The document discusses pathology of the cervix, including: 1. Benign diseases like inflammations (acute and chronic cervicitis), metaplasias, hyperplasias, and benign tumors like endocervical polyps and leiomyomas. 2. Precancerous lesions like squamous intraepithelial lesions and glandular intraepithelial lesions. 3. Cancerous tumors including invasive carcinomas, mesynchymal tumors, mixed epithelial mesynchymal tumors, and other rare tumor types. Chronic cervicitis is most often caused by sexually transmitted pathogens like Chlamydia trachomatis and Neisseria gonorrhoeae. Squamous metaplasia and other

1. PATHOLOGY OFPATHOLOGY OF
CERVIXCERVIX
Suraj DharaSuraj Dhara
(Midnapore Medical College)(Midnapore Medical College)

2. Cervix AnatomyCervix Anatomy
Lower 1/3 of uterusLower 1/3 of uterus
 Connects uterus to vagina via endocervical canal;Connects uterus to vagina via endocervical canal;
consists of portio vaginalis (protrudes into vagina) andconsists of portio vaginalis (protrudes into vagina) and
supravaginal portionsupravaginal portion
 Endocervix:Endocervix: relates to endocervical canal, lined byrelates to endocervical canal, lined by
glandular or columnar epithelium that secretes mucusglandular or columnar epithelium that secretes mucus
 Ectocervix (exocervix):Ectocervix (exocervix): vaginal portion of cervix,vaginal portion of cervix,
covered by stratified squamous epitheliumcovered by stratified squamous epithelium
(nonkeratinizing); has basal, midzone and superficial(nonkeratinizing); has basal, midzone and superficial
layers.layers.
 after menopause, has high N/C ratio that resemblesafter menopause, has high N/C ratio that resembles
dysplasia.dysplasia.

5.  1-Benign diseases of the cervix:1-Benign diseases of the cervix:
 A-InflammationsA-Inflammations
 Acute and chronic CervicitisAcute and chronic Cervicitis
 B-Metaplasias,Hyperplasias, Arias Stella andB-Metaplasias,Hyperplasias, Arias Stella and
EndometriozisEndometriozis
 C-Benign Tumors:
 Endocervical polypsEndocervical polyps
 LeiomyomaLeiomyoma
 AdenomyomaAdenomyoma
 D-Cysts:D-Cysts:
 Nabothian cystNabothian cyst
 Tunnel clustersTunnel clusters
 Inclusion cystInclusion cyst

6.  2-Precancerous lesions of the cervix2-Precancerous lesions of the cervix
 Squamous intraepithelial lesions:Squamous intraepithelial lesions:
 A-Low grade squamous intraepithelial lesionsA-Low grade squamous intraepithelial lesions
 -Condyloma-Condyloma
 -Cervical intraepithelial lesion Grade 1(CIN-I)-Cervical intraepithelial lesion Grade 1(CIN-I)
 B-High grade intraepithelial lesionsB-High grade intraepithelial lesions
 -Cervical intraepithelial lesionGrade 2(CINII)-Cervical intraepithelial lesionGrade 2(CINII)
 -Cervical intraepithelial lesionGrade 3(CINIII)-Cervical intraepithelial lesionGrade 3(CINIII)
 Glandular intraepithelial lesions:Glandular intraepithelial lesions:
 A-Low grade glandular intraepithelial lesionsA-Low grade glandular intraepithelial lesions
 B- High grade glandular intraepithelial lesionsB- High grade glandular intraepithelial lesions

7. CARCINOMA AND OTHERCARCINOMA AND OTHER
TUMORS OF CERVIXTUMORS OF CERVIX
 Invasive carcinomaInvasive carcinoma
 Squmaous cell carcinomaSqumaous cell carcinoma
 Adenocarcinoma (Clear cell, Mucinous, Serous..)Adenocarcinoma (Clear cell, Mucinous, Serous..)
 Adenosqumaous carcinomaAdenosqumaous carcinoma
 Glassy cell carcinomaGlassy cell carcinoma
 MucoepidermoidMucoepidermoid
 Adenoid cystic carcinomaAdenoid cystic carcinoma
 Neuroendocrine tumorsNeuroendocrine tumors
 Smalll cell carcinomaSmalll cell carcinoma
 Undifferentiated carcinomaUndifferentiated carcinoma

8. MESENCYMAL TUMORS AND TUMOR-LIKEMESENCYMAL TUMORS AND TUMOR-LIKE
CONDITIONSCONDITIONS
 LeiomyosarcomasLeiomyosarcomas
 Endometrial stromal sarcomasEndometrial stromal sarcomas
 Sarcoma bortyroidesSarcoma bortyroides
 Alveolar soft part sarcomaAlveolar soft part sarcoma
 AngiosarcomaAngiosarcoma
 Malignant peripheral nerve sheath tumourMalignant peripheral nerve sheath tumour
 LeomyomaLeomyoma
 Genital rhabdomyomaGenital rhabdomyoma
 Post operative spindle cell nodulePost operative spindle cell nodule

9. MIXED EPITHELIAL MESENCYMALMIXED EPITHELIAL MESENCYMAL
TUMOURSTUMOURS
 CarcinosarcomaCarcinosarcoma
 AdenosarcomaAdenosarcoma
 Wilms tumourWilms tumour
 AdenofibromaAdenofibroma
 AdenomyomaAdenomyoma

10.  Melanocytic tumorsMelanocytic tumors
 Lymphoid and haematopoetic tumoursLymphoid and haematopoetic tumours
 Metastatic tumorsMetastatic tumors
 Other tumors: Yolk sac tumourOther tumors: Yolk sac tumour
Dermoid cystDermoid cyst
Mature cystic teratomaMature cystic teratoma

11. ACUTE AND CHRONICACUTE AND CHRONIC
CERVICITISCERVICITIS
 Menarche- the production of estrogens by theMenarche- the production of estrogens by the
ovary stimulates maturation (glycogen uptake) ofovary stimulates maturation (glycogen uptake) of
cervical and vaginal squamous mucosa.cervical and vaginal squamous mucosa.
 These cells are shed, the glycogen provides aThese cells are shed, the glycogen provides a
substrate for endogenous vaginal aerobes andsubstrate for endogenous vaginal aerobes and
anaerobes, streptococci, enterococci,anaerobes, streptococci, enterococci, EscherichiaEscherichia
colicoli, and staphylococci., and staphylococci.
 The bacterial growth produces a drop in vaginalThe bacterial growth produces a drop in vaginal
pH.pH.

12.  MorphologyMorphology
 Acute and chronic cervicitis include:Acute and chronic cervicitis include:
 Epithelial spongiosis (intercellular edema),Epithelial spongiosis (intercellular edema),
 Submucosal edema, and a combination of epithelial andSubmucosal edema, and a combination of epithelial and
stromal changes.stromal changes.
 Acute cervicitis:Acute cervicitis:
 Acute inflammatory cells, erosion, and reactive orAcute inflammatory cells, erosion, and reactive or
reparative epithelial change.reparative epithelial change.
 Chronic cervicitis:Chronic cervicitis:
 Mononuclear, with lymphocytes, macrophages, andMononuclear, with lymphocytes, macrophages, and
plasma cells. Necrosis and granulation tissue may also beplasma cells. Necrosis and granulation tissue may also be
present.present.
 HSV :HSV :
 Epithelial ulcers (often with intranuclear inclusions inEpithelial ulcers (often with intranuclear inclusions in
epithelial cells) and a lymphocytic infiltrateepithelial cells) and a lymphocytic infiltrate
 C. Trachomatis:C. Trachomatis:
 Lymphoid germinal centers and a prominent plasmacyticLymphoid germinal centers and a prominent plasmacytic
infiltrate.infiltrate.

13.  Cervicitis is most often caused by sexuallyCervicitis is most often caused by sexually
transmitted pathogens, but may also be caused bytransmitted pathogens, but may also be caused by
 systemic diseases (such as autoimmune diseases, Stevens-systemic diseases (such as autoimmune diseases, Stevens-
Johnson Syndrome, or viral infections),Johnson Syndrome, or viral infections),
 neoplasia,neoplasia,
 mechanical/chemical trauma.mechanical/chemical trauma.
 The two main sexually transmitted agentsThe two main sexually transmitted agents
responsible for clinically apparent mucopurulentresponsible for clinically apparent mucopurulent
endocervicitis areendocervicitis are
 C. trachomatisC. trachomatis (CT)(CT)
 N. gonorrhoeaeN. gonorrhoeae (GC).(GC).
 Herpes simplex virus (HSV) causes an ectocervicitis,Herpes simplex virus (HSV) causes an ectocervicitis,
as mayas may Trichomonas vaginalis.Trichomonas vaginalis.

15.  The exposed endocervix is sensitive to theseThe exposed endocervix is sensitive to these
changes in chemical environment and bacterialchanges in chemical environment and bacterial
flora and responds by undergoing a variety offlora and responds by undergoing a variety of
changes including proliferation of reserve cellschanges including proliferation of reserve cells
leading toleading to squamous metaplasia (squamous metaplasia (in thein the
reproductive years)reproductive years)
 This process is invariably associated with anThis process is invariably associated with an
inflammatory infiltrate composed of a mixture ofinflammatory infiltrate composed of a mixture of
polymorphonuclear leukocytes and mononuclearpolymorphonuclear leukocytes and mononuclear
cells, and if the inflammation is severe, it may becells, and if the inflammation is severe, it may be
associated with loss of the epithelial liningassociated with loss of the epithelial lining (erosion(erosion
or ulceration)or ulceration) and epithelial repairand epithelial repair (reparative(reparative
atypia ).atypia ).
 All of these components characterize what isAll of these components characterize what is
known asknown as chronic cervicitischronic cervicitis

16. Squamous Metaplasia of CervixSquamous Metaplasia of Cervix
 Etiology:Etiology: Associated with irritation,Associated with irritation,
inflammation, low vaginal pHinflammation, low vaginal pH
 Pathogenesis:Pathogenesis: Appropriate stimulus triggersAppropriate stimulus triggers
squamous rather than glandularsquamous rather than glandular differentationdifferentation
from the basal cells.from the basal cells.
 Epidemiology:Epidemiology:Normal finding in theNormal finding in the
reproductive age womanreproductive age woman
 General Gross Description:General Gross Description: Tan gray surfaceTan gray surface
similar to mature squamous epitheliumsimilar to mature squamous epithelium

17. General Microscopic DescriptionGeneral Microscopic Description
 Seen in the transformation zone bound by a proximalSeen in the transformation zone bound by a proximal
margin of current squamocolumnar junction and distalmargin of current squamocolumnar junction and distal
margin of the original squamocolumnar junctionmargin of the original squamocolumnar junction
 Epithelium in between derived from squamous metaplasia.Epithelium in between derived from squamous metaplasia.
 Mature metaplastic epithelium is indistinguishable fromMature metaplastic epithelium is indistinguishable from
non-metaplastic stratified squamous epithelium, a look atnon-metaplastic stratified squamous epithelium, a look at
the submucosa will show underlying endocervical clefts.the submucosa will show underlying endocervical clefts.
 Begins as a proliferation of the subcolumnar reserve cells.Begins as a proliferation of the subcolumnar reserve cells.
The nuclei are large with prominent nucleoli and basalThe nuclei are large with prominent nucleoli and basal
mitoses. Initially little maturation of the squamousmitoses. Initially little maturation of the squamous
epithelium is seen but this changes over time into theepithelium is seen but this changes over time into the
typical stratified non-keratinizing pattern as the cytoplasmtypical stratified non-keratinizing pattern as the cytoplasm
in these cells develops.in these cells develops.

18. Squamous metaplasiaSquamous metaplasia

19. Microglandular hyperplasiaMicroglandular hyperplasia
 Results fromResults from progesterone stimulationprogesterone stimulation of theof the
endocervixendocervix
 pregnancy,pregnancy,
 old-fashioned contraceptive pills.old-fashioned contraceptive pills.
 The glands are abundant and have only a lacyThe glands are abundant and have only a lacy
stroma between them, along with many neutrophils.stroma between them, along with many neutrophils.

20. Arias-Stella reaction in endocxArias-Stella reaction in endocx
 Nuclear changes similar to that in endometrium,Nuclear changes similar to that in endometrium,
commonly seen during pregnancy or post-commonly seen during pregnancy or post-
partum.partum.
 Microscopy:Microscopy:
 enlarged, dilated glandsenlarged, dilated glands
 lined by polyhedral cells with abundant eosinophiliclined by polyhedral cells with abundant eosinophilic
cytoplasm with large clear vacuolescytoplasm with large clear vacuoles
 hyperchromatic, and enlarged nuclei.hyperchromatic, and enlarged nuclei.

21. Nabothian cystsNabothian cysts
As the squamous epithelium overgrows andAs the squamous epithelium overgrows and
obliterates the surface columnar papillae, itobliterates the surface columnar papillae, it
covers and obstructs crypt openings, with thecovers and obstructs crypt openings, with the
accumulation of mucus in deeper crypts (glands)accumulation of mucus in deeper crypts (glands)
to form mucous (to form mucous (nabothiannabothian) cysts.) cysts.

22. In the diagram (upper), reserve cells in the transformation zone are continuous with the
basal cells of the ectocervix (right) and may undergo columnar and squamous
differentiation (metaplasia). Photomicrographs at bottom depict (from left to right)
quiescent subcolumnar reserve cells, reserve cells undergoing columnar differentiation
(second from left), reserve cells undergoing squamous metaplasia (second from right)
and ectocervical squamous epithelium (right).

23. Colposcopic view of the cervix in a reproductive age woman. The portio epithelium (peripheral) merges
with (at dotted boundary) and eventually replaces the endocervical columnar epithelium (red and grapelike)
to form the transformation zone. The os is in the center.

24. B, The postmenopausal cervix. The epithelial surface is smooth and completely covered by
squamous epithelium. The squamocolumnar junction is not visible and is inside the endocervical
canal.

28.  Cervical leiomyomasCervical leiomyomas are much less commonare much less common
uterine leiomyomas. They usually occur singlyuterine leiomyomas. They usually occur singly
and produce unilateral enlargement of theand produce unilateral enlargement of the
cervical portio. Leiomyomas are spherical andcervical portio. Leiomyomas are spherical and
firm , the sut surfaces are white to ten, withfirm , the sut surfaces are white to ten, with
whorled trabecular pattern. Microscopicwhorled trabecular pattern. Microscopic
finding : typical leiomyomas are composed offinding : typical leiomyomas are composed of
whorled, anastomosing fascicles of uniformwhorled, anastomosing fascicles of uniform
fusiform smooth muscle cell.fusiform smooth muscle cell.

30. ENDOCERVICAL POLYPSENDOCERVICAL POLYPS
 Inflammatory tumorsInflammatory tumors
 Occur in 2% to 5% of adult women.Occur in 2% to 5% of adult women.
 The major significance of polyps lies in their production ofThe major significance of polyps lies in their production of
irregular vaginal "spotting" or bleeding.irregular vaginal "spotting" or bleeding.
 Most polyps arise within the endocervical canal and varyMost polyps arise within the endocervical canal and vary
from small and sessile to large, 5-cm masses that mayfrom small and sessile to large, 5-cm masses that may
protrude through the cervical os.protrude through the cervical os.
 Morphology:Morphology: Soft, almost mucoid, and are composed of aSoft, almost mucoid, and are composed of a
loose fibromyxomatous stroma harboring dilated, mucus-loose fibromyxomatous stroma harboring dilated, mucus-
secreting endocervical glands, often accompanied bysecreting endocervical glands, often accompanied by
inflammation and squamous metaplasiainflammation and squamous metaplasia
 Simple curettage or surgical excision effects a cure.Simple curettage or surgical excision effects a cure.

31. Endocervical polyp composed of a dense fibrous stroma covered with
endocervical columnar epithelium.
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© 2005 Elsevier

32. Intraepithelial and InvasiveIntraepithelial and Invasive
Squamous NeoplasiaSquamous Neoplasia

33. Risk factorsRisk factors
 HPVHPV infectioninfection
 High risk types – 16, 18, 31, 33 (Bound-DNA)High risk types – 16, 18, 31, 33 (Bound-DNA)
 Low risk types – 6, 11, 42-44 (Free DNA)Low risk types – 6, 11, 42-44 (Free DNA)
 Oncogene E6 (p53) & E7 (Rb)Oncogene E6 (p53) & E7 (Rb) A wealth of molecular epidemiologicA wealth of molecular epidemiologic
data has established the following risk factors for cervical neoplasia,data has established the following risk factors for cervical neoplasia,
all of which indicate a complex interaction between host and virus:all of which indicate a complex interaction between host and virus:
 Early age at first intercourseEarly age at first intercourse
 Multiple sexual partnersMultiple sexual partners
 Increased parityIncreased parity
 A male partner with multiple previous sexual partnersA male partner with multiple previous sexual partners
 The presence of a cancer-associated HPVThe presence of a cancer-associated HPV
 The persistent detection of a high-risk HPV, particularly inThe persistent detection of a high-risk HPV, particularly in
high concentration (viral load)high concentration (viral load)
 Certain HLA and viral subtypesCertain HLA and viral subtypes
 Exposure to oral contraceptives and nicotineExposure to oral contraceptives and nicotine
 Genital infections (chlamydiaGenital infections (chlamydia))

34.  Experimental data indicate that viralExperimental data indicate that viral ((E6E6 andand E7E7)) genes ofgenes of
high risk HPVs can disrupt the cell cycle via binding to RBhigh risk HPVs can disrupt the cell cycle via binding to RB
with up-regulation of Cyclin E (E7) and p16INK4; interruptwith up-regulation of Cyclin E (E7) and p16INK4; interrupt
cell death pathways by binding to p53 (E6); inducecell death pathways by binding to p53 (E6); induce
centrosome duplication and genomic instability (E6, E7);centrosome duplication and genomic instability (E6, E7);
and prevent replicative senescence by up-regulation ofand prevent replicative senescence by up-regulation of
telomerase (E6).telomerase (E6).
 HPV E6 induces rapid degradation of p53 via ubiquitin-HPV E6 induces rapid degradation of p53 via ubiquitin-
dependent proteolysis, reducing p53 levels by two- to three-dependent proteolysis, reducing p53 levels by two- to three-
fold. E7 complexes with the hypophosphorylated (active)fold. E7 complexes with the hypophosphorylated (active)
form of RB, promoting its proteolysis via the proteosomeform of RB, promoting its proteolysis via the proteosome
pathway. Because hypophosphorylated RB normallypathway. Because hypophosphorylated RB normally
inhibits S-phase entry via binding to the E2F transcriptioninhibits S-phase entry via binding to the E2F transcription
factor, the two viral oncogenes cooperate to promote DNAfactor, the two viral oncogenes cooperate to promote DNA
synthesis while interrupting p53-mediated growth arrestsynthesis while interrupting p53-mediated growth arrest
and apoptosis of genetically altered cells. Thus, the viraland apoptosis of genetically altered cells. Thus, the viral
oncogenes are critical in extending the life span of genitaloncogenes are critical in extending the life span of genital
epithelial cells-a necessary component of tumorepithelial cells-a necessary component of tumor
development.development.

35. Role of RB as a cell-cycle regulator. Various growth factors promote the formation of the cyclin
D-CDK4 complex. This complex (and to some extent cyclin E-CDK2) phosphorylates RB,
changing it from an active (hypophosphorylated) to an inactive state (hyperphosphorylation). RB
inactivation allows the cell to pass the G1/S restriction point. Growth inhibitors such as TGF-
β and p53 and the Cip/Kip (e.g., p21, p57) and INK4a (p16INK4a and p19ARF) cell-cycle
inhibitors prevent RB activation. Transforming proteins of oncogenic viruses bind
hypophosphorylated RB and cause its functional inactivation. Virtually all cancers show
dysregulation of the cell cycle by affecting the four genes marked by an asterisk.

36. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 9 February 2009 07:33 PM)
© 2007 Elsevier

37. A, Postulated steps in the pathogenesis of cervical neoplasia. Conditions influencing
progression are listed at the lower center of the diagram.

38.  The physical state of the virus differs in differentThe physical state of the virus differs in different
lesions, being integrated into the host DNA in cancers,lesions, being integrated into the host DNA in cancers,
and present as free (episomal) viral DNA inand present as free (episomal) viral DNA in
condylomata and most precancerous lesions.condylomata and most precancerous lesions.
 Certain chromosome abnormalities, including deletionsCertain chromosome abnormalities, including deletions
at 3p and amplifications of 3q, have been associatedat 3p and amplifications of 3q, have been associated
with cancers containing specific (HPV-16)with cancers containing specific (HPV-16)
papillomavirusespapillomaviruses
 Most compelling, recent data indicate that vaccinesMost compelling, recent data indicate that vaccines
directed against papillomaviruses can prevent infectiondirected against papillomaviruses can prevent infection
and the development of precancerous disordersand the development of precancerous disorders
 However, the evidence does not implicate HPV asHowever, the evidence does not implicate HPV as
the only factorthe only factor..

39. B, Approximate lifetime risks of acquiring HPV infection (left) and dying of cervical cancer (right).
The intermediate steps include risks of infection with high-risk HPV types, development of
advanced cervical intraepithelial neoplasia (CIN), and progression to invasive carcinoma.

40. Cervical intraepithelial neoplasiaCervical intraepithelial neoplasia (CIN)(CIN)
 Can exist for years or decades before invasive squamousCan exist for years or decades before invasive squamous
cancer happens.:cancer happens.:
-Low grade intraepithelial neoplasia (CIN-I)-Low grade intraepithelial neoplasia (CIN-I)
-High grade intraepithelial neoplasia (CIN-High grade intraepithelial neoplasia (CIN II-III)II-III)
 CIN exploration with PAP smear technique:CIN exploration with PAP smear technique:
 Low grade intraepithelial neoplasiaLow grade intraepithelial neoplasia -CIN I –-CIN I –
(LGSIL)(Koilocytes* only)(LGSIL)(Koilocytes* only)
 A condyloma acuminatum or a flat wart or simplyA condyloma acuminatum or a flat wart or simply
squamous metaplasia of the endocervixsquamous metaplasia of the endocervix..

41.  --High grade intraepithelial neoplasia-High grade intraepithelial neoplasia-
(HGSIL)(HGSIL)
 CIN II:CIN II:
 Plenty of atypical cells in the lower portions, normalPlenty of atypical cells in the lower portions, normal
maturation toward the surface (The old "moderatematuration toward the surface (The old "moderate
dysplasia" and "severe dysplasia").dysplasia" and "severe dysplasia").
 CIN III:CIN III:
 The cells no longer mature as they reach the surfaceThe cells no longer mature as they reach the surface
(The old "carcinoma in situ").(The old "carcinoma in situ").
Koilocyte:Koilocyte: A squamous cell, often binucleated,A squamous cell, often binucleated,
showing a perinuclear halo; characteristic ofshowing a perinuclear halo; characteristic of
condyloma acuminatum.condyloma acuminatum.

42. MorphologyMorphology
 On the extreme low end of the spectrum areOn the extreme low end of the spectrum are
lesions that are often indistinguishablelesions that are often indistinguishable
histologically from condylomata acuminata andhistologically from condylomata acuminata and
may be either raised (acuminatum) or macular (flatmay be either raised (acuminatum) or macular (flat
condyloma) in appearancecondyloma) in appearance

Such changes fall within the range of CIN I-Such changes fall within the range of CIN I- LowLow
grade intraepithelial neoplasiagrade intraepithelial neoplasia -. CIN I-. CIN I
often contains abundant papillomavirus nucleicoften contains abundant papillomavirus nucleic
acids.acids.
 Raised lesions (acuminatum) often contain low-Raised lesions (acuminatum) often contain low-
risk HPVs.risk HPVs.
 Flat CIN usually contain high-risk HPVs.Flat CIN usually contain high-risk HPVs.

43.  These lesions typically exhibit nuclearThese lesions typically exhibit nuclear
enlargement and hyperchromasia in theenlargement and hyperchromasia in the
superficial epithelial cells, signifying the effectssuperficial epithelial cells, signifying the effects
of active viral replication in the maturing cellsof active viral replication in the maturing cells
(viral cytopathic effect).(viral cytopathic effect).
 The nuclear changes may be accompanied byThe nuclear changes may be accompanied by
cytoplasmic halos (koilocytotic atypia) with fewcytoplasmic halos (koilocytotic atypia) with few
alterations in the lower epithelial cells.alterations in the lower epithelial cells.

44.  The next change in the spectrum consists of theThe next change in the spectrum consists of the
appearance of atypical cells in the lower layers of theappearance of atypical cells in the lower layers of the
squamous epithelium but nonetheless with persistentsquamous epithelium but nonetheless with persistent
(but abnormal) differentiation toward the prickle and(but abnormal) differentiation toward the prickle and
keratinizing cell layers.keratinizing cell layers.
 The atypical cells show changes in nucleo-cytoplasmicThe atypical cells show changes in nucleo-cytoplasmic
ratio; variation in nuclear size; loss of polarity; increasedratio; variation in nuclear size; loss of polarity; increased
mitotic figures, including abnormal mitoses; andmitotic figures, including abnormal mitoses; and
hyperchromasia-in other words, they take on some ofhyperchromasia-in other words, they take on some of
the characteristics of malignant cells. These lesions fallthe characteristics of malignant cells. These lesions fall
within the range of CIN II-within the range of CIN II- High gradeHigh grade
intraepithelial neoplasiaintraepithelial neoplasia
 These features have been associated with aneuploidThese features have been associated with aneuploid
cell populations and correlate strongly with high-riskcell populations and correlate strongly with high-risk
HPV types.HPV types.

45.  Presumably they reflect early changes in the replicatingPresumably they reflect early changes in the replicating
(basal/parabasal) cell population associated with the(basal/parabasal) cell population associated with the
effects of the E6/E7 oncogenes on cell cycle andeffects of the E6/E7 oncogenes on cell cycle and
genomic stability. These include cell cycle disregulationgenomic stability. These include cell cycle disregulation
and up-regulation ofand up-regulation of p16INK4p16INK4
 Increased expression ofIncreased expression of p16p16, a cyclin-dependent kinase, a cyclin-dependent kinase
inhibitor, is possibly a compensatory response to cellinhibitor, is possibly a compensatory response to cell
disturbances brought on by the viral oncogenes. As thedisturbances brought on by the viral oncogenes. As the
lesion evolves, there is progressive loss oflesion evolves, there is progressive loss of
differentiation accompanied by greater atypia in moredifferentiation accompanied by greater atypia in more
layers of the epithelium, until it is totally replaced bylayers of the epithelium, until it is totally replaced by
immature atypical cells, exhibiting no surfaceimmature atypical cells, exhibiting no surface
differentiation (CIN III)-differentiation (CIN III)- High gradeHigh grade
intraepithelial neoplasiaintraepithelial neoplasia ..

46.  Predictably, lesions that have completely evolvedPredictably, lesions that have completely evolved
(CIN III-(CIN III- High grade intraepithelialHigh grade intraepithelial
neoplasianeoplasia ) constitute the greatest cancer risk.) constitute the greatest cancer risk.
CIN III is most frequently associated withCIN III is most frequently associated with
invasive cancer when the latter is identified.invasive cancer when the latter is identified.
 Progression to invasive carcinoma, when itProgression to invasive carcinoma, when it
occurs, may develop in a few months to moreoccurs, may develop in a few months to more
than 20 years.than 20 years.

48. Spectrum of cervical intraepithelial neoplasia: normal squamous epithelium
for comparison

49. CIN I-LGSIL with koilocytotic atypia

50. CIN II -HGSILwith progressive atypia in all layers of the epithelium

51. CIN III (carcinoma in situ) with diffuse atypia and loss of maturation.

53. Carcinoma insituCarcinoma insitu

55. Condyloma acuminatumCondyloma acuminatum
 Genital warts are spread byGenital warts are spread by
sexual contact.sexual contact.
 Approximately two thirds ofApproximately two thirds of
individuals who have sexualindividuals who have sexual
contact with an infectedcontact with an infected
partner develop genital warts.partner develop genital warts.
 HPV causes spectrum ofHPV causes spectrum of
changes ranging fromchanges ranging from
condyloma accuminatum tocondyloma accuminatum to
invasive squamous cellinvasive squamous cell
carcinoma.carcinoma.

56. A. Histology of CIN I (flat condyloma), illustrating the prominent koilocytotic atypia in the
upper epithelial cells, as evidenced by the prominent perinuclear halos. B, Nucleic acid in
situ hybridization of the same lesion for HPV nucleic acids. The blue staining denotes HPV
DNA, which is typically most abundant in the koilocytes. C, Diffuse immunostaining of CIN
II for Ki-67, illustrating widespread deregulation of cell cycle controls. D, Up-regulation of
p16ink4 (seen as intense immunostaining) characterizes high-risk HPV infections.
© 2005 Elsevier

57. The cytology of cervical intraepithelial neoplasia as seen on the Papanicolaou smear.
Cytoplasmic staining in superficial cells (A&B) may be either red or blue. A, Normal
exfoliated superficial squamous epithelial cells. B, CIN I. C, CIN II. D, CIN III. Note the
reduction in cytoplasm and the increase in the nucleus to cytoplasm ratio, which occurs
as the grade of the lesion increases. This reflects the progressive loss of cellular
differentiation on the surface of the lesions from which these cells are exfoliated
© 2005 Elsevier

58. SQUAMOUS CELL CARCINOMASQUAMOUS CELL CARCINOMA
 Squamous cell carcinoma may occur at any age fromSquamous cell carcinoma may occur at any age from
the second decade of life to senility.the second decade of life to senility.
 The peak incidence is occurring at an increasinglyThe peak incidence is occurring at an increasingly
younger age: 40 to 45 years for invasive cancer andyounger age: 40 to 45 years for invasive cancer and
about 30 years for high-grade precancers.about 30 years for high-grade precancers.
 This represents the combination of earlier onset ofThis represents the combination of earlier onset of
sexual activity (i.e., earlier acquisition of HPV infection)sexual activity (i.e., earlier acquisition of HPV infection)
and active Papanicolaou smear screening programs inand active Papanicolaou smear screening programs in
the United States, which detect either cancers orthe United States, which detect either cancers or
precancerous lesions at an earlier point in life.precancerous lesions at an earlier point in life.

59. Clinical featuresClinical features
 Asymptomatic – Abnormal cells in smearsAsymptomatic – Abnormal cells in smears
 Vaginal BleedingVaginal Bleeding
 80% Squamous80% Squamous Ca, 20% other.Ca, 20% other.
 Early diagnosis by cytological PAP test.Early diagnosis by cytological PAP test.
 Adenocarcinoma, Adenosquamous, Clear-cellAdenocarcinoma, Adenosquamous, Clear-cell
carcinoma etc.carcinoma etc.
 40-50 peak age.40-50 peak age.
 Treatments – Cone biopsy, hysterectomyTreatments – Cone biopsy, hysterectomy
 5 year survival5 year survival
 Stage1->80%, Stage2–75%, Stage3-35% & 10-15% withStage1->80%, Stage2–75%, Stage3-35% & 10-15% with
Stage 4 disease.Stage 4 disease.

60. MorphologyMorphology
 Invasive cervical carcinomaInvasive cervical carcinoma manifests inmanifests in
three somewhat distinctive patterns:three somewhat distinctive patterns:
 1-Fungating (or exophytic),1-Fungating (or exophytic),
 2-Ulcerating2-Ulcerating
 3-Infiltrative cancers3-Infiltrative cancers..
 When obvious to the naked eye, the mostWhen obvious to the naked eye, the most
common variant is the fungating tumor, whichcommon variant is the fungating tumor, which
produces an obviously neoplastic mass thatproduces an obviously neoplastic mass that
projects above the surrounding mucosa.projects above the surrounding mucosa.

61.  On histologic examinationOn histologic examination: about 95% of squamous: about 95% of squamous
carcinomas are composed of relatively large cells, eithercarcinomas are composed of relatively large cells, either
keratinizing (well-differentiated) or nonkeratinizingkeratinizing (well-differentiated) or nonkeratinizing
(moderately differentiated) patterns.(moderately differentiated) patterns.
 A small subset of tumors (less than 5%) are poorlyA small subset of tumors (less than 5%) are poorly
differentiated small cell squamous or, more rarely, smalldifferentiated small cell squamous or, more rarely, small
cell undifferentiated carcinomas (neuroendocrine or oatcell undifferentiated carcinomas (neuroendocrine or oat
cell carcinomas). The latter closely resemble oat cellcell carcinomas). The latter closely resemble oat cell
carcinomas of the lung and have an unusually poorcarcinomas of the lung and have an unusually poor
prognosis owing to early spread by lymphatics andprognosis owing to early spread by lymphatics and
systemic spread.systemic spread.
 These tumors are also frequently associated with aThese tumors are also frequently associated with a
specific high-risk HPV, type 18.specific high-risk HPV, type 18.

62. SpreadingSpreading
 Direct:Direct:
 Down – Vagina, LabiaDown – Vagina, Labia
 Lateral – adnexa, ureter, ovary, Pelvic wallLateral – adnexa, ureter, ovary, Pelvic wall
 Anterior – bladderAnterior – bladder
 Posterior – RectumPosterior – Rectum
 Lymphatic:Lymphatic:
 Paracervical, Obturator, Int & Ext iliac,Paracervical, Obturator, Int & Ext iliac,
Sacral,Common iliac, Aortic.Sacral,Common iliac, Aortic.
 Blood: Liver, lungs etc.Blood: Liver, lungs etc.

65. Morphology of cervical cancers. A, Squamous carcinoma.
© 2005 Elsevier

68.  Cervical cancer is staged as follows:Cervical cancer is staged as follows:
 Stage 0.Stage 0. Carcinoma in situ (CIN III)Carcinoma in situ (CIN III)
 Stage I.Stage I. Carcinoma confined to the cervixCarcinoma confined to the cervix
 Ia.Ia. Preclinical carcinoma, that is, diagnosed only by microscopyPreclinical carcinoma, that is, diagnosed only by microscopy
 Ia1.Ia1. Stromal invasion no greater than 3 mm and no wider than 7 mm (so-Stromal invasion no greater than 3 mm and no wider than 7 mm (so-
calledcalled microinvasive carcinomamicroinvasive carcinoma) .) .
 Ia2.Ia2. Maximum depth of invasion of stroma greater than 3 mm and noMaximum depth of invasion of stroma greater than 3 mm and no
greater than 5 mm taken from base of epithelium, either surface or glandular,greater than 5 mm taken from base of epithelium, either surface or glandular,
from which it originates; horizontal invasion not more than 7 mmfrom which it originates; horizontal invasion not more than 7 mm
 Ib.Ib. Histologically invasive carcinoma confined to the cervix and greater thanHistologically invasive carcinoma confined to the cervix and greater than
stage Ia2stage Ia2
 Stage II.Stage II. Carcinoma extends beyond the cervix but not onto theCarcinoma extends beyond the cervix but not onto the
pelvic wall. Carcinoma involves the vagina but not the lower third.pelvic wall. Carcinoma involves the vagina but not the lower third.
 Stage III.Stage III. Carcinoma has extended onto pelvic wall. On rectalCarcinoma has extended onto pelvic wall. On rectal
examination, there is no cancer-free space between the tumor andexamination, there is no cancer-free space between the tumor and
the pelvic wall. The tumor involves the lower third of the vagina.the pelvic wall. The tumor involves the lower third of the vagina.
 Stage IV.Stage IV. Carcinoma has extended beyond the true pelvis or hasCarcinoma has extended beyond the true pelvis or has
involved the mucosa of the bladder or rectum. This stage obviouslyinvolved the mucosa of the bladder or rectum. This stage obviously
includes those with metastatic dissemination.includes those with metastatic dissemination.

72.  Ten per cent to 25% of cervical carcinomas areTen per cent to 25% of cervical carcinomas are
adenocarcinomas, adenosquamous carcinomas,adenocarcinomas, adenosquamous carcinomas,
undifferentiated carcinomasundifferentiated carcinomas, or other rare histologic types., or other rare histologic types.
 The adenocarcinomasThe adenocarcinomas ::
 Arise in the endocervical glands and are often preceded by anArise in the endocervical glands and are often preceded by an
intraepithelial glandular neoplasm (precancer) termedintraepithelial glandular neoplasm (precancer) termed
adenocarcinoma in situadenocarcinoma in situ that is approximately one fifth asthat is approximately one fifth as
common as its squamous counterpart.common as its squamous counterpart.
 Once invasion develops, adenocarcinomas appear grossly andOnce invasion develops, adenocarcinomas appear grossly and
behave like the squamous cell lesions,behave like the squamous cell lesions, with the exception ofwith the exception of
association with HPV type 18.association with HPV type 18.
 TheThe adenosquamous carcinomasadenosquamous carcinomas ::
 Mixed glandular and squamous patterns and are thought to ariseMixed glandular and squamous patterns and are thought to arise
from the multipotent reserve cells in the basal layers of thefrom the multipotent reserve cells in the basal layers of the
endocervical epithelium.endocervical epithelium.
 They tend to have a less favorable prognosis than does squamousThey tend to have a less favorable prognosis than does squamous
cell carcinoma of similar stage.cell carcinoma of similar stage.
 Clear cell adenocarcinomas of the cervixClear cell adenocarcinomas of the cervix in DES-exposedin DES-exposed
women are similar to those occurring in the vagina, describedwomen are similar to those occurring in the vagina, described
earlier. Their relationship to papillomaviruses is uncertain.earlier. Their relationship to papillomaviruses is uncertain.

73. Adenocarcinoma in situ (lower), associated with CIN 3 (upper).
© 2005 Elsevier

74. C, Adenocarcinoma.
© 2005 Elsevier

75. Adenocarcinoma of cervixAdenocarcinoma of cervix

76. D, Neuroendocrine carcinoma.
© 2005 Elsevier

77.  Clinical Course and ManagementClinical Course and Management
 Cervical cancer prevention and control can be dividedCervical cancer prevention and control can be divided
into several components:into several components:
 One includes cytologic screening and management ofOne includes cytologic screening and management of
Papanicolaou smear abnormalities, both of which mayPapanicolaou smear abnormalities, both of which may
entail the use of HPV testing.entail the use of HPV testing.
 Another is the histologic diagnosis and removal ofAnother is the histologic diagnosis and removal of
precancers. Still another component is surgical removalprecancers. Still another component is surgical removal
of invasive cancers, with adjunctive radiation andof invasive cancers, with adjunctive radiation and
chemotherapy.chemotherapy.
 A final aspect that is currently under investigation is theA final aspect that is currently under investigation is the
use of vaccines, either for preventing HPV infection oruse of vaccines, either for preventing HPV infection or
treating existing disease.treating existing disease.

78.  CIN lesions are characterized on colposcopic exam byCIN lesions are characterized on colposcopic exam by
white patches on the cervix after the application of aceticwhite patches on the cervix after the application of acetic
acid . In addition, distinct vascular mosaic or punctuationacid . In addition, distinct vascular mosaic or punctuation
patterns can be observed. Highly abnormal vascularpatterns can be observed. Highly abnormal vascular
patterns regularly accompany invasive cervical cancer.patterns regularly accompany invasive cervical cancer.
 If abnormalities are visualized, they must be confirmed byIf abnormalities are visualized, they must be confirmed by
histologic examination of a punch biopsy. This ishistologic examination of a punch biopsy. This is
facilitated by both the application of morphologic criteriafacilitated by both the application of morphologic criteria
and also, recently, the immunohistochemical identificationand also, recently, the immunohistochemical identification
of increased expression of host cell biomarkers (such asof increased expression of host cell biomarkers (such as
p16INK4p16INK4, cyclin E, and Ki-67)., cyclin E, and Ki-67).
 These markers are expressed in a greater proportion ofThese markers are expressed in a greater proportion of
cells in precancerous lesions (due to cell cyclecells in precancerous lesions (due to cell cycle
disturbances) and will frequently distinguish these fromdisturbances) and will frequently distinguish these from
non-neoplastic epithelial changes.non-neoplastic epithelial changes.

79.  Treatment of precursor lesions includes Papanicolaou smearTreatment of precursor lesions includes Papanicolaou smear
follow-up for Low grade intraepithelial neoplasiafollow-up for Low grade intraepithelial neoplasia-(CIN-(CIN I)I), and, and
cryotherapy, laser, loop electrical excision procedurescryotherapy, laser, loop electrical excision procedures
(LEEP), and cone biopsy for High grade intraepithelial(LEEP), and cone biopsy for High grade intraepithelial
neoplasia (neoplasia (CIN II or CIN III).CIN II or CIN III).
 Rarely (approximately 1 in 500) a patient with a treated CINRarely (approximately 1 in 500) a patient with a treated CIN
III eventually develops an invasive cancer. The risk isIII eventually develops an invasive cancer. The risk is
minimized by follow-up pap smears.minimized by follow-up pap smears.
 Although very early invasive cancers (microinvasiveAlthough very early invasive cancers (microinvasive
carcinomas) may be treated by cone biopsy alone, mostcarcinomas) may be treated by cone biopsy alone, most
invasive cancers are managed by hysterectomy with lymphinvasive cancers are managed by hysterectomy with lymph
node dissection and, for advanced lesions, radiation.node dissection and, for advanced lesions, radiation.
 The prognosis and survival for invasive carcinomas dependThe prognosis and survival for invasive carcinomas depend
largely on the stage at which cancer is first discovered and tolargely on the stage at which cancer is first discovered and to
some degree on the cell type, with small cell neuroendocrinesome degree on the cell type, with small cell neuroendocrine
tumors having a poor prognosis.tumors having a poor prognosis.

80.  There is a 5-year survival rate of at least 95% for stageThere is a 5-year survival rate of at least 95% for stage
IA (including microinvasive) carcinomas,IA (including microinvasive) carcinomas,
 About 80% to 90% with stage IB,About 80% to 90% with stage IB,
 75% with stage II,75% with stage II,
 Less than 50% for stage III and higher.Less than 50% for stage III and higher.
 Most patients with stage IV cancer die as a consequenceMost patients with stage IV cancer die as a consequence
of local extension of the tumor (e.g., into and about theof local extension of the tumor (e.g., into and about the
urinary bladder and ureters, leading to ureteralurinary bladder and ureters, leading to ureteral
obstruction, pyelonephritis, and uremia) rather thanobstruction, pyelonephritis, and uremia) rather than
distant metastases.distant metastases.
 Early detection has reduced the number of patients withEarly detection has reduced the number of patients with
stage IV cancer by over two-thirds in the past 50 years.stage IV cancer by over two-thirds in the past 50 years.

81.  Recent publications have shown that HPVRecent publications have shown that HPV
vaccines may prevent cervical HPV infection and,vaccines may prevent cervical HPV infection and,
by inference, cervical cancer.by inference, cervical cancer.
 Assuming vaccination trials against cervicalAssuming vaccination trials against cervical
papillomaviruses bear fruit, it is conceivable thatpapillomaviruses bear fruit, it is conceivable that
the next 20 years will witness the beginning of athe next 20 years will witness the beginning of a
significant and sustained reduction in not onlysignificant and sustained reduction in not only
cervical cancer incidence but also of othercervical cancer incidence but also of other
papillomavirus-related diseases in both men andpapillomavirus-related diseases in both men and
women.women.

82. Electron micrograph of virus-like papillomavirus particles (VLPs) produced in
eukaryotic cells by expression of the late region and used as vaccines.
(Courtesy of Ian Frazer, MD, Princess Alexandra Hospital, University of
Queensland, Australia.)
© 2005 Elsevier

83. Cervical carcinoma screening:Cervical carcinoma screening:
PAP SmearPAP Smear
"Where there is love of medicine, there is love of humankind"
- Hippocrates

84. Since the Pap examination was introduced afterSince the Pap examination was introduced after
World War II, death rates from uterine cervicalWorld War II, death rates from uterine cervical
cancer have decreased by 70% in the US.cancer have decreased by 70% in the US.
““PAP smear is the most effective cancerPAP smear is the most effective cancer
screening test so far”screening test so far”

85.  14,000 women still die from cervical cancer14,000 women still die from cervical cancer
every year,every year,
 related primarily to the fact that 80% of theserelated primarily to the fact that 80% of these
women have never had a Pwomen have never had a PAPAP smear or aresmear or are
tested only infrequentlytested only infrequently..

86. CytopathologyCytopathology
 Cytopathology is diagnosis of disease in cells.Cytopathology is diagnosis of disease in cells.
 Exfoliative & Non-Exfoliative - cytology.Exfoliative & Non-Exfoliative - cytology.
 Exfoliative:Exfoliative: Cell samples are collected fromCell samples are collected from
normally shedding tissues like epitheliumnormally shedding tissues like epithelium:: useuse spatulaspatula
or brush to enhances collection.or brush to enhances collection.
 Non-Exfoliative:Non-Exfoliative: Cells samples collected by needlesCells samples collected by needles
with suction pressurewith suction pressure..
 Cytology specimen is fixed, stained and studiedCytology specimen is fixed, stained and studied
under microscope.under microscope.

87.  Screening test for cervical cancer.Screening test for cervical cancer.
 It is a type ofIt is a type of exfoliative cytologyexfoliative cytology test.test.
 Simple, safe, non-invasive methodSimple, safe, non-invasive method..
 Developed by “Developed by “George PapanicolaouGeorge Papanicolaou””
 Exfoliated cells from cervix are collected usuallyExfoliated cells from cervix are collected usually
enhanced by using a variety of spatulas orenhanced by using a variety of spatulas or
brushes.brushes.
 The specimen is processed and studied forThe specimen is processed and studied for
morphology.morphology.

88.  Every woman should have an annual PEvery woman should have an annual PAPAP
examination when she becomes sexually activeexamination when she becomes sexually active
or turns 18 years old.or turns 18 years old.
 Regular PRegular PAPAP examinations (yearly) shouldexaminations (yearly) should
continue even after menopause and after acontinue even after menopause and after a
hysterectomyhysterectomy..

89.  The best time for a PThe best time for a PAPAP examination is duringexamination is during
the two weeks following the end of menstrualthe two weeks following the end of menstrual
flowflow (Proliferative phase)(Proliferative phase)..
 If menopause, PIf menopause, PAPAP examination can beexamination can be
scheduled anytimescheduled anytime..

90. Risk of Cervix CarcinomaRisk of Cervix Carcinoma
• Any woman can develop CAny woman can develop Cervix carcinomaervix carcinoma
• Multiple sex partners or a partner who has hadMultiple sex partners or a partner who has had
multiple female partnersmultiple female partners
• Have had genital wartsHave had genital warts (HPV)(HPV)
• Sexual relations before the age of 18Sexual relations before the age of 18
• Previous abnormal PPrevious abnormal PAPAP examinationexamination

91. Pathology of CervixPathology of Cervix
 The uterine cervix is continually beingThe uterine cervix is continually being
bombarded by a variety of stress includingbombarded by a variety of stress including
mechanical, microbiologic, chemical, andmechanical, microbiologic, chemical, and
hormonal insults.hormonal insults.
 The cervix responds byThe cervix responds by
 Acute or chronic inflammatory reactionsAcute or chronic inflammatory reactions
 Adaptive proliferative responses like Hyperplasia,Adaptive proliferative responses like Hyperplasia,
Metaplasia & Dysplasia.Metaplasia & Dysplasia.
 Anaplasia - Benign & Malignant tumors.Anaplasia - Benign & Malignant tumors.

92. PAP: NormalPAP: Normal

93. Pathology: Non-neoplastic lesionsPathology: Non-neoplastic lesions
1.1. Chronic cervicitisChronic cervicitis
2.2. Hyperplasia –Hyperplasia – NumberNumber
3.3. Metaplasia –Metaplasia – Change to squamousChange to squamous
4.4. Dysplasia –Dysplasia – no-maturation, disorderno-maturation, disorder
(CIN 1-3, CIS)(CIN 1-3, CIS)
Cervical Intraepithelial Neoplasia (CIN)Cervical Intraepithelial Neoplasia (CIN)
Carcinoma in situ (CIS)Carcinoma in situ (CIS)

94.  Malignant (Cervical Cancer)Malignant (Cervical Cancer)
 Invasion & Spreading.Invasion & Spreading.
Pathology: Neoplastic lesionsPathology: Neoplastic lesions

96. HerpesvirusHerpesvirus

97. LSIL(Low grade intraepithelialLSIL(Low grade intraepithelial
lesion)lesion)

100. HSIL(High grade IntraepithelialHSIL(High grade Intraepithelial
Lesion)Lesion)

101. Yüksek Gradeli intraepitelyal lezyon (HSIL):lezyon olarak karşılığı: orta yada ağırYüksek Gradeli intraepitelyal lezyon (HSIL):lezyon olarak karşılığı: orta yada ağır
displazi, karsinoma insitu, CIN2 ve CIN3displazi, karsinoma insitu, CIN2 ve CIN3

103. Squamous cell carcinomaSquamous cell carcinoma

104. PAP smear: ResultsPAP smear: Results
Bethesda Classification-2001Bethesda Classification-2001
 Intraepithelial neoplasia: negativeIntraepithelial neoplasia: negative
 A-Normal sitological findingsA-Normal sitological findings
 B-Benign cellular changes:InflammationB-Benign cellular changes:Inflammation
 Intraepithelial neoplasia: Positive-negativeIntraepithelial neoplasia: Positive-negative
 Positive:Positive:
 Squamous lesions:Squamous lesions:
 ASCUSASCUS
 LGSILLGSIL
 HGSILHGSIL
 Insitu squamous cell carcinomaInsitu squamous cell carcinoma
 Invasive squamous cell carcinomaInvasive squamous cell carcinoma

105.  Glandular lesions:Glandular lesions:
 AGUSAGUS
 EndometrialEndometrial
 EndoservicalEndoservical
 ADENOCARCINOMA INSITUADENOCARCINOMA INSITU
 INVASIVE ADENOCARCINOMAINVASIVE ADENOCARCINOMA

106. Benign Cellular ChangesBenign Cellular Changes
 InfectionInfection ---- These are common sexuallyThese are common sexually
transmitted and non-sexually transmittedtransmitted and non-sexually transmitted
infrections. If they are suseptible to antibiotics,infrections. If they are suseptible to antibiotics,
then the woman will be treated.then the woman will be treated.
 Trichomonas vaginalisTrichomonas vaginalis ---- this is sexuallythis is sexually
transmitted and the woman's partner will have totransmitted and the woman's partner will have to
be treated as well .be treated as well .
 Fungal organismsFungal organisms morphologically consistent withmorphologically consistent with
Candida ssp. This is yeast.Candida ssp. This is yeast.
 Predominance of coccibacilli consistent withPredominance of coccibacilli consistent with
ActinomycesActinomyces ssp.ssp.
 Cellular changes associated with herpes simplexCellular changes associated with herpes simplex
virusvirus ---- this is sexually transmitted, but not curable.this is sexually transmitted, but not curable.

107. Reactive and reparative changesReactive and reparative changes
 Reactive and reparative changesReactive and reparative changes -- these may be due to-- these may be due to
gynecologic procedures or childbirth related.gynecologic procedures or childbirth related.
 Inflamation (includes typical repair)Inflamation (includes typical repair) ---- the woman may bethe woman may be
re-tested. Even if none of the definitive signs of infectionre-tested. Even if none of the definitive signs of infection
above is present, her doctor may treat her with antibiotics,above is present, her doctor may treat her with antibiotics,
especially if the inflammatory result is persistent.especially if the inflammatory result is persistent.
 Atrophy with inflamation ("atrophic vaginitis")Atrophy with inflamation ("atrophic vaginitis") This isThis is
usually seen in post-menopausal women. Hormoneusually seen in post-menopausal women. Hormone
replacement, vaginal estrogen creasm, or lubricants may bereplacement, vaginal estrogen creasm, or lubricants may be
suggested.suggested.
RadiationRadiation
Intrauterine contraceptive device (IUD).Intrauterine contraceptive device (IUD).

108. Epithelial Changes (Squamous Cell)Epithelial Changes (Squamous Cell)
 Atypical squamous cells of undetermined significanceAtypical squamous cells of undetermined significance
(ASCUS) --(ASCUS) -- the most common type of abnormal result.the most common type of abnormal result.
 It is not cancer. It is often due to infection or irritation. Many timesIt is not cancer. It is often due to infection or irritation. Many times
these resolve on their own.these resolve on their own.
 Most women will be re-tested in a few months. High risk womenMost women will be re-tested in a few months. High risk women
will have colposcopy right away.will have colposcopy right away.
 Squamous intraepithelial lesion (SIL)Squamous intraepithelial lesion (SIL)
Low-grade squamous intraepithelial lesion (LSIL)--Low-grade squamous intraepithelial lesion (LSIL)-- AA
woman with these result will usually have a colposcopywoman with these result will usually have a colposcopy
within 4 weeks. It is not yet cancer.within 4 weeks. It is not yet cancer.
Mild dysplasia (cervical intraepithelial neoplasia [CIN]-I)Mild dysplasia (cervical intraepithelial neoplasia [CIN]-I)
---- a woman will usually have a colposcopy right away. Thisa woman will usually have a colposcopy right away. This
is not yet cancer.is not yet cancer.
 High-grade squamous intraepithelial lesion (HSIL) SevereHigh-grade squamous intraepithelial lesion (HSIL) Severe
dysplasia and carsinoma in situ (CIN-III) --dysplasia and carsinoma in situ (CIN-III) -- this is cancer,this is cancer,
but limited to the cervix and still has an excellent chance ofbut limited to the cervix and still has an excellent chance of
cure.cure.
 Squamous cell carcinomaSquamous cell carcinoma

109. Epithelial Changes (Glandular Cell)Epithelial Changes (Glandular Cell)
 Presence of unexpected endometrial cellsPresence of unexpected endometrial cells ---- thesethese
are from the uterine lining.are from the uterine lining.
 Atypical glandular cells of undeterminedAtypical glandular cells of undetermined
significance(AGUS)significance(AGUS) ---- It could indicate cervical orIt could indicate cervical or
endometrial problems (due to cells from theendometrial problems (due to cells from the
uterine lining being picked up on the Pap).uterine lining being picked up on the Pap).
 This is handled the sometimes with endocervicalThis is handled the sometimes with endocervical
curettage and endometrial biopsy.curettage and endometrial biopsy.
 Endocervical adenocarcinomaEndocervical adenocarcinoma
 Endometrial adenocarcinomaEndometrial adenocarcinoma
 Other AdenocarcinomaOther Adenocarcinoma

110. The final diagnosisThe final diagnosis
Examples of final diagnoses include:Examples of final diagnoses include:
 Within normal limits;Within normal limits;
 Absence of endocervical cells on the Pap smear;Absence of endocervical cells on the Pap smear;
 Unreliable Pap smear due to inflammation;Unreliable Pap smear due to inflammation;
 Atypical squamous cells of undetermined significanceAtypical squamous cells of undetermined significance
(ASCUS);(ASCUS);
 Low-grade squamous intraepithelial lesion (LSIL); orLow-grade squamous intraepithelial lesion (LSIL); or
 High-grade squamous intraepithelial lesion (HSIL)High-grade squamous intraepithelial lesion (HSIL)

111. PPAPAP smearsmear
 Parabasal cells indicate no estrogen orParabasal cells indicate no estrogen or
progesterone effectprogesterone effect
 Superficial squamous cells indicateSuperficial squamous cells indicate estrogenestrogen
eeffect,ffect,
 IIntermediate squamous cells indicatentermediate squamous cells indicate
progesterone effectprogesterone effect
 A normal, non-pregnant woman has a mixA normal, non-pregnant woman has a mix
depending ondepending on the stage of her cycle.the stage of her cycle.

112. THANK YOUTHANK YOU