Endoscopic and pathological manifestations of the gastrointestinal tract in familial amyloidotic polyneuropathy type I (Met30)

Abstract

Objectives. To evaluate the characteristic changes in the gastrointestinal tract in familial amyloidotic polyneuropathy (FAP) (Met30), both fibre gastroscopy and colonoscopy studies were performed in FAP (Met30) patients. Microscopic changes were also examined in autopsied and biopsied materials from patients with FAP, and compared with data from autopsied samples from patients with AL amyloidosis, and secondary amyloidosis patients. Design. Endoscopic and histopathological study. Setting. Kumamoto University Hospital, Kumamoto, Japan. Subjects. Nine patients with FAP (Met30) underwent fibre gastroscopy and colonoscopy. Six autopsied and 23 biopsied gastrointestinal samples from FAP patients, four from autopsied amyloidosis (including two myeloma associated form), and two from autopsied secondary amyloidosis patients were examined for histopathological study. Main outcome measures. Fibre gastroscopy and colonoscopy were employed for macroscopic study. Congo red and H-E staining were performed for histopathological study. Macroscopic changes in the gastrointestinal tract and microscopic differences in the amyloid distribution pattern were compared between the different types of amyloidosis. Results. Fibre gastroscopy and colonoscopy for nine FAP patients revealed that four showed a fine granular appearance in the duodenum, three showed lack of lustre, and two showed mucosal friability in the gastrointestinal tract; however, no macroscopic abnormality was observed in four other FAP patients. Histopathological examination of tissue from FAP patients revealed that, although a small amount of amyloid was recognized in the submucosa perivascular layer, a significant amount of amyloid was seen in and around the nerves of the gastrointestinal tract, but very little in Auerbach's nerve plexus. In total, the amount of deposited amyloid in the tissues was small compared with that in other types of systemic amyloidosis, such as AL and secondary amyloidosis. Conclusion. These results suggest that the major reason why FAP patients show such severe gastrointestinal symptoms, compared with other types of systemic amyloidosis, may be because of the deposition of a significant amount of amyloid in the nerves in the gastrointestinal tract.

Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathy

“…Such possible contributing factors may be a depletion of the GI neuroendocrine cells and a destruction of the enteric nervous system. [22][23][24][25] However, the enteric nervous system seems to be unaffected in FAP Val30Met 26,27 and no improvement of the GI function has been shown after Ltx, 28,29 although a normalization of the endocrine cell count was noted. 30 In diabetes mellitus a down-regulation of ghrelin and its receptor is linked to GI dysfunction, 31,32 and it would be of interest to study if this is also the case in FAP patients.…”

“…Such possible contributing factors may be a depletion of the GI neuroendocrine cells and a destruction of the enteric nervous system 22–25. However, the enteric nervous system seems to be unaffected in FAP Val30Met26,27 and no improvement of the GI function has been shown after Ltx,28,29 although a normalization of the endocrine cell count was noted 30.…”

Systemic amyloidosis with gastrointestinal involvement: Diagnosis from endoscopic and histological views

“…In FAP, endoscopic findings of the GI tract are mostly a mild, fine granular appearance, and the amount of amyloid deposition in the mucosa is small compared with that in AL and AA amyloidosis. However, a significant amount of deposition is evident in the nerves of the GI tract, which may cause severe diarrhea and malabsorption occasionally observed in FAP patients despite mild macroscopic findings . Cases of patients with ATTR were limited …”

“…However, a significant amount of deposition is evident in the nerves of the GI tract, which may cause severe diarrhea and malabsorption occasionally observed in FAP patients despite mild macroscopic findings. 47 Cases of patients with ATTR were limited. 48,49 As described previously, the endoscopic findings of GI amyloidosis vary by the organ and depositing amyloid, showing various features, making it difficult to obtain specific findings.…”

Amyloid in surgical pathology

“…However, amyloid does not stain with van Gieson's elastica stain [32,40,96]. The amyloid fibril proteins originate most commonly from transthyretin [91,124], serum amyloid A [58,60] or immunoglobulin light chains [91,122]. The rectal biopsy was introduced by Joseph Gafni and Ezra Sohar in 1960 [30] and has become a standard procedure for biopsy confirmation of amyloid.…”