TIMOMA Y CARCINOMA TIMICO · tumor is composed of highly atypical cells with pleomorphic nuclei and...
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TIMOMA Y CARCINOMA TIMICO
Ricardo Segura FangMIR 1º AÑO MFyC
Sesión Clínica de M. Interna15-02-2011
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CASO CLINICO
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CASO CLINICO• ANTECEDENTES PERSONALES:
– Varón de 30 años.– No alergias farmacológicas conocidas. – Fumador esporádico. – Dos pólipos nefríticos no complicados desde el 2006. – No tratamiento farmacológico habitual.
• ENFERMEDAD ACTUAL: Desde julio de 2010 el paciente relata dolor en región torácica derecha asociado a sibilancias autoaudiblesen los grandes esfuerzos. No relata fiebre, sudoración nocturna, anorexia, ni pérdida de peso. No clínica neurológica. El paciente acude a su Neumólogo de ambulatorio a últimos de octubre que le realiza un Rx de tórax donde se aprecia elevación del diafragma derecho.
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CASO CLINICO
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CASO CLINICO
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CASO CLINICO• Por este motivo solicita un TAC TORACO-
ABDOMINO-PÉLVICO que se realiza el 3.12.2010: masa en mediastino anterior de 8x5.4x3.5 cm. con densidad de partes blandas y presencia de calcificaciones. Sugestivo de timoma, teratoma y mucho más improbable linfoma. Elevación del hemidiafragmaderecho que puede estar en relación a parálisis frénica. Cambios atelectásicos en lóbulo inferior, dada la elevación del hemidiafragma derecho.
• El paciente es remitido a Urgencias de Medicina para ingresar al paciente para estudio.
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CASO CLINICO• EXPLORACIÓN FÍSICA: Normotenso y afebril.
Buen estado general. Pares craneales normales. A.C: rítmica a 80 x‘. A.P: hipoventilación en base derecha. Abdomen: no masas ni visceromegalias. Extremidades: normales. No adenomegalias periféricas.
• ANALÍTICA: Perfil general y hepático: normal. CK y LDH: normales. Proteinograma, Beta 2MG, alfafetoproteina y HCG-B: normales. Hb 14 con volúmenes normales. Plaquetas 239.000; leucocitos 5.900 con fórmula normal. Orina y sedimento: normal. H. tiroideas: normales. Colinesterasa: normal. Estudio de coagulación: normal
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CASO CLINICO• E.C.G.: Sinusal, BIRDHH.• PRUEBAS DE FUNCIÓN
RESPIRATORIA: Restricción leve. • PET : Sobre mediastino anterior se
observa un incremento patológico de captación con morfología abigarrada y distribución heterogénea del trazador de moderada-elevada actividad metabólica (SUV entre 4,3-6,6) que es congruente con la masa mediastínica conocida.
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CASO CLINICO• EVOLUCIÓN:
Paciente estable durante todo el ingreso manteniendo buen estado general, aquejando únicamente malestar torácico sobre todo en decúbito supino. Se intenta biopsia guiada por ecografía de masa mediastínica, no siendo por esta técnica accesible. Se comenta con Servicio de Radiología (TAC) para intentar biopsia por este método, recomendando dicho Servicio y estando de acuerdo en que el rendimiento diagnóstico iba a ser escaso y sería mucho más rentable la biopsia quirúrgica con resección de la masa en el mismo acto si fuera posible. Valorado por Servicio de Cirugía Torácica absolutamente de acuerdo con la decisión tomada. Alta de M. Interna el 15-12-10.
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CASO CLINICO• 28-12-2010: Intervención quirúrgica:
Hallazgos: Masa mediastínica anterior de aproximadamente 5x8 cm con infiltración importante de hemipericardio derecho. Adherido de forma importante a tronco venoso innominado y vena cava superior. El tumor infiltra el nervio frénico derecho congruente con la parálisis frénica derecha conocida preoperatoria.
• Técnica: Resección del tumor en bloque incluyendo el nervio frénico derecho y hemipericardio derecho. Reconstrucción pericárdica con parche de goretex. Sin
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CASO CLINICO• EVOLUCION POSTOPERATORIA: Satisfactoria en
el Servicio de Reanimación y planta de hospitalización encontrándose el paciente en todo momento afebril y hemodinámicamente estable. A las primeras 48-72 h elevación difusa del ST en todas las derivaciones del ECG en probable relación a pericarditis postoperatoria. Coincidiendo con el bajo débito de líquido seroso a través de los drenajes torácicos son retirados los mismos comprobándose en Rx de tórax de control al alta reexpansión pulmonar completa y ausencia de complicaciones. En las analíticas seriadas de control postoperatorio se objetiva anemizaciónmoderada sin precisar trasfusiones.
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CASO CLINICO• INFORME DE ANATOMIA PATOLÓGICA:
Tumoración mediastínica parcialmente capsulada de 116 gr de peso y dimensiones de 9 x 8 x 5 cm. En cortes seriados se observa una tumoración blanquecina con punteado amarillento y aspecto trabecular. Presenta áreas calcificadas. En uno de los extremos superficie anfractuosa infiltrada por tumor.Secciones muestran tumor epitelial maligno tipo adenocarcinoma, interpretado como tímico. Cápsula incompleta e infiltración de pericardio.INMUNOHISTOQUÍMICA: Sorprendentemente CD5 negativo. Sin embargo, conclusión: adenocarcinoma tímico (clínica, topografía).
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CASO CLINICO• SEGUIMIENTO:
TAC CÉRVICO-TORÁCICO (08-02-2011):Motivo: Control de resección de carcinoma tímico para inicio de QT adyuvante.Elevación de diafragma derecho. Derrame encapsulado LID.
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MEDIASTINO
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MEDIASTINOEs el espacio extrapleural que existe entre ambos pulmones. Sus límites son el istmo cervical por arriba, el diafragma por abajo, la columna y arcos costales por atrás y el esternón por delante.Engloba por tanto normalmente :
•Corazón y grandes vasos •Hilios pulmonares •Timo •Tráquea •Esófago
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MEDIASTINODIVISION
• División:• Anterior : por delante del
pericardio, la aorta y los vasos braquiocefálicos.
• Medio: entre las hojas del pericardio e incluye los grandes vasos.
• Posterior: entre el pericardio y los canales vertebrales.
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MEDIASTINODIVISION
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MEDIASTINOCONTENIDO
• Anterior: – Timo.– Aorta extrapericárdica y sus ramas.– Ramas de las arterias y venas mamarias internas.– Ganglios y tejido adiposo.
• Medio:– Pericardio.– Corazón.– Grandes vasos intrapericárdicos.– Arterias y venas braquiocefálicas.– Nervio frénico y porción superior del vago.– Tráquea, tejido ganglionar.– Arterias y venas pulmonares.
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MEDIASTINOCONTENIDO
• Posterior:–Aorta descendente.–Esófago.–Conducto torácico.–Vena ácigos y hemiácigos.–Tejido adiposo y ganglionar.–Nervios autonómicos.
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MEDIASTINODIAGNOSTICO DIFERENCIAL MASA
MEDIASTINAL
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EPIDEMIOLOGIAMASA MEDIASTINAL
• Incidencia:– Primarios 1 cada 100.000 habitantes– Secundarios > de 20 cada 100.000 habitantes
• Relación hombre/mujer: – Primarios 1/1– Secundarios 5/1
• Distribución por edades (primarios): – Adultos: 30% son malignos – Niños: 50% son malignos
• Distribución por localización:– Adultos: Anterior > Medio > Posterior– Niños: Posterior > Anterior > Medio– Secundarios: Medio > Anterior > posterior
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MASA MEDIASTINALCompartimiento Probabilidad de
afectación (%)Probabilidad de malignidad (%)
Anterosuperior 56 59
Medio 19 29
Posterior 25 16
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MEDIASTINOSINTOMATOLOGIA
• Compresión o infiltración: – Respiratoria: tos, disnea, estridor, hemoptisis– Pleural: derrame pleural– Digestiva: disfagia, reflujo– Cardíaca: ICC, taponamiento, arritmias– Nerviosa: dolor, parálisis frénica, síndrome
medular, Claude Bernard Horner, disfonía– Vascular: síndrome de vena cava superior
• Neurohormonal: Fiebre, miastenia gravis, aplasia medular, hipogammaglobulinemia, osteopatía hipertrófica, ginecomastia, HTA, taquicardia, sudoración, hipoglucemia.
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MEDIASTINOMASA MEDIASTINAL ANTERIOR• 4 “T”:
–Timo–Tiroides–Tumores de células germinales
(Teratoma).–Terrible linfoma.
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TIMOMA
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TIMOMA• Neoplasia tímica benigna o de bajo grado de origen epitelial
• 2da. neoplasia mediastinal (20% en adultos), primera causa en mediastino anterior.
• Adultos, edad media ( 70% encima de 40 años)
• Encapsulados, circunscritos, sólidos, polilobulados. Bandas deestroma fibroso.
• Van de lesiones microscópicas hasta más de 30cm de diámetro. Quísticos en 40%, con necrosis en 25%.
• Mayoría rodeados de cápsula fibrosa que puede estar calcificada.Bandas colágenas gruesas conectadas a la cápsula dividen el tumor en múltiples lóbulos, esta arquitectura es característica.
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TIMOMA
Photomicrograph shows the multilobulated architecture characteristic of thymoma, with thick fibrous trabeculaethat separate the tumor into lobules of varying size. (Hematoxylin and eosin, magnification 25x).
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TIMOMA
Noninvasive thymomaSurgical specimen shows a well- circumscribed, solid mass with a tan-ivory and lobulated cut surface.
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TIMOMA
• Lento crecimiento. Metástasis infrecuentes.
• Variedad histológica : Compuestos por células neoplásicas epiteliales y linfocitos T no neoplásicos inmaduros:– Predominantemente epiteliales– Predominantemente linfocíticos– Mixtos linfoepiteliales
• 2 tipos de células neoplásicas:– Poligonales– Fusiformes
• Espacios perivasculares: 70% de timomas.
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TIMOMACLASIFICACION WHO
Clase de Timoma Hallazgos Citológicos Frecuencia
(%)Invasividad
/ GVSV 20 a
Tipo A Medular y Fusiformes 6.5 11.1%/ 0%
100%
Tipo AB Mixto 28.2 41.6%/3.9%
87%
Tipo B1 Rico en linfocitos, Linfocitico,
Predominantemente cortical, Organoide
20.3 47.3%/ 7.3% 91%
Tipo B2 Cortical 35.5 69.1%/17.5%
59%
Tipo B3 Epitelial atípico, Celescamosas, Ca tímico
bien diferenciado
9.5 84.6%/19.2%
36%
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TIMOMA
Predominantly lymphocytic, invasivethymoma
This thymoma is predominantly composed of lymphocytes with scattered epithelial cells; it invades the surrounding mediastinal fat tissue but does not reach the inked surgical margin. (Hematoxylin and eosin, magnification 25x)
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TIMOMAHISTOQUIMICA
• Células epiteliales: Leu-7• Linfocitos:
–LCA–CD3–CD1–CD99 (MIC2)
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TIMOMA Presentación clínica
Asintomática: 50%.Sintomática:– Síntomas locorregionales: compresión,
invasión– Síndromes paraneoplásicos: 70%
• Miastenia gravis: 40%• Aplasia de serie roja: 5%• Hipogamaglobulinemia• Otros: LES, Addison, DM-PM, PAR, ES
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TIMOMAParaneoplastic syndromes associated with thymoma
Autoimmune
Systemic lupus erythematosus
Polymyositis
Myocarditis
Sjogren's syndrome
Ulcerative colitis
Hashimoto's thyroiditis
Rheumatoid arthritis
Sarcoidosis
Scleroderma
Endocrine disorders
Addison's disease
Hyperthyroidism
Hyperparathyroidism
Panhypopituitarism
Hematologic disorders
Red cell aplasia
Hypogammaglobulinemia
T-cell deficiency syndrome
Pancytopenia
Erythrocytosis
Amegakaryocytic thrombocytopenia
Neuromuscular syndromes
Myasthenia gravis
Eaton Lambert syndrome
Myotonic dystrophy
Myositis
Miscellaneous
Hypertrophic pulmonary osteoarthropathy
Nephrotic syndrome
Minimal change nephropathy
Pemphigus
Chronic mucocutaneous candidiasis
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TIMOMA
Thymoma
CT scan of a thymoma originating from the right lobe of the thymus. A large rounded mass is seen in the retrosternal location, to the right of the midline (arrow).
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TIMOMA
Thymoma
Thymoma originating from the left lobe of the thymus. There is a large rounded inhomogeneous retrosternal mass located to the left of the midline (arrow).
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TIMOMA
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TIMOMA
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TIMOMA
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TIMOMAESTADIAJE
Masaoka's clinical stage
Stage I: Macroscopically completely encapsulated and microscopically no capsular invasion
Stage II: Macroscopic invasion into surrounding fatty tissue or mediastinal pleura, or microscopic invasion into capsule
Stage III: Macroscopic invasion into neighboring organs, ie, pericardium, great vessels, or lung
Stage IVa: Pleural or pericardial dissemination
Stage IVb: Lymphogenous or hematogenous metastasis
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TIMOMAPRONOSTICO
–FUNDAMENTALMENTE : Invasión capsular
–Multifactorial??:•Tipo histológico•Estadio•Resecabilidad
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TIMOMATRATAMIENTO
• Resección quirúrgica completa es el tratamiento de entrada siempre que sea posible.
• Estadío Masaoka I: NO RT o QT adyuvante .• Estadío Masaoka II con resección completa: RT
adyuvante postoperatoria .• Estadío Masaoka II o III con resección incompleta o
márgenes quirúrgicos positivos: RT postoperatoria.• Estadío Masaoka III o IVa inicialmente no resecables:
QT neoadyuvante → Si buena respuesta: Cirugía → RTadyuvante. Alternativamente RT sola o RT + QT si cirugía de entrada no es técnicamente posible.
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CARCINOMA TIMICO
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CARCINOMA TIMICO• Compuesto de células altamente atípicas con
citoarquitectura similar a carcinomas de otras localizaciones.
• Linfocitos B, células plasmáticas y Linfocitos T maduros(CD1a-, CD3+, CD4+, CD8+).
• Aparentemente: Timoma → Carcinoma tímico.• Masas infiltrantes firmes con frecuentes áreas de
cambios quísticos y necrosis. Áreas calcificadas.Encapsulados en 15%.
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CARCINOMA TIMICO
Poorly differentiated thymiccarcinoma
Low power photomicrograph shows cystic changes within a thymic carcinoma. The cysts are filled with pale eosinophilicsecretions and are reminiscent of an acquired multilocularthymic cyst. (Hematoxylin and eosin, magnification 2.5x).
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CARCINOMA TIMICOWHO histologic typing of tumors of the
thymusEpithelial Tumors
Thymoma
Type A (spindle cell; medullary)
Type AB (mixed)
Type B1 (lymphocyte-rich; lymphocytic; predominantly cortical; organoid)
Type B2 (cortical)
Type B3 (epithelial; atypical; squamoid; well-differentiated thymic carcinoma)
Thymic carcinoma (type C thymoma)
Epidermoid keratinizing (squamous cell) carcinoma
Epidermoid non-keratinizing carcinoma
Lymphoepithelioma-like carcinoma
Sarcomatoid carcinoma (carcinosarcoma)
Clear cell carcinoma
Basaloid carcinoma
Mucoepidermoid carcinoma
Papillary carcinoma
Undifferentiated carcinoma
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CARCINOMA TIMICO• Raro: < 1% NM timo.• Usualmente no asociado a síndromes paraneoplásicos.• No patrón lobulado.• CD5 tiñen las células epiteliales de varios carcinomas tímicos, 40%
de timomas atípicos pero no carcinomas de otros sitios incluido pulmón.
• p53 con alta frecuencia de expresión ha sido reportada en carcinoma tímico pero no en timoma, pero no confirmada por experiencia clínica.
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CARCINOMA TIMICO
Poorly differentiated squamous cell carcinoma of the thymus
The multilobulated appearance of a thymoma is lacking. This tumor is composed of highly atypical cells with pleomorphicnuclei and a high mitotic rate. Although immature lymphocytes of T cell type are missing, a lymphoplasmacytic reaction can be prominent.
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CARCINOMA TIMICO
Tomografía de tórax en paciente con carcinoma tímico.
Fotografía de la pieza quirúrgica de un carcinoma tímico.
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CARCINOMA TIMICOPRONOSTICO
Suster & Rosai (Cancer 1991; 67:1025).
Low-grade histology
Well differentiated squamous cell carcinoma
Basaloid carcinoma
Well differentiated mucoepidermoid carcinoma
High-grade histology
Lymphoepithelioma-like carcinoma
Small cell neuro-endocrine carcinoma
Undifferentiated/anaplastic carcinoma
Clear cell carcinoma
Sarcomatoid carcinoma
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CARCINOMA TIMICOPRONOSTICO
• Grado histológico tiene significado pronóstico.
• Hallazgos de peor pronóstico:–Márgenes tumorales infiltrados.–Ausencia de patrón lobular de
crecimiento.–Atipia nuclear de alto grado y necrosis.–> 10 mitosis/10 campos.
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CARCINOMA TIMICOTRATAMIENTO
• De acuerdo a Estadiaje de Masaoka.
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GRACIAS!!