metaplasia of fgtract & recent advances

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.

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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

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(


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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.

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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

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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

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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.

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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

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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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metaplasia of fgtract & recent advances

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