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Abordaje del paciente con síndrome linfoproliferativo.

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Presentación sobre el abordaje del paciente adulto con síndrome linfoproliferativo.

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Abordaje del paciente con síndrome linfoproliferativo.

  1. 1. Abordaje del paciente con síndrome linfoproliferativo Jonathan Rubio T. Residente de Primer Año Medicina Interna CES
  2. 2. Caso Clínico No. 1 • Paciente masculino de 73 años, etnia negra • Antecedente de HTA • 4 meses de evolución de astenia/adinamia, palidez generalizada, sin otros síntomas • Sin adenopatías periféricas • Se documenta anemia (Hb 4), Coombs directo (+) – fraccionado C3 • TC toracoabdominal: Hepatomegalia, no esplenomegalia o adenomegalias
  3. 3. Caso Clínico No. 2 • Paciente masculino de 54 años • Antecedente de tabaquismo pesado • 20 días de evolución de astenia/adinamia, palidez; en revisión por sistemas síntomas LUTS • Adenopatías cervicales izquierdas duras de 1.5 cm • Hb 6, Coombs directo (-) • TC toracoabdominal: Adenomegalias mediastinales y retroperitoneales de hasta 8 cm
  4. 4. ¿CUÁL CREEN QUE TIENE UN TRASTORNO LINFOPROLIFERATIVO?
  5. 5. Recorderis Imagen contenida en: Abbas et al. Cellular and Molecular Immunology. 7th edition. Elsevier. Consultada el 04/05/14 en: https://www.inkling.com/read/cellular-and-molecular-immunology-abbas- 7th/chapter-2/anatomy-and-functions-of
  6. 6. Origen Imagen contenida en: Hematopoietic and Lymphoid Systems, capítulo de: Kumar et al. Robbins Basic Pathology. 9th edition. Elsevier 2013.
  7. 7. Imagen contenida en: Lymphoid Neoplasms, capítulo de: Longo et al. Harrison’s Principles of Internal Medicine. 18th edition. McGraw-Hill 2012.
  8. 8. Imagen contenida en: Lymphoid Neoplasms, capítulo de: Longo et al. Harrison’s Principles of Internal Medicine. 18th edition. McGraw-Hill 2012.
  9. 9. Fisiopatología • T(14;18) – BCL2 (Linfoma folicular, DLBCL) • T(8;14) – c-MYC (Burkitt) • T(2;5) – ALK (Linfoma anaplásico de células grandes) • T(11;14) – Ciclina D1 (Manto) • T(9;22) – BCR/ABL (ALL) Mutaciones Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012. Shankland K, Armitage J, Hancock B. Non-Hodgkin Lymphoma. Lancet 2012; 380: 848–57
  10. 10. Küppers R, Engert A, Hansmann M. Hodgkin Lymphoma. J Clin Invest. 2012;122(10):3439–3447
  11. 11. Fisiopatología • Factores de riesgo – Infecciosos • EBV • VIH • H. pylori • HTLV-1 • Hep C • Otros – No infecciosos • Inmunodeficiencia heredada y adquirida • Autoinmunidad • Químicos (< 1980) • Tabaco • Tratamiento oncológico Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012. Shankland K, Armitage J, Hancock B. Non-Hodgkin Lymphoma. Lancet 2012; 380: 848–57 Word Z, Matasar M. Advances in the Diagnosis and Management of Lymphoma. Blood and Lymphatic Cancer: Targets and Therapy 2012:2 29–55
  12. 12. Clasificación Leucemias • Agudas – ALL • Crónicas – CLL típica – Linfomas con comportamiento leucémico • Folicular • Manto • Marginal • Tricoleucemia • Linfoplasmacítico • Células T del adulto Linfomas • Hodgkin – Clásico – Esclerosis nodular – Celularidad mixta – Nodular linfocítico – Rico/pobre en linfocitos • No Hodgkin
  13. 13. Leucemia linfoide aguda (ALL) Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  14. 14. Linfoma No Hodgkin Clasificaciones diversas • Rappaport (1966) • Kiel/Lukes & Collins (1974) • Formulación de Trabajo Internacional (1982) • REAL (1994) • WHO (2008) Word Z, Matasar M. Advances in the Diagnosis and Management of Lymphoma. Blood and Lymphatic Cancer: Targets and Therapy 2012:2 29–55
  15. 15. REAL 1994 Harris N et al. A Revised European-American Classification of Lymphoid Neoplasms. Blood, Vol 84, No 5 (September l), 1994p:p 1361-1392
  16. 16. WHO 2008 Shankland K, Armitage J, Hancock B. Non-Hodgkin Lymphoma. Lancet 2012; 380: 848–57
  17. 17. Epidemiología Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  18. 18. Diferentes datos • Europa (2013) – Hodgkin: 10 – No Hodgkin • Folicular: 36 • CLL/SLL: 27 • PTLD: 26.2 • Primario cutáneo de células T: 24 • DLBCL: 20 • España (Novelli et al 2013) – 74 casos por año – Más comunes: DLBCL, folicular, marginal • EEUU (Morton et al 2006) – Hodgkin: 2.6 – No Hodgkin B: 26 • DLBCL • CLL/SLL • Células plasmáticas • Folicular – No Hodgkin T: 1.8 – ALL: 1.6 • Centro/Suramérica (Laurini et al 2012) – DLBCL: 40% – Folicular: 20% – MALT: 7% Informes Periódicos de Orphanet - Prevalencia de las enfermedades raras : Datos bibliográficos - Noviembre 2013 - Número 2 http://www.orpha.net/orphacom/cahiers/docs/ES/Prevalencia_de_las_enfermedades_raras_por_prevalencia_decreciente_o_casos.pdf Novelli et al. Epidemiology of lymphoid malignancies: last decade update. SpringerPlus 2013, 2:70 Morton et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood. 2006;107:265-276 Laurini et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood. 2012;120(24):4795-4801
  19. 19. En Colombia Carrascal et al. Epidemiología y patología de la leucemia/linfoma de células T del adulto en Cali y el suroccidente colombiano. Colomb Med 2004; 35: 12-17
  20. 20. ¿Cuándo una adenopatía es significativa? BENIGNA • Tamaño < 1 cm • Localización submandibular (niños, adultos jóvenes) • Localización inguinal (adultos mayores) • Consistencia blanda • Asociaciones MALIGNA • Tamaño > 2 – 2.25 cm • Localización supraclavicular/escalénica/ axilar/epitroclear • Consistencia dura/adhesión a planos profundos • Indolora • Síntomas y signos asociados Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012. Brown J, Skarin A. Clinical Mymics of Lymphoma. The Oncologist 2004; 9: 406-416.
  21. 21. Presentación clínica - ALL Signos de falla medular • Fiebre y síntomas/signos de infección • Síntomas de anemia • Hemorragias Adenopatías Hepato/esplenomegalia Compromiso en otros sistemas Síntomas de hiperviscosidad Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  22. 22. Presentación clínica – CLL típica Linfocitosis Adenopatía asintomática Esplenomegalia Astenia/adinamia Infecciones Fenómenos autoinmunes (AIHA, PTI) Aplasia eritroide Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  23. 23. Presentación clínica – Hodgkin clásico Adenopatía indolora (cervical, supraclavicular, axilar, mediastinal) Diseminación por contigüidad Síntomas B (33%) Fiebre de Pel-Ebstein Otras manifestaciones • Prurito intratable • Dolor en adenopatías al consumir OH • Lesiones cutáneas/subcutáneas • Manifestaciones paraneoplásicas/autoinmunes/renales Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  24. 24. La célula de Reed-Sternberg Küppers R, Engert A, Hansmann M. Hodgkin Lymphoma. J Clin Invest. 2012;122(10):3439–3447
  25. 25. Presentación clínica – No Hodgkin • Adenopatías – MALT – ALL pre-B – Tricoleucemia – Marginal esplénico – Subtipos de células T periféricas • Síntomas B – DLBCL – Manto – Anaplásico de células T – Angioinmunoblástico • Compromiso medular – Manto – Folicular – Células T periféricas – Burkitt • Compromiso gastrointestinal/abdomen – MALT – DLBCL – Células T periféricas – Burkitt – Manto/folicular Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  26. 26. Presentación clínica – No Hodgkin • Compromiso en SNC – DLBCL – Burkitt – MALT (dura) • Esplenomegalia – Tricoleucemia – Marginal esplénico – Linfoplasmacítico – Células T del adulto – Tipo T γδ hepatoesplénico • Compromiso en piel – Mycosis fungoides – Células T del adulto – Anaplásico de células T – Células T periféricas, subtipo paniculitis • Síndrome hemofagocítico – Células T periféricas, subtipos T/NK nasal, paniculitis Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  27. 27. Presentación clínica – No Hodgkin • AIHA – Varios (incluso antes de desarrollar linfoma) • Von Willebrand adquirido – Varios (mecanismos autoinmunes) • Hiperviscosidad – Presentaciones leucémicas – Linfoplasmacítico (IgM) Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  28. 28. Diagnósticos diferenciales! • Estreptococos • Estafilococos • Toxoplasmosis • Arañazo de gato • TB/micobacterias • EBV • VIH Infecciones • LES • AR • Sjogren Autoinmunes • Fenitoina/CBZ • Sulfas/penicilinas • ASA • Alopurinol Medicamentos • Sarcoidosis • Amiloidosis • Depósito Infiltrativas • Kikuchi (linfadenitis histiocitaria necrotizante) • Rosai-Dorfman (histiocitosis sinusal con adenopatía masiva) • Castleman (HHV-8) Otros linfoproliferativos Brown J, Skarin A. Clinical Mymics of Lymphoma. The Oncologist 2004; 9: 406-416.
  29. 29. Abordaje diagnóstico y estadificación Hemograma + extendido periférico Estudios de hemólisis (LDH) Función de órganos Estudios de médula ósea Imágenes (tórax-abdomen-pelvis) •TC •PET •Endoscopia* Punción lumbar* Electroforesis de proteínas Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  30. 30. Importante en linfoma… Estudio HISTOLOGICO!!! •Biopsia ojalá escisional •Revisión por hemato-patólogo Word Z, Matasar M. Advances in the Diagnosis and Management of Lymphoma. Blood and Lymphatic Cancer: Targets and Therapy 2012:2 29–55
  31. 31. Estadificación Word Z, Matasar M. Advances in the Diagnosis and Management of Lymphoma. Blood and Lymphatic Cancer: Targets and Therapy 2012:2 29–55
  32. 32. Puntajes pronósticos No Hodgkin • IPI • FLIPI-1, FLIPI-2 • MIPI Hodgkin • IPS CLL/SLL • Rai • Binet • Expresión de ZAP-70, CD38 Tasa proliferativa (tinción Ki-67) Word Z, Matasar M. Advances in the Diagnosis and Management of Lymphoma. Blood and Lymphatic Cancer: Targets and Therapy 2012:2 29–55 Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  33. 33. Tratamiento Hodgkin: QT +/- RT •AVBD, BEACOPP, Stanford V •Recaídas: Brentuximab, otros •Nodular linfocítico: Como No Hodgkin No Hodgkin: R-CHOP +/- RT •Marginal esplénico: Esplenectomía •CLL/SLL: Observar, fludarabina, alemtuzumab •Burkitt: CODOX-M/IVAC, Hiper-CVAD •PTCL: CHOP •MALT: H. pylori ALL • Inducción: HiperCVAD, asparaginasa, mitoxantrona/AraC •Consolidación •Mantenimiento QT intratecal: ALL, DLBCL Word Z, Matasar M. Advances in the Diagnosis and Management of Lymphoma. Blood and Lymphatic Cancer: Targets and Therapy 2012:2 29–55 Lymphoid Neoplasms. En: Harrison’s Internal Medicine. 18th Edition. McGraw-Hill. 2012.
  34. 34. Respuesta correcta: Caso 1! GRACIAS!

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