Idelalisib-associated enterocolitis

Christine Y. Louie, Michael A. Dimaio, Karen Matsukuma, Steven E. Coutre, Gerald J. Berry, Teri A. Longacre

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Idelalisib is a highly specific small-molecule phosphoinositide-3-kinase δ inhibitor that was recently approved by the Food and Drug Administration for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. The known side effects of idelalisib include severe diarrhea and colitis. Here we report the histologic findings in idelalisib-associated enterocolitis in 11 patients with chronic lymphocytic leukemia or follicular lymphoma receiving idelalisib over a 5-year period (2011 to 2015) at our institution. All 11 patients were receiving idelalisib and underwent colonoscopy for the evaluation of diarrhea. None of the patients had previously received a stem cell transplant. Histologically, the colon biopsies in all 11 cases showed some degree of apoptosis within crypts, with 5 cases showing moderate to severe apoptosis involving the majority of the crypts with loss of goblet cells. No viral inclusions were seen in any case and immunohistochemical stains for cytomegalovirus performed in 9/11 cases were negative. All cases showed at least focal acute cryptitis, and 8 of these cases showed mild architectural distortion. Increased inflammation within the lamina propria was seen in 7 cases, and increased intraepithelial lymphocytes within crypts was seen in 8 cases; the lymphocytes were mostly T cells with a predominance of CD8 + T cells, with the majority expressing the α/β T-cell receptor. Diagnoses of graft-versus-host disease, autoimmune enteropathy, infectious enterocolitis, and although thought to be less likely, inflammatory bowel disease were considered in each case. The presence of numerous intraepithelial lymphocytes in addition to severe villous blunting and apoptosis in the small intestinal biopsies from a subset of these patients additionally raised the possibility of autoimmune enteropathy, common variable immunodeficiency, or less likely, celiac disease. Awareness of the histologic features of idelalisib-associated enterocolitis is important to distinguish it from potential mimics, particularly graft-versus-host disease, autoimmune enteropathy, and cytomegalovirus/infectious enterocolitis.

Original languageEnglish (US)
Pages (from-to)1653-1660
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume39
Issue number12
DOIs
StatePublished - Jan 1 2015

Fingerprint

Enterocolitis
B-Cell Chronic Lymphocytic Leukemia
Follicular Lymphoma
Graft vs Host Disease
Lymphocytes
Apoptosis
Cytomegalovirus
Diarrhea
Common Variable Immunodeficiency
T-Lymphocytes
Biopsy
Goblet Cells
1-Phosphatidylinositol 4-Kinase
Celiac Disease
United States Food and Drug Administration
Colitis
Colonoscopy
T-Cell Antigen Receptor
Inflammatory Bowel Diseases
idelalisib

Keywords

  • apoptosis
  • CLL
  • enterocolitis
  • gastrointestinal
  • idelalisib

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Louie, C. Y., Dimaio, M. A., Matsukuma, K., Coutre, S. E., Berry, G. J., & Longacre, T. A. (2015). Idelalisib-associated enterocolitis. American Journal of Surgical Pathology, 39(12), 1653-1660. https://doi.org/10.1097/PAS.0000000000000525

Idelalisib-associated enterocolitis. / Louie, Christine Y.; Dimaio, Michael A.; Matsukuma, Karen; Coutre, Steven E.; Berry, Gerald J.; Longacre, Teri A.

In: American Journal of Surgical Pathology, Vol. 39, No. 12, 01.01.2015, p. 1653-1660.

Research output: Contribution to journalArticle

Louie, CY, Dimaio, MA, Matsukuma, K, Coutre, SE, Berry, GJ & Longacre, TA 2015, 'Idelalisib-associated enterocolitis', American Journal of Surgical Pathology, vol. 39, no. 12, pp. 1653-1660. https://doi.org/10.1097/PAS.0000000000000525
Louie CY, Dimaio MA, Matsukuma K, Coutre SE, Berry GJ, Longacre TA. Idelalisib-associated enterocolitis. American Journal of Surgical Pathology. 2015 Jan 1;39(12):1653-1660. https://doi.org/10.1097/PAS.0000000000000525
Louie, Christine Y. ; Dimaio, Michael A. ; Matsukuma, Karen ; Coutre, Steven E. ; Berry, Gerald J. ; Longacre, Teri A. / Idelalisib-associated enterocolitis. In: American Journal of Surgical Pathology. 2015 ; Vol. 39, No. 12. pp. 1653-1660.
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