Myofibrotic malformation vessels: unique angiodysplasia toward the progression of hemorrhoidal disease

Abstract

Background: The etiology and pathogenesis of hemorrhoids is unclear, although hemorrhoids are a worldwide disease in men and women, with peak prevalence at 45-65 years of age. Hemorrhoidal cushions as the anal venous plexi are normal anatomical structures from infancy. This study attempts to reveal the angiodysplasia and other pathological changes in association with different degrees of symptomatic hemorrhoids.

Materials and methods: A total of 281 patients with internal hemorrhoids from degree I to IV underwent hemorrhoidectomy. The vascular changes were analyzed by microscopic assessment and software analysis, with Masson's trichrome, CD34, and smooth muscle actin.

Results: The hemorrhoidal tissues exhibited abnormal vessels in the mucosae and submucosae that we termed them as myofibrotic malformation vessels (MMVs). MMVs are not ascribed to arteries or veins because they exhibit enlarged and tortuous lumens with smooth muscle dysplasia and fibrotic deposition in the walls without overlying mucosal ulceration. The muscularis mucosae also showed smooth muscle dysplasia and fibrosis, even if it were interrupted by the intruding MMVs. The statistical data indicated that the severity of all the changes correlate positively with the progression of hemorrhoids (P<0.001). Hemorrhoidal patients are prone for reoccurrence even with prolapsing hemorrhoid when compared with the conventional hemorrhoidectomy. Multiple logistic regression analysis showed that MMVs in mucosal propria, mean thickness of mucosal muscularis layer, and fibrotic changes in MMV were independent risk factors for MMVs in hemorrhoidal disease.

Conclusion: MMVs and muscularis mucosae dysplasia reciprocally contribute to hemorrhoidal exacerbation. The novel findings of this study propose that the characteristic features of MMVs and muscularis mucosae dysplasia of the anorectal tube ultimately cause symptomatic hemorrhoids, which could affect the clinical management of hemorrhoidal disease through the use of surgery to target the malformed vessels.

Keywords: anorectal disease; hemorrhoidal progression; internal hemorrhoids; muscularis mucosae dysplasia; myofibrotic malformation vessels.

Figure 1

Representative images of the pathological changes in the mucosal propria, muscularis mucosa, and submucosae by H&E, Masson’s trichrome staining, CD34, and SMA staining from consecutive sections. Notes: Asterisks label the muscularis mucosa, solid arrows for normal veins in the submucosa, and hollow arrows for MMVs. (A) Control group: normal mucosae and submucosae, without fibrotic deposition in the mucosal propria, regular veins in the submucosae, and a thin layer of uniform smooth muscle in the muscularis mucosa. The mucosal propria does not have arteries and veins with enlarged lumens. (B) Hemorrhoid degree I: mucosal erosion with limited fibrotic deposition and an increase of small vessels in the mucosae; smooth muscle dysplasia and fibrotic deposition in the muscularis propria; MMVs and a normal vein in the submucosae. These changes were increasingly remarkable in hemorrhoids of degree II (C) and III (D), even if MMVs presented in the mucosal propria, especially malformed vessels that crossed over the muscularis propria (C) and tortuous dilated lumen vessels with heavy fibrotic deposition in the walls (D). (E) The enlarged images in the frame of panel (D). Abbreviations: H&E, hematoxylin and eosin staining; MMVs, myofibrotic malformation vessels; SMA, smooth muscle actin.