of tumors, suggesting defective utilization of lipid stores. atg7 deficiency reduced fatty acid oxidation (FAO) and increased sensitivity to FAO inhibition, indicating that with p53 loss, Ras-driven tumors require autophagy for mitochondrial function and lipid catabolism. Thus, autophagy is required for carcinoma fate, and autophagy defects may be a molecular basis for the occurrence of oncocytomas. Moreover, cancers require autophagy for distinct roles in metabolism that are oncogene- and tumor suppressor gene-specific.


Asunto(s)
Adenoma Oxifílico/fisiopatología , Autofagia , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Genes ras/fisiología , Metabolismo de los Lípidos , Neoplasias Pulmonares/fisiopatología , Animales , Línea Celular Tumoral , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Genes p53/genética , Homeostasis , Longevidad/genética , Ratones , Mitocondrias/patología , Células Tumorales Cultivadas
3.
Lancet Oncol ; 18(12): 1610-1623, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29129443

RESUMEN

BACKGROUND: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC. METHODS: We did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805. FINDINGS: Between June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment. INTERPRETATION: Addition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC. FUNDING: National Cancer Institute of the National Institutes of Health.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Selección de Paciente , Neumonectomía/métodos , Análisis de Supervivencia , Resultado del Tratamiento
4.
Lancet Oncol ; 17(12): 1661-1671, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27825638

RESUMEN

BACKGROUND: Erlotinib is approved for the treatment of all patients with advanced non-small-cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We compared the efficacy of cabozantinib alone or in combination with erlotinib versus erlotinib alone in patients with EGFR wild-type NSCLC. METHODS: This three group, randomised, controlled, open-label, multicentre, phase 2 trial was done in 37 academic and community oncology practices in the USA. Patients were eligible if they had received one or two previous treatments for advanced non-squamous, EGFR wild-type, NSCLC. Patients were stratified by performance status and line of therapy, and randomly assigned using permuted blocks within strata to receive open-label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was done every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single-drug group to receive combination treatment. The primary endpoint was to compare progression-free survival in patients given erlotinib alone versus cabozantinib alone, and in patients given erlotinib alone versus the combination of erlotinib plus cabozantinib. We assessed the primary endpoint in the per-protocol population, which was defined as all patients who were eligible, randomly assigned, and received at least one dose of treatment. The safety analysis population included all patients who received study treatment irrespective of eligibility. This trial is registered with ClinicalTrials.gov, number NCT01708954. FINDINGS: Between Feb 7, 2013, and July 1, 2014, we enrolled and randomly assigned 42 patients to erlotinib treatment, 40 patients to cabozantinib treatment, and 43 patients to erlotinib plus cabozantinib treatment, of whom 111 (89%) in total were included in the primary analysis (erlotinib [n=38], cabozantinib [n=38], erlotinib plus cabozantinib [n=35]). Compared with erlotinib alone (median 1·8 months [95% CI 1·7-2·2]), progression-free survival was significantly improved in the cabozantinib group (4·3 months [3·6-7·4]; hazard ratio [HR] 0·39, 80% CI 0·27-0·55; one-sided p=0·0003) and in the erlotinib plus cabozantinib group (4·7 months [2·4-7·4]; HR 0·37, 0·25-0·53; one-sided p=0·0003). Among participants included in the safety analysis of the erlotinib (n=40), cabozantinib (n=40), and erlotinib plus cabozantinib (n=39) groups, the most common grade 3 or 4 adverse events were diarrhoea (three [8%] cases in the erlotinib group vs three [8%] in the cabozantinib group vs 11 [28%] in the erlotinib plus cabozantinib group), hypertension (none vs ten [25%] vs one [3%]), fatigue (five [13%] vs six [15%] vs six [15%]), oral mucositis (none vs four [10%] vs one [3%]), and thromboembolic event (none vs three [8%] vs two [5%]). One death due to respiratory failure occurred in the cabozantinib group, deemed possibly related to either drug, and one death due to pneumonitis occurred in the erlotinib plus cabozantinib group, deemed related to either drug or the combination. INTERPRETATION: Despite its small sample size, this trial showed that, in patients with EGFR wild-type NSCLC, cabozantinib alone or combined with erlotinib has clinically meaningful, superior efficacy to that of erlotinib alone, with additional toxicity that was generally manageable. Cabozantinib-based regimens are promising for further investigation in this patient population. FUNDING: ECOG-ACRIN Cancer Research Group, National Cancer Institute of the National Institutes of Health.


Asunto(s)
Anilidas/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Clorhidrato de Erlotinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Anciano , Anilidas/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Receptores ErbB/genética , Clorhidrato de Erlotinib/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-met/análisis , Piridinas/administración & dosificación
5.
J Low Genit Tract Dis ; 17(4): e5-7, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23609586

RESUMEN

OBJECTIVE: The study aimed to report the case of a patient with a polypoid vulvar lesion clinically thought to be an aggressive angiomyxoma. MATERIALS AND METHODS: On examination, a 4.0 × 2.0 × 1.5-cm polypoid lesion was seen on the right labium majus. RESULTS: Histopathological findings of the excised mass were consistent with pseudoangiomatous stromal hyperplasia of the vulva CONCLUSIONS: Pseudoangiomatous stromal hyperplasia is a lesion of breast tissue but can occur in anogenital mammary-like glands. It must be distinguished from low-grade angiosarcoma.


Asunto(s)
Angiomatosis/diagnóstico , Enfermedades de la Mama/diagnóstico , Hiperplasia/diagnóstico , Pólipos/diagnóstico , Vulva/patología , Enfermedades de la Vulva/diagnóstico , Diagnóstico Diferencial , Femenino , Histocitoquímica , Humanos , Microscopía , Persona de Mediana Edad , Mixoma/diagnóstico
6.
Int J Surg Pathol ; 30(7): 789-791, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35234082

RESUMEN

Carcinomas metastatic to the brain are common, however, metastatic disease to the hypothalamic- pituitary region is uncommon and account for less than 3.6% of all resected malignant pituitary tumors. Most metastatic disease in that region derives from a lung or breast primary, with both ductal and lobular carcinoma reported. We report what we believe is the first case of pleomorphic lobular carcinoma metastatic to the hypothalamus. This case is also reaffirms that late metastasis from breast cancer should be considered in the differential diagnosis. It is important for the clinician to consider the clinical history of breast cancer, even when remote, in the differential diagnosis.


Asunto(s)
Neoplasias de la Mama , Carcinoma Lobular , Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Carcinoma Lobular/patología , Diagnóstico Diferencial , Femenino , Humanos , Hipotálamo/patología
7.
J Histochem Cytochem ; 56(4): 347-58, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18071065

RESUMEN

Fibroblasts are critical for tissue homeostasis, and their inappropriate proliferation and activation can result in common and debilitating conditions including fibrosis and cancer. We currently have a poor understanding of the mechanisms that control the growth and activation of fibroblasts in vivo, in part because of a lack of suitable fibroblast markers. We have taken advantage of an antibody previously shown to stain stromal cells in frozen tissues (TE-7) and identified conditions in which it can be used to stain fibroblasts and myofibroblasts in the paraffin-embedded tissue samples routinely collected for pathological analysis. We show that this antibody recognizes growing and quiescent fibroblasts and myofibroblasts by immunohistochemistry, immunofluorescence, and ELISA assays. We also present its staining patterns in normal tissue samples and in breast tumors.


Asunto(s)
Fibroblastos/citología , Especificidad de Anticuerpos , Neoplasias de la Mama/patología , Células del Tejido Conectivo/citología , Vasos Coronarios/citología , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibroblastos/metabolismo , Fijadores , Formaldehído , Humanos , Inmunohistoquímica , Músculo Esquelético/irrigación sanguínea , Adhesión en Parafina , Piel/citología , Células del Estroma/citología , Timo/citología
8.
J Thorac Oncol ; 12(2): 334-346, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27998793

RESUMEN

INTRODUCTION: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise κ scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC. METHODS: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3). RESULTS: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, κ scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64. CONCLUSIONS: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Neuroendocrino/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Diagnóstico Diferencial , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Adenocarcinoma/clasificación , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Carcinoma Neuroendocrino/clasificación , Carcinoma Neuroendocrino/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/clasificación , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Humanos , Técnicas para Inmunoenzimas , Agencias Internacionales , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/metabolismo , Estadificación de Neoplasias , Pronóstico , Reproducibilidad de los Resultados , Carcinoma Pulmonar de Células Pequeñas/clasificación , Carcinoma Pulmonar de Células Pequeñas/metabolismo
9.
Diagn Cytopathol ; 34(10): 704-6, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16955479

RESUMEN

Rhabdomyosarcoma is the most common childhood sarcoma that occurs in the soft tissues of the head and neck, genitourinary system, and extremities. While this tumor may also be seen in young adults, it is distinctly unusual to see this neoplasm beyond the fifth decade. The use of fluorescence in situ hybridization (FISH) probes on fine-needle aspiration material for chromosomal analysis to detect chromosomal translocations are not well established. Herein we present a case of metastatic alveolar rhabdomyosarcoma originating in the nasal sinus and recurring in the neck of an adult man 5 yr after his initial presentation. The ThinPrep smear demonstrated isolated malignant tumor cells similar to his previous histologic material. The cytologic findings of alveolar rhabdomyosarcoma were confirmed utilizing a dual color break apart FISH probe which identified the FKHR translocation on the cytospin preparation prepared from a ThinPrep vial and processed as a cytospin preparation. In addition to routine and immunocytologic staining, we demonstrate that aspirated tumor cells can be analyzed using a FISH probe to identify specific chromosomal abnormalities.


Asunto(s)
Factores de Transcripción Forkhead/genética , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/genética , Rabdomiosarcoma Alveolar/diagnóstico , Rabdomiosarcoma Alveolar/genética , Translocación Genética/genética , Biopsia con Aguja Fina/métodos , Cromosomas Humanos Par 13/genética , Citodiagnóstico/métodos , ADN de Neoplasias/genética , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Reordenamiento Génico/genética , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Hibridación Fluorescente in Situ/métodos , Masculino , Persona de Mediana Edad , Rabdomiosarcoma Alveolar/metabolismo
10.
Radiol Case Rep ; 11(4): 430-433, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27920874

RESUMEN

Leiomyoma of deep soft tissue is an unusual entity reported in less than 60 cases in the English literature. The lesion is now accepted as a rare neoplasm. Leiomyomata of deep soft tissue have been divided into 2 groups, those occurring primarily in women in the retroperitoneum, histologically similar to leiomyomata of the uterus, and those occurring equally in both sexes in the somatic deep soft tissues. Irrespective of location, these lesions can demonstrate calcification, and even less commonly ossification. We report a unique case of a leiomyoma of deep soft tissue that mimicked the clinical and radiographic features of calcific myonecrosis, also a rare mass forming soft-tissue lesion. Clinical and radiographic information are often critical in the diagnosis of soft-tissue lesions; however, this case demonstrates that a lesion can deviate from the standard clinical and radiographic interpretations most commonly attributed to it.

11.
J Clin Oncol ; 22(2): 293-9, 2004 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-14722038

RESUMEN

PURPOSE: To determine the objective response rate, duration of remission and toxicity of octreotide alone or with the later addition of prednisone in patients with unresectable, advanced thymic malignancies in whom the pretreatment octreotide scan was positive. PATIENTS AND METHODS: Forty-two patients with advanced thymoma or thymic carcinoma were entered onto the trial, of whom 38 were fully assessable (one patient had inconclusive histology; three patients had negative octreotide scan). Patients received octreotide 0.5 mg subcutaneously tid. At 2 months, patients were evaluated. Responding patients continued to receive octreotide alone; patients with progressive disease were removed from the study. All others received prednisone 0.6 mg/kg orally qid for a maximum of 1 year. RESULTS: Two complete (5.3%) and 10 partial responses (25%) were observed (four partial responses with octreotide alone; the remainder with octreotide plus prednisone). None of the six patients without pure thymoma responded. The 1- and 2-year survival rates were 86.6% and 75.7%, respectively. Patients with an Eastern Cooperative Oncology Group performance status of 0 lived significantly longer than did those with a performance status of 1 (P =.031). CONCLUSION: Octreotide alone has modest activity in patients with octreotide scan-positive thymoma. Prednisone improves the overall response rate but is associated with increased toxicity. Additional studies with the agent are warranted.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Octreótido/uso terapéutico , Prednisona/uso terapéutico , Timoma/tratamiento farmacológico , Neoplasias del Timo/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/farmacología , Carcinoma/patología , Femenino , Estado de Salud , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Octreótido/administración & dosificación , Octreótido/farmacología , Prednisona/administración & dosificación , Prednisona/farmacología , Análisis de Supervivencia , Timoma/patología , Neoplasias del Timo/patología , Resultado del Tratamiento
12.
J Clin Oncol ; 29(15): 2060-5, 2011 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-21502559

RESUMEN

PURPOSE: The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. PATIENTS AND METHODS: We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. RESULTS: From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. CONCLUSION: Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carcinoma/tratamiento farmacológico , Paclitaxel/administración & dosificación , Timoma/tratamiento farmacológico , Neoplasias del Timo/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad
13.
J Clin Oncol ; 29(13): 1709-14, 2011 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-21422434

RESUMEN

PURPOSE: Inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase have demonstrated modest anticancer activity in advanced bronchioloalveolar carcinoma (BAC). We conducted a phase II study to evaluate cetuximab for the treatment of advanced BAC. PATIENTS AND METHODS: Patients with advanced-stage pure BAC or adenocarcinoma with BAC features, fewer than two prior chemotherapy regimens, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 were eligible. Those with prior EGFR inhibitor therapy were excluded. Cetuximab was given as a weekly intravenous infusion at 250 mg/m(2) after an initial loading dose of 400 mg/m(2) in week 1. The primary end point was determination of response rate. EGFR and KRAS mutations were evaluated by pyrosequencing. RESULTS: Seventy-two patients were enrolled and 68 met eligibility requirements. Characteristics of patients included median age, 71 years; sex, 57% females; PS 0 or 1, 88% of patients; and smoking status, 19% never-smokers. Central pathology review confirmed the diagnosis in 45 of 49 available specimens. Approximately 50% of patients received more than two cycles of therapy (> 8 weeks). Skin rash was the most common toxicity (grade 3, 15%). The confirmed response rate was 7%, and stable disease was observed in 35%. The median survival and progression-free survival were 13 and 3.3 months, respectively. Only one of the six patients with an EGFR mutation and one of the seven patients with a KRAS mutation had a partial response. CONCLUSION: Cetuximab was associated with modest efficacy in patients with advanced BAC, despite a low response rate. EGFR and KRAS mutations were not predictive of response to cetuximab.


Asunto(s)
Adenocarcinoma Bronquioloalveolar/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma Bronquioloalveolar/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Cetuximab , Femenino , Proteínas Fluorescentes Verdes/antagonistas & inhibidores , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad
14.
J Thorac Oncol ; 5(6): 885-92, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20421818

RESUMEN

BACKGROUND: Advanced or recurrent nonresectable thymic epithelial tumors show only a modest response to standard chemotherapy. A recent study using octreotide and prednisone in thymic tumors, Eastern Cooperative Oncology Group study E1C97, was conducted to verify the activity of octreotide for thymic tumors. The aim of this study was to determine whether epidermal growth factor receptor (EGFR) immunoreactivity correlated with outcomes and to identify new biologic markers for potential targeted therapy. Three markers, EGFR, C-kit, and Her2/neu, were selected for evaluation in patients with advanced thymic epithelial tumors treated on E1C97. METHODS: Of the 42 patients entered onto E1C97, 34 patients (World Health Organization [WHO] categories: type A = 1, type AB = 1, type B1 = 10, type B2 = 11 type B3 = 8, and type C = 3) had sufficient tissue available for immunohistologic study. Each tumor was assessed to have 0, 1+, 2+, or 3+ immunoreactivity in the cytoplasm or membranes of the neoplastic cells for Her2/neu and EGFR and for the presence or absence of C-kit immunoreactivity. RESULTS: EGFR immunoreactivity of 2+ or 3+ was associated with more aggressive thymic tumors (WHO types B2 and B3). However, strong EGFR immunoreactivity was not consistently seen with thymic carcinoma. The presence of EGFR within cells was associated with a significantly improved progression-free survival (PFS) and a trend for overall survival (OS). Twelve patients demonstrated C-kit immunoreactivity; the lack of C-kit immunoreactivity was significantly associated with superior PFS but not OS. Her2/neu immunoreactivity was uniformly negative for all tumors evaluated. There was no association between response and biomarker status. CONCLUSIONS: High EGFR immunoreactivity is seen in more aggressive thymic neoplasms as classified according to the 2004 WHO, but regardless of classification, the presence of EGFR in tumor cells (1+, 2+, and 3+) is associated with improved performance free survival (PFS) and a trend for better OS. In contrast, the absence of C-kit immunoreactivity was associated with improved PFS. These data suggest that EGFR and C-kit may be prognostic, and further studies of these markers in subcategories of thymic malignancies is warranted.


Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Receptores ErbB/análisis , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Octreótido/administración & dosificación , Prednisona/administración & dosificación , Proteínas Proto-Oncogénicas c-kit/análisis , Receptor ErbB-2/análisis , Neoplasias del Timo/tratamiento farmacológico , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/química , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias del Timo/química , Neoplasias del Timo/mortalidad , Neoplasias del Timo/patología , Organización Mundial de la Salud
15.
Skeletal Radiol ; 37(11): 1047-51, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18594808

RESUMEN

Alveolar soft part sarcoma is a rare soft tissue tumor typically affecting young adults. These tumors are most often seen in the deep soft tissues of the extremities and patients generally present with advanced disease. Primary bone involvement is extremely rare and has only been reported in seven cases. This is the first case of alveolar soft part sarcoma in bone documenting the ASPL-TFE3 gene product. Herein, we report a rare presentation of alveolar soft part sarcoma presenting as a primary bone neoplasm involving the proximal fibula in a 41-year-old woman.


Asunto(s)
Peroné/patología , Sarcoma de Parte Blanda Alveolar/diagnóstico , Adulto , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Diagnóstico Diferencial , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Imagen por Resonancia Magnética , Proteínas de Fusión Oncogénica , Sarcoma de Parte Blanda Alveolar/patología , Tomografía Computarizada por Rayos X
16.
Ann Diagn Pathol ; 8(6): 352-7, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15614740

RESUMEN

Liposarcomas of the head and neck region are rare; only a few cases have been reported to arise in the cheek or buccal mucosa. Dedifferentiated liposarcoma has rarely been reported in the head and neck region and, to the best of our knowledge, this is the first reported case of dedifferentiated liposarcoma of the cheek. Dedifferentiated liposarcoma is a mixed histologic subtype defined by the association of an atypical lipomatous tumor or well-differentiated liposarcoma and a nonlipogenic sarcoma. The patient was a 61-year-old man who presented with a soft-tissue mass of the left cheek and a presumptive diagnosis of salivary neoplasm based on a fine needle aspiration. The tumor was excised and consisted histologically of an atypical lipomatous tumor/well-differentiated liposarcoma composed a well-differentiated lipomatous neoplasm with atypical cells and rare lipoblasts. The tumor recurred in the same location 5 months after surgery. The recurrent tumor was primarily composed of a nonlipogenic spindle sarcoma with focal rhabdomyoblastic differentiation associated with areas of an atypical lipomatous tumor/well-differentiated liposarcoma.


Asunto(s)
Mejilla/patología , Neoplasias Faciales/patología , Liposarcoma/patología , Biomarcadores de Tumor/análisis , Biopsia con Aguja Fina , Mejilla/cirugía , Diagnóstico Diferencial , Neoplasias Faciales/química , Neoplasias Faciales/cirugía , Humanos , Técnicas para Inmunoenzimas , Liposarcoma/química , Liposarcoma/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias de las Glándulas Salivales/patología , Resultado del Tratamiento
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