Tufting Enteropathy / Intestinal Epithelial Dysplasia

Definition

Severe intractable diarrhea presents in first days of life
- Rarely later
- Changes may not be well developed early in disease
Villous atrophy of variable severity
- Crypt dilation and branching may be present
- Mild or no lamina propria lymphocytosis
Surface epithelial disorganization with focal crowding and extrusion of cells and apical cytoplasm or “tufting”
- Accentuated at villous tips
- Seen in small and large intestine
Basement membrane shows decreased laminin and increased heparan sulfate proteoglycan
- Appears to correlate with tufting changes
- Increased desmoglein staining of epithelial cell membranes
Electron microscopy reveals desmosomes increased in number and length
Autosomal recessive mutation in EpCAM at 2p21
Associations reported with:
- Various congenital abnormalities of epithelial lined organs
  - 60% have punctuated keratitis

Presentation at birth, lack of inflammation and presence of epithelial tufting exclude other causes of villous atrophy and diarrhea
In early cases without well developed tufting, rebiopsy may be necessary

Tufting Enteropathy	Microvillus Inclusion Disease
Surface epithelial tufts	Apical cytoplasmic inclusions

Both may have scant inflammation with villous atrophy

Enteroendocrine Cell Dysgenesis	Tufting Enteropathy
Normal villi	Variable villus atrophy
No enterocyte disorder or tufting	Surface epithelial crowding and tufting at villus tips
Markedly decreased or absent endocrine cells	Endocrine cells present

Both present with neonatal diarrhea and lack significant inflammation

Goulet O, Salomon J, Ruemmele F, de Serres NP, Brousse N. Intestinal epithelial dysplasia (tufting enteropathy). Orphanet J Rare Dis. 2007 Apr 20;2:20.
Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, Schork NJ, Lavine JE, Taylor S, Newbury RO, Kolodner RD, Hoffman HM. Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology. 2008 Aug;135(2):429-37.
Bird LM, Sivagnanam M, Taylor S, Newbury RO. A new syndrome of tufting enteropathy and choanal atresia, with ophthalmologic, hematologic and hair abnormalities. Clin Dysmorphol. 2007 Oct;16(4):211-21
Al-Mayouf SM, Alswaied N, Alkuraya FS, Almehaidib A, Faqih M. Tufting enteropathy and chronic arthritis: a newly recognized association with a novel EpCAM gene mutation. J Pediatr Gastroenterol Nutr. 2009 Nov;49(5):642-4.
Martin BA, Kerner JA, Hazard FK, Longacre TA. Evaluation of intestinal biopsies for pediatric enteropathy: a proposed immunohistochemical panel approach. Am J Surg Pathol. 2014 Oct;38(10):1387-95. doi: 10.1097. PubMed PMID: 25188866.

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342