1Department of Obstetrics and Gynecology, Medical School, Health Science University of Mongolia, 2Department of Pathology and Forensic medicine, Medical School, Health Science University of Mongolia,
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The uterus comprises the myometrium and the endometrium. The endometrium undergoes dynamic reorganization through each menstrual cycle in response to the steroid hormones. Uterine leiomyomas account for more than 75% of the benign tumours in women of reproductive age group. They are dependent upon the steroid hormones for their growth and maintenance. Hence, it is not surprising that the endometrium would respond to the pathobiologic state of the leiomyomatous uteri. We aimed to study the histopathological changes in endometrium in association with uterine leiomyomas and to identify endometrial changes which help to suggest a diagnosis of uterine leiomyomas on endometrial curettings.
100 cases wherein the uteri revealed leiomyoma were studied. Following receipt of the specimen, a detailed gross examination was done after formalin fixation. Further, microscopic examination was performed after processing, obtaining sections of 5 microns thickness and staining with routine H & E.
Leiomyomas occurred mostly in women aged between 41-50 years and in multiparous women. Menorrhagia was the commonest presentation. Endometrial pattern commonly seen was proliferative phase or hyperplasia. Other epithelial cell changes seen were dilated, elongated or distorted glands, glands parallel to muscle fibres and glands separated by muscle fibres.
Leiomyomas are steroid dependent tumours wherein the endometrium manifests mostly as proliferative phase or hyperplasia suggesting estrogenic prevalence. Association with multiparity explains the need for progesterone in maintenance of leiomyomas. The presence of mixed findings such as glandular atrophy, endometrial hyperplasia or polyposis, together with distorted, dilated or elongated glands and muscle fibres between glands in endometrial curettings, could suggest a possibility of uterine leiomyoma.
Introduction
The endometrium is a dynamic tissue which shows structural changes during the menstrual cycle. Structural reorganisation occurs with each menstrual cycle in preparation for implantation. If no implantation occurs, the superficial layer is partially / completely shed and remodelled in preparation for the next cycle. 1
Studies have shown the presence of estrogen and progesterone receptors in the endometrium and myometrial tissue. They play an important role in regulating their growth.3
Uterine leiomyomas account for more than 75% of the benign tumours in women of reproductive age group.3 The content of the hormone receptors has been shown to be higher in the fibroid tissue.2
In our hospital, hysterectomies are mostly performed for the management of leiomyomas and dysfunctional uterine bleeding. Hence, this study will help to study the histopathologic changes in endometrium in cases of uterine leiomyomas.
The cause of uterine leiomyoma is undetermined. Many factors have been considered on theoretical grounds but practical support is lacking. Heredity is considered to be a factor “fibroids run in families”. From the clinical and epidemiological surveys in the USA, it is known that fibroids are 3-9 times more common in Negroes than in Caucasians. It has been suggested that, this is due to the higher prevalence of pelvic infections in black women, with abnormal uterine growth occurring secondarily to the myometrial irritation caused by these infections. An alternative view may be the presence of a gene encoding for fibroid development, as there is often a positive family history of fibroids in patients who develop these tumours.6
They are true neoplasms rather than hyperplastic proliferations. This has been convincingly demonstrated by analysis of iso-enzymes of glucose-6-phosphate-dehydrogenase.5
The factors involved in the initiation and growth of leiomyomas remain poorly understood. They probably involve complex interactions of sex steroid hormone and local growth factors with somatic mutations in the normal myometrium. Uterine leiomyomas appear during the reproductive years and regress after the menopause, indicating ovarian steroid-dependent growth potential. Further evidence for the role of female sex hormones in the growth of leiomyomas is their occasional rapid growth and haemorrhagic degeneration associated with pregnancy, clomiphene and progesterone treatment.5 6 Oestrogen and progesterone promote the development of myofilaments and dense bodies ultrastructural features of smooth muscle differentiation.5
MATERIALS AND METHODS
The study conducted at the First Maternity Hospital ¹1, Gynecology department, Ulaanbaatar city, Mongolia from June 2010 to December 2012. The hysterectomy specimens received at the Pathology Department, Medical College, Health Science University of Mongolia.
A total of 100 cases were studied in which leiomyoma was present. The study material was obtained from patients admitted at Department of Gynecology, 1st Maternity Hospital, Ulaanbaatar, Mongolia who underwent hysterectomy.
Brief clinical data was obtained from patients or patient records with respect to age, clinical presentation, parity and menstrual phase. Following the receipt of surgical specimens, they were fixed in 10% formalin for 24-48 hours. A detailed gross examination was performed with respect to size and weight of uterus, location and size of fibroids, secondary changes like cystic change, red degeneration, calcification, mucoid degeneration or fatty degeneration and status of endometrium and endometrial polyp if any was noted.
Tissue bits from representative areas of the fibroids and endometrium were taken for histopathological examination, processed and paraffin blocks were made. Sections were cut at 5 micron thickness and stained with hematoxylin and eosin. Microscopic sections were studied and following histologic features were recorded:
1. Endometrial parameters- thickness of endometrium, phase, number and appearance of glands within the given area and stromal changes.
2. Myometrial parameters- presence/ absence of adenomyosis, type/ variant of leiomyoma and secondary/ degenerative changes in the leiomyoma.
The endometrial area was calculated using a standard 2-mm length multiplied by the measured width.F urther, the obtained parameters were evaluated using descriptive statistical analysis. Significance was assessed at 5 % level of significance. Chi-square/ Fisher Exact test have been used to find the significance of study parameters on categorical scale between two or more groups. 95% Confidence Interval has been computed to find the significant features. Confidence Interval with lower limit more than 50% is associated with statistical significance.
RESULTS:
Endometrial phase on microscopy: Of the 100 cases, proliferative endometrium was noted in 38% , followed by secretory endometrium in 24%, endometrial hyperplasia in 20% and atrophic endometrium in 18% of the cases. (Table 1)
Table 1
Endometrial phase
|
Endometrial Phase |
Number (n=100) |
% |
|
Proliferative phase |
38 |
38.0
|
|
Secretory phase |
24 |
24.0
|
|
Simple hyperplasia |
20 |
20.0
|
|
Senile cystic atrophy |
18 |
18.0
|
|
Secretory hyperplasia |
8 |
8.0
|
Endometrial epithelial cell changes: Among the various epithelial cell changes encountered in the endometrium of leiomyomatous uteri, dilated or distorted glands and arrangement of glands parallel to the long axis of myometrium were seen in 43% of the cases, followed by 31% of the cases showing endometrial glands separated by muscle fibres. Other changes seen are as listed in the table 2.
Table 2.
Epithelial Cell Changes
|
Epithelial cell changes |
Number (n=100) |
% |
95%CI |
|
Dilated/ distorted glands |
43 |
43.0 |
43.29-62.49 |
|
Endometrial glands parallel to myometrium |
53 |
53.0 |
43.29-62.49 |
|
Endometrial glands separated by muscle fibres |
31 |
31.0 |
22.78-40.63 |
|
Total glandular atrophy |
13 |
13.0 |
7.76-20.98
|
|
Subtotal glandular atrophy |
4 |
4.0 |
1.78-9.83 |
Further, total and subtotal endometrial glandular atrophy showed significant association (p value<0.001 and <0.002 respectively) with submucosal leiomyoma.
The above findings suggest that if endometrial curettings obtained show a mixed picture of glandular atrophy, endometrial hyperplasia or polyposis, together with many distorted, elongated or dilated glands and muscle fibres between glands, one can suggest the presence of uterine leiomyoma.
Endometrial Stromal Changes: of the various stromal changes, haemorrhage was seen in 33% of the cases and stromal edema in 3% (Table 3)
Table 3. Endometrial stromal changes
|
Stromal Changes |
Number (n=100) |
% |
|
Haemorrhage |
28 |
28.0 |
|
Edema |
15 |
15.0 |
|
Chronic Endometritis |
1 |
1.0 |
|
Absent |
56 |
56.0 |
Endometrial hyperplasia, polyposis, edema and haemorrhage can result from hormonal disturbances, mainly hyperestrogenism.
Correlation of presenting illness with endometrial area : Majority of the patients who had endometrial area of more than 1 sq.mm presented with symptoms of excessive bleeding. (Table 4)
|
Table 4 Correlation of Presenting Illness with Endometrial Area
|
Discussion
The present study included topographical investigation of the pathological changes of the endometrium with special reference to the site of leiomyoma within the uterus. We suggest that the contradictory descriptions and interpretations that have been reported may be partly explained by the varied changes.
Proliferative endometrium and endometrial hyperplasia, both of which represent estrogenic phase accounted for 57% of the endometrial phase, suggesting a prevalence of estrogenic activity in the leiomyomatous uteri. The incidence of complex hyperplasia was only 2%, which substantiates for the higher content of estrogen and progesterone receptors in the myometrium than in the endometrium. Thereby, the brunt of excess hormones was borne by the myometrium in the form of leiomyoma, while endometrium mostly showed either proliferative phase or simple hyperplasia.
These different pathological patterns may be the result of a mechanical factor and a hormonal factor. Atrophy of the endometrium , elongation , and distortion of the glands may result from mechanical pressure exerted by the nodular mass of the leiomyoma on the overlying or nearby endometrium.
Conclusion:
Alterations of the endometrial cycle in these 100 women were due to hormonal variations which may represent a common cause for both the leiomyoma and some of the endometrial changes. The remaining endometrial abnormalities appeared to have been due to mechanical factors that mainly affected the endometrium lying over , opposite , or close to the leiomyoma
2. Gull B, Karlson B, Milsom I, Gramberg S. Factors associated with endometrial thickness and uterine size in random samples of post¬menopausal women. Am J Obstet Gynecol 2001; 185(2): 386-91
3. Crum CP. Body of uterus and endometrium. In: Kumar V, Abbas AK, Fausto N, editors. Robbins and Cotran Pathologic Basis of Disease. 7th edn. Philadelphia: Saunders, 2004: 1089-90.
4. Hendrickson MR, Kempson RL. Pure Mesenchymal Tumours of the Uterine Corpus. In: Fox H, Wells M, editors. Obstetrical and Gynaecological Pathology. 5th edn, vol.2. New York: Churchill Livingstone, 2003: 538-545.
5. Uterus. In: Standring S, editor. Gray’s Anatomy, The Anatomical Basis of Clinical Practice. 39th edn. Spain: Elsevier, 2005: 1331-9.
6. Vollenhoven BJ, Lawrence AS, Healy DL. Uterine fibroids: A clinical review. Br J Obstet Gynaecol 1990; 97: 285-98.
