classificação dos tumores neuroendócrinos oms 2017 · resumo rindi g, arnold r, bosman ft,...
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Classificação dos tumores neuroendócrinosOMS 2017
Teresina Amaro
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WHO 1980 WHO 2000/2004 WHO 2010 WHO 2017
Islet cell tumor(adenoma/carcinoma)
Well differentiated endocrinetumor/ carcinoma
(WDET/WDEC)
Neuroendocrine tumorNET G1/G2
Neuroendocrine tumorNET G1/G2/G3
(well differentiatedneuroendocrine neoplasm)
Poorly differentiatedendocrine tumor
Poorly differentiated endocrinecarcinoma/small cell carcinoma
(PDEC)
Neuroendocrine carcinomaNEC G3
Large or small cell type
Neuroendocrine carcinomaNEC G3
(poorly differentiatedneuroendocrine neoplasm)
Large or small cell type
Mixed exocrine-endocrinecarcinoma
(MEEC)
Mixed adeno-neuroendocrinecarcinoma
MANEC
Mixed neuroendocrine-nonneuroendocrine neoplasm
MiNEN/MENEN
Pseudotumor lesionsTumor-like lesions
(TLL)Hyperplastic and preneoplastic
lesions Klöppel G
WHO 2017 Grading System
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Recomendações sobre Ki67• Hotspots
• Mínimo 500 células
• Arredondar percentagem à unidade
• Discordância entre índice mitótico e Ki67• Prevalece a mais elevada (geralmente Ki67)
• Fotografar e contagem manual (Reid et al, 2015)• Eyeballing – não é recomendado
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- Estudos com base em trabalhos internacionais com grande nº de pacientes mostram que no subgrupo de tumors G1 / G2- O risco de progressão era significativamente mais alto quandose usa os 5%
O índice proliferativo: arredondado para o número inteiro Reconhecimento de que o valor era muito baixo
Scarpa A et al Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol. 2010 Jun;23:824-33.Pelosi G et al Endocrine tumorsof the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictorfor malignancy: a comparative study with proliferating-cell nuclear antigen and progesterone receptor proteinimmunostaining, mitotic index, and other clinicopathologicvariables Hum Pathol. 1996;27:1124-34.Rindi G et al TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study J Natl Cancer Inst.2012 May 16;104(10):764-77. doi: 10.1093/jnci/djs208. Epub2012 Apr 23.
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WHO 2017 Grading System
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1072 patients
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Ki-67 < 55% Pior resposta (15 vs. 42%) Melhor sobrevida (14 vs. 10 m).
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Nordic NEC study
Questões
• Não é correto considerar todos os NET com Ki-67 > 20 %
uma única entidade de doença !
• Devem os NET G3 com Ki-67 de 21-55% ser tratados de
forma diferente? Como NET G2?
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Estudo retrospectivo: 28 casos
NEC G3
16 pouco diferenciados PD
12 bem diferenciados WD
– relevância prognostica
Sobrevida WD NEC vs. PD NEC
40 vs. 17 m
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115 casos
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WHO 2017 Grading System
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NET ou NEC?
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(MiNEN/MENEN)
• Neoplasia mista (pelo menos 30% cada)• Neuroendócrino• Não-neuroendócrino
• Abrange mais subtipos (adenocarcinoma ductal, ca. epidermoide, ca. de células acinares)
• Não é uma entidade na OMS, embora ocorra em múltiplos orgãos
• Geralmente alto grau (G3)• Graduação independente se G1/G2
Diferentes características clinicopatológicas
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• Alteração do cut-off do índice de proliferação celular (Ki67)
• Subdivisão das neoplasias com Ki67 > 20%
• NET G3 bem diferenciado
• NEC G3 pouco diferenciado
• Recomendações sobre Ki67
• MiNEN/MENEN substitui MANEC
Resumo
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Rindi G, Arnold R, Bosman FT, Capella C, Klimstra DS, Klöppel G, Komminoth P, Solcia E: Nomenclature andclassification of digestive neuroendocrine tumours; in Bosman TF, Carneiro F, Hruban RH, Theise ND (eds): World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of the DigestiveSystem. Lyon: International Agency for Research on Cancer (IARC) Press , 2010, pp 10‐12.
Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, Dueland S, Hofsli E, Guren MG, Ohrling K, Birkemeyer E, Thiis‐Evensen E, Biagini M, Gronbaek H, Soveri LM, Olsen IH, Federspiel B, Assmus J, Janson ET, Knigge U: Predictive and prognostic factors for treatment and survival in 305 patients with advancedgastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol 2013;24:152‐ 160.
Heetfeld M, Chougnet CN, Olsen IH, Rinke A, Borbath I, Crespo G, Barriuso J, Pavel M, O'Toole D, Walter T; other Knowledge Network members: Characteristics and treatment of patients with G3 gastroenteropancreaticneuroendocrine neoplasms. Endocr Relat Cancer 2015;22:657‐664.
Vélayoudom‐Céphise FL, Duvillard P, Foucan L, Hadoux J, Chougnet CN, Leboulleux S, Malka D, Guigay J, GoereD, Debaere T, Caramella C, Schlumberger M, Planchard D, Elias D, Ducreux M, Scoazec JY, Baudin E: Are G3 ENETS neuroendocrine neoplasms heterogeneous? Endocr Relat Cancer 2013;20:649‐657.
Basturk O, Yang Z, Tang LH, Hruban RH, Adsay V, McCall CM, Krasinskas AM, Jang KT, Frankel WL, Balci S, SigelC, Klimstra DS: The High‐grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically andbiologically heterogenous and includes both well‐differentiated and poorly‐differentiated neoplasms. Am J SurgPathol 2015;39:683‐690.
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Tumores neuroendócrinos surgem em todo o corpo.
São reconhecidos com base em padrões morfológicos característicos e imunoexpressão de marcadores de diferenciação neuroendócrinas
A classificação patológica dos tumores neuroendócrinos evoluiu ao longo das últimas décadas, com a compreensão do comportamento biológico, características histológicas e genéticas
Muitos aspectos do sistema de classificação continuam confusos ou controversos. A falta de uniformidade na abordagem inclui a diversidade de tumores neuroendocrinos, o estado funcional, as diferenças específicas de órgãos
A padronização da classificação dos tumores neuroendócrinos gastroenteropancreático têm sido razoavelmente bem sucedidamas outros sistemas de órgãos, como o pulmão e timo, usam diferentes terminologia e critérios de classificação.
Os achados genéticos ajudaram a estabelecer relações entre os diferentes tipos de neoplasias neuroendócrinas, mas também revelaram potenciais alvos terapêuticos.
A abordagem patológica das neoplasias neuroendócrinas está mais consistente e clinicamente mais relevantes.