**3. Clinical features of endometriosis**

Endometriosis is a condition described in European Medical history for over 300 years (Knapp , 1999) and afflicts women in their reproductive years. It is the third leading cause of gynecologic hospitalization in the USA and although the true incidence is unknown, it is estimated that it afflicts about 4-13% of all women in reproductive age,25-50% of women with infertility problems, 5-25%of those that are hospitalized because of pelvic pain,50% of young girls with severe dysmenorrhea and up to 7% of women hospitalized with the diagnosis of pelvic masses(Cramer & Missmer, 2002, Allaire, 2006, Anaf et al, 2000).There is a shift of the time of diagnosis from the late thirties and early forties to the twenties and the cause of this my be extensive use of laparoscopy and delayed childbearing. The use of hormones in menopausal women and obesity may be responsible for the occurrence of endometriosis in postmenopausal age. Most women with endometriosis present some or all of four major problems: infertility, secondary dysmenorrhea, dyspareunia and pelvic pain, but many women are asymptomatic. The intensity of the pain is poorly correlated with the

Pathological Aspects of Endometriosis 103

The many theories proffered to explain the histogenesis of endometriosis may be divided in

b. theories that favor the induction of mesenchyme to produce endometriotic tissues

c. theories proposing that endometriosis arise on sites of metaplastic change of the

The theory of transplantation is the most widely accepted. According to this theory the menstrual flow products flow in a retrograde fashion through the fallopian tubes into the peritoneal cavity. The endometrial products implant, grow and produce tissues with morphology of endometrial glands and stroma. Laparoscopic studies show that during menstruation there is blood in the peritoneal cavity of most women and the retrograde menstrual flow is indeed a usual phenomenon which explains the endometriotic implantation in the ovary and the uterosacral ligaments. Sigmoid colon partly forms a shield and entraps the retrograde menstrual flow products and this fact explains the finding that endometriosis is observed mainly in the left ovary. Also the uterine position is important for the development of endometriosis which is observed anteriorly in patients with anterior uteri. Experimental findings support the transplantation theory and suggest that endometriosis develop in two distinct phases. In the first phase the uterine products are invasive and ovarian hormone -dependent and in the second phase express endogenous estrogen biosynthesis. By the first month after inoculation of primate models with menstrual endometrial tissues these elements attach, grow and invade through the peritoneal mesothelial covering and express estrogen receptor-beta, although aromatase activity is expressed later (Fazleabas et al, 2002 ). Other routes of implantation such as vascular and/or lymphatic spread and direct implantation are reported and explain the development of

a. theories that propose the transplantation on endometrium in extra-uterine site,

endometriosis in distant and unusual places such as lung or lymph nodes.

**7. The theory of the secondary Mullerian system** 

The metaplastic theory proposes that the peritoneum adjacent to ovaries is a multipontential tissue which may obtain characteristics of endometrial tissue (Lauchlan 1972, Lauchlan, 1994). This theory is supported by the observation that endometriosis may develop in cases where no retrograde menstrual flow is possible such as in Rokitansky-Kuster-Hauser syndrome (Acien et al, 1988), in young girls and in men. Finally, according to the induction theory which adds information to transplantation theory, the endometriotic glands and stroma develop de novo from the host tissues, stimulated by the transplanted endometrium. Most pathologists favor a combination of the metastatic and metaplastic theories and support the theory that endometriosis represents a polygenetic disorder, with alterations in multiple biological pathways (Donnez et al, 2002, Sasson & Taylor, 2008) leading to a metaplastic process under the irritating effect of endometrial tissue shed during retrograde

Lauchlan (1972) first used this term to describe the propensity of the peritoneum which covers the ovary and the lower peritoneal cavity to Mullerian differentiation. The mesothelial covering and the sub-mesothelial stroma of peritoneum exhibit a full spectrum

**6. Theories about the histogenesis of endometriosis** 

under the influence of various factors and

coelomic peritoneum.

menstrual flow.

actual extend of the disease and the various local biochemical factors and the local action of activated mast cells may be responsible for this symptom. In rare cases with ovarian endometriosis, acute abdomen because of rupture of ovarian cystic masses and ascites raise the suspicion of malignancy (Henkel et al, 1999).
