RESUMO
The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.
Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Abordagem GRADE , Neoplasias Pulmonares/patologia , Adenocarcinoma/patologiaRESUMO
AIMS: To gather the best available evidence regarding Ki-67% values in large-cell neuroendocrine carcinoma (LCNEC) and determine whether certain cut-off values could serve as a prognostic feature in LCNEC. METHODS AND RESULTS: Aperio ScanScope AT Turbo, eSlide Manager and ImageScope software (Leica Biosystems) were used to measure Ki-67% in 77 resected LCNEC diagnosed by World Health Organisation (WHO) criteria. Cases were stratified into six classes by 10% Ki-67 increments. Using the Kaplan-Meier method, overall (OS) and disease-free survivals (DFS) were compared by AJCC stage, by six Ki-67% classes and with Ki-67% cut-points ≥20% and ≥40%. Tumours were from 0.9 to 11.5 cm and pathological stages 1-3. The system measured Ki-67% positivity using 4072-44 533 tumour nuclei per case (mean 16610 ± 8039). Ki-67% ranged from 1 to 64% (mean = 26%; median = 26%). Only 16 (21%) tumours had Ki-67% ≥40%. OS ranged from 1 to 298 months (median follow-up = 25 months). DFS ranged from 1 to 276 months (median follow-up = 9 months). OS and DFS differed across AJCC stage (overall log-rank P = 0.038 and P = 0.037). However, neither OS nor DFS significantly correlated with Ki-67% when six or two classes were used with either ≥20% Ki-67 or ≥40% Ki-67 as cut-point. A literature review identified 14 reports meeting our inclusion criteria with ≥10 LCNEC. Reported Ki-67% ranged from 2% to 100%. Problems contributing to variability in Ki-67% measurements are discussed. CONCLUSION: Our findings caution against a blanket use of 20%, 40% or other Ki-67% cut-points for LCNEC diagnosis or prognostication.
Assuntos
Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Antígeno Ki-67/análise , Prognóstico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/diagnóstico , Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM). In whole sections and tissue microarrays, respectively, membranous HEG1 was expressed in 93.0% and 85.5% of EM, 81.3% and 69.4% of BM, 0% and 0% of SM. HEG1 was not expressed in pulmonary adenocarcinomas. HEG1 was expressed as cytoplasmic immunoreactivity in pulmonary squamous cell carcinomas (21.7%). Membranous HEG1 staining was seen in ovarian carcinomas (66.7%), thyroid carcinomas (100%), reactive conditions (16.7%), and mesenchymal tumors (18.8%). The sensitivity of membranous HEG1 expression to distinguish EM/BM from all carcinomas was 88.8%. The specificity for the differential diagnosis between EM/BM and all carcinomas and pulmonary carcinomas was 92.3% and 98.7%, respectively.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Proteínas de Membrana/metabolismo , Mesotelioma Maligno/diagnóstico , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Epitélio/patologia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Proteínas de Membrana/genética , Mesotelioma Maligno/patologia , Análise Serial de TecidosRESUMO
Median Arcuate Ligament Syndrome (MALS) is a rare entity characterized by severe post-prandial epigastric pain, nausea, vomiting, and/or weight loss. Symptoms have been attributed to vascular compression (celiac artery compression syndrome, CACS), but it remains controversial whether they could be secondary to neural compression. Literature review identified rare description of pathologic findings in surgery journals. The clinico-pathologic findings of four MALS patients who underwent robotic or laparoscopic surgery in our hospital are described. All our patients were female with a median age of 32.5 (range 25-55 years), and a median BMI of 23.5 kg/m2. They presented with chronic often post-prandial abdominal pain (4/4), nausea (3/4), emesis (2/4), anorexia (1/4), and weight loss (1/4). Two patients had a history of Crohn's disease. At intraoperative exploration, the celiac artery and adjacent nerves and ganglia were encased and partially compressed by fibrotic tissue in each patient. In each case laparoscopic excision of fibrotic tissue, celiac plexus and ligament division and was performed; celiac plexus nerve block was also performed in one patient. After surgical intervention, symptoms improved in three of the patients whose specimens show periganglionic and perineural fibrosis with proliferation of small nerve fibers. Our findings support neurogenic compression as a contributing factor in the development of pain and other MALS symptoms, and favor the use of MALS rather than CACS as diagnostic terminology. To further study the pathogenesis of this unusual syndrome, surgeons should submit all tissues excised during MALS procedures for histopathologic examination.
Assuntos
Artéria Celíaca/patologia , Plexo Celíaco/patologia , Fibrose/patologia , Gânglios Simpáticos/patologia , Síndrome do Ligamento Arqueado Mediano/patologia , Dor Abdominal/etiologia , Adulto , Índice de Massa Corporal , Artéria Celíaca/cirurgia , Plexo Celíaco/cirurgia , Constrição Patológica/etiologia , Feminino , Fibrose/cirurgia , Gânglios Simpáticos/cirurgia , Humanos , Laparoscopia/métodos , Síndrome do Ligamento Arqueado Mediano/diagnóstico , Síndrome do Ligamento Arqueado Mediano/cirurgia , Pessoa de Meia-Idade , Náusea/etiologia , Bloqueio Nervoso/métodos , Avaliação de Resultados em Cuidados de Saúde , Período Pós-Prandial , Procedimentos Cirúrgicos Robóticos/métodos , Vômito/etiologia , Redução de PesoRESUMO
Localized malignant mesotheliomas (LMM) is an uncommon and poorly recognized neoplasm. Its pathologic diagnosis is often surprising in patients with serosal/subserosal based localized tumors that are clinically suspicious for metastatic lesions or primary sarcomas. Once a tumor is diagnosed as "mesothelioma", LMM is often mistaken for diffuse malignant mesothelioma (DMM). Best currently available evidence about LMM was collected from the literature and cases diagnosed by members of the International Mesothelioma Panel (IMP). One hundred and one (101) LMM have been reported in the English literature. Patients had localized tumors with identical histopathologic features to DMM. Patients ranged in age from 6 to 82 years; 75% were men. Most (82%) of the tumors were intrathoracic. Others presented as intrahepatic, mesenteric, gastric, pancreatic, umbilical, splenic, and abdominal wall lesions. Tumors varied in size from 0.6 to 15 cm. Most patients underwent surgical resection and/or chemotherapy or radiation therapy. Median survival in a subset of patients was 29 months. Seventy two additional LMM from IMP institutions ranged in age from 28 to 95 years; 58.3% were men. Sixty tumors (83.3%) were intrathoracic, others presented in intraabdominal sites. Tumors varied in size from 1.2 to 19 cm. Median survival for 51 cases was 134 months. Best evidence was used to formulate guidelines for the diagnosis of LMM. It is important to distinguish LMM from DMM as their treatment and prognosis is different. A multidisciplinary approach is needed for the diagnosis of LMM as it shows identical histopathology and immunophenotype to DMM.
Assuntos
Mesotelioma Maligno/patologia , Neoplasias Pleurais/patologia , Tumor Fibroso Solitário Pleural/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Diagnóstico Diferencial , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Mesotelioma Maligno/diagnóstico por imagem , Mesotelioma Maligno/mortalidade , Mesotelioma Maligno/terapia , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Valor Preditivo dos Testes , Prognóstico , Tumor Fibroso Solitário Pleural/diagnóstico por imagem , Tumor Fibroso Solitário Pleural/mortalidade , Tumor Fibroso Solitário Pleural/terapia , Carga Tumoral , Adulto JovemRESUMO
Kappa statistics have been widely used in the pathology literature to compare interobserver diagnostic variability (IOV) among different pathologists but there has been limited discussion about the clinical significance of kappa scores. Five representative and recent pathology papers were queried using clinically relevant specific questions to learn how IOV was evaluated and how the clinical applicability of results was interpreted. The papers supported our anecdotal impression that pathologists usually assess IOV using Cohen's or Fleiss' kappa statistics and interpret the results using some variation of the scale proposed by Landis and Koch. The papers did not cite or propose specific guidelines to comment on the clinical applicability of results. The solutions proposed to decrease IOV included the development of better diagnostic criteria and additional educational efforts, but the possibility that the entities themselves represented a continuum of morphologic findings rather than distinct diagnostic categories was not considered in any of the studies. A dataset from a previous study of IOV reported by Thunnissen et al. was recalculated to estimate percent agreement among 19 international lung pathologists for the diagnosis of 74 challenging lung neuroendocrine neoplasms. Kappa scores and diagnostic sensitivity, specificity, positive and negative predictive values were calculated using the majority consensus diagnosis for each case as the gold reference diagnosis for that case. Diagnostic specificity estimates among multiple pathologists were > 90%, although kappa scores were considerably more variable. We explain why kappa scores are of limited clinical applicability in pathology and propose the use of positive and negative percent agreement and diagnostic specificity against a gold reference diagnosis to evaluate IOV among two and multiple raters, respectively.
Assuntos
Benchmarking/estatística & dados numéricos , Técnicas e Procedimentos Diagnósticos/estatística & dados numéricos , Pulmão/patologia , Tumores Neuroendócrinos/diagnóstico , Patologistas/normas , Benchmarking/métodos , Consenso , Técnicas e Procedimentos Diagnósticos/tendências , Medicina Baseada em Evidências/métodos , Humanos , Variações Dependentes do Observador , Patologia/normas , Valor Preditivo dos Testes , Projetos de Pesquisa/tendências , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
Survival data from 225 patients with resected pulmonary typical carcinoids were analyzed with Kaplan-Meier statistics (K-M) and "deep learning" methods to illustrate the difference between establishing "correlations" and "prognostications". Cases were stratified into G1 and G2 classes using a ≤5% Ki-67% cut-point. Overall survival, number of patients at risk and 95% confidence intervals (CI) were estimated for the two classes. Seven neural network models (NN) were developed with GMDH Shell 3.8.2 and Statgraphics Centurion 18.1 software, using variable prior probabilities and different numbers of training vs testing cases. The NNs used age, sex, and pTNM, G1 and G2 as input neurons and "alive" and "dead" as output neurons. Areas under the curve (AUC) and other performance measures were evaluated for all models. Log-rank test showed a significant difference in overall survival between G1 and G2 (p < 0.001). However, 95% CI estimates showed considerable variability in survival at different time intervals. Including the number of patients at risk at different time intervals showed that most G2 patients had been censored by 100 weeks. The NN models provided variable "prognostications", with AUC ranging from 0.5 to 1 and variability in the sensitivity, specificity, and other performance measures. The results illustrate the limitations of survival statistics and NNs in predicting the prognosis of individual patients. The need for pathologists not to overinterpret the finding of significant correlations as "prognostic" or "predictive" for individual patients is discussed.
Assuntos
Tumor Carcinoide/mortalidade , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Redes Neurais de Computação , Patologia Clínica/métodos , Humanos , Patologia Clínica/normas , PrognósticoRESUMO
"Personalized medicine" has been proposed as a new paradigm for patient care that, based on the integration of genomics and other "omics" data with clinical and other multidisciplinary information, promises early disease detection, improved outcomes and reduced side effects to therapies. Pathologists have become important participants in this new approach as the guardians of tissues and experts in the performance of molecular and other laboratory tests. Large amounts of new laboratory data in multiple neoplasms and other entities are being reported but there has been limited discussion about how best to evaluate the clinical significance of this information and how to integrate it into currently available diagnostic and therapeutic modalities. This article introduces a variety of epistemological problems presented by the "personalized medicine" paradigm and briefly discusses various topics that will be evaluated in further detail in future articles of this new series on Evidence-Based Pathology.
Assuntos
Genômica/métodos , Imuno-Histoquímica/métodos , Neoplasias/metabolismo , Neoplasias/terapia , Medicina de Precisão/métodos , Diagnóstico Precoce , Medicina Baseada em Evidências/métodos , Humanos , Conhecimento , Laboratórios/estatística & dados numéricos , Neoplasias/patologia , Patologistas/estatística & dados numéricos , Medicina de Precisão/normas , Projetos de Pesquisa/normasRESUMO
It is uncertain whether thymic neuroendocrine tumors (NET) associated with Cushing's syndrome (CS) produce corticotropin-releasing hormone (CRH) and adrenocorticotropin hormone (ACTH) and whether the thymus contains ACTH and/or CRH cells that could originate NET. The clinicopathologic features of 5 typical (TC) and 6 atypical carcinoids (ATC), 10 additional non-neoplastic thymi, 6 adrenal glands with bilateral nodular hyperplasia and 8 adrenal cortical adenomas were reviewed. Representative slides were immunostained for ACTH and CRH. Four (36.4%) of the 11 patients had CS. The incidence of Masaoka stage IV was higher (pâ¯<â¯0.0001) in patients with ATC than TC. Only 2 (18.1%) of the 11 patients were alive at follow-up. Ten NET were CRH immunoreactive and 6 were ACTH immunoreactive. Thymic NET with CS exhibited stronger immunoreactivity for ACTH and CRH than those without CS. Non-neoplastic thymi exhibited scattered ACTH and CRH immunoreactive cells. Normal adrenal cortex and glands with bilateral nodular hyperplasia showed diffuse CRH immunoreactivity while adrenal adenomas showed no or only focal CRH immunoreactivity. Literature review showed no association between thymic NET and adrenal adenomas. The thymus contains CRH and ACTH immunoreactive cells that are probably the origin of thymic NET. Neoplasms associated with CS exhibit strong immunoreactivity for both hormones, suggesting that CRH probably plays a role in the pathogenesis of CS. As adrenals with bilateral nodular hyperplasia exhibit diffuse CRH immunoreactivity and adrenal cortical adenomas either lack this finding or show few immunoreactive cells, this marker may be useful to distinguish these lesions.
Assuntos
Tumor Carcinoide/patologia , Síndrome de Cushing/etiologia , Células Neuroendócrinas/patologia , Neoplasias do Timo/patologia , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Idoso , Tumor Carcinoide/complicações , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células Neuroendócrinas/metabolismo , Neoplasias do Timo/complicações , Adulto JovemRESUMO
Although Ki-67 labeling index (Ki-67%) is not a diagnostic or grading criterion in the World Health Organization classification of pulmonary carcinoid tumor, oncologists often request this test. A survey was administered at a North American Society for Neuroendocrine Tumors meeting to understand how Ki-67% is used in oncologic practices. A systematic literature review was performed to gather best evidence regarding the use of Ki-67%. Consecutive pulmonary carcinoids were stratified into pulmonary typical carcinoids with Ki-67% <5% (group A, n = 187), typical carcinoids with Ki-67% ≥5% (group B, n = 38) and atypical carcinoids irrespective of Ki-67% (group C, n = 31). Overall survival, progression-free survival, recurrence proportions and time to recurrence were compared, by group, using the log-rank test, chi-square statistics and ANOVA, respectively. Our survey confirmed that Ki-67% is frequently used by specialists caring for these patients. Ki-67% of 1-7% significantly correlated with overall survival in the literature but we found no information about Ki-67% cut-off values that would accurately distinguish pulmonary typical from atypical carcinoids or estimate the prognosis of patients stratified by World Health Organization diagnosis and Ki-67% cut-off. Overall survival was significantly different in our 3 patient groups (p < 0.001), with survival probabilities decreasing from groups A to C. Progression-free survival was significantly longer in group A than B (p < 0.007). Our results support the concept that by combining World Health Organization diagnosis and Ki-67%, pulmonary carcinoids can be stratified into 3 grades: G1 (typical carcinoids with Ki-67% <5), G2 (typical carcinoids with Ki-67% ≥5%) and G3 (atypical carcinoids) with different prognoses.
Assuntos
Antígeno Ki-67/análise , Neoplasias Pulmonares/patologia , Oncologia/métodos , Gradação de Tumores/métodos , Tumores Neuroendócrinos/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Tumor Carcinoide/classificação , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/classificação , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/mortalidade , Padrões de Prática Médica , Prognóstico , Inquéritos e QuestionáriosRESUMO
AIMS: The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit organization formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists-Association Canadienne des Pathologists in association with the Canadian Partnership Against Cancer, and the European Society of Pathology. Its goal is to produce standardized, internationally agreed, evidence-based datasets for use throughout the world. METHODS AND RESULTS: This article describes the development of a cancer dataset by the multidisciplinary ICCR expert panel for the reporting of thymic epithelial tumours. The dataset includes 'required' (mandatory) and 'recommended' (non-mandatory) elements, which are validated by a review of current evidence and supported by explanatory text. Seven required elements and 12 recommended elements were agreed by the international dataset authoring committee to represent the essential information for the reporting of thymic epithelial tumours. CONCLUSIONS: The use of an internationally agreed, structured pathology dataset for reporting thymic tumours provides all of the necessary information for optimal patient management, facilitates consistent and accurate data collection, and provides valuable data for research and international benchmarking. The dataset also provides a valuable resource for those countries and institutions that are not in a position to develop their own datasets.
Assuntos
Oncologia/normas , Neoplasias Epiteliais e Glandulares , Patologia Clínica/normas , Projetos de Pesquisa/normas , Neoplasias do Timo , HumanosRESUMO
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is recognized as a preneoplastic condition by the World Health Organization. We reviewed our experience with 30 patients and performed a systematic review of the English literature to collect best evidence on the clinical features and disease course in 169 additional patients. Some patients presented with one or more carcinoid tumors associated with multiple small pulmonary nodules on imaging studies and showed DIPNECH as a somewhat unexpected pathologic finding. Others presented with multiple small pulmonary nodules that raised suspicion of metastatic disease on imaging. A third subset was presented with previously unexplained respiratory symptoms. In most patients, DIPNECH was associated with a good prognosis, with chronological progression into a subsequent carcinoid tumor noted in only one patient and death attributed directly to DIPNECH in only two patients. There is no best evidence to support the use of octreotide, steroids, or bronchodilators in DIPNECH patients.
Assuntos
Tumor Carcinoide/terapia , Pneumopatias/terapia , Neoplasias Pulmonares/terapia , Pulmão/patologia , Células Neuroendócrinas/patologia , Lesões Pré-Cancerosas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Tumor Carcinoide/complicações , Tumor Carcinoide/diagnóstico , Tosse/etiologia , Progressão da Doença , Dispneia/etiologia , Feminino , Humanos , Hiperplasia/complicações , Hiperplasia/diagnóstico , Hiperplasia/terapia , Pneumopatias/complicações , Pneumopatias/diagnóstico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/etiologia , Nódulos Pulmonares Múltiplos/terapia , Pneumonectomia , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/diagnóstico , Radiografia , Testes de Função Respiratória , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Resultado do TratamentoRESUMO
Small cell carcinoma of the lung (SCLC) is a well characterized form of lung cancer that is frequently already metastatic at diagnosis. Thus, patients with SCLC are usually treated with chemotherapy, and therefore emphasis has been placed on distinguishing that tumor from squamous cell carcinomas, large cell carcinomas and other pulmonary neoplasms that can more often be managed surgically. SCLC can be readily and accurately diagnosed in biopsy specimens or cytological preparations, but in selected cases, it can pose difficult diagnostic dilemmas. This review discusses selected problems encountered during the pathologic diagnosis of SCLC, including its distinction from other neuroendocrine lesions such as large cell neuroendocrine carcinoma and "carcinoid" tumors." The role of immunohistology is also considered in this context.
Assuntos
Neoplasias Pulmonares/patologia , Células Neuroendócrinas/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Biópsia , Proliferação de Células , Tamanho Celular , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Neoplasias Pulmonares/química , Neoplasias Pulmonares/terapia , Gradação de Tumores , Células Neuroendócrinas/química , Valor Preditivo dos Testes , Carcinoma de Pequenas Células do Pulmão/química , Carcinoma de Pequenas Células do Pulmão/terapiaRESUMO
Neuroendocrine neoplasms of the lung continue to undergo scrutiny, with respect to the diagnostic terminology recommended for them and details of their clinicopathologic profiles. This overview considers the nosological evolution of such lesions and presents current views on classification schemes that pertain to them.
Assuntos
Neoplasias Pulmonares/patologia , Células Neuroendócrinas/patologia , Tumores Neuroendócrinos/patologia , Terminologia como Assunto , Apoptose , Biomarcadores Tumorais/análise , Biópsia , Proliferação de Células , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/química , Neoplasias Pulmonares/classificação , Necrose , Células Neuroendócrinas/química , Células Neuroendócrinas/classificação , Tumores Neuroendócrinos/química , Tumores Neuroendócrinos/classificação , Valor Preditivo dos Testes , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a pre-invasive generalized proliferation of pulmonary neuroendocrine (PNE) cells, which has been described in combination with carcinoid tumorlets, obliterative bronchiolitis, and other fibrotic lung changes. Since its first recognition as a distinct syndrome in 1992, variable clinico-pathologic features have been used to diagnose DIPNECH in small case series and case reports. We recently proposed the use of the following criteria for the pathologic diagnosis of the syndrome on lung resection specimens: the presence of multifocal neuroendocrine cell hyperplasia, as defined by the presence of 5 or more PNE cells in at least 3 separate small airways combined with 3 or more carcinoid tumorlets. At diagnosis, 53% of DIPNECH patients present with a synchronous carcinoid tumor and 24% have obliterative bronchiolitis. To our knowledge, only 1 patient has been diagnosed with a carcinoid tumor subsequent to a DIPNECH diagnosis and the syndrome is not associated with an increased incidence of high-grade neuroendocrine neoplasms. Patients have usually a stable disease and only 26% experience clinical and/or radiographic deterioration. There is no evidence that treatment with octreotide or other medications improves the prognosis of DIPNECH patients.
Assuntos
Proliferação de Células , Pneumopatias/patologia , Pulmão/patologia , Células Neuroendócrinas/patologia , Idade de Início , Biomarcadores/metabolismo , Biópsia , Humanos , Hiperplasia , Imuno-Histoquímica , Pulmão/metabolismo , Pneumopatias/epidemiologia , Pneumopatias/metabolismo , Pneumopatias/terapia , Células Neuroendócrinas/metabolismo , Fenótipo , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
The potential usefulness of the squamous markers p40 and desmoglein 3 (DSG-3) for the diagnosis and staging of selected thymic lesions is uncertain. We investigated their expression and distribution pattern in 66 thymomas, 12 thymic squamous carcinomas, 6 undifferentiated thymic carcinomas, 5 hyperplastic thymi, and 5 normal thymi. p40 nuclear and DSG-3 cytoplasmic/membranous immunoreactivity in greater than or equal to 10% of thymic epithelial cells was interpreted as positive, and DSG-3 distribution pattern was classified as organotypic and nonorganotypic. All nonneoplastic thymic tissues, 100% of thymic squamous carcinomas, 97% of thymomas, and 50% of undifferentiated thymic carcinomas were positive for p40. Expression of p40 in almost all thymomas and in 50% of undifferentiated carcinomas that lacked squamous features suggests that p40 is not a good marker for the diagnosis of thymic squamous carcinoma. All normal and hyperplastic thymi, 51.5% of thymomas, and 0% of thymic squamous carcinomas expressed DSG-3 in an organotypic pattern, and 13.6% of thymomas and 83% of thymic squamous carcinomas were DSG-3 positive in a nonorganotypic pattern. Findings suggest that nonorganotypic DSG-3 expression favors the diagnosis of squamous cell carcinoma over thymoma. In 26 (60.5%) of the 43 cases where neoplastic and nonneoplastic thymus were present on the same slide, the presence/absence or distribution pattern of DSG-3 immunoreactivity was different in the 2 components, suggesting that this marker can be helpful in staging thymomas with incomplete encapsulation. The presence of DSG-3-positive and DSG-3-negative thymomas raises the possibility that these tumors may originate from 2 different types of thymic epithelial cells.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Desmogleína 3/metabolismo , Epitopos Imunodominantes/metabolismo , Doenças Linfáticas/metabolismo , Fragmentos de Peptídeos/metabolismo , Timoma/metabolismo , Neoplasias do Timo/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , Criança , Pré-Escolar , Desmogleína 3/análise , Feminino , Humanos , Epitopos Imunodominantes/análise , Técnicas Imunoenzimáticas/métodos , Doenças Linfáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fragmentos de Peptídeos/análise , Timoma/patologia , Neoplasias do Timo/patologia , Adulto JovemRESUMO
Carcinomas from either pulmonary or extrapulmonary sites can metastatise to supraclavicular lymph nodes. Immunohistochemistry (IHC) is invaluable to comment on the possible primary site. However, the optimal number of antibodies to be tested is debatable. Seven antibodies were tested on 135 metastatic supraclavicular lymph node biopsies to propose a "best minimal" IHC panel to infer lung carcinoma, incorporating the principles of "evidence-based medicine." The 135 cases were divided into the following: category I (110 cases), wherein the primary was in the lung based on histologic analysis (Ia, n = 14 [12.7%]), cytologic analysis (Ib, n = 43 [39.1%]), or strong clinicoradiologic evidence (Ic, n = 53 [48.2%]), and category II (25 cases) with a histologically proven extrapulmonary primary site. Categories Ia and Ib were together designated as the "control group," and category Ic was designated as the "test group." The antibodies tested were cytokeratin (CK 7, CK20), epithelial membrane antigen, carcinoembryonic antigen, thyroid transcription factor-1 (TTF-1), surfactant protein B (SPB), and vimentin. Results of both individual and panels of antibodies were statistically evaluated. The sensitivity and specificity of single antibodies for inferring a lung primary was as follows: CK7 (90%/56%), CK20 (98%/40%), epithelial membrane antigen (90.9%/4%), carcinoembryonic antigen (80.9%/36%), TTF-1 (62.7%/100%), SPB (65.6%/100%), and vimentin (60.9%/60%). The highest sensitivity (85%) and specificity (100%) were seen with a 4-antibody panel: CK7, CK20, TTF-1, and SPB. This panel revealed the highest binomial probability (.8), for diagnosing lung cancer. The results were validated using a "split sample method," and a high concordance was noted between the control and test groups. To conclude, such evidence-based validated studies analyzing IHC results would be invaluable to guide the practice of surgical pathology in the future.
Assuntos
Anticorpos Antineoplásicos , Biomarcadores Tumorais/análise , Carcinoma/secundário , Neoplasias Pulmonares/diagnóstico , Linfonodos/patologia , Biópsia , Carcinoma/metabolismo , Clavícula , Demografia , Medicina Baseada em Evidências , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Linfonodos/metabolismo , Metástase Linfática , Masculino , Sensibilidade e EspecificidadeRESUMO
CONTEXT.: Robotic-assisted navigation bronchoscopy (R-ANB) is used to target peripheral pulmonary nodules that are difficult to biopsy using conventional approaches. Frozen sections are requested to confirm these lesions have been localized and/or to diagnose neoplasms that can be immediately resected. OBJECTIVE.: To estimate diagnostic concordance between frozen section diagnosis (FSD) and formalin-fixed tissue diagnosis (FFTD) in biopsies obtained with R-ANB, calculate the sensitivity and specificity of FSD and FFTD for a diagnosis of malignancy, and evaluate whether the residual tissue that can be fixed in formalin after frozen section still has sufficient material for molecular studies. DATA SOURCES.: The results of consecutive FSD rendered on biopsies performed with R-ANB during a 30-month period were used to calculate the metrics listed above. FFTD and/or the diagnoses rendered on computed tomography-guided core biopsy subsequently performed in patients with negative R-ANB and/or lung resections in patients with malignancies were used as true-positive results. The overall concordance between FSD and FFTD in 226 lesions from 203 patients was 72%. Frozen section diagnosed 76 of 123 malignancies with 100% specificity and 68% sensitivity. Adequate material was available in 92% of biopsies where next-generation sequencing and other molecular studies were requested. CONCLUSIONS.: Intraoperative consultations are helpful to diagnose a variety of lung lesions and help surgeons confirm that targets have been accurately reached by R-ANB. Malignancies can be diagnosed with 100% specificity but only 68% sensitivity. The performance of frozen section did not interfere with the subsequent analysis of tissue with molecular studies in most cases.