Sociedad Española de Anatomía Patológica y División Española de la International Academy of Pathology  XXV Congreso de la Sociedad Española de Anatomía Patológica
y División Española de la International Academy of Pathology
XX Congreso de la Sociedad Española de Citología
I Congreso de la Sociedad Española de Patología Forense
   Sociedad Española de Patología Forense
Zaragoza, 18 a 21 de mayo de 2011


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Comunicación oral nº 24. Tema: Patología gastrointestinal y hepatología

Lymphocytic colitis secondary to ipilimumab treatment
A García Varona (1), RD Odze (2)
(1) Hospital Universitario Central de Asturias, (2) Brigham and Women´s Hospital

Introducción:Ipilimumab, is an infusion administered, T-cell potentiator that specifically blocks the inhibitory signal of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a molecule on T-cells that plays a critical role in regulating natural immune responses. Suppression of CTLA-4 can augment the immune system’s T-cell response. Lymphocytic colitis is a clinicopathological syndrome of watery diarrhea, grossly normal colonoscopy and mucosal inflammatory changes.

Material y métodos:A 65-year-old Caucasian male, was diagnosed with ocular melanoma in 2002 and was treated with I-125 plaque therapy. In 2009, he was diagnosed with metastatic malignant melanoma and began treatment with interleuquin-2, but developed further metastatic disease. On November 24, 2010, ipilimumab was initiated as part of a compassionate use trial for unresectable melanoma. On January 6, 2011, the patient was admitted to the hospital after developing watery diarrhea with abdominal discomfort, for the prior five days. The patient underwent a flexible sigmoidoscopy that showed a diffuse area of mildly erythematous and congested mucosa. Biopsies were taken from the rectum, sigmoid and descendent colon.

Resultados:The biopsies consisted of multiple tan-pink soft tissues, which were submitted in total. They showed a well-preserved architectural colonic mucosa with markedly increased intraepithelial lymphocytes and superficial epithelial damage. Isolated apoptotic bodies and mitotic figures were present. The lamina propria revealed a diffuse lymphoplasmacytic infiltrate with scattered eosinophils. A mild degree of vascular congestion was also noticed. No Paneth cell metaplasia was seen.

Conclusión:To our knowledge, this is the first case described of lymphocytic colitis due to ipilimumab therapy. Immune-related events are the most common adverse events and include diarrhea and pruritus. Previous studies have reported panenteritis associated to ipilimumab. Histological samples were characterized by a dense lymphocytic infiltrate along with plasma cells and eosinophils. Foci of neutrophilic cryptitis, crypt abscesses, glandular destruction and erosion of the mucosal surface have also been described. Several potential mechanisms for generating enterocolitis have been described. Intestinal microflora and bacterial antigens, as well as polymorphism in the CTLA4 gene. Transfer of CD25+CD4+ into mice with an experimental immune-mediated colitis leads to resolution of colitis. Therefore, it has been concluded that antibody to CTLA4 might deplete regulatory T cells and thus induce autoimmunity.

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Actualizado: 11/06/2011