Amyloidosis of the Gastrointestinal Tract and Liver

Amyloidosis is a localized or systemic disease characterized by congophilic protein deposition in many locations throughout the body. The protein can be derived from a number of sources: immunoglobulin light chains (AL), serum amyloid proteins in systemic chronic inflammatory disease (AA), and multiple, rare mutant proteins usually inherited in an autosomal dominant fashion (Chap. 5) (Pettersson and Konttinen, Semin Arthritis Rheum 39:356–368, 2010; Picken, Arch Pathol Lab Med 134:545–551, 2010; Rocken et al., Histopathology 29:325–335, 1996; Hirschfield, Semin Cell Dev Biol 15:39–44, 2004). The localized form of amyloid—“amyloidoma”—is more typically encountered outside the GI tract and liver, although it can occur there (Kyle et al., Amyloid 10:36–41, 2003; Paccalin et al., Amyloid 12:239–245, 2005). Unfortunately, one cannot distinguish the localized disorder from the systemic disease by histomorphology alone. The systemic disease is serious, often progressive, commonly affecting the heart and/or kidney. When the disease affects these major organs, it comes to early attention because of the dramatic clinical signs and symptoms. The kidney is commonly biopsied to evaluate the clinical dysfunction, so renal amyloid is well recognized and studied. However, amyloid affecting the GI tract and liver tends to be relatively asymptomatic and only occasionally presents late in the course of the disease with clinical signs. When a patient is clinically suspected of having amyloid, rectal biopsies are often performed to assess whether or not it is systemic and pathologists are well aware of the histopathology in this setting. However, the primary manifestation of amyloid in the liver and GI tract is uncommon and often is discovered as an incidental finding or in autopsy material. Since the GI tract and liver are not commonly sampled to make a primary diagnosis (the rectal biopsy not withstanding), many pathologists are not well acquainted with the histopathology of amyloidosis in these sites. Some of the unusual patterns of amyloid could be easily overlooked by the unwary. Also, there is very little literature regarding the surgical pathology of amyloid in the GI tract and liver. The American Journal of Surgical Pathology, one of the most widely read histopathology journals, has published only four articles (one being a case report) on amyloid relating to the GI tract or liver over a 30-year time span. The following is an attempt to present the panorama of amyloidosis involving the GI tract and liver employing an atlas-like approach. Most of the photo micrographs are H&Es, but all the examples have also been stained with Congo red and examined with other techniques to confirm the presence of amyloid. However, most of these confirmatory studies are not illustrated here in order to avoid redundancy. The different types of amyloid have been discussed in Chaps. 2– 8 and will not be further reviewed here. Neither will the many modalities—histochemical stains, ultrastructure, immunohistochemistry, immunofluorescence, protein sequencing, etc.—used in diagnosis be discussed here (see Chaps. 13– 24). Also, the details of clinical diagnosis and treatment are beyond the scope of the chapter (see Chaps. 36– 38).