Carcinoma cervix pre management workup

1. Carcinoma cervix
Premanagement
By-Dr Satyajeet Rath

2. Topics Covered
• Clinical Presentation
• Examination
• Diagnostic Work up
• Staging

3. Clinical Presentation
• Asymptomatic - Most common presentation in western
countries due high rate of screening
• Intraepithelial or early invasive carcinoma of the cervix may
be detected by cytological smears before symptoms appear
• Abnormal vaginal bleeding– earliest symptom of invasive
cervical cancer (most commonly post coital bleeding)
• Metrorrahgia – Inter menstrual bleeding
• Menorrhagia – Heavier than usual flow
• Fowl smelling discharge – May or may not be mixed with
blood
• Exophytic/ulceroproliferative mass visible on examination

4. Symptoms of Advanced Carcinoma Cervix
• Anemia,Fatigue – Due to chronic blood loss
• Bowel obstruction —vomiting , abdominal pain
and distention
• Anuria -- Renal failure – due to pressure effect on
ureter leading to back pressure on kidney
• Rectal bleeding- venous engorgement due to
pressure effect
• Constipation
• Dysuria

5. Contd…
• Hematuria
• Persistent edema of lower limb – Obstruction of
lymphatic channel from lower limb
• Pelvic pain-
• Flank or leg pain – Both may be due to
Associated with pelvic inflammatory disease
Para aortic lymph node involvement
lumbosacral root involvement
Hydroureteronephrosis

6. Contd…
Ascites- Due to peritoneal deposits
Dribbling of urine per vaginum –Due to vesico
vaginal fistula formation
Fecal matter per vaginum- Rectovaginal fistula
• Metastasis as Cervical Malignancy
• Metastasis of distant tumors to the uterine cervix is rare
(about 4% of all tumors) and should be considered in the
differential diagnosis.
• Metastases to the cervix from the breast, ovary, and kidney
have been reported.

7. WHO histological classification of tumours of the
uterine cervix.
• epithelial tumours
• squamous tumours and precursors
• glandular tumours and precursors
• others
• mesenchymal tumours and tumour-like
conditions
• mixed epithelial and mesenchymal
tumours
• melanocytic tumours
• miscellaneous tumours
• lymphoid and haematopoetic
• secondary tumours

8. Histologic Subtypes
• Squamous-Cell Carcinoma(>90%)
• Large cell-Keratinizing or Nonkeratinizing or
small cell carcinomas
• Verrucous-
• very well differentiated scc, tendency to recur
locally but not metastasize
• Papillary transitional
• Lymphoepithelioma-like
• Adenocarcinoma (7-10%)
• (arises from the cylindrical mucosa of the
endocervix or the mucus secreting
endocervical glands
• Mucinous
• Endometrioid- MC Endocervical adeno ca
• Clear Cell
• Serous
• Mesonephric
• Well differentiated villoglandular
• Minimal deviation (adenoma malignum)-
associated with Peutz-Jeghers,ominous
natural history
• Other epithelial
• Adenosquamous
• Glassy Cell
• Carcinoid Tumor
• Neuroendocrine
• Small-cell
• Undifferentiated
• Basaloid Ca
• Primary Sarcoma of cervix
• Cervical malignant Mixed
Mullerian Tumours,
compared to their
counterparts are confined
at presentation and
better prognosis.

9. • DIAGNOSTIC WORKUP FOR CARCINOMA
OF THE UTERINE CERVIX

10. Patterns of Spread
• Local Invasion
• Lymphatic
• Risk relates to depth of invasion
• Pelvic nodes before paraaortic or supraclavicular
• Hematogenous
• More likely in adenocarcinoma, neuroendocrine or small
cell tumors
• Intraperitoneal
• Unknown incidence
• Poor prognosis

11. Patterns of Lymphatic Spread

12. Distribution of pelvic node metastases in 14 patients with stages IB to IIA cervical cancer, tumor size <4 cm (A), and 38
patients with locally advanced cervical cancer treated with neoadjuvant chemotherapy (B). (From Benedetti-Panici P,
Maneschi F, Scambia G, et al. Lymphatic spread of cervical cancer: an anatomical and pathological study based on 225
radical hysterectomies with systematic pelvic and aortic lymphadenectomy.

13. Incidence of
pelvic lymph
node mets
Leibel and Philips,Textbook of Radiation Oncology, 3rd Edition
 The most commonly
involved groups were
the parametrial,
obturator, external iliac,
and common iliac
nodes.

14. • CARCINOMA OF THE UTERINE CERVIX (MALLINCKRODT
INSTITUTE OF RADIOLOGY 1959–1986): ANATOMIC SITE OF FIRST
METASTASIS
• Bone metastases occurred in 16% of patients, most commonly
to the lumbar and thoracic spine.

15. Thorough History & Examination

16. Pretreatment Evaluation
• HISTORY-
--Age
--Menstrual status –Pre or post menopausal
Menstrual frequency
Amount, Duration
Associated pain
Post Coital Bleed
--Early Age of onset of sexual activity
--Promiscuity
--Multiple sexual partners
--Associated comorbidity – DM , HTN
--Addiction history- smoking
--Long term OCP use
--IUD use
--having multiple full term pregnancies
--younger than 17 at 1st full term pregnancy
--DES use
--Family History of cervical cancer

17. Contd…
-- Discharge per vaginum-
Amount
Duration
Nature – serous or serosanguinous
Odour – fowl smelling or not
-- Pain – Site ,Intensity ,Radiating to any part
-- Pain during intercourse.
-- Swelling of lower limb
-- Dribbling of urine per vaginum or fecal matter through vagina
--immunosuppression – HIV AIDS
 HPV Infection is the most important risk factor

18. Examination
There are three steps:
1. The External Genital Exam
2. The Speculum Exam
3. The Bimanual Exam
Prerequisites :
• Patient must be counselled properly regarding the procedures to be done.
• A female attendant should be present by the side(nurse/or relative).
• A light source should be available.
• Sterile gloves,swabs,speculum,sponge holding forceps required.
1.Shaws’s Gynaecology,The gynaecology examination
2.Dutta’s Textbook of Gyanecology5th edition

19. Step 1. The External Genital Exam
• Visually examine the soft folds of the vulva and the opening of
the vagina to check for signs of irritation, discharge, cysts,
genital warts, or other conditions.
• Note character of visible
vaginal discharge if any.
• Elicit the signs of Stress
incontinence and Genital
prolapse.
• Look for hemorrhoids,any
other palpable pathology
over the area.

20. Step 2. The Speculum Exam
• Speculum
examination should
preferably be done
prior to bimanual
examination.
• Advantages :
• Cervical scrape
cytology and
endocervical
sampling can be
taken as screening
in the same sitting.
• Discharge P/V can
be sent for
examination if
need be
• Cervical lesion may
bleed during
bimanual
examination which
makes the lesion
difficult to visualise • Anterior vaginal wall is to be visualized by Sim’s
speculum

21. Step 2. The Speculum Exam
• Insert a speculum into the vagina
usually in lithotomy position .
• When opened, it separates the
anterior and posterior lip of the
vagina, which normally are closed
and touch each other, so that the
cervix can be seen.
• Patient may feel some degree of
pressure or mild discomfort when
the speculum is inserted and
opened.
• Will likely feel more discomfort if
tensed or if vagina or pelvic organs
are infected so it is essential that
patient must be advised to relax

22. Contd..
• The position of the cervix or
uterus may affect the
comfort as well.
• May feel the chill of the
metal, if a metal speculum
is used
• Lubricate the speculum and
warm it to body
temperature for more
comfort.
PER SPECULUM

23. BIMANUAL DIGITAL EXAMINATION
1) Assessing the cervix:
Vaginal fingers locate the cervix and the
external cervical os:
- Determine whether it is open or closed
- Directed posteriorly when the uterus is
anteverted
- Consistency
- usually firm when normal,
- but hard due to fibrosis or carcinoma,
- soft in pregnancy
- Note any mass its
- size,
- shape,
- consistency,
- position,
- mobility ,
- extension

24. BIMANUAL DIGITAL EXAMINATION
2 Assessing the anae:
• The vaginal fingers are now
moved into one of the lateral
fornices with the abdominal
hand moving to the
corresponding iliac fossa.
• Assess for any adnexal
masses (ovaries and fallopian
tubes) on both sides - size,
shape, tenderness, etc.

25. BIMANUAL DIGITAL EXAMINATION
3 Assessing the Pouch of
Douglas (recto-uterine
pouch):
-The vaginal fingers now placed
into the posterior fornix of the
vagina and its shape is
assessed (normally concave
away from the fingers, but
may be convex towards the
fingers if there is a mass in the
Pouch of Douglas).

26. Combined PR and PV Examination
• It is done with one finger inserted per vaginally
and the second finger of same hand per rectally
• Aim of the examination is to evaluate the extension
of tumor up to lateral pelvic wall
• Both the fingers are moved towards lateral pelvic
wall
• If tumor extends to pelvic wall the 2 fingers do not
converge

27. PAP Smear
• Insert the spatula with the endocervical
tip ( the longest part), into the
endocervical canal and turn 360
degrees.
• Apply the smear onto the slide – 2
strokes.
• The Craigbrush is superior to the
spatula if the transition zone is high and
you cannot see it.
• Turn it gently in five complete circles
and apply the smear to the slide in
gentle strokes.
• Within 20 seconds of taking it, apply the
smear onto the glass slide with a light
sweeping motions.
• Spray immediately with one spray of
fixative, holding the spray bottle upright
at about 30cm from the slide, to prevent
drying and decay of the smear
• Conventional
• Liquid based cytology

28. Liquid Based Cytology:
•Taken using plasctic spatula
•Rinsed in a buffered methanol solution
•Sepatrated by centrifugation
Advantages :
• avoids false positive,false negative
• reduces number of unstaisfactory
smears

29. Pap tests can detect
• The presence of abnormal
cells in the cervix
• Infections and
inflammations of the cervix
• Symptoms of STDs (With
the exception of
trichomoniasis, Pap tests
cannot identify specific
STDs, )
• Thinning of the vaginal
lining from lack of estrogen
commonly related to
menopause

30. De Vita Oncology , 9th edition

31. • The U.S. Food and Drug Administration has approved the use of HPV
testing in combination with Pap screening as a primary screen
• for cervical disease in women age 30 and above in addition to reflex testing within
the ASCUS patient population.
• The FDA concluded that HPV testing was more sensitive than cytology
but was concerned about the specificity of primary testing, especially in
young women, in whom the prevalence is high and which would lead to
excessive follow-up studies.
• An overview of studies on HPV testing in primary cervical cancer
screening showed an average sensitivity for detection of CIN 2 or higher
of 96%, which was unaffected by patient age.
• Specificity (less than CIN 2) varied between 76% and 96% and was
significantly on the lower end in young women.
• Adjusting for women 35 years and above, specificity was 93%.
De Vita Oncology ,9 th Edition , Cancer Screening

32. Categories for Pap test results:
• Normal results:
• If no abnormal cells are seen, then the test result is normal.
• If only benign changes are seen, usually resulting from inflammation or
irritation, then the test result is normal.
• Abnormal results:
• Atypical cells of undetermined significance (ASCUS, AGUS).
• Low-grade squamous intraepithelial lesions (LSIL) or cervical
intraepithelial neoplasia (CIN) 1. These are mild, subtle cell changes, and
most go away without treatment.
• High-grade squamous intraepithelial lesions (HSIL) or CIN 2 or 3.
Moderate and severe cell changes which require further testing or
treatment.
• Carcinoma.

33. Management options if the Pap test
result is abnormal:
• For women with low-grade squamous abnormalities
(ASCUS or LSIL), give periodic Pap tests until the
abnormality resolves, or a colposcopy referral for
persistent lesions.
• Women with glandular abnormalities (AGUS) usually are
referred for colposcopy.
• Women with HSIL usually are referred for colposcopy.
• Women with HSIL should be treated to remove or destroy
the abnormal cells.

34. Pap test performance:
• Sensitivity = 51% for CIN I or higher
• Range of 37% to 84%
• Specificity = 98% for CIN I or higher
• Range of 86% to 100%
• meta-analyses of cross-sectional studies (AHCPR 1999).
• Historical success in developed countries.
• High specificity, meaning women with no cervical
abnormalities are correctly identified by the test with
normal test results.
• A well characterized screening approach.
• May have the potential to be cost-effective in middle-
income countries.
Strengths of cytology:

35. Limitations of cytology:
• Moderate to low sensitivity:
• High rate of false-negative test results
• Women must be screened frequently
• Requires complex infrastructure
• Results are not immediately available
• Requires multiple visits
• Likely to be less accurate among post-menopausal women
ACCP. Pap smears: An important but imperfect method. Cervical
Cancer Prevention Fact Sheet. (October 2002).

36. Comparison of Cytology Classification Systems for Cervical Neoplasms

37. Bethesda system
• The Bethesda System used for reporting uniform cervical
cytology results was initially developed in 1988.
• It was updated in 1991 and 2001 to incorporate laboratory
and clinical experience.
• The Bethesda System includes a descriptive diagnosis and
an evaluation of specimen adequacy.
• Overall, cervical cytology screening programs for the
detection of CIN 3 or cancer have reported a range of
sensitivities (50% to 75%) and specificities (69% to 94%).

38. Leibel & Phillips

39. ENDOCERVICAL CURETTAGE: scraping of mucus
membrane by endocervical brush or curettage.

40. Punch Biopsy
• Multiple punch biopsy of the grossly visible lesion should
be adequate to diagnose invasive carcinoma
• It is advised that the specimen be taken from all the four
quadrant
• Important thing is to obtain specimen from periphery of
lesion with some normal tissue
• Biopsy specimen from central area of necrosis or
ulceration may not be sufficient for diagnosis
• Dilatation and curettage

41. Colposcopy

42. COLPOSCOPY
• Binocular stereoscope giving 10-20 times magnification
To study cervix when pap smear detect abnormal cells
To locate the abnormal areas and take biopsy
Conservative surgery under colposcopic guidence
Follow up
• Visual inspection of acetowhite areas;
• Applying 5% acetic acid
• Acid coagulates protein of nucleus and
cytoplasm and makes the protein opaque
and white
• Dull white plaque with faint border: LSIL
• Thick plaque with sharp border: HSIL

43. • Visual inspection of acetowhite areas;
• Applying 5% acetic acid
• Acid coagulates protein of nucleus and
cytoplasm and makes the protein
opaque and white
• Dull white plaque with faint border: LSIL
• Thick plaque with sharp border: HSIL

44. Abnormal areas
• Punctation:
Dilated capillaries
terminating on
the surface
appear from the
ends as a
collection of dots

46. • Atypical vascular pattern: looped vessels,branching
vessels,reticular vessels

47. Cone Biopsy
• Diagnostic and therapeutic
• Large abnormalities,inner wall
receded into cervical canal,SCJ
not visible
• Cold knife technique under GA
• Large loop excision of
transformation zone
• Laser excision

48. • Conization must be performed in the
following situations:
• no gross lesion of the cervix is noted and an endocervical
tumor is suspected;
• the entire lesion cannot be seen with the colposcope;
• diagnosis of microinvasive carcinoma is made on biopsy;
• discrepancies are found between the cytologic and the
histologic appearances of the lesion; or
• the patient is not reliable for all necessary follow-up.
• With careful selection of patients who have a negative
positron emission tomography (PET) scan and an MRI with a
central lesion <2 cm in width, knife conization with
lymphadenectomy may be considered for fertility
preservation.

49. CT
• CT provides diagnostic information about the
• presence of metastases,
• enlarged lymph nodes, and
• the primary tumor.
• On a CT scan,
• cervical tumor seen as
• an enlarged, irregular, hypoechoic mass with ill-defined margins.
• Parametrial regions
• appear dense when involved, and uterosacral involvement may be seen.
• Lymph nodes appear
• enlarged, with most >1 cm on axial dimension considered pathologic.
• The overall accuracy of CT scanning in staging cervical cancer
ranges from 63% to 88%.50,52
• In the detection of lymph node abnormalities, the overall
accuracy of conventional CT scanning is 77% to 85%,
• Sensitivity - 44%
• Specificity - 93%.53

50. MRI
• MRI is frequently used for the
• initial assessment of
• the cervical tumor and
• of extracervical tumor extension
T1W: isointense
T2W:
hyperintense
CE-T1W:
hyperintense
• Advantages
• Superior imaging resolution
• Better soft tissue contrast

51. • MRI was superior to both TRUS and EUA (examination
under anesthesia) in assessing the full extent of bulky
tumors and lymph node enlargement.
• MRI was significantly better than clinical examination or CT
for detecting uterine-body involvement or measuring
tumor size, but no method was accurate at evaluating the
cervical stroma.
• MRI was significantly better at detecting the tumor and
parametrial involvement.
• MRI also increased detection of involved lymph nodes.
• The tumor is less likely to be as visible on MRI for
adenocarcinoma cases, compared to squamous cell cancer.
Perez &Brady,6th edition

52. CT vs MRI$ Sensitivity Specificity Accuracy *
CT MRI CT MRI CT MRI
Parametrial
invasion
55%
[44-66 %]
74%
[68-79 %]
- - 76% 94%
Lymph nodes 43%
[37-57 %]
60%
[52-68 %]
- - 86% 86%
Bladder invasion - - 73%
[52-87 %]
91%
[83-95 %]
- -
Bladder and rectal
invasion
71% 75% - - - -
Stromal invasion - - - - 78% 88%
Staging - - - - 65% 90%
$ Bipat S,et al, Gynecol Oncol. 2003 Oct;91(1):59-66
*Obs&Gyn,1995;86(1):43-5

53. Positron Emission Tomography
• PET scanning is increasingly used in the evaluation of
patients with invasive cervical cancer, using 2-[18F]-fluoro-
2-deoxy-D-glucose (FDG).
• Rose et al.
• observed uptake in 91% of the primary tumors in 32 patients
with locally advanced carcinoma of the cervix.
• Compared with surgical staging, PET scanning has a
• sensitivity of 75% &
• specificity of 92% in detecting para-aortic metastasis.
• PET-CT –
• highly accurate localization of focal radiotracer uptake
• significantly improved diagnostic accuracy when compared with
PET or CT alone.
• The most significant prognostic factor for progression-free
survival was the presence of positive para-aortic lymph nodes on
PET imaging.
Grisby et al, JCO 2001

54. 1.PET has a higher sensitivity than CT and higher specificity than MR in
detecting bone metastases.
2.The most significant prognostic factor for progression-free survival was
the presence of positive para-aortic lymph nodes on PET imaging.
• Maximum standardized uptake value (SUV max) is an
independent predictor of death from cervical cancer and is
associated with persistent disease.
• The SUV of the pelvic node predicts pelvic disease
recurrence.
• Squamous cell carcinoma is more often FDG avid than is
adenocarcinoma.
Perez & Brady,6 th edition

55. FIGO STAGING
• International Federation of Gynecology and
Obstetrics has put forth a staging system that
depends mainly on clinical examination
• It includes– Inspection
Palpation
Colposcopy
Endo cervical curettage
Hysteroscopy
Cystoscopy
Proctoscopy
Intravenous urography
X ray to rule out lung and bone mets

56. STAGING
• Clinical rather than surgical staging
• This allows staging to occur in low resource settings
• Correlation of FIGO to TNM is poor
• Minor changes to 2009 FIGO staging
• Deletion of Stage 0
• Subdivision of Stage IIA
• IIA1: tumor ≤ 4 cm with involv. < 2/3 upper vag
• IIA2: tumor > 4 cm with involv. <2/3 upper vag
• Not included in the FIGO Staging are-
• Lymphangiography
• FNAC or Biopsy of LN
• MRI,CT,PET

57. FIGO Staging

58. Comparing TNM and FIGO
• T X – Primary tumor cant be assessed
• T 0 – No evidence of primary tumor
• T is – Carcinoma in situ(preinvasive ca)
• T 1- T3b are similar
• T 4 /IV A – Tumor invades mucosa of bladder or rectum and/or extends
beyond,true pelvis
• NX-Regional LN cant be assessed
• N0-No regional LN Mets
• N I/IIIB-Regional LN mets
• M0-No distant mets
• M 1/IV B – Distant mets(including peritoneal spread,involvement of
supraclavicular,mediastinal,paraaortic ln,lung,liver,bone)
1.AJCC 2010
2.Leibel & Phillips

59. AJCC 2010 CANCER STAGING OF UTERINE CERVIX
 FIGO no longer includes Stage 0.

60. • All macroscopically visible lesion even with superficial lesion are
staged as IB.
• Patients with hydronephrosis or nonfunction of the kidney ascribed
to extension of the tumor are classified as stage IIIB regardless of
the pelvic findings.
• Other prognostic factors,such as endometrial extension of cervical
carcinoma,stromal invasion,lymphatic/vascular permeation and
involvement of lateral parametrium(as opposed to medial
parametrium) in Stage II B ,are not included in the system.
• Suspected invasion of the bladder or rectum should be confirmed
by biopsy.
• Bullous edema of the bladder and swelling of the mucosa of the
rectum are not accepted as definitive criteria for staging.

61. • A few caveats about clinical staging should be remembered:
• A biopsy, not a cervical cytologic smear, is necessary to establish the
diagnosis.
• The physical examination should include a survey of the skin, careful
palpation of lymph node-bearing areas, speculum examination, and a
bimanual rectovaginal examination.
• Only the procedures and studies allowed by FIGO can be used in clinical
staging.
• Once the stage is determined, it cannot be changed. For instance, a woman
who has clinical stage IB and has a metastatic para-aortic node detected at
the time of radical hysterectomy still has stage IB disease.
• Patients seen after treatment initiation should be listed as having unstaged
cervical carcinoma.
• If cancer remains after therapy has been completed or if invasive cancer is
documented within 6 months of treatment conclusion, the patient still has
the original stage disease, but it is classified as “persistent” in most
institutions.

63. • figure

64. • figure

66. THANK YOU