RESUMO
Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.
Assuntos
Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia , Antígeno Ki-67/metabolismo , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Adulto JovemRESUMO
BACKGROUND: Histopathological features associated with coexistent invasive adenocarcinoma in large colorectal adenomas have not been described. This study aimed to determine the association of histopathological features in areas of low-grade dysplasia with coexistent invasive adenocarcinoma. METHODS: High-grade lesions (containing high-grade dysplasia or adenocarcinoma) from a cohort of large (at least 20 mm) colorectal adenomas removed by endoscopic resection were subjected to detailed histopathological analysis. The histopathological features in low-grade areas with coexistent adenocarcinoma were reviewed and their diagnostic performance was evaluated. RESULTS: Seventy-four high-grade lesions from 401 endoscopic resections of large adenomas were included. In the low-grade dysplastic areas, a coexistent invasive adenocarcinoma was associated significantly with a cribriform or trabecular growth pattern (P < 0.001), high nuclear grade (P < 0.001), multifocal intraluminal necrosis (P < 0.001), atypical mitotic figures (P = 0.006), infiltrative lesion edges (P < 0.001), a broad fibrous band (P = 0.001), ulceration (P < 0.001), expansile nodules (P < 0.001) and an extensive tumour-infiltrating lymphocyte pattern (P = 0.04). Lesions with coexistent invasive adenocarcinoma harboured at least one of these features. The area under the receiver operating characteristic curve (AUROC) for coexistent invasive adenocarcinoma, using frequencies of adverse histopathological factors in low-grade areas, was 0.92. The presence of two or more of these adverse histopathological features in low-grade areas had a sensitivity of 86 per cent and a specificity of 84 per cent for coexistent invasive adenocarcinoma. CONCLUSION: Several histopathological features in low-grade dysplastic areas of adenomas could be predictive of coexistent adenocarcinoma.
Assuntos
Adenocarcinoma , Adenoma , Pólipos Adenomatosos , Neoplasias Colorretais , Neoplasias Retais , Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Adenoma/complicações , Adenoma/cirurgia , Pólipos Adenomatosos/complicações , Pólipos Adenomatosos/cirurgia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , HumanosRESUMO
Experimental models of Graves' hyperthyroid disease accompanied by Graves' orbitopathy (GO) can be induced efficiently in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. In this study, we report on the development of a bona fide murine model of autoimmune Graves' disease induced with homologous mouse TSHR A-subunit plasmid. Autoimmune thyroid disease in the self-antigen model was accompanied by GO and characterized by histopathology of hyperplastic glands with large thyroid follicular cells. Examination of orbital tissues showed significant inflammation in extra-ocular muscle with accumulation of T cells and macrophages together with substantial deposition of adipose tissue. Notably, increased levels of brown adipose tissue were present in the orbital tissue of animals undergoing experimental GO. Further analysis of inflammatory loci by 19 F-magnetic resonance imaging showed inflammation to be confined to orbital muscle and optic nerve, but orbital fat showed no difference in inflammatory signs in comparison to control ß-Gal-immunized animals. Pathogenic antibodies induced to mouse TSHR were specific for the self-antigen, with minimal cross-reactivity to human TSHR. Moreover, compared to other self-antigen models of murine Graves' disease induced in TSHR knock-out mice, the repertoire of autoantibodies to mouse TSHR generated following the breakdown of thymic self-tolerance is different to those that arise when tolerance is not breached immunologically, as in the knock-out models. Overall, we show that mouse TSHR A-subunit plasmid immunization by electroporation overcomes tolerance to self-antigen to provide a faithful model of Graves' disease and GO.
Assuntos
Autoantígenos/imunologia , Doença de Graves/imunologia , Oftalmopatia de Graves/imunologia , Inflamação/imunologia , Nervo Óptico/imunologia , Receptores da Tireotropina/imunologia , Tireoidite Autoimune/imunologia , Animais , Autoanticorpos/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Humanos , Imunização , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Miosite Orbital , Plasmídeos/imunologia , Receptores da Tireotropina/genética , Tolerância a Antígenos PrópriosAssuntos
Carcinoma Basocelular/complicações , Deformidades do Pé/etiologia , Dermatoses da Mão/etiologia , Hipotricose/complicações , Psoríase/etiologia , Neoplasias Cutâneas/complicações , Idoso , Carcinoma Basocelular/diagnóstico , Diagnóstico Diferencial , Feminino , Deformidades do Pé/diagnóstico , Dermatoses da Mão/diagnóstico , Humanos , Hipotricose/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Psoríase/diagnóstico , Pele/patologia , Neoplasias Cutâneas/diagnósticoRESUMO
BACKGROUND: Parathyroid cancer has a poor mid-term prognosis, often because of local recurrence, observed in half of all patients. Modern diagnostic workup increasingly enables a preoperative diagnosis of parathyroid cancer. There is limited evidence that more comprehensive oncologic surgery can reduce the risk of local recurrence. This study aims to identify the best specific surgical approach in parathyroid cancer. METHODS: This observational cohort study comprises 19 consecutive patients who had undergone oncologic or nononcologic resection for parathyroid cancer. Baseline parameters were compared by using univariate analysis; outcomes were assessed by χ (2) testing and Kaplan-Meier statistics. RESULTS: Fifteen of 19 patients were primarily operated on in our tertiary center between 1996 and 2013, and four were referred for follow-up because of their cancer diagnosis. Patient cohorts defined by histologic R-status were comparable for established risk factors: sex, calcium levels, low-risk/high-risk status, and presence of vascular invasion. Oncologic resections were performed in 13 of 15 patients primarily treated in the center and 0 of 4 treated elsewhere (χ (2) = 5.6; p < 0.01). R0 margins were achieved in 11 of 13 (85 %) undergoing oncologic resection and 1 of 6 (17 %) undergoing local excision (χ (2) = 8.1; p < 0.01). R0 margins and primary oncologic resection were associated with higher disease-free survival rates (χ (2) = 7.9; p = 0.005 and χ (2) = 4.7; p = 0.03, respectively). Revision surgery achieved R0 margins in only 2 of 4 (50 %) of patients. CONCLUSIONS: In parathyroid cancer, a more comprehensive surgery (primary oncologic resection) provides significantly better outcomes than local excision as a result of reduction of R1 margins and locoregional recurrence.
Assuntos
Esvaziamento Cervical , Recidiva Local de Neoplasia , Neoplasias das Paratireoides/mortalidade , Neoplasias das Paratireoides/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Reoperação , Estudos RetrospectivosRESUMO
Varicella zoster virus (VZV) causes the common childhood disease chickenpox (varicella), or upon reactivation, the dermatomal vesiculopustular eruption seen in shingles (herpes zoster). The clinical course of herpes zoster in immunocompromised patients is often recurrent, protracted and multidermatomal, and it can result in myelitis, meningoencephalitis, and cerebral or small-vessel vasculopathic or vasculitic changes. Commonly, the vesicular rash settles with aciclovir therapy and does not involve motor neuropathy. We report a 63-year-old man with a prolonged, multidermatomal, nonvesicular rash, and limb paresis secondary to brachioplexitis. PCR for VZV was positive, and the histological results were consistent with granulomatous vasculopathy. Prolonged treatment with valaciclovir was required to resolve the eruption and help improve the patient's motor function. We discuss the problems faced in clinical decision-making about immunosuppressive treatment of granulomatous vasculopathy and motor neuropathy, when any increase in immunosuppressive therapy may increase the likelihood of central nervous system complications.
Assuntos
Neurite do Plexo Braquial/virologia , Granuloma/etiologia , Herpesvirus Humano 3/isolamento & purificação , Doenças Vasculares Periféricas/etiologia , Neurite do Plexo Braquial/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a heterogeneous group of severe adverse reactions to medications. The cutaneous phenotype has a number of guises, accompanied by a variety of systemic features including fever, haematological abnormalities and visceral involvement, most commonly the liver. Clinical markers of prognosis have not been identified. OBJECTIVES: To assess the cutaneous signs and dermatopathological features of DRESS in order to identify potential prognostic markers. METHODS: We reviewed the clinical features, dermatopathology and outcomes of 27 consecutive cases of DRESS presenting to a single unit. RESULTS: Four distinct patterns of cutaneous involvement were identified: an urticated papular exanthem (13/27 patients), a morbilliform erythema (three of 27), an exfoliative erythroderma (three of 27) and an erythema multiforme-like (EM-like) reaction consisting of atypical targets (eight of 27). All patients mounted a fever, most developed lymphadenopathy (24/27) and peripheral eosinophilia (25/27) and the most common organ involved was the liver (27/27). Review of the dermatopathic features of patients with DRESS demonstrated a superficial spongiotic dermatitis in the majority of cases (16/27). A smaller number of cases showed basal cell vacuolar degeneration and necrotic keratinocytes (nine of 27). The patients with these biopsy findings more commonly had an EM-like cutaneous phenotype, and more severe hepatic involvement. Three patients died, two following failed liver transplants. CONCLUSIONS: Our series is the first in which a detailed dermatological assessment has been made of consecutive patients presenting with DRESS, and the largest U.K. series to date. Our results suggest a possible prognostic role of the cutaneous and dermatopathic findings in DRESS in predicting the severity of visceral involvement in this syndrome. What's already known about this topic? ⢠Drug reaction with eosinophilia and systemic symptoms (DRESS) has a heterogeneous clinical presentation, with a skin eruption of variable morphology. ⢠DRESS carries considerable morbidity and mortality, usually hepatic in origin, although renal, pulmonary and pericardial involvement can be seen. What does this study add? ⢠The cutaneous phenotype in DRESS can be categorized as an urticated papular exanthem, a morbilliform erythema, exfoliative erythroderma or erythema multiforme-like (EM-like). ⢠An EM-like eruption DRESS may be prognostic of more severe hepatic involvement.
Assuntos
Toxidermias/patologia , Eosinofilia/patologia , Pele/patologia , Adulto , Idoso , Biópsia , Criança , Pré-Escolar , Dermatite Esfoliativa/etiologia , Dermatite Esfoliativa/patologia , Eritema/etiologia , Eritema/patologia , Exantema/etiologia , Exantema/patologia , Feminino , Febre/etiologia , Febre/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
Mucormycosis is a rare fungal infection with a high mortality that affects immunocompromised patients. This is an unusual case of necrosis of the tongue in a patient with pulmonary mucormycosis, diabetes mellitus, and aplastic anaemia.
Assuntos
Pneumopatias Fúngicas/complicações , Mucormicose/complicações , Doenças da Língua/microbiologia , Idoso , Anemia Aplástica/complicações , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Hospedeiro Imunocomprometido , Necrose , Infecções Oportunistas/microbiologiaAssuntos
Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Fita Cirúrgica , Feminino , Humanos , MasculinoRESUMO
INTRODUCTION: Congenital segmental emphysema (CSE) is a newly-recognised sub-type of congenital parenchymal lung anomaly. It is characterised by antenatal detection and post-natal evolution from an initially solid segmental appearance to a hyperlucent and hyperinflated segment. METHODS: A retrospective review of a single-centre tertiary referral database between Jan 1994 and Dec 2007 was performed. MAIN RESULTS: 130 infants had antenatally detected lung anomalies, and of these 12 (9.2%) infants (initially labelled as congenital cystic adenomatoid malformation (CCAM)), showed features better defined as CSE. The lesions were described antenatally as non-progressive microcystic (n=6), hyperechogenic (n=2) or both (n=2). Early post-natal CT scans showed areas of solid segmental parenchyma, initial hyperlucency or microcysts. Subsequent CT imaging, however, showed evolution to segmental hyperlucency in areas previously solid and in 2 cases a central bronchocele was noted. Ten children underwent resectional surgery (segmentectomy n=4, lobectomy n=6) at a median age of 1 (range 0.4-5.2) year and the gross appearance of the resected specimen confirmed hyperinflated (not cystic) segments. Histological review showed localised abnormally dilated alveolar spaces in 7 cases. Adjacent areas consistent with type 2 CCAM were also seen (n=3). CONCLUSION: CSE lies within the spectrum of both CCAM and sequestration but there is a definite post-natal evolution and volume change which presage symptoms. This may be associated with segmental bronchial atresia and progressive air trapping via collateral airways such as the interalveolar pores of Kohn.
Assuntos
Enfisema Pulmonar/patologia , Enfisema Pulmonar/cirurgia , Anormalidades do Sistema Respiratório/patologia , Anormalidades do Sistema Respiratório/cirurgia , HumanosRESUMO
We describe a case of drug rash with eosinophilia and systemic symptoms (DRESS) and graft-versus-host disease (GvHD) developing sequentially in a patient displaying reactivation of CMV. We discuss the possibility that similar pathogenic mechanisms may be involved in the development of DRESS and GvHD.
Assuntos
Infecções por Citomegalovirus/induzido quimicamente , Toxidermias/etiologia , Eosinofilia/induzido quimicamente , Doença Enxerto-Hospedeiro/induzido quimicamente , Infecções por Bactérias Gram-Negativas , Antibacterianos/efeitos adversos , Citomegalovirus/isolamento & purificação , Toxidermias/patologia , Eosinofilia/tratamento farmacológico , Eosinofilia/patologia , Doença Enxerto-Hospedeiro/patologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfocinas/imunologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Ativação ViralRESUMO
This review highlights the importance of morphology-molecular correlations for a proper implementation of new markers. It covers both general aspects of tumorigenesis (which are normally omitted in papers analysing molecular pathways) and the general mechanisms for the acquired capabilities of neoplasms. The mechanisms are also supported by appropriate diagrams for each acquired capability that include overlooked features such as mobilization of cellular resources and changes in chromatin, transcription and epigenetics; fully accepted oncogenes and tumour suppressor genes are highlighted, while the pathways are also presented as activating or inactivating with appropriate colour coding. Finally, the concepts and mechanisms presented enable us to understand the basic requirements for the appropriate implementation of molecular tests in clinical practice. In summary, the basic findings are presented to serve as a bridge to clinical applications. The current definition of neoplasm is descriptive and difficult to apply routinely. Biologically, neoplasms develop through acquisition of capabilities that involve tumour cell aspects and modified microenvironment interactions, resulting in unrestricted growth due to a stepwise accumulation of cooperative genetic alterations that affect key molecular pathways. The correlation of these molecular aspects with morphological changes is essential for better understanding of essential concepts as early neoplasms/precancerous lesions, progression/dedifferentiation, and intratumour heterogeneity. The acquired capabilities include self-maintained replication (cell cycle dysregulation), extended cell survival (cell cycle arrest, apoptosis dysregulation, and replicative lifespan), genetic instability (chromosomal and microsatellite), changes of chromatin, transcription and epigenetics, mobilization of cellular resources, and modified microenvironment interactions (tumour cells, stromal cells, extracellular, endothelium). The acquired capabilities defining neoplasms are the hallmarks of cancer, but they also comprise useful tools to improve diagnosis and prognosis, as well as potential therapeutic targets. The application of these concepts in oncological pathology leads to consideration of the molecular test requirements (Molecular Test Score System) for reliable implementation; these requirements should cover biological effects, molecular pathway, biological validation, and technical validation. Sensible application of molecular markers in tumour pathology always needs solid morphological support.
Assuntos
Biomarcadores Tumorais/análise , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos , Neoplasias/genética , Neoplasias/patologia , Progressão da Doença , Genes Supressores de Tumor , Humanos , Biologia Molecular , Neoplasias/químicaRESUMO
We report a 12-mm nodular, cream-coloured skin lesion that appeared on the left nasal ala in an 81-year-old man. This trabecular infiltrative tumour showed keratin microcysts, stromal hyalization, cytoarchitectural malignancy features, colonizing melanocytes, and immunoexpression of epithelial membrane antigen, cytokeratin 15/20, chromogranin, synaptophysin and CD56. To our knowledge, this is the first documented case of a trichilemmal carcinoma with neuroendocrine differentiation and melanocyte colonization, which is suggested by the trabecular growth pattern and requires immunohistochemical confirmation. The colonization of the epithelial nests by nonatypical dendritic or spindle melanocytes is a clue to morphological recognition of pilar neoplasms, along with the presence of stromal induction (CD34-positive peritumoral spindle cells), catagen-like apoptotic bodies, calcifications, keratin microcysts and cell balls.
Assuntos
Carcinoma Neuroendócrino/patologia , Carcinoma de Apêndice Cutâneo/patologia , Neoplasias Nasais/patologia , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/química , Carcinoma de Apêndice Cutâneo/química , Diagnóstico Diferencial , Progressão da Doença , Evolução Fatal , Humanos , Masculino , Melanócitos/patologia , Neoplasias Nasais/química , Fenótipo , Neoplasias Cutâneas/químicaRESUMO
BACKGROUND/OBJECTIVES: Merkel cell carcinomas (MCC) reveal epithelial and neuroendocrine differentiation, but its topographic cell kinetics remains unknown. This study analyses proliferation, apoptosis, and DNA ploidy by topography, features that can help planning therapeutic protocols. This study topographically analyses proliferation, apoptosis, and DNA ploidy. METHODS: We selected 27 small-cell MCCs (expressing one epithelial and two neural markers, with consistent ultrastructural findings) to evaluate mitotic figure counting, Ki-67 index, apoptosis index based on the in situ end labelling of fragmented DNA (using Escherichia coli DNA polymerase I, Klenow fragment), DNA ploidy, and BCL2 and TP53 immuno-expression. At least 50 high-power fields were screened per topographic compartment (superficial or papillary dermis, and deep or reticular dermis), recording average and standard deviation for each variable. Variables were statistically compared in each tumour compartment using analysis of variance and Student's t-test (significant if P < 0.05). RESULTS: MCCs revealed superficial aneuploid DNA content, and no topographic differences for proliferation markers. Apoptosis showed significantly lower values in the deep compartment (average, P = 0.0050, and standard deviation, P = 0.0074), correlating with increased BCL2 and TP53 immuno-expressions. CONCLUSIONS: High homogeneously distributed proliferation and superficial aneuploid DNA content defines MCCs. Apoptosis follows proliferation in superficial compartments, being less variable and proliferation independent in deep compartments, where it is inversely correlated with BCL2/TP53 expression.
Assuntos
Carcinoma de Célula de Merkel/patologia , Neoplasias Cutâneas/patologia , Antígenos de Neoplasias/metabolismo , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma de Célula de Merkel/metabolismo , Proliferação de Células , DNA de Neoplasias/análise , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Ploidias , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Cutâneas/metabolismo , Coloração e Rotulagem , Proteína Supressora de Tumor p53/metabolismoRESUMO
AIMS: To correlate histological infiltration patterns with genetic and mismatch repair (MMR) profiles in muscle-invasive bladder urothelial carcinomas (UroC). METHODS AND RESULTS: Infiltration patterns were assessed in the deep compartment of muscle-invasive UroC (nodular-trabecular, 45 cases; infiltrative, 27 cases). Tumour compartment (superficial and deep to muscularis mucosa) analysis included: microsatellite pattern of TP53, RB1, WT1 and NF1 by polymerase chain reaction/denaturing gradient gel electrophoresis; mitotic, Ki67, in situ end labelling (ISEL) indices and DNA ploidy. MMR was assessed by MLH1 and MSH2 sequencing and immunohistochemistry in UroC with two or more abnormal microsatellite loci. Statistical differences were tested using anova and Fisher's exact tests. Infiltrative UroC showed lower Ki67 index 14.94 +/- 4.28, ISEL index 14.1 +/- 10.0 and shorter median survival (20 months) than nodular-trabecular UroC (Ki67 index 20.65 +/- 4.94, ISEL 20.2 +/- 22.7, 37-month survival, respectively). The genetic profile was significantly different for RB1 (P = 0.0003) and NF1 (P = 0.0023) only, being more frequently abnormal in nodular-trabecular UroC. A significant decrease in MLH1 or MSH2 protein expression with no gene mutations was identified in UroC with microsatellite abnormalities and a nodular-trabecular growth pattern. CONCLUSIONS: Somatic down-regulation of MMR proteins in nodular-trabecular muscle-invasive UroC results in RB1/NF1 microsatellite abnormalities, correlating with higher cellular turnover and longer survival.
Assuntos
Carcinoma de Células de Transição/genética , Reparo de Erro de Pareamento de DNA , Instabilidade de Microssatélites , Neurofibromatose 1/genética , Proteína do Retinoblastoma/genética , Neoplasias da Bexiga Urinária/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Carcinoma de Células de Transição/patologia , Núcleo Celular/patologia , Proliferação de Células , DNA de Neoplasias/genética , Humanos , Pessoa de Meia-Idade , Músculo Liso/patologia , Proteína 1 Homóloga a MutL , Proteínas MutL , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína Supressora de Tumor p53/genética , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Proteínas WT1/genéticaAssuntos
Adenocarcinoma Folicular/patologia , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/metabolismo , Apoptose , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/análise , Cinética , Glândula Tireoide/química , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismoRESUMO
AIMS: The diagnosis of follicular thyroid carcinomas is mainly based on capsular and vascular invasion. The aim of this study was to determine the diagnostic relevance of nuclear features, inflammation and stromal changes. METHODS AND RESULTS: Anisokaryosis, chromatin pattern, nucleolus, nuclear pleomorphism, nuclear/cytoplasmic ratio, necrosis, stromal changes and tumour interstitial lymphocytes (TIL) were analysed in adenomatous hyperplastic nodules (39), adenomas (43) and carcinomas (28 minimally invasive, 48 widely invasive and 27 anaplastic). Ki67 immunostaining, in situ end labelling (ISEL) for apoptosis and the Ki67/ISEL index were analysed by topographical compartments. Variables were compared by histological diagnosis using Fisher's exact test, analysis of variance and Student's t-tests and considered significant if P < 0.05. TIL were absent in 96% of neoplasms and 54% of adenomatous hyperplastic nodules. Conspicuous nucleoli, increased nuclear-cytoplasmic ratio and coexistent apoptosis-myxoid changes distinguished minimally invasive carcinomas from adenomas. The most specific variables of high-grade carcinoma were vasculonecrotic patterns, nuclear hyperchromatism and pleomorphism. A kinetic advantage predominated in the internal compartments of benign lesions and in the peripheral compartments of malignant lesions. CONCLUSIONS: Follicular carcinomas show up-regulation of proliferation markers and the distinctive topographical kinetic profiles provide a basis for the distinction between benign and malignant and an explanation for the circumscription and encapsulation of benign lesions.