LIV Reunión del Club Español de LinfomasMadrid, 13 de noviembre de 2006

Caso del Hospital U. de Getafe

Carlos Santonja, José Antonio Aramburu (A. Patológica)José Antonio García-Vela (Hematología)

Caso del Hospital U. de Getafe

• Mujer de 59 años con trasplante cardiaco en 2000, en tratamiento con Tacrolimus y Azatioprina.

• En mayo de 2006 presenta astenia, molestias en la región lumbar izquierda y cuadro suboclusivo acompañado de fiebre y síntomas sistémicos.

• Clínica suboclusiva: Estudio Endoscópico

Muestra laparoscópica de nódulo en la superficie peritoneal

DIAGNÓSTICO INTRAOPERATORIO: LINFOMA

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CD-20

Bcl-2

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CD-30

Ki-67

INMUNOFENOTIPO(IHQ &CF)

• CD20• BCL6• CD10• BCL2• CD30

• CD19• CD22• CD79B• CD38• HLADR

EBER (CNIO):

Negativo

Clasificación de la OMS de los Trastornos Linfoproliferativos Post-trasplante

(Post-transplant Lymphoproliferative Disorders, PTLD)

• Lesiones Incipientes• PTLD Polimorfo• PTLD Monomorfo• Linfoma de Hodgkin

PTLD en Trasplante Cardiaco

• 5-15 % de pacientes con trasplante cardiaco o cardiopulmonar

• Linfomas no-Hodgkin• Fenotipo B• Afectación extranodal• Alto grado histológico• Evolución clínica agresiva • Frecuente asociación con el virus de Epstein-Barr

Conclusions:The overall incidence of PTLD was 6.3%. It was not altered by sequentialmodifications in treatment regimens. Younger recipient age and higher rejectionfrequency were associated with increased PTLD occurrence. The 15% prevalenceof PTLD in 58 long-term survivors was unexpectedly high.

Conclusions:The overall incidence of PTLD was 6.3%. It was not altered by sequentialmodifications in treatment regimens. Younger recipient age and higher rejectionfrequency were associated with increased PTLD occurrence. The 15% prevalenceof PTLD in 58 long-term survivors was unexpectedly high.

SUMMARYEpstein–Barr virus (EBV) post-transplantation B lymphoproliferative disease (BLPD) may undergo regression after immunosuppressionwithdrawal and restoration of EBV-specific cytotoxic T-cell (CTL) activityin the immunocompromisedallografted host. Thepresence of morphologically normal T cells in the BLPD micro-environment may influence tumour behaviour in vivo. In thisimmunopathologicalstudy, the phenotype and the number of T cells and other immunoregulatorycells have been investigated in sevenprimary and four recurrent BLPD biopsies from nine solid organ transplant recipients. BLPD with either viral lymphadenopathic orpolymorphic lymphoma appearances was found to contain sizeable T-cell populations, mainly of memory/helper (TCRá/â+, CD3+,CD4+, CD45RO+) type. Cytotoxic (TCRá/â+, CD3, CD8+, Tia-1+) T cells were strikingly low in all samples. Low CD28 and CD25expression suggested that secondary signals for functional and sustained T-cell activation may be deficient in these tumours. No closecorrelation was found between the degree of T-cell infiltration and clinical outcome, although appreciably higher numbers of CD8+ Tcells were detected in three BLPD tumours showing prolonged clinical remission after treatment. While some level of EBV-specific T-cellfunction may be present in untreated BLPD, the overall findings of this study suggest that the nature of T-cell infiltrates may reflect aresponse to immunosuppressive therapy rather than to EBV infection per se. The possibilitythat a local EBV-specific T-cell response isgenerated in BLPD undergoing regression after treatment needs to be investigated.

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PTLD Negativos para EVB

• 3-33% (20% según la OMS).• Trasplante de larga evolución• No está claro si

– constituyen un subgrupo de los PTLD– linfomas esporádicos originados

independientemente de la inmunosupresión

• Implicación de otros virus (HHV8, SV40)

Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?Leblond V et al. JClin Oncol 1998;16:2052

Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinctentity? Nelson BP et al. Am J Surg Pathol. 2000;24:375

Post renal transplantation human herpesvirus 8-associated lymphoproliferativedisorder and Kaposi's sarcoma.Kapelushnik J et al BrJ Haematol 2001 113: 425

Simian virus 40 in posttransplant lymphoproliferative disordersBVilchez RA et al Human Pathology 2006;37:1130

Tratamiento y Evolución

• Se disminuye la dosis de inmunosupresores, sin mejoría.

• Rituximab durante cuatro semanas.• Quimioterapia (tres ciclos hasta octubre

de 2006) según esquema R-CHOP (doxorrubicina liposomal como antraciclina, menos cardiotóxica según la literatura).

• Noviembre 2006: Remisión Completa

DiagnósticoCaso Hospital U. de Getafe

Linfoma B de célula grandeEBV-negativo en paciente

con trasplante cardiaco