RESUMEN
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumour cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating patients with MCC with advanced disease, new therapeutic options are still urgently required. OBJECTIVES: To produce and evaluate the therapeutic performance of a new antibody-drug conjugate (Adcitmer® ) targeting CD56 in preclinical models of MCC. METHODS: CD56 expression was evaluated in a MCC cohort (immunohistochemistry on a tissue microarray of 90 tumour samples) and MCC cell lines. Interaction of an unconjugated CD56-targeting antibody with CD56+ MCC cell lines was investigated by immunohistochemistry and imaging flow cytometry. Adcitmer® product was generated by the bioconjugation of CD56-targeting antibody to a cytotoxic drug (monomethyl auristatin E) using the McSAF Inside® bioconjugation process. The chemical properties and homogeneity of Adcitmer® were characterized by hydrophobic interaction chromatography. Adcitmer® cytotoxicity was evaluated in vitro and in an MCC xenograft mice model. RESULTS: Similar to previous reports, CD56 was expressed by 66% of MCC tumours in our cohort, confirming its relevance as a therapeutic target. Specific binding and internalization of the unconjugated CD56-targeting antibody was validated in MCC cell lines. The high homogeneity of the newly generated Adcitmer® was confirmed by hydrophobic interaction chromatography. The CD56-mediated cytotoxicity of Adcitmer® was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer® significantly reduced tumour growth in a MCC mouse model. CONCLUSIONS: Our study suggests that Adcitmer® should be further assessed as a therapeutic option in patients with MCC, as an alternative therapy or combined with immune checkpoint inhibitors.
Asunto(s)
Carcinoma de Células de Merkel , Neoplasias Cutáneas , Animales , Carcinoma de Células de Merkel/tratamiento farmacológico , Carcinoma de Células de Merkel/patología , Humanos , Inmunohistoquímica , Ratones , Oligopéptidos/farmacología , Oligopéptidos/uso terapéutico , Neoplasias Cutáneas/patologíaRESUMEN
HHV-6A and HHV-6B are found as inherited and chromosomally integrated forms (iciHHV-6A and -6B) into all germinal and somatic cells and vertically transmitted in a Mendelian manner in about 1% of the population. They were occasionally shown to be horizontally transmitted through hematopoietic stem cell transplantation. Here, we present a clinical case of horizontal transmission of iciHHV-6A from donor to recipient through liver transplantation. Molecular analysis performed on three viral genes (7.2 kb) in the recipient and donor samples supports transmission of iciHHV-6A from the graft. Transmission was followed by reactivation, with high viral loads in several compartments. The infection was uncontrollable, leading to severe disease and death, despite antiviral treatments and the absence of resistance mutations. This case highlights the fact that physicians should be aware of the possible horizontal transmission of iciHHV-6 and its consequences in case of reactivation in immunocompromised patients.
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Cromosomas Humanos , Herpesvirus Humano 6/genética , Trasplante de Hígado , Integración Viral , Resultado Fatal , Herpesvirus Humano 6/fisiología , Humanos , Activación ViralRESUMEN
BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.
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Antígenos Virales de Tumores/sangre , Biomarcadores de Tumor/sangre , Proteínas de la Cápside/sangre , Carcinoma de Células de Merkel/inmunología , Neoplasias Cutáneas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/mortalidad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Poliomavirus de Células de Merkel/inmunología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/mortalidad , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/mortalidad , Pronóstico , Medición de Riesgo/métodos , Neoplasias Cutáneas/mortalidad , Infecciones Tumorales por Virus/inmunologíaRESUMEN
BACKGROUND: MicroRNA expression signatures can promote personalised care for non-small cell lung cancer (NSCLC) patients. Our aim was to evaluate the previously unexplored prognostic potential of miR-197, a key oncogenic molecule for NSCLC. METHODS: Total RNA isolation (n=124 NSCLC and n=21 tumour-adjacent normal tissues), was performed using the QIAsymphony SP workstation. The quantity and quality of RNA were assessed by spectrophotometric analysis and an Agilent 2100 bioanalyzer. Polyadenylation and reverse transcription were subsequently carried out. MiR-197 expression levels were measured by qPCR, after quality control (inter-assay CV=7.8%). Internal validation procedures were followed by assigning training and test sets and robust biostatistical analyses were performed, including bootstrap resampling. RESULTS: MiR-197 is associated with larger tumours (P=0.042) and the squamous cell carcinoma histotype (P=0.032). Interestingly, after adjusting for important prognostic indicators, miR-197 expression was identified as a novel independent predictor of unfavourable prognosis for NSCLC patients (HR=1.97, 95% CI=1.10-3.38, P=0.013). We also demonstrate that miR-197 retains its prognostic performance in both early-stage I (P=0.045) and more advanced-stage individuals (P=0.036). CONCLUSIONS: The cost-effective expression analysis of miR-197 could constitute a novel molecular tool for NSCLC management.
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Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de SupervivenciaRESUMEN
BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.
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Carcinoma de Células de Merkel/complicaciones , Neoplasias Cutáneas/complicaciones , Deficiencia de Vitamina D/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/patología , Carcinoma de Células de Merkel/terapia , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptores de Calcitriol/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Resultado del Tratamiento , Vitamina D/sangre , Deficiencia de Vitamina D/metabolismo , Deficiencia de Vitamina D/patologíaRESUMEN
OBJECTIVE: Gonadotropin-secreting pituitary adenomas carry a high risk of local recurrence or progression (R/P) of remnant tumor after first surgery. The clinical characteristics and the long-term outcome of these silent adenomas, which show no signs of endocrine hyperfunction, differ from those of other types of pituitary adenomas. However, to date, no study has focused specifically on gonadotropic adenomas. MATERIALS AND METHODS: To identify prognostic factors of R/P of remnants, we studied the postoperative outcome of 32 gonadotropic pituitary adenomas, defined on immunohistochemical staining, according to their clinical and radiological characteristics as well as the Ki-67 labeling index (LI). RESULTS: The Ki-67 LI failed to provide independent information for the identification of patients at risk of progression of remnants or recurrence. Multivariate survival analysis (Cox regression) showed that neither invasiveness nor remnant tumors nor hyposomatotropism influenced tumor recurrence. The strongest predicting factors of R/P were the antero-posterior (AP) diameter in the sagittal plane (P = 0.014), and the age of the patient at surgery (P = 0.047), with younger patients being at greater risk. Hazard ratios were 2.11 for each 5 mm increase in AP diameter and 0.57 for every 10 years of age. CONCLUSION: The two simple clinical criteria revealed by our study, the AP diameter of the tumor and the age of the patient, should be helpful in planning clinical management and radiological monitoring after first surgery of gonadotropic adenomas, while awaiting the identification of other pathological parameters.
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Adenoma/sangre , Adenoma/patología , Gonadotropinas/sangre , Antígeno Ki-67/sangre , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/patología , Adenoma/cirugía , Adulto , Anciano , Envejecimiento/fisiología , Biomarcadores , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Hipofisarias/cirugía , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Regresión , Resultado del TratamientoRESUMEN
Routine calcitonin assay programs and recent studies on the natural history of familial medullary thyroid carcinoma (MTC) have greatly added to our understanding of C-cell hyperplasia (CCH) and refined its classification. This article is an update on CCH physiopathology related to clinical presentation. With this combined approach, two types of CCH that differ by their physiological characteristics can be identified: neoplastic CCH and reactive (also called physiological) CCH. Neoplastic CCH is caused by a germline mutation of the RET protooncogene in a multiple endocrine neoplasia type 2 (MEN 2) syndrome. It progresses to MTC following a time line that depends on the RET mutation involved. CCH may actually be a misnomer for a neoplastic condition that some authors have proposed to call "in situ-MTC". Reactive CCH is considered to be caused by a stimulus that is external to the C-cell, and its premalignant potential is not documented. Many situations such as hypercalcemia, hyperparathyroidy, chronic lymphocytic thyroiditis or follicular tumors have been associated with reactive CCH, the pathogenesis of which remains unclear. But C-cell density in normal patients is subject to important variability, and several studies have demonstrated the dramatic male predominance in physiological CCH when hypercalcitoninemia was a random discovery. These data suggest that a number of conditions which were previously associated with reactive CCH might be purely fortuitous. Our clinical/pathological confrontation contributes to appropriately distinguishing between various CCH types, and in turn to identify the best way of managing patients.
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Hiperplasia/patología , Animales , Calcitonina/genética , Calcitonina/fisiología , Humanos , Hiperplasia/genética , Neoplasia Endocrina Múltiple Tipo 2a/patología , Mutación/fisiología , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas c-ret/fisiologíaRESUMEN
Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor that inhibits plasmin-dependent activation of several metalloproteinases. Downregulation of TFPI-2 could thus enhance the invasive potential of neoplastic cells in several cancers, including lung cancer. In this study, TFPI-2 mRNA was measured using a real-time PCR method in tumours of 59 patients with non-small-cell lung cancer (NSCLC). Tumour TFPI-2 mRNA levels appeared well correlated with protein expression evaluated by immunohistochemistry and were 4-120 times lower compared to those of nonaffected lung tissue in 22 cases (37%). Hypermethylation of the TFPI-2 gene promoter was demonstrated by restriction enzyme-polymerase chain reaction in 12 of 40 cases of NSCLC (30%), including nine of 17 for whom tumour TFPI-2 gene expression was lower than in noncancerous tissue. In contrast, this epigenetic modification was shown in only three of 23 tumours in which no decrease in TFPI-2 synthesis was found (P=0.016). Decreased TFPI-2 gene expression and hypermethylation were more frequently associated with stages III or IV NSCLC (eight out of 10, P=0.02) and the TFPI-2 gene promoter was more frequently hypermethylated in patients with lymph node metastases (eight out of 16, P=0.02). These results suggest that silencing of the TFPI-2 gene by hypermethylation might contribute to tumour progression in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Metilación de ADN , ADN de Neoplasias/metabolismo , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/genética , Neoplasias Pulmonares/genética , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , ADN Complementario/síntesis química , Femenino , Humanos , Immunoblotting , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , ARN Mensajero/metabolismo , ARN Neoplásico/metabolismoRESUMEN
Oxyphilic tumors (oncocytomas or Hürthle cell tumors) form a rare subgroup of thyroid tumors characterized by cells containing abundant mitochondria. The relationship between the mitochondrial proliferation and the pathogenesis of these tumors is unknown. We have assessed the expression of the mitochondrial ND2 and ND5 (subunits of the nicotinamide adenine dinucleotide dehydrogenase complex) genes and the nuclear UCP2 (uncoupling protein 2) gene in 22 oxyphilic thyroid tumors and matched controls. The consumption of oxygen in mitochondria from tumors was determined by polarography. ATP assays were used to explore the mitochondrial respiratory chain activity and the oxidative phosphorylation coupling in seven fresh thyroid tumors and controls. Adenosine triphosphate synthesis was significantly lower in all the tumors, compared with controls, suggesting that a coupling defect in oxidative phosphorylation may be a cause of mitochondrial hyperplasia in oxyphilic thyroid tumors.
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Adenoma Oxifílico/metabolismo , Adenosina Trifosfato/biosíntesis , Proteínas de Transporte de Membrana , Mitocondrias/metabolismo , Proteínas Mitocondriales , Neoplasias de la Tiroides/metabolismo , ADN Mitocondrial/análisis , Humanos , Inmunohistoquímica , Canales Iónicos , NADH Deshidrogenasa/genética , Polarografía , Proteínas/genética , Proteína Desacopladora 2RESUMEN
Usually, thyroid carcinoma presents as a cold nodule on radioiodine scintigraphy. High-uptake nodules on iodine thyroid scans are associated with an exceedingly low incidence of malignancy. Only 29 cases of carcinomas appearing as hot or warm nodules have as yet been reported. From 1993 to 1999, we have observed eight similar cases (4 hot and 4 warm thyroid nodules) suggesting that thyroid carcinomas may not be as rare as usually considered in these circumstances. Four tumors were available for molecular analysis on paraffin-embedded sections. Because no mutations were found in the whole coding portions of thyrotropin-receptor (TSH-R) gene and fragments encompassing the mutational hot spots of the G(s alpha) gene, it is unlikely that activating mutations of the TSH-R or G(s alpha) genes were involved in these carcinomas.
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Proteínas de Unión al GTP Heterotriméricas/genética , Radioisótopos de Yodo , Mutación , Receptores de Tirotropina/genética , Neoplasias de la Tiroides/genética , Adenocarcinoma Folicular/diagnóstico por imagen , Adenocarcinoma Folicular/genética , Adulto , Carcinoma Papilar/diagnóstico por imagen , Carcinoma Papilar/genética , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Cintigrafía , Análisis de Secuencia de ADN , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patologíaRESUMEN
OBJECTIVE: Determine a means of establishing the diagnosis of parathyroid cysts preoperatively. PATIENTS AND METHODS: Classically, crystal-clear watery fluid removed by fine-needle aspiration of a suspected thyroid mass raises the suspicion of a parathyroid cyst. Immunoradiometric assay of parathyroid hormone level in the fluid may give the diagnosis sparing unnecessary surgery. RESULTS: Over the last 5 years, among the 12 patients presenting a suspected thyroid cyst containing a crystal-clear fluid, we were able to diagnose 3 cases of parathyroid cysts due to the considerable elevation of parathyroid hormone in the puncture fluid. None of these patients had hyperparathyroidism. In patients with a thyroid cyst, parathyroid hormone level in the puncture fluid was nil. CONCLUSION: The parathyroid nature of cervical cysts containing crystal-clear fluid can be established by assaying parathyroid hormone in the puncture fluid. Non-functional parathyroid cysts may be treated by repeated aspiration. Serum calcium level must be checked regularly to detect potential hyperparathryoidism.
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Quistes/diagnóstico , Enfermedades de las Paratiroides/diagnóstico , Hormona Paratiroidea/análisis , Adulto , Biopsia con Aguja , Quistes/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Enfermedades de las Paratiroides/patología , Glándulas Paratiroides/patología , UltrasonografíaAsunto(s)
Carcinoma Medular/patología , Proteínas de Drosophila , Neoplasias de la Tiroides/patología , Carcinoma Medular/diagnóstico , Carcinoma Medular/genética , Humanos , Hiperplasia , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genéticaRESUMEN
Thirty-eight patients (25 women, 13 men; mean age, 57.8 [32 to 91]) showing one or more medullary thyroid microcarcinomas (ie, < 1 cm), with no prior MEN II or medullary thyroid carcinoma history in their family, were reviewed. Follow-up was available for 29 patients (mean, 53.6 months [1 to 147]). 21 patients (72.4%) are alive and free of disease, four patients (13.8%) died during follow-up without disease, 2 patients are alive with disease (local recurrence and persistent hypercalcitoninemia) after 80 and 99 months, respectively, and 2 patients died of disease after 24 and 46 months. Most tumors were incidental pathological findings (19 of 38) or were discovered by systematic blood calcitonin measurement for a nodular thyroid disease (15 of 38). Only the four patients who had an unfavorable outcome were symptomatic cases (palpable micro-MTC, diarrhea, cervical lymph node metastasis and pulmonary metastatic disease). The two patients with metastatic disease at diagnosis died during follow-up. In univariate analysis, a symptomatic medullary thyroid carcinoma was a strong predictor of an unfavourable outcome (p < .00008), as were the preoperative calcitonin level (P = .007) and an elevated postoperative calcitonin level (P = .004). Among 30 histopathological criteria, only the presence of amyloid correlated with an unfavorable outcome (P = .018).
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Carcinoma Medular/patología , Neoplasias de la Tiroides/patología , Adulto , Anciano , Anciano de 80 o más Años , Calcitonina/metabolismo , Carcinoma Medular/diagnóstico , Carcinoma Medular/metabolismo , Carcinoma Medular/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/mortalidadRESUMEN
Frozen section examination for intraoperative diagnosis is often difficult in thyroid pathology. Fine-needle aspiration is widely used in the patients selection for surgery. Such a selection is accompanied by an increase in difficult frozen section cases, whose diagnosis is often differed to permanent sections. Thus, frozen section sensitivity is relatively low. In the era of cost containment, an increasing number of authors suggest that frozen section examination is unnecessary, and that surgical planning could rely on preoperative cytology only. Others consider fine-needle aspiration cytological evaluation and frozen section examination as complementary tools and recommend their association. The authors describe the technical aspects and difficulties of frozen section examination in thyroid pathology, and discuss its interest in surgical planning, in the light of preoperative cytology. Each team has to estimate local thyroid cytology development and accuracy, to define new indications for frozen section examination in thyroid pathology, according to local therapeutic choices. Such an approach could consistently reduce the number of intraoperative consultation for thyroid pathology, without prejudice for the patients.
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Enfermedades de la Tiroides/patología , Glándula Tiroides/patología , Neoplasias de la Tiroides/patología , Biopsia con Aguja , Secciones por Congelación/métodos , Humanos , Enfermedades de la Tiroides/cirugía , Neoplasias de la Tiroides/cirugíaRESUMEN
In order to evaluate the prognostic value of the anatomical stage (pTNM 1992) and of the histological factors (Führman's grade, cellular and architectural types), 170 renal cell carcinoma diagnosed between 1971 and 1991 were reviewed. In univariate analysis, the prognosis was correlated with the anatomical stage and Führman's grade: for the 125 patients without metastasis, grades 1 and 2 had a good prognosis, whereas grades 3 and 4 did poorly. The cellular type was not related to survival. Among architectural types, only the pseudo-sarcomatous type was correlated with prognosis. Multivariate analysis revealed that grade and metastasis at diagnosis were two independent predictors of survival; the grade was prognostically superior to metastasis. Führman's grade is essential in determining prognosis; its statistical value is superior to anatomical stage in multivariate analysis.
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Carcinoma de Células Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: Nodular thyroid disease, indicated by the presence of single or multiple nodules within the thyroid gland is a common clinical problem, the main question remains the malignancy. Radionuclide scanning, ultrasonography and fine needle aspiration biopsy have been helpful to distinguish benign from malignant nodules and to select patients for surgery. METHODS: We performed a prospective study to assess the comparative value of fine needle nonaspiration biopsy and thyroid scinti scan in the management of 412 patients operated for solitary thyroid nodule. RESULTS: Sensitivity and negative predictive values were the same for both methods, but specificity of cytology was greater than that of thyroid scinti scan (80.53% vs. 10.47%, p < 0.001). DISCUSSION: Thyroid radionuclide scanning remains valuable in the evaluation of a cytological benign solitary thyroid nodule when TSH value is low, in order to distinguish toxic adenoma from cold nodule in Graves' disease.
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Biopsia con Aguja , Nódulo Tiroideo/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Cintigrafía , Sensibilidad y Especificidad , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Tirotropina/sangreRESUMEN
We report a prospective quantitative image analysis study of C cells in 57 normal autopsy thyroid glands, serially sectioned and wholly embedded in paraffin; all slides were immunohistochemically stained for calcitonin. Computerized quantitative image analysis was performed on 47 cases to measure C cell surface area and parenchymatous surface area after immunoperoxidase staining for calcitonin. The method was time-effective, with a good reproducibility. C cells were mainly found in the middle third of each lobe. Important inter-individual variations were observed; the maximum C cell surface area in a section (Amax) ranged from 28 x 10(3) to 470 x 10(3) microns2 (mean, 167 x 10(3) microns2) among 42 adults. Of particular interest was the important difference observed between sexes; Amax was twice as high in men (mean, 201 x 10(3) microns2) as in women (mean, 91 x 10(3) microns2; P = 0.0009). Moreover, 14 (33%) adult subjects [2 women (15%) and 12 men (41%)] fulfilled C cell hyperplasia criteria, i.e. at least 3 fields at x 100 magnification containing more than 50 C cells, suggesting that a substantial part of the normal adult population could have C cell hyperplasia.