RESUMEN
OBJECTIVE: There exist controversial and discrepant results on the risk of spontaneous abortions and teratogenesis induced by interferon treatment in people with MS.Aim of this study is to evaluate risks of the administration of INFbeta related not only to the foetus, but also to children development up to 12-months developmental milestones. METHODS: The study design is retrospective with a follow-up of babies until 18-months of their life. Thirty-eight women out of 240 with MS followed-up at Clinic MS Center of the University Hospital of Catania, Italy became pregnant in the period june 1997-may 2006. Patients were grouped into three arms: in utero exposed to INFbeta, never treated and patients who discontinued INFbeta before starting conception. Pregnancy outcomes, birth weight, 12-month developmental milestones were collected with an ad hoc questionnaire. RESULTS: Newborns of in utero exposed to INFbeta patients were little smaller for birth weight (3079.6 +/- 313.3 g), but not statistically significant, if compared with the other groups. Developmental milestones appeared within the normal range in all groups. CONCLUSIONS: Our results were particularly favourable on pregnancy outcomes, because we observed only a smaller birth weight which was not detrimental for the further development of children. We believe that INFbeta therapy might not be considered to be a reason for interruption of an intact pregnancy once the drug has been discontinued until delivery.
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Factores Inmunológicos/efectos adversos , Interferón beta/efectos adversos , Complicaciones del Embarazo/inducido químicamente , Resultado del Embarazo , Adulto , Análisis de Varianza , Peso al Nacer/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Esclerosis Múltiple/tratamiento farmacológico , Embarazo , Complicaciones del Embarazo/epidemiología , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
We report a rare case of malignant melanoma arising in a cystic teratoma of the ovary occurring in a 60-year-old woman who died in four months despite the combined treatment administrated (surgery and chemotherapy). Diagnosis of ovarian melanoma was confirmed by immunohistochemical positivity to S-100 protein and HMB 45. There was no evidence of extra-ovarian primary melanoma on clinical examination; therefore the diagnosis was primary ovarian melanoma. Melanoma metastases were detected on the uterus, the right ovary, the omentum and in one of the three excised left external iliac lymph nodes. A review of the literature is analyzed and discussed.
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Melanoma/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Ováricas/diagnóstico , Teratoma/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Melanoma/tratamiento farmacológico , Melanoma/secundario , Melanoma/cirugía , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/secundario , Neoplasias Primarias Múltiples/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Teratoma/tratamiento farmacológico , Teratoma/secundario , Teratoma/cirugíaRESUMEN
BACKGROUND: Progression of cutaneous squamous neoplasms from actinic keratosis (AK) to Bowen's disease (BD; squamous cell carcinoma in situ) has important implications for clinical management and treatment, thus requiring accurate diagnosis. p16INK4a is a cell cycle regulatory tumour suppressor protein that negatively regulates D-type cyclins in the G1 cell cycle phase via intimate interplay with the retinoblastoma gene. Expression of a paraffin-reactive p16INK4a marker has recently been shown to increase in cervical squamous neoplasms as lesions progress from low-grade dysplasia to squamous cell carcinoma in situ. p16INK4a expression in the progression of squamous cutaneous neoplasia, however, has not been evaluated. OBJECTIVES: To evaluate p16INK4a expression in the progression of squamous cutaneous neoplasia. METHODS: Biopsies of 203 squamous cutaneous neoplasms with unequivocal features of AK (n = 87) and BD (n = 116) as well as a benign squamous control group (verruca vulgaris: n = 10; seborrhoeic keratosis: n = 11; scar tissue: n = 8) obtained between January and December 2001 at Henry Ford Hospital (Detroit, MI, U.S.A.) were immunostained for p16INK4a (Dako; clone E6H4; dilution 1 : 50) using large core (1.5 mm) tissue microarray analysis. Nuclear/cytoplasmic immunoreactivity in > 10% of neoplastic cells was considered positive. RESULTS: Of 203 cases, 166 (81.8%) were interpretable (AK 59; BD 107). Mean patient age was 71.0 years (range 33-93); 57% were male. Sites of involvement were: head and extremities 75.9%, trunk/buttocks 21.7%, genital region 2.4%. p16INK4a immunostaining was positive in 90 of 107 (84.1%) BD cases, four of 59 (6.8%) AK cases and none of 29 benign squamous controls. The sensitivity and specificity of p16INK4a for a diagnosis of BD (vs. benign squamous controls/AK) was 84.1% and 95.5%, respectively (P < 0.0001, Fisher's exact test, two-sided). CONCLUSIONS: p16INK4a is a sensitive and specific marker for distinguishing BD from AK/benign squamous cutaneous lesions and may be helpful as an adjunct to histomorphology in the diagnosis and appropriate clinical management of these lesions.
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Biomarcadores de Tumor/metabolismo , Enfermedad de Bowen/diagnóstico , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Queratosis/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Bowen/metabolismo , Enfermedad de Bowen/patología , Progresión de la Enfermedad , Femenino , Humanos , Queratosis/metabolismo , Queratosis/patología , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Sensibilidad y Especificidad , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
About a third of all gynecological consultations are carried out for abnormal uterine bleeding and this ratio rises to 70% in women in peri- and postmenopause. The diagnosis of dysfunctional uterine bleeding (DUB) which is generally due to a chronic anovulatory condition, is only arrived at after objective examination has excluded transvaginal echography, sonohysterography, hysteroscopy and if necessary biopsy to check for the presence of organic pathology. The drugs commonly used in DUB are methylergometrine, the antifibrinolytics, the FANS, estrogens, progesterone and its derivaties, the estroprogestinics, danazol and the superagonist analogues of GnRH. Following these simple guidelines, all derived from evidence-based medicine, medical treatments for DUB are certainly together with patient satisfaction but there is also a marked reduction in costs linked above all to the diminution in the number of hysterectomy operations.
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Hemorragia Uterina/tratamiento farmacológico , Femenino , Humanos , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/etiologíaRESUMEN
We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.
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Adenoma/genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Hiperparatiroidismo/genética , Neoplasias de las Paratiroides/genética , Proteínas/genética , Adenoma/patología , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 1 , Exones , Etiquetas de Secuencia Expresada , Genes Supresores de Tumor , Ligamiento Genético , Pruebas Genéticas , Genotipo , Heterocigoto , Humanos , Repeticiones de Microsatélite , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Neoplasias de las Paratiroides/química , Neoplasias de las Paratiroides/patología , Linaje , Proteínas/química , Síndrome , Proteínas Supresoras de TumorRESUMEN
BACKGROUND: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. OBJECTIVE: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). DESIGN: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. RESULTS: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. CONCLUSION: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.
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Angiomiolipoma/inmunología , Angiomiolipoma/patología , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Actinas/metabolismo , Adipocitos/patología , Adulto , Anciano , Angiomiolipoma/metabolismo , Antígenos CD/metabolismo , Antígenos de Neoplasias , Proteínas de Unión al Calcio/metabolismo , Femenino , Humanos , Inmunofenotipificación , Neoplasias Renales/metabolismo , Masculino , Antígenos Específicos del Melanoma , Melanosomas/patología , Proteínas de Microfilamentos , Microscopía Electrónica , Persona de Mediana Edad , Monofenol Monooxigenasa/metabolismo , Músculo Liso/patología , Proteínas de Neoplasias/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo , Tetraspanina 30 , CalponinasRESUMEN
OBJECTIVE: To develop breast cancer outcomes data relating pathologic tumor variables at diagnosis with clinical method of detection. DESIGN: Anatomic pathologists assessed 30 consecutive breast cancers at each institution, resulting in an aggregate database of 4232 breast cancers. SETTING: Hospital-based laboratories from the United States (98%), Canada, Australia, and Belgium. PARTICIPANTS: One hundred ninety-nine laboratories in the 1999 College of American Pathologists Q-Probes voluntary quality improvement program. MAIN OUTCOME MEASURES: Pathologic variables indicative of favorable outcomes included percentage of carcinomas detected at the in situ stage, tumors < or = 1 cm in diameter, and invasive cancers with lymph nodes negative for metastases. RESULTS: All outcomes measures, including percent in situ carcinomas (26.9% vs 13.8%), tumor size < or = 1 cm (57.8% vs 36.5%), and lymph node-negative status (77.8% vs 64%), were more favorable when tumors were detected by screening mammography (P <.001) compared to all other detection methods. CONCLUSIONS: This study demonstrates an opportunity for pathologists to develop outcomes information of interest to health care organizations, providers, patients, and payers by integrating routine oncologic surgical pathology and clinical breast cancer detection data. Such readily obtained interim outcomes data trended and benchmarked over time can demonstrate the relative clinical efficacy of preventive breast care provided by health care systems long before mortality data are available.
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Neoplasias de la Mama/diagnóstico , Carcinoma/diagnóstico , Patología Quirúrgica/normas , Adulto , Anciano , Anciano de 80 o más Años , Australia , Bélgica , Biopsia , Neoplasias de la Mama/terapia , Canadá , Carcinoma/secundario , Carcinoma/terapia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patología , Femenino , Humanos , Laboratorios de Hospital , Mamografía , Tamizaje Masivo , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del Tratamiento , Estados Unidos , Recursos HumanosRESUMEN
CONTEXT: DNA flow cytometry of breast cancer is a proposed tumor marker of prognostic significance that is of controversial clinical utility because of lack of standardization and confirmatory studies. OBJECTIVE: To evaluate the prognostic significance of the more informative technique of multiparametric 2-color DNA flow cytometry as recommended by the 1992 DNA Cytometry Consensus Conference. DESIGN: Three hundred thirty-two breast carcinomas with 7 to 12 years of follow-up were prospectively analyzed as fresh tumors that were mechanically dissociated into whole cell suspensions. These suspensions were dual fluorescence-labeled with propidium iodide (DNA) and antibodies to cytokeratin (epithelium) and leukocyte common antigen (internal leukocyte control) for gated analysis of subpopulations. Multicycle software with histogram-dependent algorithms employing background, aggregate, and debris correction were used in DNA and cell-cycle quantitation. Data were analyzed according to the DNA Flow Cytometry Consensus Conference recommendations. RESULTS: DNA ploidy and proliferation stratified into 3 categories were not predictive of overall or disease-free survival. Sixty-five percent of tumors were nondiploid, and 35.4% were diploid. Two hundred six tumors were able to be evaluated for synthesis-phase fraction (SPF) analysis, with 74 of 206 cases in the low range (<13.4%), 36.4% in the intermediate range (>13.5 to <25.4%), and 27.6% in the high SPF (>25.5%) category. Aneuploid tumors tended to have a higher SPF. Univariate survival analysis showed prognostic significance of the following: tumor size, stage, TNM components, vascular invasion, nuclear grade, and histologic grade. Only T classification, presence of positive axillary lymph nodes, and distant metastases were significant independent predictors of survival in multivariate Cox regression models. Age and hormone receptor status showed no prognostic significance. Synthesis-phase fraction was significantly correlated with tumor size, stage, T classification, nuclear and histologic grade, presence of estrogen or progesterone receptors, and axillary lymph node status. None of the histologic parameters showed any significant association with DNA aneuploidy, except for high nuclear and histologic grade and the absence of estrogen receptors. CONCLUSIONS: Despite the use of state-of-the-art processing and flow cytometry analytic techniques, DNA ploidy and proliferation measurements were not predictive of survival in any stage of breast cancer. However, select histopathologic parameters and TNM stage were significant predictors of survival in univariate and multivariate analyses. We conclude that DNA ploidy and proliferation measurements do not provide significant prognostic information for clinicians to integrate into therapeutic decision making for patients with breast cancer.
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Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , ADN de Neoplasias/análisis , Citometría de Flujo , Queratinas/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/secundario , División Celular , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Estadificación de Neoplasias , Ploidias , Fase S , Tasa de SupervivenciaAsunto(s)
Ameloblastoma/diagnóstico por imagen , Neoplasias Maxilomandibulares/diagnóstico por imagen , Adulto , Ameloblastoma/patología , Ameloblastoma/cirugía , Femenino , Humanos , Neoplasias Maxilomandibulares/patología , Neoplasias Maxilomandibulares/cirugía , Ortodoncia Correctiva , Radiografía DentalRESUMEN
The finding of possibly contaminant tissues or cells in surgical or cytology case material can be a challenging problem in diagnostic anatomical pathology samples. The reported rates of occurrence have ranged from 0 to 8.8% (including prospective and retrospective cases). A diagnostically dissimilar tissue fragment, whether contiguous with other tissue or among other fragments within a paraffin section, and which is not incompatible with the case tissue, often requires a rigorous investigation to confirm or deny its relevance to the case. Fluorescence in situ hybridization using dual red and green DNA probes to regions of the X and Y chromosomes, respectively, were used in one case where the potential contaminant was suspected to have originated from a male patient. The putative contaminant tissue fragment was confirmed as male, with cells having one X and one Y chromosome, unlike the other tissue fragments on the slide with two X chromosomes. In a second case, DNA polymorphisms were used to compare allelic patterns that were informative not only in proving the extraneous tissue as a contaminant, but in addition, could be used to trace the latter to its original tissue source. The molecular tools of fluorescence in situ hybridization in sex-mismatched cases and of DNA microsatellite probes that are applicable to paraffin sections can provide definitive identifiers of tissues and individual cells. They are important adjuncts to histology for the anatomical pathologist when faced with the diagnostic problems of tissue contamination encountered in routine practice.
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Artefactos , Patología Clínica/métodos , Control de Calidad , Anciano , Biopsia , Gastroscopía , Humanos , Hibridación Fluorescente in Situ , Masculino , Repeticiones de Microsatélite , Sondas de Oligonucleótidos , Próstata/cirugíaRESUMEN
The use and interpretation of cytokeratin (CK) immunostains of sentinel lymph node specimens for breast carcinoma remain controversial. Variable immunoreactivity with anti-CK antibodies and CK-positive interstitial reticulum cells may complicate interpretation. The authors examined a series of reactive lymph nodes selected from patients without a history of malignancy. To demonstrate potential diagnostic pitfalls, three different CK antibody combinations were studied to characterize the immunostaining patterns. Formalin-fixed sections of lymph nodes were immunostained with a labeled streptavidin-biotin method using a DAKO autostainer. The anti-CK antibody preparations evaluated were AE1/AE3, CAM 5.2, and an in-house-prepared CK cocktail composed of 7 antibodies. The authors observed that up to 10% of cells in benign, reactive lymph nodes may be immunoreactive with anti-CK antibodies. AE1/AE3 stained 2 of 20 cases with rare immunoreactive reticulum cells, whereas CAM 5.2 and the CK cocktail immunostained cells in 85% of cases with reticulum cells in sinuses and the paracortex. Rare positive to 2+ cells were present in a similar distribution with these two antibodies. Careful interpretation of CK immunostaining of sentinel lymph node biopsies is essential, as is awareness of the presence of CK-positive native reticulum cells, to avoid confusion with single cells of metastatic carcinoma.
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Queratinas/metabolismo , Seudolinfoma/diagnóstico , Biopsia del Ganglio Linfático Centinela/normas , Adolescente , Adulto , Anticuerpos Monoclonales , Niño , Preescolar , Errores Diagnósticos/prevención & control , Femenino , Humanos , Inmunohistoquímica , Queratinas/inmunología , Ganglios Linfáticos/química , Ganglios Linfáticos/patología , Masculino , Seudolinfoma/metabolismo , Seudolinfoma/patología , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
HYPOTHESIS: Amplification of the HER-2/neu oncogene in 25% of breast cancers is associated with a shortened disease-free survival. DESIGN: Retrospective analysis of a patient population referred to a tertiary care facility for HER-2/neu testing. The mean follow-up was 56 months. SETTING: Large, urban, tertiary care hospital. PATIENTS: From 1995 to 1999, a consecutive sample of 190 patients with breast cancer had tissue samples tested for overexpression of the cell surface oncoprotein by immunostaining (IM) or amplification of the HER-2/neu oncogene by fluorescence in situ hybridization or both. Forty-nine subjects were excluded because they had tissue samples tested at our institution but received their treatment elsewhere. All patients tested for HER-2/neu after diagnosis with breast cancer in 1999 (n = 47) were excluded from analysis because of short follow-up time. One patient was excluded who had in situ ductal carcinoma. The remaining 93 patients were analyzed. RESULTS: Of 93 patients, 40 (43%) had gene amplification. Overall, patients with oncogene amplification had a shorter median disease-free interval (22 months) compared with controls (40 months) (P =.003). Analysis by the Cox regression model showed that the HER-2/neu status remained significantly associated with time to relapse even after adjusting for age and tumor grade (P =.002; adjusted relative risk, 2.4; 95% confidence interval, 1.4-4.4). No association was found between gene amplification and tumor grade (P =.98), estrogen/progesterone receptor status (P = .29 and P = .43, respectively), or lymph node status (P = .98). Seventy-two patients (77%) eventually had disease recurrence, with 18 (25%) of these recurring locally. CONCLUSIONS: The HER-2/neu oncogene is an independent prognostic indicator of a subset of breast cancers that are at high risk of early recurrence, regardless of tumor grade, estrogen/progesterone receptor status, and lymph node status. Patients amplifying the HER-2/neu oncogene have a shorter disease-free survival than patients without the oncogene.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Amplificación de Genes , Genes erbB-2/genética , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/genética , Neoplasias de la Mama/terapia , Terapia Combinada , Estudios de Seguimiento , Humanos , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
On light microscopic examination, the morphologically overlapping features of granular eosinophilic cytoplasm in renal oncocytoma and the eosinophilic variants of chromophobe renal cell carcinoma and conventional (clear cell) renal cell carcinoma may pose difficulties in diagnosis. We investigated the ultrastructure of 5 renal oncocytomas, 7 eosinophilic variants of chromophobe renal cell carcinoma, and 5 eosinophilic variants of conventional (clear cell) renal cell carcinoma. Special attention was paid to mitochondria and microvesicles and interrelations thereof. The electron microscopic features were correlated with the light microscopic findings. All of the tumors had abundant mitochondria. Although abundant microvesicles were present in all of the chromophobe renal cell carcinomas, scant numbers of microvesicles were also sometimes present in renal oncocytomas (2 of 5) and in the eosinophilic variant of conventional (clear cell) renal cell carcinoma (1 of 5). The mitochondria in all three types of renal neoplasms studied differed in morphology, being predominantly uniform and round with predominantly lamellar cristae in renal oncocytoma, variable in shape and size with predominantly tubulocystic cristae in chromophobe renal cell carcinoma, and swollen and pleomorphic with rarefied matrix and attenuated cristae in the eosinophilic variant of conventional (clear cell) renal cell carcinoma. Variable numbers of mitochondria in all of the chromophobe renal cell carcinomas had outpouchings of the outer membranes, some of which carried parts of inner membrane within them. These outpouchings closely resembled the nearby cytoplasmic microvesicles, as did the tubulocystic cristae of the mitochondria. Some microvesicles contained homogeneous, electron-dense, finely granular matrix, similar to that seen in mitochondria. In one of seven chromophobe renal cell carcinomas, microvesicles were present in rough endoplasmic reticulum, and in two others, mitochondria were present within some vesicles. These features strongly suggest a close relationship between the microvesicles and mitochondria. Based on the role of vesicle formation in normal mitochondriogenesis, and some of our observations, we propose that defective mitochondriogenesis may be the source of microvesicles in chromophobe renal cell carcinomas.
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Adenocarcinoma de Células Claras/ultraestructura , Adenoma Oxifílico/ultraestructura , Carcinoma de Células Renales/ultraestructura , Eosinófilos/patología , Neoplasias Renales/ultraestructura , Mitocondrias/ultraestructura , Vacuolas/ultraestructura , Adenocarcinoma de Células Claras/patología , Adenoma Oxifílico/patología , Carcinoma de Células Renales/patología , Núcleo Celular/ultraestructura , Vesículas Cubiertas/ultraestructura , Citoplasma/ultraestructura , Humanos , Neoplasias Renales/patología , Microscopía ElectrónicaRESUMEN
OBJECTIVE: To review tenets of basic quality assurance and identify opportunities for quality improvement in the laboratory assessment of prognostic factors. DESIGN: College of American Pathologists Q-Probes data obtained from hundreds of American laboratories throughout the 1990s are used to illustrate laboratory performance and practice opportunities in the preanalytic, analytic, and postanalytic phases of the total testing process. RESULTS: A wide range of performance deficiencies are documented, most in the preanalytic and postanalytic phases, and contributed by individuals outside and not under the control of the laboratory. In the analytic phase, the effectiveness of checklists on the content and completeness of reported diagnostic and prognostic data for breast and colon cancers is proven. CONCLUSIONS: In the preanalytic phase, marked enhancements in quality would result from improvements in (1) patient and specimen identification, (2) adherence to patient-sampling and specimen-handling requirements, and (3) communication to the laboratory of the pertinent clinical context of the individual test. Once basic analytic quality control and laboratory quality assurance issues are resolved, a focus on standardization and enhancement of preanalytic and postanalytic communications and satisfaction of clinical expectations becomes the source of improved laboratory performance.
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Oncología Médica/normas , Patología Clínica/normas , Humanos , Neoplasias/patología , Pronóstico , Garantía de la Calidad de Atención de Salud , Sociedades Médicas , Estados UnidosRESUMEN
HYPOTHESIS: The density of vasoactive endothelial growth factor receptor 3-immunostained microvessels in primary breast cancers correlates with the incidence of axillary lymph node metastasis. DESIGN: Breast cancer microvessel clusters ("hot spots") were sequentially immunostained for factor VIII, type IV collagen, and vasoactive endothelial growth factor receptor 3. Microvessels were counted under light microscopy at a magnification of x 200. Axillary lymph nodes were evaluated for metastases by light microscopy. SETTING: A multidisciplinary breast cancer clinic and laboratory. PATIENTS: Sixty patients with T2 breast cancers treated by lumpectomy (or mastectomy) and axillary lymphadenectomy. MAIN OUTCOME MEASURES: Putative lymphatic microvessel density compared with axillary metastases. RESULTS: There were 16% (SE, 1.4%) vs 4% (SE, 0.8%) vasoactive endothelial growth factor receptor 3-immunostained microvessels (P<.001), 38% (SE, 3.9%) vs 65% (SE, 3.1%) type IV collagen-immunostained microvessels (P<.001), and 46% (SE, 4.1%) vs 31% (SE, 3.2%) unstained microvessels (P = .004) in node-positive vs node-negative patients, respectively. A fitted logistic model based on the relative percentage of putative lymphatic microvessels to blood microvessels correctly predicted that 23 (96%) of 24 patients would have a low risk and that 26 (96%) of 27 patients would have a high risk of lymph node metastases. Six (67%) of 9 patients predicted to have an intermediate risk had lymph node metastases. CONCLUSION: The odds of a patient with breast cancer having axillary lymph node metastasis increased substantially as the proportion of putative lymphatic microvessels increased and the relative proportion of blood microvessels in angiogenic hot spots decreased (log likelihood = 14.6; chi2 = 53.4; P<.001; area under the receiver operation characteristic curve = 0.97).
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Neoplasias de la Mama/irrigación sanguínea , Ganglios Linfáticos/irrigación sanguínea , Neovascularización Patológica/patología , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Mastectomía Radical Modificada , Mastectomía Segmentaria , Microcirculación/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Proteínas Tirosina Quinasas Receptoras/análisis , Receptores de Superficie Celular/análisis , Receptor 3 de Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: To evaluate cellular composition of salivary gland adenomas using 3 monoclonal antibodies that recognize a smooth muscle phenotype confirmed to be sensitive for myoepithelial differentiation. DESIGN: Immunohistochemical evaluation of 25 salivary gland basal cell and canalicular adenomas. SETTING: Archival pathology material from the files of Henry Ford Hospital, Detroit, Mich, and the University of California at San Francisco. RESULTS: All basal cell adenoma variants exhibit some degree of myoepithelial cell participation with periductal, epithelioid, and spindled (stromal-like) morphologic structures. Only the canalicular adenomas, even if mixed with trabecular and solid patterns, are devoid of staining with these 3 antibodies, suggesting an adenoma composed exclusively of ductal luminal cells. CONCLUSIONS: There is an overlapping histomorphologic and common cellular composition of the basal cell adenoma variants with other recognized adenomas, such as pleomorphic adenoma and myoepithelioma. Relative differentiation toward 3 cell phenotypes (ductal luminal, basal, and myoepithelial) and the character of extracellular matrix production in varying proportions by the neoplastic myoepithelial cells distinguishes the spectrum of salivary gland adenomas identified in current classification schemes.
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Adenoma/patología , Células Epiteliales/patología , Músculo Liso/patología , Neoplasias de las Glándulas Salivales/patología , Actinas/inmunología , Actinas/metabolismo , Adenoma/clasificación , Adenoma/metabolismo , Adenoma Pleomórfico/clasificación , Adenoma Pleomórfico/patología , Anticuerpos Monoclonales/inmunología , Proteínas de Unión al Calcio/inmunología , Proteínas de Unión al Calcio/metabolismo , Células Epiteliales/metabolismo , Humanos , Técnicas para Inmunoenzimas , Proteínas de Microfilamentos , Músculo Liso/inmunología , Músculo Liso/metabolismo , Mioepitelioma/clasificación , Mioepitelioma/patología , Cadenas Pesadas de Miosina/inmunología , Cadenas Pesadas de Miosina/metabolismo , Neoplasias de las Glándulas Salivales/clasificación , Neoplasias de las Glándulas Salivales/metabolismo , CalponinasRESUMEN
From January 1992 to December 1998, 219 women (aged between 30 and 81 yrs; average 55 years) affected by breast cancer were treated. These women in addition to the usual adjuvant therapy, were treated with TAM 20 mg/day, for a period between 24 and 72 months (average 40). In this group there were 84 postmenopausal and 31 premenopausal women. In 8 fertile patients ovarian activity was suppressed with GnRh analogue therapy and one patient underwent attinic castration. Before performing TAM therapy, a hysteroscopic exam was done and patients were followed-up with an annual check-up. None had any endometrial side-effects after the first check-up. After two years, 31 women (26.9%) complained of endometrial alterations (hyperplasia, polyps and endometrial cancer). One women only after 6 years of follow-up, had metrorrhagia; an endometrial adenocarcinoma was found. We would like to point out the necessity of monitoring these patients with an annual check-up (transvaginal sonography and/or hysteroscopy).
Asunto(s)
Adenocarcinoma/inducido químicamente , Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Endometriales/inducido químicamente , Tamoxifeno/efectos adversos , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/uso terapéutico , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/epidemiología , Endometrio/efectos de los fármacos , Endometrio/patología , Femenino , Estudios de Seguimiento , Humanos , Histeroscopía , Incidencia , Persona de Mediana Edad , Tamoxifeno/administración & dosificación , Tamoxifeno/uso terapéutico , Ultrasonografía , Vagina/diagnóstico por imagenRESUMEN
From January 1996 to December 1998, 33 patients with endometrial carcinoma were preoperatively examined in our department; 30 women underwent transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI), and 3 only TVUS. Diagnosis was obtained by histopathological examination of the tissue removed by hysteroscopically controlled biopsy or by curettage of the uterine cavity. TVUS and MRI were performed a few days before surgery. After surgery the uterus was histopathologically examined by a pathologist in order to evaluate the depth of myometrial invasion. The results were compared with TVUS and MRI data to determine sensibility and specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two methods. According to the results of the present study we conclude that: TVUS is a low cost, easily performed and reliable method in a high percentage of cases if carried out by a skilled ecographist. MRI, is more expensive and has a lower specificity and sensibility index; it is a valid method if the cervical canal is involved and/or myometrial invasion is > 50% (M2) and if lymphatic invasion has to be investigated.
Asunto(s)
Neoplasias Endometriales/diagnóstico , Miometrio/patología , Vagina/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/patología , Femenino , Humanos , Metástasis Linfática , Imagen por Resonancia Magnética , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
This article describes the art and science of continuous performance measurement and applications for quality improvement in anatomic pathology. Numerous novel benchmarks derived from multi-institutional data acquired from the College of American Pathologists Q-Probes quality improvement program are illustrated as they relate to specific disciplines in anatomic pathology and aspects of the total testing cycle. Comparative data quantifying performance deficiencies and opportunities for practice improvement are also identified.