International Journal of Pathology; 2011;9(1): 15-19
Original Article
Thickened Blood Vessels in Endometrial Curettings
in Dysfunctional Uterine Bleeding – a pilot study
Anwar Ul Haque and Sara Haque
Islamabad Institute of Pathology, Islamabad, Pakistan
Background: Dysfunctional uterine bleeding (DUB) is common ailment. It accounts for about 10% of
gynaecology outpatient department (OPD) registrants in developed countries. There is disturbance of
rhythmic cyclic menstruation resulting in excessive and irregular hemorrhage. Anovulation or oligoovulation leads to the sustained estrogen effects with unopposed progesteronal effects. Other causes of
estrogen dominance may also cause similar effects. The relative estrogen dominance results in various
changes in the endometrial vasculature causing menorrhagia.
Objective: To determine the frequency and significance of thickened blood vessels in the endometrial
curettings in dysfunctional uterine bleeding.
Study Design: Retrospective cross sectional pilot study.
Place of Study: Islamabad Institute of Pathology & Labs, Islamabad, Pakistan
Materials & Method: Hematoxylin and Eosin (H&E) stained sections of 30 consecutive random cases of the endometrial curetting from dysfunctional uterine bleeding were studied by light microscopy for
with particular emphasis on numbers of thickened blood vessels.
Inclusion Criteria: All endometrial curetting with history of dysfunctional uterine bleeding
Exclusion Criteria: Endometrial curetting from patients with specific etiologies such as endometritis,
atypical hyperplasia, retained products, Intra uterine devices (IUDS)
Results: Over 50% of the patients were in perimenopausal age group i.e. 40-55. All endometrial curettings contained thickened blood vessels. On average there were about 8 thickened blood vessels per
endometrial curetting.
Conclusion: Estrogen induced vascular changes result in increased permeability which may in turn
cause deposits of various plasma proteins in the wall with enhanced intramural vascular thickening.
Such thickened vessels may not contract properly thus causing and prolonging excessive bleeding.
Key Words: Endometrial curetting, Dysfunctional uterine bleeding, Vascular Pathology
hyperplasia, endometrial polyps and clusters of
Introduction
thick walled blood vessels.
Menorrhagia is profuse and excessive menstrual
These thick walled blood vessels may play key
hemorrhage. It is frequently seen in perimenorole in persistence of profuse hemorrhage. We
pausal women. The endometrial curettings often
examined 30 endometrial curettings for presence
reveal “hemorrhagic endometrium” characterized
of thick walled blood vessels; either singly or in
by thin walled fragile endometrial stromal vessels
clusters.
leaking red blood cells and fibrin thrombi which is
usually indicative of anovulatory cycle. However
Material & Methods
the endometrial curettings may also endometrial
30 endometrial curetting biopsies submitted with
the history of dysfunctional uterine bleeding
From Islamabad Institute of Pathology Fazl e
(DUB) were microscopically examined in consecHaq Road, Blue Area, Islamabad, Pakistan.
utive manner. All endometrial curettings were
Correspondence may be directed to
specifically evaluated for presence of thickened
Prof. Anwar Ul Haque
blood vessels. Hematoxylin and Eosin stained
15
International Journal of Pathology; 2011;9(1): 15-19
routinely processed slides were examined and
appropriate photography of the lesions was done
when required. Presence of large thick blood
vessels singly or in focal clusters was determined
and recorded in each biopsy.
Table 1: Number of thick blood vessels in
individual endometrial biopsies
The sections of the endometrium reveal variable
patterns. At many places thick vessels were present either singly or in clusters. The vessel walls
were markedly thickened with relatively narrow
lumina. The vessels walls appeared quite fibrotic.
(Figure 1)
Results
All biopsies contained thick walled blood vessels
(Table 1)
Serial #
Age
# thick blood vessels
1
32 yrs
5
2
39 yrs
15
3
40 yrs
7
4
40 yrs
4
5
40 yrs
4
6
30 yrs
4
7
35 yrs
4
8
51 yrs
18
9
42 yrs
7
10
25 yrs
4
11
45 yrs
7
12
50 yrs
12
13
43 yrs
4
14
44 yrs
12
15
37 yrs
19
16
36 yrs
5
17
32 yrs
7
18
28 yrs
5
19
40 yrs
12
20
42 yrs
10
21
45 yrs
17
22
25 yrs
3
23
40 yrs
7
24
32 yrs
4
25
50 yrs
5
26
31 yrs
7
27
31 yrs
5
28
43 yrs
10
29
26 yrs
6
30
26 yrs
07
Total
Figure 1: Clusters of thickened vessels (H&E
X 100)
At times these vessels compressed the endometrial glands causing cystic changes in the glands
and further aggravating vascular hemodynamic of
endometrium. (Figure 2)
236
Average 7.87
Figure 2: Thickened vessels compressing and
distorting the glands (H&E X 100)
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International Journal of Pathology; 2011;9(1): 15-19
On the other hand the clusters of vessels at places were arranged in rounded clusters clearly
leading to the pseudopolyp formation. (Figure 3)
fragile more permeable thin walled vessels.
These vessels themselves also become cystically dilated vessels due to increased pressure of
edematous stroma. The glands themselves in
these areas were small and simple perhaps due
to ischemia secondary to frequent small hemorrhages. (Fig 5)
Figure 3: The vessels are arranged in nodular
configuration leading to pseudopolyp formation (H&E X 100)
These clusters of thickened vessels also appeared in parallel giving rise to pedicle of pseudo
polyp formations. (Figure 4)
Figure 5: Thinned large vessels (arrows). Note
also the compression of the these vessels
due to edematous stroma. (H&E X 100)
Discussion
Menorrahagia is quite common in perimenopausal states when frequency of anovulation and oligoovulation is increased. This however can also
be seen in relative younger age groups. The
relative increased estrogen is supposed to be the
most important etiological factor. This results in
various morphological manifestations at microscopic level. One of these appears to be increased angiogenesis and another is thickening
of the blood vessels that result in poor contraction
thus contributing to persistent bleeding.
Our all cases of DUB biopsies contained several
thickened blood vessels. The minimum number of
vessels was 4 and maximum was 19 with an average of 7.87 (Table 1) Over 50% of the patients
16/40) were over 40 years of age. Only 5 patients
were less than 30 years of age. No patient was
below 20 years of age.
The endometrial vessels are quite sensitive to
estrogen. Chakraborty et all concluded that increased receptor levels and altered endometrial
morphology suggest an unopposed estrogen role
Figure 4: Several vessels arranged in parallel
with formation of pseudopolyp. (H&E X 100)
Frequently one observed a pattern of hemorrhagic endometrium which is characteristic of anovulatory cycle. There was exudation of the plasma
and scattered stromal hemorrhages mostly due to
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International Journal of Pathology; 2011;9(1): 15-19
in DUB 1. Hickey suggested that protracted estrogen stimulation may cause endometrial proliferation leading to erratic bleeding as it breaks down
and therefore cyclical progesterone is used in the
second half of the cycle to provoke a regular
withdrawal bleed.2 Due to various mechanisms
such as hormonal receptors and angiogenic
chemicals small vessels proliferate in the milliu of
stromal edema and hemorrhages which have occurred due to unopposed estrogen effect. However with passage of time the vessel walls start
getting thickened perhaps due to deposits of
plasma and red cells components within the vessel walls and subsequent intramural fibrosis.
These thickened clusters of vessels are perhaps
not efficient and effective in contracting and shutting down. Persistence of these defiant vessels
may cause persistence of hemorrhages. Due micro hemorrhages ischemia may cause atrophy of
the glands in focal areas. Estrogen dominance on
the other hand may lead to glandular hyperplasia
in areas where ischemia is not operative.
It seems that vascular pathology plays important
role in causing various divergent conditions such
as leiomyomas, lichen sclerosis atrophicus, simple cystic hyperplasia.
Complex interaction of vascular pathology i.e.
increased proliferation, increased permeability,
stromal edema may stimulate smooth muscles of
myometrium that may culminate into leiomyoma
formation. Such vascular changes are not uncommonly seen in leiomyomas.
Ischemia and edema in the skin in perineal areas
may lead to lichen sclerosis atrophicus. The increased vascular permeability with resultant decreased oxygen supply and edema may explain
various zones and features of lichen sclerosis of
atrophicus.
Our study sheds light which may be useful in
solving some aspects of this puzzle. Chang et all
described an association between the angiogenic
like growth factors e.g. vascular endothelial
growth factor (VEGF ) and leiomyoma. 3 VEGF is
one of the most important angiogenic growth factors. VEGF regulates angiogenesis and mediates
sex steroid-induced cell growth and differentiation. VEGF-mediated activities seem to contribute
to the pathogenesis of leiomyoma. Genetic variations, including polymorphisms, in VEGF might
also be associated with the complex pathogenesis of leiomyomas. 3. Livingstone all pointed out
that ovulatory dysfunctional uterine bleeding
(DUB) is associated with decreased vasoconstriction and hemostatic plug formation whereas
anovulatory DUB and breakthrough bleeding is
associated with disturbed endometrial angiogen-
esis and vascular fragility4. The role of hormones
particularly estrogen as etiology of various vascular lesions is undeniable. This includes both genital and non genial lesions. Hepatic hemangiomas,
lichen sclerosis atrophicus, leiomyomas, endometrial hyperplasia etc all are to some extent dependent on aberrations of hormones particularly
estrogen. Paradoxically as it may seem hormones are also used for treatment of certain vascular tumors such as cutaneous hemangiomas.
Jaffe claimed that Disease states such as dysfunctional uterine bleeding, endometriosis, and
endometrial hyperplasia or cancer may be associated with aberrant uterine angiogenesis.5 Hickey M, et all also suggested an altered angiogenesis in fibroids and adenomyosis 6. In endometrium if the clusters of thickened blood vessels predominates then there is a tendency toward lobulations and formations of pseudopolyps. As expected these clusters of thickened blood vessels
are more common in the endometrial and Endocervical polyps which in turn are also reflection
of estrogen excess or dominance. (Figure 6)
Figure 6: Similar changes in Endocervix. Arrow points to the Endocervical glands. Large
thickened vessels are marked by red arrow.
This may be a precursor to Endocervical polyp formation. (H&E x 100)
Ultrastructural studies on the vessel abnormalities
are quite conclusive and support the primary pathology at the vascular level. Makhija, et all
showed that the congestion and dilatation of endometrial blood vessels was increased in DUB
and confirmed a positive correlation between altered angiogenesis and menstrual disturbances 7.
Lockwood CJ, et all noted that aberrant angiogenesis and enhanced vascular fragility promotes
DUB 8. Ferenczy described a primary vascular
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International Journal of Pathology; 2011;9(1): 15-19
alteration in both hyperestrogenic and progestational type endometrium. 9
2.
Conclusion
3.
We have found thickened blood vessels; singly or
in clusters in all endometrial curettings of dysfunctional uterine bleeding. It seems quite likely
that these thickened blood vessels may contribute in maintenance of menorrhagia in Dysfunctional uterine Bleeding (DUB). As the vessels are
quite sensitive to various hormonal effects and
laser therapy, in future new modalities may develop to control wide spectrum of female genital
tract pathologies including DUB, endometrial hyperplasia, polyps, leiomyomas and lichen sclerosis atrophicus. In future we inend to carry out further research in these areas..
4.
5.
6.
7.
8.
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