Subtle

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Subtle endometriosis
Prof. Aboubakr Elnashar
Benha University Hospital
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• History
• In 1981, Chatman observed that unsuspected E.
  could be found in peritoneal pockets.
• In 1986 Jansen Russel published their
  observations on non-pigmented E. They concluded
  that
• Visualization of pigment is not necessary to
  diagnose E.
• E. in earlier stages of histogenesis may display
  only non-pigmented lesions.

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Definition (Subtle,atypical, non-pigmented) Endome
triotic lesions that lack the typical black-blue,
powder-burn appearance (Jansen Russel,1986)
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Prevalence Diagnosis of SE increased from 15 in
1986 to 65 in 1988 (Nisole et al,1993). SE are
more common than the classic lesions in the
adolescents with pelvic pain (Davis et
al,1993). The incidence decreases with age
(Konincks et al,1991). The most common is white
opacification of the peritoneum The next most
common is a glandular-like excrescence. The
least common, but nevertheless characteristic, is
the red flame like (Jansen Russel,1986).
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• Classification morphology
• Red lesions
• Red flame-like lesions or red vesicular
  excrescences more commonly affecting the broad
  ligament uterosacral ligaments.
• Histologically active E surrounded by stroma

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2. Glandular excrescences resemble the mucosal
surface of the endometrium seen at hysteroscopy
Histologically numerous endometrial glands. 3.
Areas of petechial peritoneum or areas with
hypervascularization resemble the peticheal
lesions due to manipulation of the peritoneum or
to hypervascularization of the peritoneum. They
frequently affect the bladder the broad ligam.
Histologically red blood cells are very rare.
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White lesions 1. White opacification appears
as peritoneal scaring or as circumscribed patches
often thickened sometimes raised.
Histologically an occasional retroperitoneal
glandular structure scanty stroma surrounded by
fibrotic tissue or connective tissue.
2. Subovarian adhesions. Histologically
connective tissue with sparse endometrial glands
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3. Yellow-brown peritoneal patches resembling
café au lait patches. Histologicallysimilar to
those observed in white opacification, but
haemosiderin among the stroma cells produces the
café au lait colour. 4.  Circular peritoneal
defects frequently occur in areas of the pelvis
which overlie loose connective tissue. 80 of
peritoneal defects are associated with E, either
on the border of the defect or in the defect
itself (Donnez et al,1992)
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NATURE E is a dynamic disease, especially in the
early phase, with S lesions emerging vanishing
again(Evers et al,1998). In the end however the
peritoneal defense system will prevail the
disease will be contained in the majority of
patients. Koninckx et al (1994) considered SE a
natural condition occurring intermittently in all
women
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Biological activity SE are thought to be more
biologically active than typical forms. Vernon et
al (1986) demonstrated that red peticheal
implants produce twice the amount of PGF than
brown lesions, which in turn produce more PGF
than typical powder-burn implants. On other hand
Muzii et al (2000) found that the biologic
activity of red black implants was similar The
sample size of their study was relatively small
to draw firm conclusions
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• Natural progression to classic lesions
• Redwine (1986) showed that
• Clear red lesions occur at a mean age 10 years
  earlier than the black lesions.
• A progression of E from clear to red to white to
  black, with increasing age.

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• Increasing age is associated with a decreasing
  incidence of SE increased incidence of typical
  E, endometrioma deeply infiltrating E (Koninckx
  et al,1991).
• SE progress to pigmented E over time (Jansen
  Russel,1986). Second look laparoscopy in
  untreated patients 6 to 24 months following the
  initial surgery, documented pigmented lesions in
  areas previously contained SE

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Prognosis 1.  Vascularization is one of the most
important factors of growth invasion of
endometrial glands in other tissue (Donnez et
al,1989). When compared with typical black
lesion, the vascularization was found to be
significantly higher in red lesions
significantly lower in white lesions. This change
was due to an increase (red) or decrease (white)
in the volume occupied by the vessels, as proved
by both mean capillary surface area the ratio
of capillaries/stroma surface area.
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• So,
• Red lesions are probably the first stage of early
  implantation of endometrial glands stroma.
• White lesions could be latent stages of E as
  suggested by the poor vascularization observed.
  They are probably non-active lesions which have
  been quiescent for a long time 

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2. Mitotic index Mitotic processes permit the
maintenance the growth of peritoneal E. MI is
significantly different in typical subtle E .
The absence of mitosis in white lesions proves
their low activity (Nisolle et al,1993)
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• American Society for Reproductive Medicine
  (ASRM) classification of E
• The only difference between the 1985 AFS
  classification 1996 ASRM classification is that
  the latter includes information on the
  morphologic appearance of the disease.
• In the new ASRM classification, peritoneal
  ovarian implants are categorized into 3
  subgroups
• Red (red, red-pink clear lesions)
• White (white, yellow-brown peritoneal defects)
• 3. Black (black blue lesions).

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The percentage of surface involvement of each
implant type (red, white, black) must be
recorded on the opposite form. The new ASRM
classification of E is the gold standard to
clearly document the extent location of the
disease (Muzii et al,2000))
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• Clinical features
• SE has the same (possibly PG related) symptoms
  that characterize classic E (Jansen
  Russel,1986)
• IFERTILITY
• PAIN dysmenorhea, dysparunia, ch.pelvic pain
• PREMENSTRUAL BLEEDING

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1.INFERTILITY SE is the most common single cause
(70) of unexplained infertility (Propst
Laufer,1999). SE can be etiologically important
in infertility.
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• 2. PAIN
• Acquired deep dysparunia was found in 18 of SE
  (Jansen Russel,1986).
• On other hand Vercellini et al(1996) observed
  that deep dysparunia was associated only with
  typical lesions not with atypical fresh clear
  implants.
•  

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• Increasing dysmenorrhea suggestive of active E is
  present in 64 of SE (Tansen Russel,1986).
• The number of typical or S implants did not
  correlate with the severity of dysmenorrhea
  (Muzii et al,1997). The S forms, however, were
  considered together were not categorized into
  red white subgroups , as in the new ASRM
  classification.
• Recently Muzi et al (2000) found no correlation
  between the ASRM classification of E associated
  dysmenorrhea.
• White implants are associated with milder pain
  symptoms than the black or red lesions. .
•  

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• Chronic pelvic pain SE is the most common single
  cause of chronic pelvic pain not responding to
  medical treatment (Propst Laufer,1999).

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3.PREMENSTRUAL SPOTTING In the absence of
pigmented E at laparoscopy, premenstrual spotting
was highly predictive of SE (Jansen
Russel,1986) .
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•  Diagnosis
• The ability to diagnose SE is directly related to
  the experience skill of the surgeon(Cook
  Rock,1993)
• Laparoscopy
• A. Standard laparoscopy Negative laparoscopy
  results do not mean that the patient has no E
  (Martin,1999)

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B. lactated Ringer or normal saline introduced
into the pelvis (Laufer,1997). Laparoscopic
visualization of of clear vesicular lesions can
be facilitated by the use of the
three-dimensional effect of the fluid. The
laparoscope is submerged so that the optical
distension medium is now liquid as opposed to
CO2. The magnification focal length of the
laparoscope is adjusted for the new refractory
index through the liquid. Vesicular lesions are
no longer falsely interpreted as light
reflection.
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C. Near-contact laparoscopy (Redwin,1987)
Visualization at magnifications of 1- to
7-power D.Peritoneal blood painting
(Redwin,1989) SE can be seen more easily by
painting the peritoneal surface with bloody
peritoneal fluid. The physical- chemical
properties of blood cause it to interact with S.
physical deformities of the peritoneal surface in
such a way as to cause flowing erythrocytes to
outline surface irregularities.     
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E. Bubble test (Amer A Omar M., 2002) During
laparoscopy, the posterior cul de sac is
irrigated with short bursts of saline under
controlled pressure. Development of dense soap
like bubbles staying for at least 5 seconds
indicates a positive test. The positivity of the
test is apparently related to increased level of
triglycerides in peritoneal fluid in cases of E.
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2. Transvaginal hydrolaparoscopy is superior to
standard laparoscopy for detection of S
endometriotic adhesions of the ovary (Brosen et
al,2001) 3. Elevated serum levels of endometrial
secretory protein (placenta protein 14). The
highest levels in patients with E are found on
days 1 to 4 of the cycle (Seppala et al,1989) 4. 
Histopathologic examination of biopsy taken from
suspected lesions.
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Differential diagnosis Not all abnormalities of
the peritoneum represent E (Cock Rock,1993).
Stripling et al (1988) confirmed E in 91 of
white lesions, 75 of red lesions, 33 of
haemosiderin lesions, 85 of other lesions 1.
White E should be differentiated from
postoperative scaring from fibrotic adhesions
resulting from inflammatory disease (Cock
Rock,1993)
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2.Other lesions which may mimic E include
hemangiomas, old suture, residual carbon from
laser surgery, reaction to oil-contrast medium,
epithelial inclusions, secondary breast ovarian
cancer, inflammatory cystic inclusions,Walthard
rests, adrenal rests(Cock Rock,1993).
Differentiation between SE other lesions may
be impossible visually but may be achieved
histologically through excision or biopsy. An
abnormality of the peritoneum, no matter what its
size, shape, or appearance, should suggest the
possibility of E.
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Treatment E, whether its lesions are pigmented
or not, does not itself demand treatment unless
it is causing, or it is likely to cause symptoms.
SE should receive the same pathophysiological
therapeutic attention that classic lesions do.
There is a substantial difference between the
expectant management of the isolated lesions
found incidentally in a woman towards the end of
reproductive years the active management for a
widespread non-pigmented lesions in a teenager
with many years of ovulation before her.
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The first question to be asked is whether
treatment is appropriate at that time (Kim,1999).
If it is, a comprehensive plan should be
formulated that takes into account the womans
primary complaint (infertility or pain)
reproductive desires. The guidelines of the
Royal College of obstetricians Gynaecologists
in management of E.( july, 2000
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1.      Endometriosis pain a. Medical
management Several drugs are effective in
temporarily relieving pain associated with E.
Non-steroidal anti-inflammatory drugs may be
effective in reducing the pain associated with E.
The choice between the combined oral
contraceptive, progestagens, danazol GnRH
agonists depends principally upon their
side-effect profiles because they relieve pain
associated with E. equally well. It seems
sensible to prescribe the safest cheapest
therapy. b. Surgical management Although there
are limited data available from RCT assessing the
effectiveness of surgery in relieving pain, it is
clearly effective for many women. However,
clinical experience shows that some women fail to
respond to surgical treatment either because of
incomplete excision or because of post-operative
disease recurrence.
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2.      Endometriosis infertility a. Medical
management There is no role for medical therapy
with hormonal drugs in the treatment of E
associated infertility. Ovarian stimulation with
intrauterine insemination (IUI) is more effective
than either no treatment or IUI alone in
infertile women with minimal or mild
E. b. Surgical management In infertile women
with minimal or mild E. detected at laparoscopy,
destruction or ablation of the endometriotic
implants lysis of adhesions at that time is
recommended to improve the chance of pregnancy.
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• SE are more common than the classic dark
  blue-black lesions in adolescents
• The most common type of SE is white opacification
  the next most common is glandular-like
  excrescence.
• SE progress to pigmented E over time
• Red lesions are probably the first stage of early
  implantation of endometrial glands stroma
  white lesions could be latent stages of E.

Conclusion
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• 5. In the new ASRM classification, peritoneal
  ovarian implants are categorized into red, white
  black
• 6. SE has the same symptoms that characterize
  classic E.
• 7. Negative laparoscopy results do not mean that
  the patient has no E
• 8. E, whether its lesions are pigmented or not,
  does not itself demand treatment unless it is
  causing, or it is likely to cause symptoms.

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Thank you
Aboubakr Elnashar