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7/27/2019 Metaplasia of Fgtract & Recent Advances
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Metaplasia of Female Genital Tract
Recent Advances Date- 27/8/13
DR GAURAV PAWAR PRESENTER
GUIDE- DR K. MALUKANI
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Definition and Pathogenesis of Metaplasia
Metaplasia is a condition in which there is a change of one
type of differentiated tissue into another type of similar
differentiated tissue or as the abnormal transformation of an
adult, fully differentiated tissue of one kind into a
differentiated tissue of another kind. The mullerian derived epithelium which lines most of the
female genital tract is well known for its capacity to
differentiate into various types of epithelium such as, ciliated,
mucinous, endometrioid, transitional and squamous types.
The metaplasias of the uterine corpus and cervix are the most
common sites of metaplasia. Metaplasia occasionally can
occur in other parts of the female genital tract such as mucosa
of the fallopian tube and the vagina.2
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Endometrial epithelial metaplasia
Is a group of non-neoplastic lesions, often coexisting with
endometrial hyperplasia or adenocarcinoma.
International society of Gynecological Pathologist
,classification of Endometrial epithelial metaplasia
Squamous metaplasia and morules
Mucinous metaplasia (including intestinal )
Ciliary change
Hobnail cell change
Clear cell change
Eosinophilic cell change(including oncocytic) Surface syncytial change
Papillary proliferation
Arias stella change 3
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Classification of Cervical metaplasia
Cervical squamous metaplasia is extremely common in the
cervix. Before full maturation is reached, there are stages of
reserve cell hyperplasia and immature squamous metaplasia,
both of which may cause diagnostic difficulty.
Squamous metaplasia occurring in the squamo-columnar
junction (transformation zone) of the cervix begins as a patchy
process, the foci of squamous metaplasia enlarging and
eventually fusing. The metaplasia involves both the surface
epithelium and underlying crypts.
4
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Cervical epithelial metaplasia may further be subdivided into:
Reserve cell hyperplasia
Immature and mature squamous metaplasia
Transitional metaplasia
Tubal metaplasia
Tuboendometrial metaplasia and endometriosis
Cervical microglandular hyperplasia
Intestinal metaplasia and oxyphil metaplasia .
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Metaplasias elsewhere in the female genital tract are
relatively very rare and can be transitional and mucinous
metaplasia of the fallopian tube.6 The abdominal and pelvic
peritoneum, as part of the secondary Mullerian system, mayundergo metaplasia into various Mullerian epithelia. Non-
neoplastic secondary mullerian lesions, which are in many
cases a form of metaplasia, comprise endometriosis,
endosalpingiosis and endocervicosis. When occurring in
combination, they have been termed as mullerianosis. It is
recognized that probably most cases of abdominal and pelvic
endometriosis are not truly metaplastic but are the result of
retrograde menstruation.
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SQUAMOUS METAPLASIA WITH MORULES
Squamous metaplasia is the commonest form of metaplasia in
the endometrium. Although this may be focal finding, it maybe widespread and involve most of the endometrium.
Microscopically, it is composed of bland squamous cells with
eosinophilic cytoplasm. Central necrosis may be present and
has no sinister connotation.
Squamous metaplasia is common in endometrioid
adenocarcinoma and in endometrial hyperplasia: these
conditions should be excluded by careful examination of the
glandular elements.
The World Health Organization (WHO) categorisesadenocarcinoma with squamous differentiation as a variant of
endometroid adenocarcinoma and no longer accepts terms
such as adenoacanthoma and adenosquamous carcinoma.7
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Morules differ from mature squamous metaplasia in that they
lack keratinisation and intercellular bridges. Morules and foci
of mature squamous elements, metaplasia often co-exist.
An endometrial lesion in which squamous elements, usually in
the form of morules, are extremely common and prominent is
an atypical polypoid adenomyoma.
Extensive squamous metaplasia of the endometrium also
occur in association with pyometra, endometritis, cervical
stenosis or an intra-uterine device. Endometrial squamous
metaplasia occurs secondary to progestogen therapy.
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Isolated Squamous Morule
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MUCINOUS METAPLASIA
This is a rarer form of endometrial metaplasia. The diagnosis
should be reserved for cases in which the endometrial
epithelial cells are replaced by cells with abundant mucin-
containing cytoplasm, which resemble endocervical cells.
Rarely, intestinal metaplasia has been described in the
endometrium, in which the mucinous epithelium contains
goblet cells. This is also the case in the cervix. As with other types of endometrial metaplasia, mucinous
metaplasia can co-exist with endometrial hyperplasia.
As mucinous metaplasia of the endometrium can have a
complex growth pattern, it can be difficult to distinguish
between mucinous metaplasia and well-differentiated
adenocarcinoma, especially in endometrial biopsy tissue.
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In biopsy tissue, a diagnosis of mucinous adenocarcinoma
should be considered in a lesion resembling cervical
microglandular hyperplasia in a postmenopausal patient,although cervical microglandular hyperplasia rarely occurs in
this age group.
Vimentin staining may be of use: adenocarcinoma usually
stains positively and microglandular hyperplasia is negative.
Rarely, mucinous metaplasia in the endometrium is
accompanied by mucinous lesions elsewhere in the female
genital system.
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Mucinous differentiation in Endometrium13
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Endometrium showing combined Mucinous
and Squamous Metaplasia
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ARIAS-STELLA CHANGE
Seen In pregnancy or trophoblastic disease, and occasionally
with hormone therapy: rarely, there is no association.
Histologically, there may be cellular stratification, secretory
activity and enlargement of the epithelial cell nuclei and
cytoplasm.
Nuclei show considerable atypia and occasional mitotic figure
may be present.
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Arias Stella change of Endometrium
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Arias- Stella Change
Recently five histological variant have been described:
minimally atypical, early secretory pattern, hypersecretory
pattern, regenerative pattern, and monstrous cell pattern.
Differential diagnosis is clear cell carcinoma but the diagnosisof Arias-Stella change is usually straightforward if there is a
history of pregnancy or if other morphological features of
pregnancy are present.
In addition, the Arias-Stella change involves pre-existing
endometrial glands and there is no evidence of stromal
infiltration. 17
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PAPILLARY SYNCYTIAL METAPLASIA
Papillary syncytial metaplasia in most cases represents a
reparative phenomenon after menstrual shedding or recentendometrial sampling. It is one of the commoner forms of
endometrial metaplasia.
Histologically it is characterised by a syncytium of endometrial
epithelial cells which have small glandular lumina and papillae
which lack fibrovascular stromal cores. The cells usually have
eosinophilic cytoplasm and there is often a heavy neutrophil
infiltrate.
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The most important differential diagnosis of papillary syncytial
metaplasia is papillary adenocarcinoma of endometriod orserous type. The changes of papillary syncytial metaplasia are
limited to the surface and are often associated with signs of
breakdown.
A lesion recently described in detail by Lehman and Hart
which is most frequently seen in endometrial polyps is
characterised by papillary proliferations with fibrovascular
cores.
This lesion is like papillary syncytial metaplasia, it has apapillary appearance and so could be misdiagnosed as
papillary endometrial carcinoma.
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Ichthyosis uteri
Another rare entity that appears to be declining in incidence,
ichthyosis uteri is a benign process in which the endometrial
lining has been replaced by a cytologically benign stratified
proliferation of cells with squamous differentiation.
It has been associated with chronic endometritis and with
heat ablation of the endometrium.
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Ichthyosis uteri
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CLEAR CELL METAPLASIA
Clear cell metaplasia is characterized by replacement of
endometrial epithelial cells by cells with abundant clearcytoplasm. This may be found in the endometrium in
pregnancy. Especially when florid, clear cell metaplasia may be
misdiagnosed as clear cell carcinoma.
Distinction is based on the bland nuclear features and the fact
that in clear cell metaplasia the endometrial glands arenormal in architecture and distribution.
When clear cell metaplasia involves architecturally complex
glands, the distinction from clear cell carcinoma may be very
difficult, especially when clear cell carcinoma may be
cytologically bland.
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Other features favoring clear cell metaplasia over clear cell
carcinoma include focality of lesion, absence of visible tumor
on hysterectomy, absence of stromal invasion and presence ofestrogen receptor positivity.
Most ovarian clear cell carcinomas are estrogen receptor
negative.
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Clear cell metaplasia endometrium
25
(
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EOSINOPHILIC (OXYPHIL,ONCOCYTIC
)METAPLASIA
The cytoplasm is granular,abundant and eosinophilic.
Some degree of cytoplasmic eosinophilia is commonly found
in endometrial epithelial cells and does not alone warrant a
diagnosis of eosinophilic metaplasia. Differential diagnosis, especially when there is architectural
complexity, is the eosinophilic or oxyphilic variant of
endometrioid adenocarcinoma.
Distinction from adenocarcinoma is made on the absence of a
visible lesion on hysteroscopy, absence of severe cytological
atypia, and absence of stromal invasion.
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Eosinophilic cell change
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CILIATED OR TUBAL METAPLASIA
Ciliated endometrial epithelial cells are normal phenomenon,
so a diagnosis of ciliated metaplasia should be made only
when one or more endometrial glands are linedpredominantly by ciliated cells.
Ciliated cells often have very eosinophilic cytoplasm.
Isolated ciliated cells are commonly found in endometrial
adenocarcinoma and a ciliated adenocarcinoma has been
described which is a variant of endometrioid adenocarcinoma
in which the tumour is composed predominantly of ciliated
cells.
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Tubal or Ciliated metaplasia of endometrium
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HOBNAIL CELL METAPLASIA
Hobnail cell metaplasia is characterized by the presence of
rounded atypical blebs
Hobnail cell metaplasia is a reparative phenomenon after
endometrial biopsy ,it also occurs in pregnancy
Hobnail are also characteristic of clear cell carcinoma and this
may enter into the D/D , especially if there is accompanying
clear cell metaplasia.
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Endometrial mesenchymal metaplasia
1] Smooth muscle metaplasia- Most common type of
metaplasia in endometrium. It is thought that multipotent cell
exists in the uterus which has capacity to differentiate into
stroma and smooth muscles.
This is shows an IHC overlap between endometrial stromaland smooth muscle neoplasm that hybrid exist.
2] Cartilaginous and osseous metaplasia- Rarely , foci of bone
or cartilage are found within endometrium. It is likely that
these foci are fetal origin. Benign osseous or cartilaginous
metaplasia in endometrium carcinoma should not be mistaken
for the sarcomatous component of a carcinosarcoma. These
tissues are found in endometrium of a young women with
past history of abortion.32
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Conti..
3]Glial metaplasia- Glial tissue is rare and the chief D/D is a
teratoma. It is presumed to a consequence of previous
abortion.
4] Adipose metaplasia- Adipose tissue may be rarely seen in
the stroma of endometrial polyp. It is found in an endometrial
biopsy or curretage specimen, so perforation must be
suspected.Other explanation of adipose tissue presence
include lipoma, lipoleiomyoma,rare uterine hamartogenous
like lesions.
33
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Smooth muscle metaplsia at center and right
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Conti.
5]Extramedullary hematopoiesis- Extramedullary
hematopoiesis, recognized by the presence of
megakaryocytes, erythroid and myeloid precursors, is
occasionally seen.
If extramedullary hematopoiesis is identified in the
endometrium in the absence of other tissues, and underlying
hematological disorder should be considered and investigated.
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CERVICAL EPITHELIAL METAPLASIA In late fetal life, the cervical canal is lined by columnar
epithelium and the ectocervix by non-keratinised stratified
squamous epithelium. The junction between the two isknown as the original squamouscolumnar junction. Later the
columnar epithelium close to the original squamouscolumnar
junction undergoes metaplastic change into squamous
epithelium. This area is known as the transformation zone of
the cervix and persists into adult life. Squamous metaplasia occurring in the transformation zone of
the cervix begins as a patchy process, the foci of squamous
metaplasia enlarging and eventually fusing.
Squamous metaplasia is extremely common in the cervix and
should be seen as a normal phenomenon rather than an
abnormal pathological process.
Before full maturation is reached, though, there are stages of
reserve cell hyperplasia and immature squamous metaplasia,
both of which may cause diagnostic difficulty.
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Squamo-columnar junction view
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RESERVE CELL HYPERPLASIA
This is the first stage in the metaplastic process which
eventually results in the transformation of columnar
epithelium into mature squamous epithelium. Reserved cell
hyperplasia is characterised by the presence of a layer of
cuboidal or low columnar cells with clear cytoplasm situated
immediately beneath the normal endocervical cells but
separated from the stroma by basement membrane. This results histological double cell layer.
Occasionally the presence of double layer may be confusing
and result in consideration of cervical glandular intra-epithelial
neoplasia (CGIN). However, the histological appearances the
characteristic and CGIN can be excluded if attention is paid to
the nuclear details.
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Reserve Cell Hyperplasia
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Immature and mature Squamous metaplasia
The progression of reserve cell hyperplasia results in the
development of a multilayered epithelium with features of
both squamous and glandular differentiation.
Squamous features are usually most prominent near the base
of the epithelium while towards the surface , glandular is inthe form of cytoplasmic mucin.
As the process continues, the immature metaplastic
squamous epithelium is converted to mature squamous
epithelium.
Immature sq. metaplasia may be mistaken for (CIN) and the
term atypical immature metaplasia been used for cases
with nuclear atypia.40
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To differentiate Immature Sq.metaplasia from CIN.
Presence of uniform population of cells with scanty cytoplasm
and nuclei which lack significant pleomorphism .
The nuclei are not hyperchromatic and abnormal mitosis maynot be seen.
The presence of mucin on the surface of cells may be useful .
A minor degree of nuclear atypia is acceptable in immature
Sq. metaplasia. When grading of CIN is difficult, a diagnosis CIN unclassified
should be made with a statement on whether this is likely to
be low gd(CIN 1) or high (CIN 2-3).
Koilocytosis may also involve Immature metaplastic Sq.
epithelium and result in atypical changes.
Using HPV typing with careful follow-up, have shown that
some cases of atypical immature sq. metaplasia are probably a
variant of high gd CIN.41
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Squamous metaplasia in cervix
42
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Squamous metaplasia of the Cervix
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Stratified mucinous intra-epithelial lesion
This lesion involves the surface epithelium and underlying
endocervical crypts and is characterized by a multilayered
epithelium resembling CIN.
Stratified mucinous intra-epithelial lesion is associated with
more extreme pleomorphism and hyperchromasia and higher
proliferation index, demonstrable by MIB1 staining, thanimmature sq. metaplasia.
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Stratified mucinous intra-epithelial lesion
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In addition, stratified mucinous intra-epithelial lesion is almost
always associated with CIN or CGIN and commonly with an
invasive carcinoma which may be squamous ,glandular or
adenosquamous in type.
It has been considered that stratified mucinous intra-epithelial
lesion is a form of reserve cell neoplasia and a marker of
phenotypic instability
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Transitional Metaplasia
Trasitional cell metaplasia of the cervix is uncommon and is
usually an incidental finding in postmenopausal women.
It may involve both the surface epithelium and underlying
Endocervical glands and is more common on the ectocervix.
Histologically it may show cells with pale, uniform ,ovoid tospindle-shaped nuclei which may contain grooves.
A useful Diagnostic feature , not always present, is that in the
deeper layers of the epithelium the nuclei are usually oriented
at right angles to the basement membrane whereas
superficially they are parallel to it.
The main problem in diagnosis is the superficial resemblance
to CIN 3,especially in those cases with tightly packed nuclei
and low N:C ratio.47
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Ectocervix showing Transitional cell
Metaplasia
48
T b l t l i T b d t i l d
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Tubal metaplasia ,Tubo-endometrial and
Endometriosis
Tubal metaplasia ,Tubo-endometrial , are very common
in cervix. In some cases the epithelium has
predominantly tubal differentiation with abundant cillia
while in other cases there is a more endometrioid
appearance with non-ciliated cuboidal and columnarepithelial cells.
When tubo-endometrial metaplasia occurs in the region
of the transformation zone of Cx ,especially when florid
,it is often a reparative phenomenon secondary to aprevious procedure such as loop or cone Bx.
The presence of cillia is always a useful pointer towards a
non-neoplastic lesion.49
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But recently a ciliated variant of CGIN has been described
(designated AdenoCA in situ of tubal type).
A panel of IHC stains comprising of MIB1,bcl2 and p16 may be of
value.
50
MIB1 Bcl2 p16
Tubo-endometaplasia
Negative or low diffuse Neg or focal
Endometriosis Neg or low Diffuse Neg or focal
Microglandularhyperplasia
Negative Negative
High gr CGIN Intermediate or
high
Negative Diffuse
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Cervical glandular hyperplasia
Microglandular hyperplasia is common within cervix and is
usually associated with exogenous hormone use and
pregnancy.
Although not a metaplasia , but is best categorized with these.
Histologically microglandular hyperplasia is characterized byclosely packed glands, most of which are small but some are
cystically dilated. Crypts are lined with cuboidal and low
columnar cells which commonly have subnuclear supranuclear
vacuolation.
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Typical microglandular hyperplsia
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Microglandular associated with basal
hyperplasia
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Intestinal metaplasia
Intestinal metaplasia involving endocervical crypts has rarely
been seen. It is characterized by the presence of goblet cells
and sometimes Paneth cells.
Co-existent appendiceal neoplasms were present anddifferential cytokeratin staining (CK7 and CK20) suggested
metastasis from appendix by a transtubal route.
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Intestinal metaplasia
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Oxyphilic metaplasia
Oxyphilic metaplasia is characterized by replacement of the
endocervical cryptal epithelium by cuboidal cells with
eosinophilic cytoplasm.
Often there is a degree of nuclear atypia and this lesion was
originally designated atypical oxyphilic metaplasia . Its only significance is that it is mistaken as CGIN.
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Oxyphilic metaplasia
57
O h ll l h h
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Other miscellaneous metaplasia within the
FGT
Metaplasias elsewhere within the female genital system are
relatively rare. In the fallopian tube, transitional metaplasia,
similar to that seen within cervix ,as well mucinous type also.
The abdominal and pelvic peritoneum ,as part of secondary
mullerian system ,may go under metaplasia into variousmullerian epithelium. Mullerian potential of this tissue is
consistent with its close embryonic relation with the mullerian
ducts.
Non-neoplastic secondary mullerian lesions, which are in
many cases a form of metaplasia, compromise endometriosis,endosalpingiosis, endocervicosis.
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1] Endosalpingiosis is characterized by the presence of non-
neoplastic glands lined by ciliated tubaltype epithelium.
It usually involves the peritoneum and the subperitonealtissues including the surface of the ovaries.
Endosalpingiosis is usually an incidental finding on
microscope , but rarely may form cystic mass referred to as
florid cystic endosalpingiosis.
Psammoma bodies are often present in glandular lumina orthe surrounding stroma. Endosalpingiosis is especially likely to
be found in patients with ovarian serous neoplasms which
may benign ,borderline and malignant.
Occasionally, foci of endosalpingiosis have multilayering withpapillary formation and mild cytological atypia.
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2] Endocervicosis is characterized histologically by the
presence of non-neoplastic mucinous glands resembling
endocervical glands. This is much less common then
endometriosis or endosalpingiosis. Involved sites haveincluded the peritoneum, pelvic lymph nodes, the urinary
bladder, the uterine serosa, the cervix, and the vagina.
Especially when florid and involving the wall of the bladder
cervix, a diagnosis of well differentiated mucinous
adenocarcinoma , including cervical minimal deviation
adenocarcinoma of mucinous type, may be considered.
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3] Another rare metaplastic lesion to arise from the secondary
Mullerian system is diffused peritoneal leiomyomatosis. This
condition is characterised by multiple small nodules of bland
smooth muscle cells involving the peritoneum and omentumand is often associated with pregnancy or exogenous hormones
Diffuse peritoneal leiomyomatosis often shows positiveimmunohistochemical staining with progesterone receptor and
persistent cases have been successfully treated with
gonadotropin-releasing hormone agonists.
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THANKS
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