RESUMEN
The reporting of lung neuroendocrine neoplasms (NENs) according to the 2021 World Health Organisation (WHO) is based on mitotic count per 2 mm2, necrosis assessment and a constellation of cytological and immunohistochemical details. Accordingly, typical carcinoid and atypical carcinoid are low- to intermediate-grade neuroendocrine tumours (NETs), while large-cell neuroendocrine carcinoma (NEC) and small-cell lung carcinoma are high-grade NECs. In small-sized diagnostic material (cytology and biopsy), the noncommittal term of carcinoid tumour/NET not otherwise specified (NOS) and metastatic carcinoid NOS have been introduced with regard to primary and metastatic diagnostic settings, respectively. Ki-67 antigen, a well-known marker of cell proliferation, has been included in the WHO classification as a non-essential but desirable criterion, especially to distinguish NETs from high-grade NECs and to delineate the provisional category of carcinoid tumours/NETs with elevated mitotic counts (> 10 mitoses per mm2) and/or Ki-67 proliferation index (≥ 30%). However, a wider use of this marker in the spectrum of lung NENs continues to be highly reported and debated, thus witnessing a never-subsided attention. Therefore, the arguments for and against incorporating Ki-67 in the classification and clinical practice of these neoplasms are discussed herein in detail.
Asunto(s)
Biomarcadores de Tumor , Proliferación Celular , Antígeno Ki-67 , Neoplasias Pulmonares , Tumores Neuroendocrinos , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Tumor Carcinoide/patología , Tumor Carcinoide/clasificación , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/metabolismo , Índice MitóticoRESUMEN
INTRODUCTION: Neuroendocrine neoplasms of the lung (Lung NENs) encompass NE tumors (NETs), which are in turn split into typical and atypical carcinoids, and NE carcinomas (NECs), which group together small-cell carcinoma and large-cell NE carcinoma. This classification is the current basis for orienting the daily practice of these patients, with diagnostic, prognostic, and predictive inferences. AREAS COVERED: The clinical implications of lung NEN classification are addressed according to three converging perspectives, which were dissected through an extensive literature overview: (1) how to put intratumor heterogeneity into the context of the current classification; (2) how to contextualize immunohistochemistry markers to improve diagnosis, prognosis, and therapy prediction; and (3) how to use immuno-oncology strategies for life-threatening NECs, which still account for 90% or more of lung NENs. EXPERT OPINION: We provide practical insights to account for intratumor heterogeneity, practice the choice of immunohistochemistry markers, and emphasize once again the added value of immuno-oncology in the setting of personalized medicine of lung NENs.
Asunto(s)
Carcinoma Neuroendocrino/clasificación , Neoplasias Pulmonares/clasificación , Tumores Neuroendocrinos/clasificación , Animales , Tumor Carcinoide/clasificación , Tumor Carcinoide/patología , Tumor Carcinoide/terapia , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/terapia , Carcinoma de Células Pequeñas/clasificación , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/terapia , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Medicina de Precisión , PronósticoRESUMEN
Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e., typical and atypical carcinoid, respectively). There is a paucity of randomised studies dedicated to advanced PCs and management principles are drawn from the larger gastroenteropancreatic NEN experience. There is growing evidence that NEN anatomic subgroups have different biology and different responses to treatment and, therefore, should be investigated as separate entities in clinical trials. In this review, we discuss the existing evidence and limitations of tumour classification, diagnostics and staging, prognostication, and treatment in the setting of PC, with focus on unmet medical needs and directions for the future.
Asunto(s)
Investigación Biomédica/tendencias , Tumor Carcinoide , Neoplasias Pulmonares , Tumores Neuroendocrinos , Tumor Carcinoide/clasificación , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/tratamiento farmacológico , PronósticoRESUMEN
The concept of neuroendocrine tumors (NETs) began in the 1900s with Oberndorfer's description of carcinoid tumors, followed by specific cytotoxic agents and the identification of somatostatin. NETs diagnosis was confirmed by World Health Organization classification. Histopathology included immunohistochemistry with specific antibodies. Imaging was refined with molecular imaging. Somatostatin is the leading agent for controlling clinical symptoms related to hormone production. Increasing interest in these tumors, previously thought rare, led to increased incidence and prevalence. Between 1960 and 1970, the true NET-concept was established with development of radioimmunoassays for peptides and hormones, and imaging with computerized tomography.
Asunto(s)
Tumores Neuroendocrinos/historia , Biomarcadores de Tumor , Tumor Carcinoide/clasificación , Tumor Carcinoide/historia , Tumor Carcinoide/patología , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Antígeno Ki-67/análisis , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapiaRESUMEN
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.
Asunto(s)
Antígeno Ki-67/análisis , Neoplasias Pulmonares/patología , Oncología Médica/métodos , Clasificación del Tumor/métodos , Tumores Neuroendocrinos/patología , Adulto , Anciano , Biomarcadores de Tumor/análisis , Tumor Carcinoide/clasificación , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/mortalidad , Tumor Carcinoide/patología , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/mortalidad , Pautas de la Práctica en Medicina , Pronóstico , Encuestas y CuestionariosRESUMEN
Goblet cell carcinoid tumors are amphicrine tumors whose biological behavior ranges from indolent to highly aggressive, depending on tumor grade. Current grading systems for these tumors are based on identifying an adenocarcinoma arising in the setting of a goblet cell carcinoid tumor, which distinguishes this tumor from other gastrointestinal tract adenocarcinomas. Because goblet cell tumors are predominantly tumors of mucin secreting cells, we propose that they be classified as goblet cell adenocarcinomas, and graded using a methodology that has parallels in colorectal adenocarcinoma grading. We graded a large series of goblet cell adenocarcinomas by assessing the proportion of the tumor that demonstrates tubular or clustered growth. Histologic grade correlated with overall survival independent of stage, with median overall survival of 204, 86, and 29 months for low-grade, intermediate-grade, and high-grade goblet cell adenocarcinomas, respectively. Tumor stage also correlated with overall survival. We also graded the tumors according to previously proposed grading systems, and found that these systems are valid, in that they segregate patients according to prognosis.
Asunto(s)
Adenocarcinoma/patología , Neoplasias del Apéndice/patología , Tumor Carcinoide/patología , Neoplasias del Colon/patología , Células Caliciformes/patología , Terminología como Asunto , Adenocarcinoma/clasificación , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Apéndice/clasificación , Neoplasias del Apéndice/mortalidad , Neoplasias del Apéndice/terapia , Biopsia , Tumor Carcinoide/clasificación , Tumor Carcinoide/mortalidad , Tumor Carcinoide/terapia , Neoplasias del Colon/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Valor Predictivo de las PruebasRESUMEN
Goblet cell carcinoid (GCC) is an uncommon tumor of the vermiform appendix. Due to a broad spectrum of morphological differentiation, subclassification and grading of GCCs remains an area of controversy. Two separate systems have proposed classifying GCC tumors into three (classical GCC; adenocarcinoma ex-GCC, signet ring cell type; adenocarcinoma ex-GCC, poorly differentiated carcinoma type) OR two subgroups (low and high grade GCC) based on morphological criteria. We independently compared the inter-observer variability associated with each classification system. Overall, both systems had moderate interobserver agreement, with the two-tiered system (κ=0.54) performing slightly better than the three-tiered system (κ=0.42). GI-specialist pathologists had substantial agreement for both two and three-tiered systems (κ=0.65 vs. 0.65). Non-GI trained pathologists had lower overall agreement than GI trained pathologists, but their agreement was better using the two-tiered system (κ=0.44) than the three-tiered system (κ=0.22). A sub-analysis of 6 cases with a high rate of discordant classification revealed several challenges that exist in applying current criteria, including differentiating "goblet" vs. "signet ring" cell morphology, applying a 1 mm2 criteria to multifocal non-contiguous glandular and single infiltrating cell architecture, differentiating fibro-inflammatory stroma from desmoplastic stroma, and solid architecture in cases with abundant extracellular mucin, and distinguishing "reactive" nuclear atypia from true "cytologic atypia". Despite these challenges, the study identified better agreement among GI pathologists than non-GI trained pathologists. While GI pathologist review may be helpful, further research on objective classification criteria remains an area of interest.
Asunto(s)
Neoplasias del Apéndice/clasificación , Tumor Carcinoide/clasificación , Neoplasias del Apéndice/diagnóstico , Neoplasias del Apéndice/patología , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patología , Humanos , Variaciones Dependientes del Observador , Patólogos/normas , Patología/normasRESUMEN
Typical and atypical carcinoid tumors belong to the neuroendocrine lung tumors. They have low recurrence and proliferation rate, lymph node, and distant metastases. Nevertheless, these tumors have shown a more aggressive behavior. In the last years, microRNAs were screened as new tumor markers for their potential diagnostic and therapeutic relevance. The expression of hsa-let-7b-5p, hsa-let-7f-5p, hsa-miR-222-3p, and their targets HMGA2 (high-mobility group A2) and CDKN1B (cyclin-dependent kynase inhibitor 1B, p27kip1) was evaluated in this rare small group of patients. We analyzed the clinical data of all typical and atypical carcinoid tumors of patients who underwent surgical operation at Marburg University Hospital (n = 18) from 2000. Quantitative reverse transcription polymerase chain reaction was performed in formalin-fixed paraffin-embedded tumor tissue versus four tumor-free lung tissue samples. HMGA2 was stable or downregulated; only one patient showed a significant overexpression. CDKN1B showed a significant overexpression or a stable level; it was downregulated in two samples only. Hsa-miR-222-3p resulted almost stable or overexpressed except for two samples (significantly downregulated). Hsa-let-7f-5p was stable or overexpressed in the majority of analyzed samples, whereas hsa-let-7b-5p was significantly downregulated. HMGA2 and CDKN1B are differently expressed between atypical and typical carcinoid tumors, thus representing valid biomarkers for the classification of the two tumor groups. Hsa-let-7f-5p and HMGA2 are inversely correlated. Hsa-miR-222-3p does not correlate with its predicted target CDKN1B.
Asunto(s)
Biomarcadores de Tumor/análisis , Tumor Carcinoide/clasificación , Tumor Carcinoide/patología , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/patología , Adulto , Anciano , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/análisis , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/biosíntesis , Femenino , Proteína HMGA2/análisis , Proteína HMGA2/biosíntesis , Humanos , Masculino , MicroARNs/análisis , MicroARNs/biosíntesis , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Lung cancer encompasses multiple malignant epithelial tumour types, each with specific targetable, potentially actionable mutations, such that precision management mandates accurate tumour typing. Molecular characterisation studies require high tumour cell content and low necrosis content, yet lung cancers are frequently a heterogeneous mixture of tumour and stromal cells. We hypothesised that there may be systematic differences in tumour cell content according to histological subtype, and that this may have implications for tumour banks as a resource for comprehensive molecular characterisation studies in lung cancer. To investigate this, we estimated tumour cell and necrosis content of 4267 samples resected from 752 primary lung tumour specimens contributed to a lung tissue bank. We found that banked lung cancer samples had low tumour cell content (33%) generally, although it was higher in carcinoids (77.5%) than other lung cancer subtypes. Tumour cells comprise a variable and often small component of banked resected tumour samples, and are accompanied by stromal reaction, inflammation, fibrosis, and normal structures. This has implications for the adequacy of unselected tumour bank samples for diagnostic and molecular investigations, and further research is needed to determine whether tumour cell content has a significant impact on analytical results in studies using tissue from tumour bank resources.
Asunto(s)
Adenocarcinoma/patología , Tumor Carcinoide/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Bancos de Tejidos , Adenocarcinoma/clasificación , Tumor Carcinoide/clasificación , Carcinoma de Células Escamosas/clasificación , Humanos , Pulmón/patología , Neoplasias Pulmonares/clasificación , Necrosis , Células del Estroma/patologíaRESUMEN
BACKGROUND: Goblet cell carcinoids belong to neuroendocrine tumors, according to the WHO classification. The tumors are diagnosed based on a typical histological pattern and using neuroendocrine markers. However, some tumors do not react with these markers and yet expression of proliferative markers is high. Do these tumors belong to G1 and G2 neuroendocrine tumors? METHODS: The sample comprised nine cases of tumors of the appendix identified by immunohistological methods as goblet cell carcinoids or adenocarcinoma ex goblet cell carcinoid. RESULTS: In six cases, hematoxylin and eosin staining revealed tumors completely or 90% made of characteristic large tumor cells observed in typical goblet cell carcinoids. The remaining three cases were identified as adenocarcinomas arising ex goblet cell carcinoids. Immunohistological examination revealed that in four cases of typical goblet cell carcinoids, expression of neuroendocrine markers was low or completely negative. Yet in two cases, the Ki-67 proliferative index exceeded the 20% cut-off for inclusion in the G1 and G2 category. CONCLUSIONS: Goblet cell carcinoids are a heterogeneous group of tumors that may express neuroendocrine markers in a small number of tumor cells or are negative to these markers. However, high expression of the proliferative marker Ki-67 exceeds the criteria for G1 and G2 neuroendocrine tumors. It is our opinion that these tumors may be classified as a specific type of carcinoma.
Asunto(s)
Adenocarcinoma/clasificación , Neoplasias del Apéndice/clasificación , Biomarcadores de Tumor/análisis , Tumor Carcinoide/clasificación , Tumores Neuroendocrinos/clasificación , Adenocarcinoma/patología , Anciano , Apendicectomía , Neoplasias del Apéndice/patología , Tumor Carcinoide/patología , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/fisiología , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología , Organización Mundial de la SaludRESUMEN
Goblet cell carcinoid (GCC) is staged and treated as adenocarcinoma (AC) and not as neuroendocrine tumor (NET) or neuroendocrine carcinoma. The term carcinoid may lead to incorrect interpretation as NET. The aim of the study was to explore pitfalls in staging and clinical interpretation of GCC and mixed GCC-AC, and propose strategies to avoid common errors. Diagnostic terminology, staging, and clinical interpretation were evaluated in 58 cases (27 GCCs, 31 mixed GCC-ACs). Opinions were collected from 23 pathologists using a survey. Clinical notes were reviewed to assess the interpretation of pathology diagnoses by oncologists. NET staging was incorrectly used for 25% of GCCs and 5% of mixed GCC-ACs. In the survey, 43% of pathologists incorrectly indicated that NET staging is applicable to GCCs, and 43% incorrectly responded that Ki-67 proliferation index is necessary for GCC grading. Two cases each of GCC and mixed GCC-AC were incorrectly interpreted as neuroendocrine neoplasms by oncologists, and platinum-based therapy was considered for 2 GCC-AC cases because of the mistaken impression of neuroendocrine carcinoma created by use of the World Health Organization 2010 term mixed adenoneuroendocrine carcinoma. The term carcinoid in GCC and use of mixed adenoneuroendocrine carcinoma for mixed GCC-AC lead to errors in staging and treatment. We propose that goblet cell carcinoid should be changed to goblet cell carcinoma, whereas GCC with AC should be referred to as mixed GCC-AC with a comment about the proportion of each component and the histologic subtype of AC. This terminology will facilitate appropriate staging and clinical management, and avoid errors in interpretation.
Asunto(s)
Adenocarcinoma/patología , Neoplasias del Apéndice/patología , Tumor Carcinoide/patología , Carcinoma Neuroendocrino/patología , Neoplasias Complejas y Mixtas/patología , Terminología como Asunto , Adenocarcinoma/química , Adenocarcinoma/clasificación , Neoplasias del Apéndice/química , Neoplasias del Apéndice/clasificación , Tumor Carcinoide/química , Tumor Carcinoide/clasificación , Carcinoma Neuroendocrino/química , Carcinoma Neuroendocrino/clasificación , Consenso , Bases de Datos Factuales , Diagnóstico Diferencial , Errores Diagnósticos , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Estadificación de Neoplasias , Neoplasias Complejas y Mixtas/química , Neoplasias Complejas y Mixtas/clasificación , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
No disponible
Asunto(s)
Humanos , Neoplasias Pulmonares/clasificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/patología , Técnicas Histológicas/métodos , Células Epiteliales/patología , Tumor Carcinoide/clasificación , Biomarcadores de Tumor/análisisRESUMEN
Primary neuroendocrine tumors (NET) in the mediastinum are very rare and among them thymic NETs are the most common. They represent 5 % of all thymic and mediastinal tumors. The WHO classification from 2015 subdivides thymic NETs into three groups; low grade (typical carcinoid), intermediate grade (atypical carcinoid) and high grade (large cell neuroendocrine carcinoma and small cell carcinoma). Through this change of mediastinal/thymic NET classification into three groups of malignancy, the nomenclature was adapted to that of the lungs, while the histological criteria for each entity remained the same. Thymic NETs typically occur in middle-aged adults and predominantly in males. Approximately 30 % are asymptomatic and the rest present with symptoms caused by local tumor growth, distant metastases and/or endocrine manifestations. Carcinoids can also occur as a part of multiple endocrine neoplasia type 1 (MEN1) and at the time of diagnosis commonly present with regional lymph node or distant metastases, which most often affect the lungs and bones. For the correct diagnosis tumor cell morphology, mitotic count and/or necrosis are crucial. Patients with typical carcinoids have the best prognosis, whereas the prognosis is slightly worse for atypical carcinoids but very poor for large cell neuroendocrine carcinomas. Small cell carcinomas have the worst prognosis and the shortest median survival time of approximately 14 months.
Asunto(s)
Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/patología , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/patología , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Adulto , Anciano , Tumor Carcinoide/clasificación , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patología , Carcinoma Neuroendocrino/clasificación , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/patología , Diagnóstico Diferencial , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patologíaRESUMEN
BACKGROUND: Due to therapeutic implications with regard to both efficiency and safety of chemotherapy agents it is important to differentiate between subtypes of NSCLC. Up to today we experience a continuous reservation regarding the use of fine needle aspiration cytology. The aim of the present study is to estimate the value of cytologic criteria for lung cancer typing on small biopsies independent from all possible technique failures. METHODS: Between January 1997 and December 2008 760 intraoperative FNAC- (fine needle aspiration cytology) specimens from 702 patients have been examined. Cytologic evaluation and immediate communication of results to the surgeons followed. Afterwards, intraoperative cytologic findings were compared with final histologic diagnoses of the resected specimens. RESULTS: Intraoperative cytologic analysis yielded a sensitivity of 94.8 %, a specificity of 98.8 %. An overall positive predictive value of 99.8 % with respect to final histologic analysis of primary lung cancer was achieved. The highest value could be reached for adenocarcinomas, followed by carcinoids and squamous cell carcinomas. CONCLUSIONS: Lung cancer typing according to cytologic criteria is feasible and accurate as well as comparable with results of histologic analysis on small specimens. Herewith, clinicians can come up to the increasing demands on minimally invasive harvested specimens with regard to therapeutic implications.
Asunto(s)
Adenocarcinoma/diagnóstico , Tumor Carcinoide/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/clasificación , Anciano , Biopsia con Aguja Fina , Tumor Carcinoide/clasificación , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Células Escamosas/clasificación , Citodiagnóstico , Femenino , Humanos , Periodo Intraoperatorio , Pulmón/patología , Neoplasias Pulmonares/clasificación , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The impact of histopathologic features on oncologic outcomes for patients with peritoneal metastases from goblet cell carcinoid (GCC) undergoing multimodality therapy, including cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), is unknown. METHODS: This study prospectively analyzed 43 patients with GCC undergoing CRS-HIPEC between 2005 and 2013. Pathology slides were re-reviewed to classify GCC into histologic subtypes according to the Tang classification. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. RESULTS: The 43 patients in this study underwent 50 CRS-HIPEC procedures for peritoneal metastases from GCC, and the majority received neoadjuvant and/or adjuvant systemic chemotherapy. The GCC demonstrated an aggressive phenotype with frequent lymph node and peritoneal metastases without systemic dissemination. The majority of the patients had Tang B GCC. The estimated median overall survival times after surgery for the patients with Tang A, B, and C GCC were respectively 59, 22, and 13 months. In a multivariate Cox-regression analysis, poor survival was associated with patients who had Tang B or C GCC, those undergoing incomplete macroscopic resection, and those with symptoms at the time of CRS-HIPEC. The patients with Tang A GCC demonstrated oncologic outcomes similar to those with intermediate-grade (American Joint Committee on Cancer [AJCC] grade 2) disseminated mucinous appendiceal neoplasms, whereas the patients with Tang B and C GCC demonstrated survival rates similar to or worse than those with high-grade (AJCC grade 3) disseminated mucinous appendiceal neoplasms. CONCLUSIONS: Tang classification is an independent prognostic factor for poor survival after multimodality therapy for GCC. Patients with Tang C GCC demonstrate limited survival and are not ideal candidates for a surgical approach.
Asunto(s)
Neoplasias del Apéndice/patología , Tumor Carcinoide/patología , Tumor Carcinoide/terapia , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Antineoplásicos/administración & dosificación , Neoplasias del Apéndice/clasificación , Tumor Carcinoide/clasificación , Tumor Carcinoide/secundario , Quimioterapia Adyuvante , Terapia Combinada/métodos , Femenino , Células Caliciformes , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias Peritoneales/clasificación , Neoplasias Peritoneales/secundario , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Advancement in the understanding of lung tumor biology enables continued refinement of lung cancer classification, reflected in the recently introduced 2015 World Health Organization classification of lung cancer. In small biopsy or cytology specimens, special emphasis is placed on separating adenocarcinomas from the other lung cancers to effectively select tumors for targeted molecular testing. In resection specimens, adenocarcinomas are further classified based on architectural pattern to delineate tissue types of prognostic significance. Neuroendocrine tumors are divided into typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma based on a combination of features, especially tumor cell proliferation rate.
Asunto(s)
Tumor Carcinoide/patología , Carcinoma Neuroendocrino/patología , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/patología , Tumores Neuroendocrinos/patología , Carcinoma Pulmonar de Células Pequeñas/patología , Tumor Carcinoide/clasificación , Carcinoma Neuroendocrino/clasificación , Humanos , Tumores Neuroendocrinos/clasificación , Carcinoma Pulmonar de Células Pequeñas/clasificaciónRESUMEN
In the recently published 2015 World Health Organization (WHO) classification of tumors of the lungs, all neuroendocrine tumors of the lungs are presented for the first time in one single chapter. In this classification, high-grade small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are differentiated from intermediate grade atypical carcinoids (AC) and low-grade typical carcinoids as well as from preinvasive lesion diffuse neuroendocrine hyperplasia DIPNECH. In the 2004 WHO classification, SCLC and carcinoids each had a separate chapter and LCNEC was listed in the chapter on large cell carcinoma of the lungs. The new WHO classification also gives some recommendations for the diagnosis on small biopsies. This review describes morphological, immunohistochemical, and genomic characteristic of these tumors according to the new classification.
Asunto(s)
Neoplasias Pulmonares/clasificación , Tumores Neuroendocrinos/clasificación , Biomarcadores de Tumor , Tumor Carcinoide/química , Tumor Carcinoide/clasificación , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patología , Diferenciación Celular , Diagnóstico Diferencial , Genes Relacionados con las Neoplasias , Humanos , Hiperplasia , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Células Neuroendocrinas/patología , Tumores Neuroendocrinos/química , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Lesiones Precancerosas/química , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Organización Mundial de la SaludRESUMEN
AIM: To extensively explore microRNA expression profiles in lung carcinoids in correlation with clinical and pathological features. METHODS: A PCR-based array was employed in the screening phase to analyze 752 microRNAs in a discovery set of 12 lung carcinoids, including 6 typical (3 with lymph node metastasis) and 6 atypical (3 with lymph node metastasis). The results were validated by means of real-time PCR in 37 carcinoids, including 22 typical (4 with lymph node metastasis) and 15 atypical (7 with lymph node metastasis), and 19 high-grade neuroendocrine carcinomas. RESULTS: Unsupervised cluster analysis segregated the pilot cases into 3 distinct groups. Twenty-four microRNAs were differentially regulated in atypical versus typical carcinoids, and 29 in metastatic versus nonmetastatic cases. Eleven microRNAs were selected for validation. All but 1 were significantly different among lung neuroendocrine tumor histotypes. Moreover, 5 (miR-129-5p, miR-409-3p, miR-409-5p, miR-185 and miR-497) were significantly upregulated in typical compared to atypical carcinoids. MiR-409-3p, miR-409-5p and miR-431-5p were also significantly downregulated in carcinoids metastatic to the lymph nodes. Predictive in silico analysis of specific target genes showed that these 3 latter microRNAs linked to metastatic potential are implicated in several cellular functions and highlighted several novel genes which may be worth exploring. CONCLUSIONS: Our findings demonstrate that lung carcinoids have distinct microRNA expression profiles as compared to high-grade neuroendocrine carcinomas and that specific microRNAs might have potential implications as diagnostic tools or clinical biomarkers.
Asunto(s)
Tumor Carcinoide/metabolismo , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Tumor Carcinoide/clasificación , Tumor Carcinoide/genética , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/genética , Masculino , MicroARNs/genética , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Adenomatous tumors are an uncommon cause of a middle ear mass. Clinical findings may be nonspecific, leading to difficulties in differentiation from other middle ear tumors. Controversy also exists whether to classify middle ear adenoma and carcinoid as separate neoplasms, or alternatively within a spectrum of the same pathologic entity. Most adenomatous middle ear tumors are indolent in behavior, with a benign histologic appearance and slowly progressive growth. The mainstay of treatment is complete surgical resection, which affords the greatest likelihood of cure.
Asunto(s)
Adenoma/patología , Tumor Carcinoide/patología , Neoplasias del Oído/patología , Oído Medio/cirugía , Adenoma/clasificación , Adenoma/cirugía , Tumor Carcinoide/clasificación , Tumor Carcinoide/cirugía , Neoplasias del Oído/clasificación , Neoplasias del Oído/cirugía , Oído Medio/patología , Humanos , Imagen por Resonancia Magnética , Pronóstico , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Pulmonary carcinoids are neuroendocrine tumors histopathologically subclassified into typical (TC; no necrosis, <2 mitoses per 2 mm) and atypical (AC; necrosis or 2 to 10 mitoses per 2 mm). The reproducibility of lung carcinoid classification, however, has not been extensively studied and may be hampered by the presence of pyknotic apoptosis mimicking mitotic figures. Furthermore, prediction of prognosis based on histopathology varies, especially for ACs. We examined the presence of interobserver variation between 5 experienced pulmonary pathologists who reviewed 123 originally diagnosed pulmonary carcinoid cases. The tumors were subsequently redistributed over 3 groups: unanimously classified cases, consensus cases (4/5 pathologists rendered identical diagnosis), and disagreement cases (divergent diagnosis by ≥2 assessors). κ-values were calculated, and results were correlated with clinical follow-up and molecular data. When focusing on the 114/123 cases unanimously classified as pulmonary carcinoids, the interobserver agreement was only fair (κ=0.32). Of these 114 cases, 55% were unanimously classified, 25% reached consensus classification, and for 19% there was no consensus. ACs were significantly more often in the latter category (P=0.00038). The designation of TCs and ACs by ≥3 assessors was not associated with prognosis (P=0.11). However, when disagreement cases were allocated on the basis of Ki-67 proliferative index (<5%; ≥5%) or nuclear orthopedia homeobox immunostaining (+; -), correlation with prognosis improved significantly (P=0.00040 and 0.0024, respectively). In conclusion, there is a considerable interobserver variation in the histopathologic classification of lung carcinoids, in particular concerning ACs. Additional immunomarkers such as Ki-67 or orthopedia homeobox may improve classification and prediction of prognosis.