cervix by wanghonghx

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									Ruth Olson                                        Cervical Pathology


                    Notes                                                         Images
Normal Anatomy      External os
                    Internal os
                    Endocervical cana
                    Transitional (transformation) zone: abrupt change
                    between squamous and glandular epithelium. When
                    you’re doing pap smears, this is the preferred site of
                    infection of HPV and the site where most dysplasia begins.
                    Visualize the cervix and where that zone begins while doing
                    a pap. The presence of metaplastic squamous cells or
                    mucus-secreting columnar cells indicates proper sampling.
                    Absence of these cells means that the pap smear must be
                    repeated.


                                                                                  You can get invasion of glandular epithelium. Transition zone visible.
Benign Conditions   Acute cervicitis: STDs  gonococcus or Chlamydia(>50%);
                    also herpes et al. VERY COMMON. Clinical: vaginal
                    discharge (most common), perlvic pain, cervical os is
                    erythematous and may be covered by an exudate.
                    Chronic cervicitis:  squamous metaplasia of endocervical
                    mucosa. This obliterates mouth of mucus glands 
                    Nabothian cysts erosions and uclers, simulate ca. These
                    can get quite large.
                    Cervicitis is the primary source for conjunctivitis and
                    pneumonia in newborns.
                    Endocervical polyps: soft, edematous stroma, epi-covered
                    may erode  bleed. Arises from ENDOCERVIX NOT CERVIX
                                                                                  Nabothian cyst. Multiple mucus filled Nabothian cysts (cervical canal has been opened)
                    “Pill” cervix: microglandular hyperplasia (progesterone
                    effect?)




                    Microglandular hyperplasia of endocervix (pill cervix).       Endocervical polyp protruding from cervix. Whole mount of benign endocervical polyp
                    Atypical cells may be seen on PAP smear.                      (arrow points to ectocervix). Polyp has sq. and gland tissue. Rx: surgical excision.
Ruth Olson                                   Cervical Pathology



Epidemiology   50,000 precancerous cases/yr, but 13,000 invasive/yr (75%
               prevented-Rx or spontaneous regression). Before we were
               aggressive in interventions, most would regress.
               13,000 invasive cases/yr, but <5,000 die (60% cure rate)
               Papanicolaou smear = effective at identifying precancerous
               lesions.
               One of few examples of value of early cancer detection!
               Historically: it’s been a deadly disease affecting younger
               women. We have a way to eradicate it now.
               Average age: 45 yo. Normally progression from CIN IIII is
               ~10 years.
Risk Factors   early age of first sexual intercourse
               multiple sexual partners
               male partner who has multiple other partners
               penile condylomas
               All of these things imply a sexually transmitted agent
               HPV!
HPV            -Causes condyloma accuminatum & warts (virus remains
               episomal)
               -Types 16, 18, 31, 33 stainable in precancerous cervical
               mucosa (virus integrates into host genome)
               -Transforms squamous epithelial cells in vitro
               -E6 oncoprotein product of HPV binds with and degrades
               p53 inhibits apoptosis
               -E7 oncoprotein binds hypophosphorylated pRb,
               frees E2F transcription factor to drive cell cycle             Roll of the E7 oncogene  binds to E2F activates transcriction (S phase genes) in
                   -double whammy on the cell cycle                           conjunction with pRb gene.
               -HPV virus (Human papillomavirus) found in ~90% of                                                                         This chart measures
               tumors
                                                                                                                                          association of HPV types
               -HPV infected cells called koilocytes inc nuclear size, inc
               Nuclear/Cytoplasmic ratio, irregular nuclear                                                                               with Condylomas, CIN
               contoursraisenoid, hyperchromasia and perinuclear                                                                         IIII and invasive ca.
               clearing
               -
               mitoses                                                                                                                    HPV types 16 & 18 are
                                                                                                                                          found in high-grade
                                                                                                                                          cervical lesions. 6 & 11 in
                                                                                                                                          condylomas
Ruth Olson                                            Cervical Pathology


Classification of     cervical intraepithelial neoplasia: CIN
precancerous lesion   Progresses through succession (CIN I II  III) of

                      moderate, severe (same as CIN III)
                      CIN III also called “carcinoma in situ”




                                                                           Grades of cervical dysplasia: level at which atypical cells are present
                                                                           Nuclei are at first oriented perpendicularly to BM and lumen; then they flatten out; then they
                                                                           become piknotic. As it progresses, the amount of dysplasia increases (1/32/33/3).
                                                                           PROGRESSION FROM IIII IS NOT INEVITABLE.
Histology of
Dysplasia
Ruth Olson                                           Cervical Pathology


Histology cont.




Biological Features   -% of cases progressing to next-highest grade - with the
                      grade (i.e., % CIN II  III more that III)
                      -lesions begins @ squamo-columnar junction
                      (“transformation zone”)
                      -initial lesions may be any grade
                      -time in any grade varies from months to many years
                      -detection: iodine (Schiller’s) test—stains glycogen in
                      normal cells
                      -Extends down into the vagina, extends out into the lateral
                      wall of the cervix and vagina, infiltrates the bladder wall
                      and obstrucs the ureters post-renal axotemia leading to
                      renal failure is a common cause of death.
                      -70-85% are squamous cell carcinoma. Small cell cancer
                      and adenocarcinoma are less common types.

                      CLINICAL: Abnormal bleeding (usu pos-coital), malodorous
                      discharge.
                                                                                     Most lower-grade lesions regressed. More from the moderate progressed than the mild.
DIagnosis             screening: “pap” smear                                             COMPARISON OF TRADITIONAL, CIN & BETHESDA NOMENCLATURE
                      definitive diagnosis:                                              Traditional Cervical Intraepithelial Neoplasia (CIN)         Bethesda System
                      pap smear repeat                                                   HPV (flat condyloma)                N/A                      Low-grade squamous
                      colposcopy: Schiller test, biopsy visible lesion, conization       Mild dysplasia                      CIN I
                      follow: with repeat smears & colposcopy                            Moderate                            CIN II                   High-grade squamous
                                                                                                                                                      intraepithelial lesion
                                                                                                                                                      (SIL)
                                                                                         Severe dysplasia                 CIN III                     Carcinoma-in-situ
Ruth Olson                                            Cervical Pathology


Invasive carcinoma   type: 80% = squamous cell carcinoma
                     remainder: undifferentiated, adenosquamous &
                     adenocarcinoma
                     In DES-Rxed patients = clear cell carcinoma
                     Staging of invasive cervical cancer:
                     Stage 0: CIN III
                     Stage I: limited to cervix
                     Stage II: beyond cervix, upper 1/3 vagina, does not
                     reach pelvic wall
                     Stage III:lower 1/2 vagina & reaches pelvic wall
                     Stage IV:beyond pelvis or invaded bladder or colon;
                     distant metastases



Rx                   CIN I, II, III: pap, cryoRx, laser, conization, wire loop
                     invasive: hysterectomy and radioRx

                     Prognosis: stage-dependent
                     Stage I = 90% 5 yr
                     Stage III = 10%

                     Complications: local invasion  bladder, ureters, colon

                     Female cancer death rate due to uterus cancer is
                     decreasing!

                                                                                 Ulcerated squamous cell carcinoma of cervix




                                                                                 Normal glands (green arrow) vs glands of adenocarcinoma of cervix .
                     Poorly differentiated
Ruth Olson                                       Cervical Pathology


Questions:

   1.   What is the most important zone to obtain cells from in a pap smear?
   2.   What two organisms cause the most cases of acute cervicitis?
   3.   Which benign condition has soft, edematous stroma, is epithelium covered, and may erode, causing bleeding?
   4.   Name risk factors for HPV infection.
   5.   Name the 2 oncoproteins associated with the development of cancer.
   6.   Which two subtypes are associated with cervical cancer? Condylomas?
   7.   T/F CIN II is more likely to progress to CIN III than CIN I is to progress to CIN II
   8.   Define stages O IV of cervical cancer.

Answers:

   1. Transitional zone
   2. Gnoncoccus and Chlamydia.
   3. Endocervical polyp
   4.   early age of first sexual intercourse
        multiple sexual partners
        male partner who has multiple other partners
        penile condylomas
   5. E6 and E7
   6. 16,18. 6,11
   7. True
   8. Staging of invasive cervical cancer:
   Stage 0:      CIN III
   Stage I: limited to cervix
   Stage II: beyond cervix, upper 1/3 vagina, does not reach pelvic wall
   Stage III:lower 1/2 vagina & reaches pelvic wall
   Stage IV:beyond pelvis or invaded bladder or colon; distant metastases

								
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