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2.
Semin Diagn Pathol ; 38(5): 72-82, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34176698

RESUMO

NUT carcinoma of the thorax is a rare and very aggressive tumor, whose definition is based on the demonstration of a nuclear protein in testis (NUTM1; also known as NUT) gene fusion on 15q14 with different partners from the bromodomain-containing proteins gene family. This fusion results in an activation of MYC oncoprotein responsible for the tumor's aggressivity. NUT carcinoma arises preferentially in young adults, presenting a large thoracic mass frequently associated with lymph nodes, bone or pleural metastases. At histology, this tumor is often poorly differentiated, mainly composed of sheets of small cells with scant cytoplasm, a round nucleus with a central nucleolus. Focal areas of squamous differentiation can be observed. Mitoses and necrosis are frequent, as well as neutrophilic infiltrate. The diagnosis is based on the detection of NUT protein expression by immunohistochemistry using the rabbit monoclonal antibody C52B1 in more than 50% of the tumor nuclei. This technique offers 87% sensitivity and nearly 100% specificity with reference to FISH or RT-PCR, which confirm the NUTM1 rearrangement. The differential diagnoses include basaloid carcinoma of the lung, small cell carcinoma, thymic carcinoma (basaloid variant), SMARCA4_deficient thoracic sarcoma, other NUTM1 rearranged undifferentiated tumors, small round cell tumors, non-Hodgkin lymphoma/leukemia, and melanoma. The prognosis of NUT carcinoma remains very poor, with a median survival of 6.7 months, and 1- and 2-year overall survival rates of 30% and 19%, respectively. NUT carcinoma is often refractory to conventional chemotherapy, but ifosfamide-based regimens or BET inhibitors could represent promising therapies.

3.
Lung Cancer ; 158: 55-59, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119933

RESUMO

NUT carcinoma (NC), formerly known as NUT midline carcinoma, is a rare and very aggressive cancer. It is genetically defined by the presence of acquired chromosomal rearrangement of the NUTM1 (NUclear protein in Testis Midline carcinoma family member 1) gene at chromosome 15q14 with a member of the bromodomain-containing protein (BRD) family gene, usually BRD4. Although primarily reported in the head and neck, and mediastinum locations of younger individuals, it is now established that NC arises in multiple sites in patients of all ages, with no gender predilection. NC is very likely to be underdiagnosed because of a lack of awareness of both clinicians and pathologists on the one hand, and of a nonspecific histological presentation on the other hand. As it is indistinguishable from other poorly differentiated carcinomas, pathologists should consider NC as a differential diagnosis of any poorly differentiated tumour. Diagnosis is now easily made by immunohistochemistry, using a highly sensitive and specific NUT monoclonal antibody. Despite chemo- or chemo-radiotherapy, the prognosis of this tumour remains very poor. We report here a series of 3 cases of NC with different clinical and pathological presentations in order to draw attention on some common morphological features that can help clinicians and pathologists to think about this rare entity.


Assuntos
Carcinoma , Neoplasias Pulmonares , Carcinoma/diagnóstico , Carcinoma/genética , Carcinoma/terapia , Proteínas de Ciclo Celular , Humanos , Masculino , Proteínas Nucleares/genética , Proteínas Oncogênicas , Fatores de Transcrição
4.
J Thorac Oncol ; 16(4): 686-696, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33662578

RESUMO

INTRODUCTION: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is required to determine the eligibility for pembrolizumab monotherapy in advanced NSCLC worldwide and for several other indications depending on the country. Four assays have been approved/ Communauté Européene-In vitro Diagnostic (CV-IVD)-marked, but PD-L1 IHC seems diversely implemented across regions and laboratories with the application of laboratory-developed tests (LDTs). METHOD: To assess the practice of PD-L1 IHC and identify issues and disparities, the International Association for the Study of Lung Cancer Pathology Committee conducted a global survey for pathologists from January to May 2019, comprising multiple questions on preanalytical, analytical, and postanalytical conditions. RESULT: A total of 344 pathologists from 64 countries participated with 41% from Europe, 24% from North America, and 18% from Asia. Besides biopsies and resections, cellblocks were used by 75% of the participants and smears by 11%. The clone 22C3 was most often used (69%) followed by SP263 (51%). They were applied as an LDT by 40% and 30% of the users, respectively, and 76% of the participants developed at least one LDT. Half of the participants reported a turnaround time of less than or equal to 2 days, whereas 13% reported that of greater than or equal to 5 days. In addition, quality assurance (QA), formal training for scoring, and standardized reporting were not implemented by 18%, 16%, and 14% of the participants, respectively. CONCLUSIONS: Heterogeneity in PD-L1 testing is marked across regions and laboratories in terms of antibody clones, IHC assays, samples, turnaround times, and QA measures. The lack of QA, formal training, and standardized reporting stated by a considerable minority identifies a need for additional QA measures and training opportunities.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Ásia , Antígeno B7-H1 , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Europa (Continente) , Humanos , Neoplasias Pulmonares/tratamento farmacológico
5.
Histopathology ; 78(3): 434-444, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32810914

RESUMO

AIMS: Mucinous adenocarcinoma arising in congenital pulmonary airway malformation (CPAM) is a rare complication, with little being known about its natural course. The aims of this article are to describe a series of mucinous adenocarcinomas arising from CPAMs, and present their clinicopathological features, genetics, and clinical outcome. METHODS AND RESULTS: Thirty-seven cases were collected within a 34-year period, and the subtype of adenocarcinoma and CPAM, tumour location, stage, growth patterns, molecular data and follow-up were recorded. The cohort comprised CPAM type 1 (n = 33) and CPAM type 2 (n = 4). Morphologically, 34 cases were mucinous adenocarcinomas (21 in situ; 13 invasive), and three were mixed mucinous and non-mucinous adenocarcinoma. Seventeen cases showed purely extracystic (intra-alveolar) adenocarcinoma, 15 were mixed intracystic and extracystic, and five showed purely intracystic proliferation. Genetically, nine of 10 cases tested positive for KRAS mutations, four with exon 2 G12V mutation and five with exon 2 G12D mutation. Residual disease on completion lobectomy was observed in two cases, and three cases recurred 7, 15 and 32 years after the original diagnosis. Two patients died of metastatic invasive mucinous adenocarcinoma. CONCLUSIONS: Most adenocarcinoma that arise in type 1 CPAMs, are purely mucinous, and are early-stage disease. Intracystic proliferation is associated with lepidic growth, an absence of invasion, and indolent behaviour, whereas extracystic proliferation may be associated with more aggressive behaviour and advanced stage. Most cases are cured by lobectomy, and recurrence/residual disease seems to be associated with limited surgery. Long-term follow-up is needed, as recurrence can occur decades later.

7.
Eur J Cancer ; 143: 158-167, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33316754

RESUMO

BACKGROUND: Classification of thymic epithelial tumours (TETs) is known to be challenging; however, the level of discordances at a nationwide level between initial and expert diagnosis and their clinical consequences are currently unknown. RYTHMIC is a national network dedicated to the management of TET based on initial histological diagnosis, followed by an additional expert review of all cases. Our aim was to evaluate the discordances between initial and expert diagnoses and whether they would have led to different clinical management. PATIENTS AND METHODS: We conducted a retrospective analysis of the cohort of patients discussed at RYTHMIC tumour board from January 2012 to December 2016. Assessment of disagreement was made for histological typing and for staging. The discordances were classified as major or minor based on whether they would have changed or not the proposed therapeutic strategy, respectively. Follow-up of the patients with major discordances was conducted until December 2018. RESULTS: Four hundred sixty-seven patients were reviewed, and 183 (39%) discordances were identified either related to histological subtype (132) and/or stage (72). Major discordances were identified in 27 patients (6%). They included 16 patients with TET for whom treatment recommendation based on the central review would have been post-operative radiotherapy, whereas it had not been the case. However, follow-up did not show any progression among the 15 patients with high-grade histology and/or stage resected thymomas. On the other hand, among the remaining 11 patients including 7 with a diagnosis other than TET, the overall management or follow-up would have been completely different with the expert diagnosis. CONCLUSION: Our real-life cohort reveals a high level of discordances considering TET diagnosis and supports expert review for optimal clinical management.


Assuntos
Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/terapia , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos
8.
Transl Lung Cancer Res ; 9(5): 2233-2244, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209646

RESUMO

Large cell neuroendocrine carcinoma (LCNECs) and small cell lung carcinomas (SCLCs) are high-grade neuroendocrine carcinomas of the lung with very aggressive behavior and poor prognosis. Their histological classification as well as their therapeutic management has not changed much in recent years, but genomic and transcriptomic analyses have revealed different molecular subtypes raising hopes for more personalized treatment. Indeed, four subtypes of SCLCs have been recently described, SCLC-A driven by the master gene ASCL1, SCLC-N driven by NEUROD1, SCLC-Y by YAP1 and SCLC-P by POU2F3. Whereas SCLC standard of care is based on concurrent chemoradiation for limited stages and on chemotherapy alone or chemotherapy combined with anti-PD-L1 checkpoint inhibitors for extensive stage SCLC, SCLC-A variants could benefit from DLL3 or BCL2 inhibitors, and SCLC-N variants from Aurora kinase inhibitors combined with chemotherapy, or PI3K/mTOR or HSP90 inhibitors. In addition, a new SCLC variant (SCLC-IM) with high-expression of immune checkpoints has been also reported, which could benefit from immunotherapies. PARP inhibitors also gave promising results in combination with chemotherapy in a subset of SCLCs. Regarding LCNECs, they represent a heterogeneous group of tumors, some of them exhibiting mutations also found in SCLC but with a pattern of expression of NSCLC, while others harbor mutations also found in NSCLC but with a pattern of expression of SCLC, questioning their clinical management as NSCLCs or SCLCs. Overall, we are probably entering a new area, which, if personalized treatments are effective, will also lead to the implementation in practice of molecular testing or biomarkers detection for the selection of patients who can benefit from them.

9.
Transl Lung Cancer Res ; 9(3): 906-916, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32676356

RESUMO

Immune checkpoint inhibitors (ICI) including programmed death 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab, or programmed death ligand 1 (PD-L1) inhibitors, such as atezolizumab and durvalumab, have recently emerged in advanced stage lung cancer as new standards of care. They are now indicated in first- line and second- or later-line treatment of metastatic or locally-advanced stage III non-small cell lung cancer (NSCLC), as well as for metastatic small cell lung cancer (SCLC), as single agent immunotherapy or in combination with chemotherapy. Four PD-L1 immunohistochemistry (IHC) assays have been established and validated in randomized trials, each for a specific ICI. They use different primary monoclonal antibodies, platforms and detection systems, as well as different scoring systems to assess PD-L1 expression either by tumor cells (TCs) and/or by infiltrating immune cells (ICs). Most studies have shown a close analytical performance of three of these clinically-validated standardized assays, but their use restricted to dedicated platforms, which are not all available in most laboratories, questions their applicability. In addition, the relative high costs of the assays have led to the development of in-house protocols in many pathology laboratories. Their use in clinical practice to assess the predictive value of PD-L1 expression for prescription of ICI raises the issue of their reliability and their validation as compared to standardized assays. This article discusses the main comparative studies available between LDT and assays, with clear evidence that LDT can reach a performance equivalent to the trial-validated assays. The requirements are an adequate validation as compared to an appropriate standard, and the participation to external quality assurance programs and training programs for PD-L1 IHC assessment for pathologists.

10.
J Thorac Oncol ; 15(9): 1409-1424, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32522712

RESUMO

Immune checkpoint inhibitor (ICI) therapies have revolutionized the management of patients with NSCLC and have led to unprecedented improvements in response rates and survival in a subset of patients with this fatal disease. However, the available therapies work only for a minority of patients, are associated with substantial societal cost, and may lead to considerable immune-related adverse events. Therefore, patient selection must be optimized through the use of relevant biomarkers. Programmed death-ligand 1 protein expression by immunohistochemistry is widely used today for the selection of programmed cell death protein 1 inhibitor therapy in patients with NSCLC; however, this approach lacks robust sensitivity and specificity for predicting response. Tumor mutation burden (TMB), or the number of somatic mutations derived from next-generation sequencing techniques, has been widely explored as an alternative or complementary biomarker for response to ICIs. In theory, a higher TMB increases the probability of tumor neoantigen production and therefore, the likelihood of immune recognition and tumor cell killing. Although TMB alone is a simplistic surrogate of this complex interplay, it is a quantitative variable that can be relatively readily measured using currently available sequencing techniques. A large number of clinical trials and retrospective analyses, employing both tumor and blood-based sequencing tools, have evaluated the performance of TMB as a predictive biomarker, and in many cases reveal a correlation between high TMB and ICI response rates and progression-free survival. Many challenges remain before the implementation of TMB as a biomarker in clinical practice. These include the following: (1) identification of therapies whose response is best informed by TMB status; (2) robust definition of a predictive TMB cut point; (3) acceptable sequencing panel size and design; and (4) the need for robust technical and informatic rigor to generate precise and accurate TMB measurements across different laboratories. Finally, effective prediction of response to ICI therapy will likely require integration of TMB with a host of other potential biomarkers, including tumor genomic driver alterations, tumor-immune milieu, and other features of the host immune system. This perspective piece will review the current clinical evidence for TMB as a biomarker and address the technical sequencing considerations and ongoing challenges in the use of TMB in routine practice.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Mutação , Estudos Retrospectivos
13.
J Thorac Oncol ; 15(10): 1599-1610, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32562873

RESUMO

INTRODUCTION: A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma. METHODS: A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I-III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics. RESULTS: The best model (area under the receiver operating characteristic curve [AUC] = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617). CONCLUSIONS: A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos
14.
J Thorac Oncol ; 15(9): 1434-1448, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32445813

RESUMO

INTRODUCTION: Access to targeted therapies for lung cancer depends on the accurate identification of patients' biomarkers through molecular testing. The International Association for the Study of Lung Cancer (IASLC) conducted an international survey to evaluate perceptions on current practice and barriers to implementation of molecular testing. METHODS: We distributed the survey to IASLC members and other health care professionals around the world. The survey included a seven-question introduction for all respondents, who then answered according to one of three tracks: (1) requesting tests and treating patients, (2) performing and interpreting assays, or (3) tissue acquisition. Barriers to implementing molecular testing were provided in free-response fields. The chi-square test was used for regional comparisons. RESULTS: A total of 2537 respondents from 102 countries participated. Most respondents who test and treat patients believe that less than 50% of patients with lung cancer in their country receive molecular testing, but reported higher rates within their own practice. Although many results varied by region, the five most frequent barriers cited in all regions were cost, quality and standards, access, awareness, and turnaround time. Many respondents expressed dissatisfaction with the current state of molecular testing for lung cancer, including 41% of those performing and interpreting assays. Issues identified included trouble understanding results (37%) and the quality of the samples (23% reported >10% rejection rate). Despite concerns regarding the quality of testing, 47% in the performing and interpreting track stated there is no policy or strategy to improve quality in their country. In addition, 33% of respondents who request tests and treat patients were unaware of the most recent College of American Pathologists, IASLC, and Association for Molecular Pathology guidelines for molecular testing. CONCLUSIONS: Adoption of molecular testing for lung cancer is relatively low across the world. Barriers include cost, access, quality, turnaround time, and lack of awareness.


Assuntos
Neoplasias Pulmonares , Quinase do Linfoma Anaplásico , Receptores ErbB/genética , Testes Genéticos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Técnicas de Diagnóstico Molecular , Inquéritos e Questionários
16.
J Thorac Oncol ; 15(6): 1037-1053, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32165206

RESUMO

INTRODUCTION: Histologic subtypes of malignant pleural mesothelioma are a major prognostic indicator and decision denominator for all therapeutic strategies. In an ambiguous case, a rare transitional mesothelioma (TM) pattern may be diagnosed by pathologists either as epithelioid mesothelioma (EM), biphasic mesothelioma (BM), or sarcomatoid mesothelioma (SM). This study aimed to better characterize the TM subtype from a histological, immunohistochemical, and molecular standpoint. Deep learning of pathologic slides was applied to this cohort. METHODS: A random selection of 49 representative digitalized sections from surgical biopsies of TM was reviewed by 16 panelists. We evaluated BAP1 expression and CDKN2A (p16) homozygous deletion. We conducted a comprehensive, integrated, transcriptomic analysis. An unsupervised deep learning algorithm was trained to classify tumors. RESULTS: The 16 panelists recorded 784 diagnoses on the 49 cases. Even though a Kappa value of 0.42 is moderate, the presence of a TM component was diagnosed in 51%. In 49% of the histological evaluation, the reviewers classified the lesion as EM in 53%, SM in 33%, or BM in 14%. Median survival was 6.7 months. Loss of BAP1 observed in 44% was less frequent in TM than in EM and BM. p16 homozygous deletion was higher in TM (73%), followed by BM (63%) and SM (46%). RNA sequencing unsupervised clustering analysis revealed that TM grouped together and were closer to SM than to EM. Deep learning analysis achieved 94% accuracy for TM identification. CONCLUSION: These results revealed that the TM pattern should be classified as non-EM or at minimum as a subgroup of the SM type.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Mesotelioma , Homozigoto , Humanos , Neoplasias Pulmonares/genética , Mesotelioma/genética , Deleção de Sequência , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética
17.
Theranostics ; 10(5): 2008-2028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104498

RESUMO

CDK4/cyclin D kinase constitutes an attractive pharmacological target for development of anticancer therapeutics, in particular in KRAS-mutant lung cancer patients, who have a poor prognosis and no targeted therapy available yet. Although several ATP-competitive inhibitors of CDK4 have been developed for anticancer therapeutics, they suffer from limited specificity and efficacy. Methods: As an alternative to ATP-competitive inhibitors we have designed a stapled peptide to target the main interface between CDK4 and cyclin D, and have characterized its physico-chemical properties and affinity to bind cyclin D1. Results: We have validated a positive correlation between CDK4/cyclin D level and KRAS mutation in lung cancer patients. The stapled peptide enters cells rapidly and efficiently, and inhibits CDK4 kinase activity and proliferation in lung cancer cells. Its intrapulmonary administration in mice enables its retention in orthotopic lung tumours and complete inhibition of their growth when co-administered with Abemaciclib. Conclusion: The stapled peptide targeting the main interface between CDK4 and cyclin D provides promising therapeutic perspectives for patients with lung cancer.


Assuntos
Aminopiridinas/farmacologia , Benzimidazóis/farmacologia , Ciclina D/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/efeitos dos fármacos , Aminopiridinas/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzimidazóis/administração & dosagem , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/genética , Camundongos , Camundongos Nus , Mutação , Imagem Óptica/métodos , Peptídeos/administração & dosagem , Peptídeos/química , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
18.
Lung Cancer ; 140: 93-98, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31901769

RESUMO

OBJECTIVES: Bone is a common location for lung cancer metastasis. Clinicians are often reluctant to biopsy bone metastases, as they are known to require a decalcification process that damages nucleic acids, which makes it incompatible with molecular testing. We performed this study to assess the diagnostic performance of histopathology and molecular testing of computed tomography (CT)-guided percutaneous bone biopsies of lytic bone lesions during the initial assessment or during the progression of lung cancer. MATERIALS AND METHODS: This retrospective study included all patients suspected of having or known to have primary lung cancer and CT-guided percutaneous bone biopsies of lytic bone from January 2010 to June 2017. The main judgment criterion was the diagnostic performance of the pathological analysis. Secondary endpoints were the diagnostic performance of molecular testing and incidence of complications. RESULTS: Fifty patients were included. The yield of CT-guided percutaneous bone biopsies for pathological analysis was 100 %, allowing for a diagnosis of certainty in all cases. The percentage of tumor cells in samples was higher than the 20 % threshold in 83.9 % of cases. The yield of molecular analysis was 94.6 %. A mutation was found in 60 % of cases; most frequently in KRAS (Kirsten rat sarcoma viral oncogene homolog) (28.6 %) and EGFR (epidermal growth factor receptor) (14.3 %). The complication rate was 2 %, i.e. a minor undrained pneumothorax. CONCLUSION: CT-guided percutaneous biopsies of lytic bone is associated with a very low complication rate and high diagnostic performance for histopathology and mutation testing.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Biópsia Guiada por Imagem/métodos , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Estadiamento de Neoplasias , Estudos Retrospectivos
19.
J Thorac Oncol ; 15(1): 29-49, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31546041

RESUMO

INTRODUCTION: Molecular and immunologic breakthroughs are transforming the management of thoracic cancer, although advances have not been as marked for malignant pleural mesothelioma where pathologic diagnosis has been essentially limited to three histologic subtypes. METHODS: A multidisciplinary group (pathologists, molecular biologists, surgeons, radiologists, and oncologists), sponsored by European Network for Rare Adult Solid Cancers/International Association for the Study of Lung Cancer, met in 2018 to critically review the current classification. RESULTS: Recommendations include: (1) classification should be updated to include architectural patterns and stromal and cytologic features that refine prognostication; (2) subject to data accrual, malignant mesothelioma in situ could be an additional category; (3) grading of epithelioid malignant pleural mesotheliomas should be routinely undertaken; (4) favorable/unfavorable histologic characteristics should be routinely reported; (5) clinically relevant molecular data (programmed death ligand 1, BRCA 1 associated protein 1 [BAP1], and cyclin dependent kinase inhibitor 2A) should be incorporated into reports, if undertaken; (6) other molecular data should be accrued as part of future trials; (7) resection specimens (i.e., extended pleurectomy/decortication and extrapleural pneumonectomy) should be pathologically staged with smaller specimens being clinically staged; (8) ideally, at least three separate areas should be sampled from the pleural cavity, including areas of interest identified on pre-surgical imaging; (9) image-acquisition protocols/imaging terminology should be standardized to aid research/refine clinical staging; (10) multidisciplinary tumor boards should include pathologists to ensure appropriate treatment options are considered; (11) all histologic subtypes should be considered potential candidates for chemotherapy; (12) patients with sarcomatoid or biphasic mesothelioma should not be excluded from first-line clinical trials unless there is a compelling reason; (13) tumor subtyping should be further assessed in relation to duration of response to immunotherapy; and (14) systematic screening of all patients for germline mutations is not recommended, in the absence of a family history suspicious for BAP1 syndrome. CONCLUSIONS: These multidisciplinary recommendations for pathology classification and application will allow more informative pathologic reporting and potential risk stratification, to support clinical practice, research investigation and clinical trials.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Adulto , Humanos , Neoplasias Pulmonares/genética , Mesotelioma/cirurgia , Neoplasias Pleurais/cirurgia , Pneumonectomia , Proteínas Supressoras de Tumor , Ubiquitina Tiolesterase
20.
Mod Pathol ; 33(2): 255-262, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31273316

RESUMO

The percentage of sarcomatoid component has an impact on prognosis in patients with biphasic malignant pleural mesothelioma. Recent study showed that the transitional pattern similar to sarcomatoid component of malignant mesothelioma has negative prognostic significance. Practice guidelines recommend quantification of sarcomatoid component despite poor diagnostic reproducibility of biphasic mesothelioma among thoracic pathologists. The aim of this study was to determine the interobserver agreement in the quantification of sarcomatoid component, and in the diagnosis of a transitional component in the biphasic malignant mesothelioma. Thirteen experts in thoracic pathology reviewed the representative H&E and cytokeratin whole-slide images of the 54 biphasic mesotheliomas, without knowledge of BAP1 or p16 deletion status, and completed the survey of 25 questions. The overall interobserver agreement in the assessment of the percentage of the sarcomatoid component in 25% increments was good (wK = 0.62). Excellent agreement was present in 14 of 54 cases (26%), and 3 cases were unanimously scored. Excellent agreement was reached for the cases with 0-24% and > 75% of the sarcomatoid component.The most commonly used criteria for the diagnosis of sarcomatoid component were malignant spindle cells, frank sarcomatoid features and high N/C ratio. The overall interobserver agreement for transitional pattern was fair (wK = 0.40). Unanimous opinion about the absence of transitional pattern was observed in only one case. At least 70% agreement regarding the presence of transitional pattern was observed in 12 cases, with the rest of the cases showing a wide range of disagreement. Morphologic characteristics that favor transitional pattern over non-transitional include sheet-like growth of cohesive, plump, elongated epithelioid cells with well-defined cell borders and a tendency to transition into spindle cells. Our study defined precise morphologic criteria that may be used in the differential diagnosis between transitional pattern and other mesothelioma subtypes including sarcomatoid and epithelioid.


Assuntos
Mesotelioma Maligno/patologia , Neoplasias Complexas Mistas/patologia , Patologistas , Neoplasias Pleurais/patologia , Sarcoma/patologia , Biópsia , Diagnóstico Diferencial , Humanos , Mesotelioma Maligno/cirurgia , Neoplasias Complexas Mistas/cirurgia , Variações Dependentes do Observador , Neoplasias Pleurais/cirurgia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
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