FINAL DIAGNOSIS: MICROVILLUS INCLUSION DISEASE
Introduction -- Microvillus inclusion disease (MID) is an inherited disorder characterized morphologically by a defective intestinal brush border and by the presence of cytoplasmic inclusions of Microvillus membrane within enterocytes.
This entity was intially known as congenital Microvillus atrophy. Cutz et al suggested the use of the term Microvillus Inclusion Disease (MID) which is more specific and emphazises the typical ultrastructural feature of this condition (1).
Symptomatology -- The absence of microvilli in the enterocyte brush border is associated with an inability to absorb even simple nutrients and the disease presents as refractory diarrhea in the newborn period (2). The infants are chronically dependent on total parenteral nutrition and the disease has a high mortality rate.
Light and electron microscopy -- H&E of the small bowel shows partial to severe villous atropy.The villous atrophy is not associated with crypt hyperplasia or inflammation (3). PAS stains highlight the absence of the normal PAS positive brush border. Also seen on PAS is cytoplasmic staining of the apical enterocyte. (4)
Normally, intestinal alkaline phosphatase activity should be limited strictly to the brush border but in MID it is missing on the surface and seen only in the apical enterocytes especailly within apical inclusions (5). These inclusions demonstrated by alkaline phosphatase are diagnostic and supplant the need for electron microscopy.
CEA immunostaining has also been used and shows findings similar to those of the alkaline phosphatase stain.
Electron microscopy shows the presence of intracytoplasmic inclusions (the ultrastructural counterpart of the alkaline phosphatase stain) within surface enterocytes, and are lined by brush border microvilli (6).
Pathogenesis -- It is postulated that MID is the result of an aberrant assembly of microvilli within intracytoplasmic vesicles, instead of at the apical surface.This aberrant assembly is thought to be due to an abnormality of the enterocyte cytoskeleton.This hypothesis is supported by the finding of decreased amounts of myosin-like protein in the brush border membrane (6). An alternative explanation is that the inclusions result from involution of preformed surface microvilli.This contention is supported by the observation that the Microvillus inclusions are situated exclusively in the apical portions of the cytoplasm (6).
Conclusion -- The pathologist plays an important role in recognising this disease. The disease can be suspected in the appropriate clinical setting but must be confirmed by recognising the light microscopic picture described above. Though electron microscopy has a very characterstic picture, the demonstration of alkaline phosphatase within the apical part of the enterocyte in routinely processed specimens provides an effective, quick and definitive test for MID. The current modality of treatment is intestinal transplantation. Since this is an inherited disorder gentic counseling of affected families is essential.
Contributed by Malathy Kapali, MD, Ronald Jaffe, MD and Rocco M Agostini Jr. B.Sc.