RESUMEN
Solitary endobronchial papillomas (SEPs) are rare benign tumors of the lung, seldom transform to malignancy. This tumor had been reported occasionally manifest like carcinomas histologically. Herein we report 2 cases of SEPs; one is a squamous cell papilloma providing a false impression of interstitial micro-invasion. The other is a mixed squamous cell and glandular papilloma with massive lipid pneumonia gross appearance, and focally resembles adenocarcinoma with lepidic-like pattern on histological examination. A review of associated literatures was provided.
Asunto(s)
Adenocarcinoma/patología , Transformación Celular Neoplásica/patología , Errores Diagnósticos , Neoplasias Pulmonares/patología , Papiloma/patología , Nódulo Pulmonar Solitario/patología , Adenocarcinoma/química , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón , Anciano , Biomarcadores de Tumor/análisis , Biopsia , Transformación Celular Neoplásica/química , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/química , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Papiloma/química , Papiloma/cirugía , Valor Predictivo de las Pruebas , Nódulo Pulmonar Solitario/química , Nódulo Pulmonar Solitario/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra- and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low- to high-grade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, ß-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P=0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenoma-carcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.
Asunto(s)
Neoplasias de los Conductos Biliares/química , Neoplasias de los Conductos Biliares/genética , Biomarcadores de Tumor , Carcinoma in Situ/química , Carcinoma in Situ/genética , Carcinoma Intraductal no Infiltrante/química , Carcinoma Intraductal no Infiltrante/genética , Papiloma/química , Papiloma/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/química , Conductos Biliares Intrahepáticos/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Carcinoma Intraductal no Infiltrante/mortalidad , Carcinoma Intraductal no Infiltrante/patología , Colangiocarcinoma/química , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Análisis Mutacional de ADN , Progresión de la Enfermedad , Europa (Continente) , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Invasividad Neoplásica , Papiloma/mortalidad , Papiloma/patología , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Transducción de Señal , Factores de Tiempo , Proteína p53 Supresora de Tumor/análisis , Proteínas ras/genéticaRESUMEN
Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is exceedingly rare, with only 18 cases reported in the literature. Herein, we report a case of mixed papilloma and its associated immunohistochemical and positron emission tomographic (PET) findings. A 60-year-old Japanese male with a smoking history of 40 pack-years presented with a smooth-edged pulmonary lesion in the right S5 segment on computed tomography (CT). F18-fluorodeoxyglucose (FDG) PET revealed abnormally increased FDG uptake in the mass (maximum standardized uptake value, 3.4). We performed right middle lobectomy and combined partial resection of the S8 segment. The 1.8-cm tumor that filled the enlarged lumen of the B5b was histologically diagnosed as mixed papilloma. Immunohistochemically, the pseudostratified columnar epithelium was positive for cytokeratin (CK) 5/6 and CK7. p40 positivity was predominant in the basal and squamous cells. Thyroid transcription factor-1 and carcinoembryonic antigen were negative on immunostaining. Malignant features were absent. The postoperative course has been uneventful for 3 months after the surgery. No recurrences were reported after the surgical resection of the mixed papilloma. Therefore, surgical resection may be considered the mainstay of curative treatment.
Asunto(s)
Neoplasias Pulmonares/diagnóstico , Neoplasias Complejas y Mixtas/diagnóstico , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias de Células Escamosas/diagnóstico , Papiloma/diagnóstico , Biomarcadores de Tumor/análisis , Biopsia , Fluorodesoxiglucosa F18 , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/química , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Imagen Multimodal , Neoplasias Complejas y Mixtas/química , Neoplasias Complejas y Mixtas/patología , Neoplasias Complejas y Mixtas/cirugía , Neoplasias Glandulares y Epiteliales/química , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias de Células Escamosas/química , Neoplasias de Células Escamosas/patología , Neoplasias de Células Escamosas/cirugía , Papiloma/química , Papiloma/patología , Papiloma/cirugía , Neumonectomía , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Radiofármacos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate clinicopathologically and immunohistochemically a spectrum of conjunctival squamous proliferations. DESIGN: Retrospective clinicopathologic study. METHODS: One large cell acanthoma, 7 epidermoid dysplasias, and 4 squamous papillomas were evaluated with microscopy and biomarkers Ki-67, p53, epithelial membrane antigen (EMA), Ber-EP4, AE1, AE3, and 8 individual cytokeratins. Normal associated conjunctiva served as a baseline for interpretation. RESULTS: The large cell acanthoma recurred 4 times but retained its benign histopathologic features. The cells were 2-3 times larger than the keratinocytes of the normal conjunctiva and did not display atypia. Immunohistochemistry revealed a low Ki-67 proliferation index (PI) in the large cell acanthoma compared with high indices in dysplasias and papillomas. p53 was negative in the nuclei of normal epithelium while positive in all neoplasms, most intensely in the dysplasias. Immunostaining showed similar staining patterns for cytokeratins in large cell acanthoma and normal conjunctiva, except for full-thickness CK14 positivity and CK7 negativity in the lesion. Dysplasias generally lost normal CK7 expression and frequently abnormally expressed CK17. The papillomas displayed a normal cytokeratin pattern but exhibited a higher than normal PI and weak p53 positivity. CONCLUSIONS: Conjunctival large cell acanthoma is a morphologically distinctive clonal entity with clinical and immunohistochemical phenotypic characteristics denoting a dysplasia of minimal severity. Because of recurrences without invasion, it requires treatment. Dysplasias exhibited more deviant biomarker abnormalities including frequent aberrant full-thickness CK17 positivity and CK7 negativity. The absence of major cytokeratin derangements in the squamous papillomas may be of ancillary diagnostic value for lesions displaying borderline cytologic features.
Asunto(s)
Acantoma/patología , Biomarcadores de Tumor/análisis , Carcinoma in Situ/patología , Neoplasias de la Conjuntiva/química , Neoplasias de la Conjuntiva/patología , Papiloma/patología , Acantoma/química , Acantoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/análisis , Carcinoma in Situ/química , Carcinoma in Situ/cirugía , Neoplasias de la Conjuntiva/cirugía , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Recurrencia Local de Neoplasia/diagnóstico , Papiloma/química , Papiloma/cirugía , Adhesión en Parafina , Estudios RetrospectivosRESUMEN
BACKGROUND: To evaluate the expression levels of cyclin D1 in breast papillomas and papillary carcinomas, and to analyze the types of cells that co-express cyclin D1 with cytokeratin 5/6 (CK 5/6) or with cytokeratin 8/18(CK 8/18). METHODS: Fifty-nine cases of papillary lesions including 36 papillomas and 23 intracystic papillary carcinomas were examined. Cyclin D1, CK 5/6 and CK 8/18 expression levels were evaluated by double immunostaining. RESULTS: Cyclin D1 is highly expressed in papillary carcinomas (27.54% ± 15.43%) compared with papillomas (8.81% ± 8.41%, p < 0.01). Cyclin D1 is predominantly expressed in cytokeratin 8/18- expressing cells, rather than in cytokeratin 5/6-expressing cells, regardless of the type of lesion. In papillomas, cyclin D1 exhibited a mean 11.42% (11.42% ± 10.17%) co-expression rate with cytokeratin 8/18 compared with a mean 2.50% (2.50% ± 3.24%) co-expression rate with cytokeratin 5/6 (p < 0.01). In papillary carcinomas, cyclin D1 exhibited a mean 34.74% (34.74% ± 16.32%) co-expression rate with cytokeratin 8/18 compared with a co-expression rate of 0.70% (0.70% ± 0.93%) with cytokeratin 5/6 (p < 0.01). CONCLUSIONS: The increase in cyclin D1 suggests an association of cyclin D1 staining with papillary carcinomas. Although cyclin D1 is an effective marker for the differential diagnosis of other papillary lesions, it cannot be used to distinguish between papilloma and papillary carcinoma lesions because its expression occurs in both lesions. Our results show that cyclin D1 and CK 5/6 staining could be used in concert to distinguish between the diagnosis of papilloma (cyclin D1 < 4.20%, CK 5/6 positive) or papillary carcinoma (cyclin D1 > 37.00%, CK 5/6 negative). In addition, our data suggest that cyclin D1 is expressed only in the cancer stem or progenitor cells that co-immunostained with CK 8/18 in papillary carcinomas, and predominantly with CK 8/18 in the papillomas. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7299340558756848.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Carcinoma Papilar/química , Ciclina D1/análisis , Queratina-18/análisis , Queratina-5/análisis , Queratina-6/análisis , Queratina-8/análisis , Papiloma/química , Adolescente , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Papilar/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Papiloma/patología , Adulto JovenRESUMEN
Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma. IPNBs are mainly found in patients from Far Eastern areas, where hepatolithiasis and clonorchiasis are endemic. According to the immunohistochemical profiles of the mucin core proteins, IPNBs are classified into four types: pancreaticobiliary, intestinal, gastric, and oncocytic. Approximately 40%-80% of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma, suggesting that IPNB is a disease with high potential for malignancy. It is difficult to make an accurate preoperative diagnosis because of IPNB's low incidence and the lack of specificity in its clinical manifestation. The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation. Simultaneous proximal and distal bile duct dilation can be detected in some cases, which has diagnostic significance. Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions. However, pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion. Surgical resection is the major treatment. Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved. Staging, histologic subtype, curative resection and lymph node metastasis are factors affecting long-term survival.
Asunto(s)
Adenocarcinoma Mucinoso/patología , Neoplasias de los Conductos Biliares/patología , Conductos Biliares/patología , Carcinoma Papilar/patología , Papiloma/patología , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/cirugía , Neoplasias de los Conductos Biliares/química , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares/química , Conductos Biliares/cirugía , Procedimientos Quirúrgicos del Sistema Biliar , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma Papilar/química , Carcinoma Papilar/mortalidad , Carcinoma Papilar/cirugía , Diagnóstico Diferencial , Diagnóstico por Imagen/métodos , Dilatación Patológica , Endoscopía del Sistema Digestivo , Humanos , Invasividad Neoplásica , Estadificación de Neoplasias , Papiloma/química , Papiloma/mortalidad , Papiloma/cirugía , Valor Predictivo de las Pruebas , Factores de Riesgo , Resultado del TratamientoRESUMEN
La infección persistente por ciertos tipos de alto riesgo oncogénico de virus papiloma humano (VPHAR) es el principal factor de riesgo para el desarrollo de cáncer de cuello uterino y sus lesiones precursoras. Los VPHAR inducen alteraciones moleculares durante todo el proceso de carcinogénesis cervical, que provocan la acumulación de errores genéticos, con la consecuente inestabilidad genética y transformación maligna. Estas alteraciones son producidas por la acción directa de las oncoproteínas virales E6 y E7 sobre las principales proteínas celulares supresoras de tumor, p53 y pRb, respectivamente, y pueden ser monitoreadas durante el surgimiento de la lesión neoplásica, mediante el uso de biomarcadores. En este artículo se revisan las últimas tendencias sobre el uso del estudio inmunocitoquímico, como una prueba complementaria a la citología y a la detección y tipificación de VPHAR en la evaluación de la expresión de biomarcadores como la proteína inhibidora de la proliferación celular p16INK4a, marcador único o combinada con otros biomarcadores, que puedan contribuir eficazmente en la detección de las pacientes con mayor riesgo a desarrollar neoplasia del cuello uterino asociada a la infección por VPHAR, durante la pesquisa de cáncer de cuello uterino de rutina y en el manejo clínico adecuado y oportuno.
Persistent infection with certain types of high oncogenic risk human papillomavirus (HR-HPV) is the main risk factor for developing cervical cancer and its precursor lesions. HR-HPV induces molecular changes during cervical carcinogenesis, causing the accumulation of genetic anomalies, with subsequent genetic instability and malignant transformation. These alterations are produced by the direct action of the E6 and E7 viral oncoproteins on principal tumor cell suppressor proteins, p53 and pRb, respectively, and can be monitored during growth of the neoplastic lesion using biomarkers. In this paper we review the latest trends on the use of immunocytochemistry as a complementary test to cytology and HR-HPV detection and typing in evaluating expression of biomarkers such as the p16INK4a cell proliferation inhibitor protein, as a single marker or combined with other biomarkers, which can contribute effectively to the detection of patients with increased risk of developing cervical neoplasia associated with HR-HPV infection during routine screening for cervical cancer and in appropriate clinical management.
Asunto(s)
Humanos , Adulto , Femenino , Adulto Joven , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/sangre , Células Epiteliales/química , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/patología , Papiloma/etiología , Papiloma/química , Papiloma/sangre , Análisis Químico de la Sangre , Hematología , Inmunohistoquímica , Oncología MédicaRESUMEN
Luminal cytokeratin (CK) expression in breast papillary lesions, and its potential diagnostic utility among other markers in distinguishing between papillomas and papillary carcinomas, has not been previously evaluated. Such expression was determined in 42 papillary lesions (18 papillary carcinomas and 24 papillomas) by immunostaining with a CK5/p63/CK8/18 antibody cocktail. The mean CK8/18 intensity score and percentage of positive cells were significantly higher in papillary carcinomas (227 and 95%, respectively, vs 86 and 42% in papillomas; both P-values <0.0001), whereas the mean CK5 intensity score and percentage of positive cells were significantly lower (7 and 5%, respectively, vs 107 and 58% in papillomas; both P-values <0.0001). Half (9/18) of the papillary carcinomas expressed p63 vs all (24/24) of the papillomas (P = 0.0001). P63 expression in papillary carcinoma was always (9/9; 100%) focal/limited in nature (expression in <10% of cells), whereas focal expression was seen in only four (17%) papillomas (P<0.0001). Both differential CK (CK8/18 and CK5) expression and p63 were equally sensitive (100%) for the diagnosis of papillary carcinoma, but differential CK expression was more specific (96 vs 83%), resulting in a greater accuracy. However, the best discriminatory power in the distinction from papilloma was achieved when all three markers were used in combination, resulting in 100% sensitivity and specificity values. It is concluded that breast papillary lesions have differential CK expression profiles that, especially in combination with p63, can be useful for their stratification, potentially also in needle biopsy material, in which more accurate and reproducible characterization is needed.
Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinoma Papilar/metabolismo , Inmunohistoquímica/métodos , Queratinas/metabolismo , Proteínas de la Membrana/metabolismo , Papiloma/metabolismo , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Carcinoma Papilar/química , Carcinoma Papilar/patología , Diagnóstico Diferencial , Femenino , Humanos , Queratinas/análisis , Proteínas de la Membrana/análisis , Papiloma/química , Papiloma/patología , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: We evaluated the presence and pattern of ProEx C stain, a marker for the proliferative capacity of cells, in laryngeal tissues, including benign, malignant, and recurrent respiratory papilloma (RRP) specimens, and compared it to hematoxylin and eosin staining for the presence of dysplasia. METHODS: We performed a retrospective study with chart review. RESULTS: A total of 26 specimens (9 benign, 7 malignant, 10 RRP) representing 21 patients were stained. ProEx C stained positive in the nuclei of laryngeal tissue, consistent with its localization in cervical cytology specimens. Seven of 9 benign and 7 of 10 RRP specimens stained positive. The benign specimens were mostly polyps. The malignant specimens were either well or moderately differentiated squamous cell carcinoma, and they stained strongly and diffusely. In benign and RRP specimens, the basal layer typically stained positive. Other areas of epithelium stained weakly in benign specimens and variably in RRP specimens. Current analysis of hematoxylin and eosin-stained RRP specimens revealed that 30% of specimens had at least moderate dysplasia and 80% exhibited viral changes (koilocytosis). CONCLUSIONS: ProEx C is a clean and reliable stain in laryngeal tissue, and stains positive in RRP. This study could not definitively correlate positive ProEx C staining in areas of greater dysplasia, although a trend was observed. Further studies are necessary to determine whether ProEx C can be used in triage of cases of clinically aggressive RRP for closer follow-up or frequent operative intervention.
Asunto(s)
Antígenos de Neoplasias/análisis , Proteínas de Ciclo Celular/análisis , ADN-Topoisomerasas de Tipo II/análisis , Proteínas de Unión al ADN/análisis , Proteínas Nucleares/análisis , Papiloma/química , Neoplasias del Sistema Respiratorio/química , Biomarcadores de Tumor/análisis , Biopsia , Proliferación Celular , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Isoenzimas , Componente 2 del Complejo de Mantenimiento de Minicromosoma , Recurrencia Local de Neoplasia , Papiloma/patología , Neoplasias del Sistema Respiratorio/patologíaRESUMEN
BACKGROUND: Previous studies have provided some evidence of a possible association between cancer and metallothioneins. Whether this relates to an exposure to carcinogenic metals remains unclear. METHODS: In order to examine the association between the expression of metallothioneins and bladder tumors, and to compare the levels of arsenic, cadmium, chromium, lead and nickel in animals with bladder tumors and animals without bladder tumors, 37 cases of bovine bladder tumors and 17 controls were collected. The detection and quantification of metallothioneins in bladder tissue of both cases and controls was performed by immunohistochemistry. And the quantification of metals in tissue and hair was assessed by inductively coupled plasma - mass spectrometry. RESULTS: Increased expression of metallothioneins was associated with bladder tumors when compared with non-tumoral bladder tissue (OR = 9.3, 95% CI: 1.0 - 480). The concentrations of cadmium, chromium, lead and nickel in hair of cases were significantly higher than those of controls. However, as for the concentration of metals in bladder tissue, the differences were not significant. CONCLUSION: Though the sample size was small, the present study shows an association between bladder tumors and metallothioneins. Moreover, it shows that concentrations of metals such as cadmium, chromium, lead and nickel in hair may be used as a biomarker of exposure.
Asunto(s)
Enfermedades de los Bovinos/metabolismo , Metalotioneína/metabolismo , Metales/metabolismo , Oligoelementos/metabolismo , Neoplasias de la Vejiga Urinaria/veterinaria , Adenoma/química , Adenoma/metabolismo , Adenoma/veterinaria , Animales , Carcinoma/química , Carcinoma/metabolismo , Carcinoma/veterinaria , Bovinos , Regulación Neoplásica de la Expresión Génica/fisiología , Cabello/química , Hemangioma/química , Hemangioma/metabolismo , Hemangioma/veterinaria , Metalotioneína/genética , Papiloma/química , Papiloma/metabolismo , Papiloma/veterinaria , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/metabolismoAsunto(s)
Neoplasias de la Mama/diagnóstico , Carcinoma Intraductal no Infiltrante/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Papiloma/diagnóstico , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Anciano , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/química , Carcinoma Intraductal no Infiltrante/clasificación , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Papilar/química , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patología , Núcleo Celular/ultraestructura , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia , Queratinas/análisis , Proteínas de la Membrana/análisis , Proteínas de Neoplasias/análisis , Neoplasias Primarias Múltiples/química , Neoplasias Primarias Múltiples/patología , Papiloma/química , Papiloma/patologíaRESUMEN
A total of 88 samples of laryngeal lesions (23 vocal cord nodules (VCNs), 23 papillomas (PAs), 18 dysplasias (DYs), and 24 carcinomas (CAs)) were analyzed for p16INK4a protein (p16) expression by immunohistochemistry and for high-risk human papillomavirus (HR-HPV) infection using chromogene in situ hybridization (CISH) and polymerase chain reaction (PCR). The series comprised 62 males and 26 females, aged 1-87 years (median 55 years). p16 expression was detected in 2 of 23 (9%) VCNs, 18 of 23 (78%) PAs, 9 of 18 (50%) DYs, and 14 of 24 (58%) CAs. Using CISH, HR-HPV DNA was detected in 3 of 23 (13%) VCNs, in 19 of 23 (83%) PAs, in 12 of 18 (67%) DYs, and in 14 of 24 (58%) CAs. HR-HPV DNA was found in six of nine (67%) PAs by PCR. A statistically significant difference in p16 expression and HR-HPV DNA presence detected by CISH was observed between VCNs and PAs (p<0.000001). The sensitivity and specificity of p16 expression for HR-HPV DNA presence detected by CISH was 0.612 and 0.773, respectively. Our study confirms a potential role of HR-HPV infection not only in the pathogenesis of malignant, but also in benign laryngeal lesions.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Carcinoma , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Neoplasias Laríngeas , Papiloma , Infecciones por Papillomavirus/virología , Lesiones Precancerosas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alphapapillomavirus/genética , Carcinoma/química , Carcinoma/patología , Carcinoma/virología , Niño , Preescolar , Sondas de ADN de HPV , ADN Viral/aislamiento & purificación , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Lactante , Neoplasias Laríngeas/química , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/virología , Masculino , Persona de Mediana Edad , Papiloma/química , Papiloma/patología , Papiloma/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas/química , Lesiones Precancerosas/patología , Lesiones Precancerosas/virología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Fibromatosis-like metaplastic carcinoma is a newly described metaplastic breast tumor, literature on which is still evolving. CASE PRESENTATION: A 77-year-old lady presented with a 2 x 2 cm mass with irregular margins in the upper and outer quadrant of left breast. Fine needle aspiration cytology (FNAC) from the lump was inconclusive. A lumpectomy was performed and sent for frozen section, which revealed presence of spindle cells showing mild atypia in a sclerotic stroma. The tumor cells revealed prominent infiltration into the adjacent fat. A differential diagnosis of a low-grade sarcoma vs. a metaplastic carcinoma, favoring the former, was offered. Final histology sections revealed an infiltrating tumor with predominant spindle cells in a collagenous background, simulating a fibromatosis. Adjacent to the tumor were foci of benign ductal hyperplasia and a micropapilloma. Immunohistochemistry (IHC) showed diffuse co-expression of epithelial markers i.e. cytokeratins (CK, HMWCK, CK7) and EMA along with a mesenchymal marker i.e. vimentin in the tumor cells. Myoepithelial markers (SMA and p63) showed focal positivity. A diagnosis of a low-grade fibromatosis-like carcinoma breast associated with a micropapilloma was formed. CONCLUSION: Fibromatosis-like carcinoma is a rare form of a metaplastic breast tumor. This diagnosis requires an index of suspicion while dealing with spindle cell breast tumors. The importance of making this diagnosis to facilitate an intra operative surgical planning is marred by diagnostic difficulties. In such cases, IHC is imperative in forming an objective diagnosis.
Asunto(s)
Neoplasias de la Mama/patología , Fibroma/patología , Papiloma/patología , Anciano , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Femenino , Fibroma/química , Humanos , Metaplasia/patología , Papiloma/químicaRESUMEN
A comparative assessment of toxic element concentrations in serum and tissue bioptates in patients with laryngeal papilloma or cancer was performed. Examinations were conducted in 60 patients (40 men and 20 women) aged 20-88 years (average 59 +/- 05). Patients were divided into 3 groups; 20 patients with laryngeal papilloma were in group I, 20 with laryngeal cancer were in group II, and 20 with deviated nasal septums were included as a control group (III). Diagnosis of laryngeal papilloma (removed by direct microlaryngoscopy--Kleinsasser method) and laryngeal cancer (removed by the Rethi method) was histopatologically confirmed in patients from groups I and II, respectively. Patients in the control group received functional surgery to repair deviated nasal septums. Serum and tissue samples were obtained from all patients before surgery. Aluminum and lead concentrations were analysed by inductively coupled plasma atomic emission spectrometry (ICP-AES) using a Spectroflame M spectrometer. The considerable rise of aluminum and lead concentration in tissue bioptates and aluminum in serum in groups I and II in comparison to the control group suggests that these elements may play a significant part in the aetiology and development of precancerous lesions and laryngeal cancers. Measuring toxic chemical element concentrations in tissue bioptates can be useful in the diagnosis and estimation of development of precancerous lesions of the larynx as well as laryngeal cancer. Toxic elements concentration may play a significant role in carcinogenesis and may determine trends in cancer aetiology.
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Aluminio/análisis , Biopsia , Neoplasias Laríngeas/química , Plomo/análisis , Papiloma/química , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Laríngeas/cirugía , Masculino , Persona de Mediana Edad , Tabique Nasal/anomalías , Tabique Nasal/cirugía , Papiloma/cirugía , Espectrofotometría AtómicaRESUMEN
The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma.
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Neoplasias Laríngeas/química , Laringe/química , Metaloproteinasa 9 de la Matriz/análisis , Lesiones Precancerosas/química , Carcinoma in Situ/química , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Queratosis/metabolismo , Queratosis/patología , Enfermedades de la Laringe/metabolismo , Enfermedades de la Laringe/patología , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Laringe/citología , Laringe/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica/patología , Papiloma/química , Papiloma/metabolismo , Papiloma/patología , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Regulación hacia ArribaRESUMEN
Enhanced prostaglandin production via upregulated cyclooxygenase-2 (COX-2) expression is a likely contributing factor in ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), which consists primarily of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). The four E prostanoid (EP) receptors, designated EP1 through EP4, are known to bind prostaglandin E2 (PGE2), the major prostaglandin present in the skin. We used murine models of UVB-induced SCC and BCC, as well as human NMSC from sun-exposed sites, to investigate the expression of EP receptors during UVB-induced tumorigenesis. We observed that UVB-induced murine SCC are associated with markedly altered expression patterns of the EP receptors when compared with non-irradiated skin. In contrast, expression of all EP receptors was largely absent in UVB-induced murine BCC. We also observed expression of all four EP receptors in human SCC, with altered expression of their mRNA levels as compared with adjacent tumor-free skin. Consistent with our murine studies, no EP receptor expression was detected in human BCC, and their mRNA expression levels showed no change from the adjacent non-tumor-bearing skin. These data suggest that altered EP receptor expression may play a differential role in the development of UVB-induced SCC and BCC in murine and human skin.
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Receptores de Prostaglandina E/análisis , Neoplasias Cutáneas/química , Animales , Carcinoma Basocelular/química , Carcinoma de Células Escamosas/química , AMP Cíclico/análisis , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/uso terapéutico , Femenino , Humanos , Inmunohistoquímica , Proteínas de la Membrana , Ratones , Ratones Pelados , Papiloma/química , Prostaglandina-Endoperóxido Sintasas/análisis , ARN Mensajero/análisis , Receptores de Prostaglandina E/genética , Subtipo EP1 de Receptores de Prostaglandina E , Subtipo EP2 de Receptores de Prostaglandina E , Subtipo EP3 de Receptores de Prostaglandina E , Subtipo EP4 de Receptores de Prostaglandina ERESUMEN
Cytokeratin (CK) 20, Ki-67, and p53 were applied to 84 noninvasive papillary urothelial tumors graded by the 1973 World Health Organization (WHO) and 1998 WHO/International Society of Urological Pathology (ISUP) systems. In the WHO/ISUP classification, all benign lesions showed normal CK20 staining and all carcinomas showed abnormal staining. The Ki-67 index was significantly different between benign and malignant lesions (P < .05) and between low- and high-grade carcinomas (P < .001). p53 was negative in all benign lesions, with a significant difference between low- and high-grade carcinomas (P < .001). Tumor recurrence was significantly different between low- and high-grade carcinomas (no recurrences among the papillary urothelial neoplasms of low malignant potential). By the 1973 WHO classification, normal CK20 staining was present both in benign lesions and in carcinomas. Ki-67 staining did not distinguish between grade 2 and grade 3 carcinomas (P > .05), and there was no difference in p53 staining in grades 1 and 2 carcinomas (P > .05). Recurrences were not different between grades 1, 2, and 3 carcinomas. All biologic markers studied and tumor recurrences were significantly different among papillary lesions classified by the WHO/ISUP system but not by the 1973 WHO system, validating the predictive value of the WHO/ISUP system and providing objective markers for the grading of papillary urothelial tumors.
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Carcinoma Papilar/patología , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patología , Biomarcadores de Tumor/análisis , Carcinoma Papilar/química , Carcinoma Papilar/clasificación , Carcinoma Papilar/cirugía , Carcinoma de Células Transicionales/química , Carcinoma de Células Transicionales/clasificación , Carcinoma de Células Transicionales/cirugía , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Proteínas de Filamentos Intermediarios/análisis , Queratina-20 , Antígeno Ki-67/análisis , Recurrencia Local de Neoplasia , Papiloma/química , Papiloma/patología , Proteína p53 Supresora de Tumor/análisis , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/clasificación , Neoplasias de la Vejiga Urinaria/cirugía , Organización Mundial de la SaludRESUMEN
OBJECTIVE: To investigate the clinical significance of the protein expression of 4 cell cycle regulators in papillomatosis of the breast. METHODS: Immunohistochemistry was used to examine the protein expression of CyclinD1, p16, E2F-1 and Rb in 4 groups (196 cases) with mild papillomatosis (MP), moderate papillomatosis (MoP), serious papillomatosis (SP) and ductal carcinoma in situ (DCIS). RESULTS: There were significant difference of the positive rate and the intensity of CyclinD1, p16, E2F-1 and Rb expression among the groups, respectively (chi(2) were 16.702, 20.742, 40.335, 42.317; 19.120, 29.469, 45.080, 46.920, P < 0.01. Meaning time there were significant difference in the expression of these 4 factors between MoP and SP (P < 0.05). There was significance of E2F-1 or Rb expression between SP and DCIS (P < 0.01), but there was no significance to be found in the expression of CyclinD1 or p16 between the two groups (P > 0.05). Rb was screened as the highest risk factor by Odd Risk Logistic Analysis. CONCLUSION: CyclinD1, p16, E2F-1 and Rb played the important roles from MP into SP and then DCIS. E2F-1 and Rb can be used as the assistant indicators on the differentiation of SP and DCIS. Rb may be helpful in screening high risk cases from SP or MoP.
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Neoplasias de la Mama/patología , Proteínas de Ciclo Celular , Proteínas de Unión al ADN , Papiloma/patología , Neoplasias de la Mama/química , Neoplasias de la Mama/diagnóstico , Ciclo Celular , Ciclina D1/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Diagnóstico Diferencial , Factores de Transcripción E2F , Factor de Transcripción E2F1 , Femenino , Humanos , Inmunohistoquímica , Modelos Logísticos , Papiloma/química , Papiloma/diagnóstico , Proteína de Retinoblastoma/análisis , Factores de Transcripción/análisisRESUMEN
Oral melanoacanthoma (MA) is rare reactive mucosal lesion that, like cutaneous MA, demonstrates hyperplasia of spinous keratinocytes and melanocytes. Unlike MA of the skin, oral MA is unrelated to seborrheic keratosis. This series adds 10 cases to the limited number of previous reports of oral MA. The clinicopathologic features of the cases in this series are generally consistent with those previously reported in the literature; that is, although documented in various intraoral locations in patients of differing ethnicity, oral melanoacanthoma most often presents as an enlarging flat or slightly raised area of hyperpigmentation on the buccal mucosa of adult black women. The current series provides evidence of occurrence over a wider age range (5-77 years) than previously reported. Additionally, the reactivity of oral melanoacanthoma to HMB-45 was investigated. Strong HMB-45 reactivity was present in all cases, thus demonstrating its limited utility in distinguishing oral MA from malignant melanoma.
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Melanoma/patología , Neoplasias de la Boca/patología , Papiloma/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Antígenos de Neoplasias , Preescolar , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Melanocitos/patología , Melanoma/química , Antígenos Específicos del Melanoma , Persona de Mediana Edad , Mucosa Bucal/patología , Neoplasias de la Boca/química , Proteínas de Neoplasias/análisis , Papiloma/química , Neoplasias Cutáneas/químicaRESUMEN
Exogenous administration of 5-aminolevulinic acid (ALA) is becoming widely used to enhance the endogenous synthesis of Protoporphyrin IX (PpIX) in photodynamic therapy. We analysed porphyrin formation in chemically induced squamous papillomas, after topical application of ALA and ALA hexyl ester (He-ALA) administered in different formulations, as well as the pattern of distribution in the internal organs, and the synthesis of porphyrins in distant tumoural and normal skins. A lotion formulation containing DMSO and ethanol was the best vehicle for topical ALA delivery to papillomas, whereas cream was the most efficient formulation for He-ALA application. Similar porphyrin concentration can be accumulated in the skin tumours employing either ALA or He-ALA delivered in their optimal formulations. The use of cream as a vehicle of both ALA and He-ALA, induces highest porphyrin tumour/normal skin ratios. The main advantage of using He-ALA is that porphyrins synthesized from the ester are more confined to the site of application, thus inducing low porphyrin levels in normal skin, liver, blood and spleen, as well as in papillomas distant from the point of application, independently on the vehicle employed, so reducing potential side effects of photodynamic therapy.