The Natural History of Uterine Leiomyomas: Light and Electron Microscopic Studies of Fibroid Phases, Interstitial Ischemia, Inanosis, and Reclamation

Gordon P Flake,Darlene Dixon,Deloris Sutton,Alicia B Moore,Grace E Kissling,David Walmer,Stanley J Robboy,John Horton,Benita Wicker

doi:10.1155/2013/528376

Abstract

We propose, and offer evidence to support, the concept that many uterine leiomyomas pursue a self-limited life cycle. This cycle can be arbitrarily divided on the basis of morphologic assessment of the collagen content into 4 phases: (1) proliferation, (2) proliferation and synthesis of collagen, (3) proliferation, synthesis of collagen, and early senescence, and (4) involution. Involution occurs as a result of both vascular and interstitial ischemia. Interstitial ischemia is the consequence of the excessive elaboration of collagen, resulting in reduced microvascular density, increased distance between myocytes and capillaries, nutritional deprivation, and myocyte atrophy. The end stage of this process is an involuted tumor with a predominance of collagen, little to no proliferative activity, myocyte atrophy, and myocyte cell death. Since many of the dying cells exhibit light microscopic and ultrastructural features that appear distinct from either necrosis or apoptosis, we refer to this process as inanosis, because it appears that nutritional deprivation, or inanition, is the underlying cause of cell death. The disposal of myocytes dying by inanosis also differs in that there is no phagocytic reaction, but rather an apparent dissolution of the cell, which might be viewed as a process of reclamation as the molecular contents are reclaimed and recycled.

Highlights

The etiology of uterine leiomyomas is unknown, and their pathogenesis has been incompletely determined
We have presented morphologic studies to support our hypothesis of the contribution of collagen synthesis to both the enlargement and the eventual involution of uterine fibroids
The excessive elaboration of extracellular matrix results in hyalinization of both the smaller vessels and the interstitium, leading to reduced microvascular density, interstitial and vascular ischemia, and nutritional deprivation of the tumor myocytes

Summary

Introduction

The etiology of uterine leiomyomas (or fibroids) is unknown, and their pathogenesis has been incompletely determined Because they are so common (80% in African-American women and 70% in Caucasian women in one study [1]), it would be reasonable to assume that women share a common risk factor for the development of fibroids. One such factor is menstruation, and perhaps more importantly is the occurrence of dysmenorrhea with associated abnormal uterine contractions [2, 3], which is estimated to occur in up to 70% of women by the fifth year after menarche [4]. In response to vascular intimal injury, smooth muscle cells of the media migrate into the intima, proliferate, and synthesize

Results

Discussion

Conclusion