Cancer cervix

Bimodal distribution

1st peak in 3-4 decade, more common here

2nd peak in 6-7 decade

Most common Ca in Indian women

Most common histology

Squamous cell Ca, 70%

Adenocarcinoma, 30%

Risk factors:

Early age at first intercourse

Early age at first child birth

Multiparity

Multiple sexual partners

Low socio economic status

Presence of STD's

Presence of pr invasive lesions

Controversial risk factors

OCP's increase the risk but only after 5 years of use

They are more related to adenocarcinoma

Cigarette smoking: only for squamous cell Ca

No relation to early menarche and late menopause

Family history has no relation

Causative agent

HPV

DNA virus

High risk: 16,18,31,33,35,45,52,58

Low risk: 6,11

Type 16,18 account for 70%

More sensitive is 16, squamous Ca and 18 is more specific,

adenocarcinoma

What type of cells are infected by HPV

Basal epithelial cells aka basal stem cells

What viral proteins are responsible for malignant transformation

E6,7

For DNS replication: E1,2

Characteristic Histopathological finding

Koilocytosis, perinuclear halo due to cytoplasmic clearing

6,11 cause condylomata accuminata

Juvenile papillomatosis in the baby

HPV vaccines

Inactivated capsid proteins

Are mandatory/ should be given to HIV positive women

Annual screening in HIV positive women

CI in pregnancy

HPV vaccine protects only against 16,18 as others may be present

so the screening should continue after vaccination

Ideal age is 11-12 years of age

But can be given anytime between 9-26 years

Penile, anal, oral other than cervical, vaginal and vulval cancers

Thus given to boys as well

Gardasil: 16,18,6,11

Can be given to boys also

0,2 and 6 months

Cervirix

More ecacious than gardasil

16,18

0,1 and 6 months

No booster required for both

Both given IM

Protection rate is 70% as 16,18 cause 70% Ca

Most common side eect is the pain at the site of injection

Other is Syncopal attack, thus should be accompanied and

observation time of 15 min

One liners

Most common or the first presenting complaint: irregular vaginal

bleeding

Most specific complaint: post coital bleeding

Most common route of spread: lymphatic spread

Q. Pt with h/o post coital bleeding, next step is PAPS

Q. H/o post coital bleeding, 3x4 cm mass on anterior lip of cervix:

do a punch biopsy

Most common cause of death: uremia secondary to renal failure

Most common LN is obturator LN

Sentinel lymph nodes are para cervical

Risk of involvement of ovaries in Ca cervix: <1%

Thus ovaries are spared during Sx

Staging of cervical Ca

This is a clinical staging

Done by the gynecologist

Certain investigations can not be used to change the staging:

USG, CT, MRI, PET

The only thing for which CT is approved is to look for hydroureter

All kind of scopies are allowed

Cystoscopy, hysteroscopy, colposcopy etc

Stage 1
A: microscopic
B: macroscopic

A1: <3 mm in depth and <7 in horizontal spread

A2:<3-5 and <7
B1:<4
B2:>4

??

Stage 2
Upper 2/3 of vagina involved

A: without parametrium

B: with parametrium

A1:<4

A2>4

Parametrium is connective tissue surrounding the cervix

Stage 3
Lower 1/3 vagina involved

A: not reaching the lateral pelvic wall

B: reaching the lateral pelvic wall with or without lower 1/3 vagina
involvement

Clues indicating lateral pelvic wall reached

Presence of hydroureter or hydronephrosis

Lower limb edema

Pain radiating down the leg

Stage 4
A: involvement of bladder and rectum

B: distant metastasis

Bullous edema of bladder mucosa indicates lymphatics are

involved, it does not change the stage

Inguinal LN are considered distant metastasis for cervical Ca

Treatment

Upto stage 2A, primary modality of treatment is surgery

>=2B, primary modality is chemo radiation

Stage 1A1: 3 options

Hysterectomy

Therapeutic Conization

Radical trachelectomy

If family is complete, hysterectomy done ka type 1 hysterectomy

aka Simple extra fascial hysterectomy

If child bearing is desired aka fertility preserving surgeries

Conization

Radical trachelectomy

Look for lymphvascular space invasion LVSI

If absent, conization

If present, radical trachelectomy

Radical trachelectomy

Fertility preserving surgery

Can be done in stage 1A1, 1A2, 1B1 if size less than 2 cm

Structures removed: cervix, parametrium, pelvic LN, small part of

vagina

Cerclage between uterus and vagina

Delivery done by CS

Stage 1A2
Werthiem's hysterectomy aka type 2 hysterectomy aka modified
radical hysterectomy

Along with this pelvic lymph adenectomy also done

Stage 1B1, 1B2, 2A

Surgery done is Meig's hysterectomy aka type 3 hysterectomy aka

radical hysterectomy

Pelvic lymph adenectomy also done

And

Para aortic LN sampling

Inoperable stages

>= 2B
Primary modality is chemo radiation

Both chemo and RT are given together

Chemotherapy:

Cisplatin aka radiation sensitizer

Can be also used

5 FU

Radiotherapy

Initially divided into

External beam RT or brachytherapy which means intracavitary RT

If both have to be given

EBRT followed by brachytherapy

EBRT can be either given to only pelvis

Or pelvis and abdomen: extended field RT

Indication is positive para aortic LN

Pelvis EBRT

25 fractions over 5 weeks

Each fraction has a dose of 1.8-2 gy

Thus total dose is 40-50 gy

Abdomen EBRT

25 fractions over 5 weeks

Dose is 1-1.2 gy per fraction

Thus total is 25-30 gy

Radio isotope used is Caesium Cs

Brachytherapy

Given two 2 points A and B

Location of point A

Two cm lateral tottering canal, corresponds to para cervical LN and

to ureter

Radiation dose at A is 8000 centigy

Point B

3 cm lateral to point A and 3 cm above external Os

Thus 5 cm from uterine canal

Corresponds to obturator LN

Dose is 6000 centigy

American brachytherapy society criteria

Point A divided into early and advanced stage

Early: 80-85 gy

Advanced:85-90 gy

Point B or lateral pelvic wall

Early:50-55 gy

Advanced:55-60 gy

Radio isotopes for brachytherapy

Low dose therapy: Caesium

High dose therapy: Iridium

Boundaries of pelvis

Upper border: disc space between L4-5 vertebra

Lateral border: 2 cm lateral to bony canal

Inferior border: lower margin of obturator foramen

When Abdomen radiated

Only the upper border changes

Disc space between T12-L1

Pelvic lymphadenectomy

Internal iliac

External iliac

Obturator

Pre sacral

Common iliac

Indications for post operative RT( Adjuvant)

Indications
Positive LN

Involvement of parametria

Positive margins

Recurrent cervical Cancer

Treatment depends on the primary modality

If first Sx was done, give RT

If primary modality was radiation, surgery can be done

Total pelvic exenteration

Dierence between type 2 and type 3 hysterectomy

Type 2

Medial half of parametrium is removed

Uterosacral and Mackenrodt ligaments are cut midway

Uterine artery is ligated after it gives the uretric branch

<1 cm of vagina is removed

Type 3

All the parametrium is removed

Uterosacral and Mackerodt are cut at their insertion

Uterine artery is ligated at its origin from the internal iliac

More than 2 cm vagina is removed

TAH
Total abdominal hysterectomy

Uterus and cervix are removed

If only uterus is removed: subtotal hysterectomy

TAH+ BSO: pan hysterectomy

Ovarian Cancer

No universal screening

Uncommon

No specific sign and symptoms

Adenexal mass

If benign or malignant

Benign

Seen in reproductive age group

Usually unilateral

History of pain

Cystic consistency on examination

Malignant

Seen in extremes of age

Bilateral

Usually no pain

Variable consistency

USG

High risk features suggestive of malignancy

Solid component

Thick septae (2-3 mm)

Presence of papillary projections

Ascites

Enlarged LN and matted bowel loops

Doppler

Increased vascularity is high risk

Resistive index

Pulsatility index

Both are low and suggest high vascularity

Indications for Sx Mx of masses

Any high risk feature on USG

Raised CA-125 in a post menopausal woman

Normal value is <35 IU

Ovarian mass >7 cm suggestive of malignancy

Adenexal mass >10 cm

Any mass that presents with acute abdomen: torsion and rupture

When the diagnosis is not confirmed

Pregnancy: except for CA-125 as physiologically rises

Rapid enlarging mass also requires Sx intervention

Ovarian mass in reproductive age women

Management depends on size of mass

3-5 cm: wait and watch

5-7 cm: serial USG at 6 weeks interval

CA-125 is not done as first line investigation in reproductive age

group because there are many benign and malignant conditions
when it is raised

Benign:

Menses

Pregnancy

PID

Endometriosis

Genital TB

Fibroid uterus

Any abdominal itis

Malignant conditions

Breast Ca

Colon Ca

Lung Ca

Pancreatic Ca

Ovarian Ca

Endometrial Ca

Important investigation in post menopausal women

OCP's are not routinely to be given for ovarian masses

As they do not aect the current mass but prevent future masses

Ovarian Cancer

Risk factors

Two pathophysiologies

More the number of ovulatory cycles, more the risk

Increased estrogen content

1. Early menarche

2. Late menopause

3. Nulliparous

4. Obesity

5. Polycystic ovarian syndrome

6. HRT

7. BRCA 1-2 and HNPCC

8. Smoking: risk factor for Mucinous cancers

Protective factors

Multi parity

Breast feeding

Use of OCP's

Salpingectomy, tubal ligation and hysterectomy: prevent ascending

mitogens

Most common type are

Epithelial ovarian Ca
90-95% of all ovarian Ca

Most commonly BL

Serous cystadenocarcinoma, 70%

Mucinous, 10%

Endometroid, 10%

Clear cell

Brenners

Mostly present in post menopausal age group, 6-7th decade

Vague abdominal symptoms

N/V, altered bowel habits, gastritis, Ascites, anorexia

Present in late stages

Highest mortality rate amongst gynecological malignancies

Most are sporadic

Mucinous have some characteristics

Remain confined to ovaries for a long time

Can attain large sizes upto 20 cms

CA-125 levels is not much raised

Asso with pseudomyxoma peritoneii

What % of epithelial Ca are familial: only 10%

Seen in women carrying mutations in BRCA 1-2 and HNPCC

With BRCA 1:35-45%

BRCA 2:25%

HNPCC:15%

Familial occur a decade earlier

Peak in 4-5th decade

Risk increases after 35 years of age every year

Thus screening done in ???

Screening done annually

CA-125 and TVS

Started at 35 years of age

Prophylactic BL BSO done ideally at 35 years of age of as soon as

family is complete

Second line agents for prevention if Sx declined

OCP's

But breast Ca and Peritoneal Carcinomatosis can still occur after

BSO

By what % is breast Ca reduced by prophylactic BSO:50%

Borderline epithelial

Also show epithelial hyperplasia, mitotic figures, abnormal shapes

and size

But do not show stromal invasion

Also occur a decade earlier

They metastatize late

Remain confined to ovary for a long time, thus late spread

Prognosis is better

It's a Histopathological diagnosis

Managed by Conservative Sx

Germ cell tumors of the ovary

Account for 5% of ovarian tumors

Dysgerminoma

Mature teratoma

Immature teratoma

Embryonal cell Ca

Endodermal sinus tumor/ yolk cell tumor

Choriocarcinoma

Mixed

Tend to be unilateral

Peak is between 10-30, usually 10-20 years of age

Vague abdominal complaints

Acute abdomen

Precocious puberty

Thus diagnosed early

Tumor markers

Alpha feto protein

HCG

They metastasize late

Managed by conservative Sx

Sex cord tumors

Least common

Granulosa cell tumors

Theca cell tumors

Fibroma- thecoma group

Sertoli leydig tumors

Sertoli tumors

Can be seen at any age but most common is peri menopausal

Vague abdominal complaints

Along with

Abnormal uterine bleeding, if producing estrogen

Virilization, if producing testosterone

No asso to the BRCA genes

Metastasis is rare

Risk of second malignancy: endometrial cancers

One liners

Specific cell types:

1. Signet ring cells: Krukenberg's tumor

It is a metastasis to ovary

Most common primary is stomach Ca

Always BL

Shape of ovary is always maintained

2. Psamomma bodies: serous Ca

3. Call Exner: granulosa cell

4. Wallthard cell: brenners

5. Reinke's crystal: leydig/ Hilus

6. Schiller Duvall: EST

7. Rokitansky protuberance: dermoid

Tumor markers

Serous cystadenoma : cA125

HE4 , human Epididymal protein 4

LDH : dysgerminoma,

It also secretes HCG, placental alkaline phosphatase

Embryonal cell Ca: HCG, AFP

Endodermal sinus: AFP, LDH

ChorioCa: HCG

Mucinous adenocarcinoma : CEA

Granulosa cell tumor: inhibin

Dermoid and fibroma don't release any tumor marker

Most common ovarian Ca: serous cystadenocarcinoma

Most common ovarian tumor: serous cystadenoma

Most common ovarian tumor in pregnancy: dermoid

Most common ovarian Ca in pregnancy: dysgerminoma

Radiosensitive: dysgerminoma, it is moderately radio sensitive

Which germ cell tumor is BL: dysgerminoma

Risk of BL is 10-15% as high as 20%

Risk of BL in dermoid is upto 10%

Dermoid is always benign

Risk of malignancy is 0.2-2%

If it occurs, it is squamous cell Ca

Most rapidly growing tumor: endodermal sinus tumor

Which germ cell tumor has best prognosis: dysgerminoma

Worst prognosis: endodermal sinus tumor

It presents as acute abdomen as rapidly growing

Which tumor involves opposite ovary by metastasis: granulosa cell

tumor

Dysgerminoma frequently occurs with another tumor,

Gonadoblastoma

Which tumor has highest risk of torsion: dermoid

Meig's syndrome

Ovarian Fibroma, Ascites, pleural eusion( more common on the rt

side)

Pseudo Meig's : any other tumor other than fibroma with same
other findings

Male counterpart of dysgerminoma: seminoma

Staging

It's a surgical staging

Stage 1
A: unilateral ovary involved

B: bilateral ovary involved

C: a or B with any of the following

Tumor in the surface

Ruptured capsule

Malignant Ascites

Stage 2
A: involvement of uterus and FT

B: any other structure in pelvis

C: any of the following with A and B

Tumor in the surface

Ruptured capsule

Malignant Ascites

Stage 3
A: microscopic peritoneal deposits

B: macroscopic, but less than 2 cm

C1: macroscopic but more than 2 cms

C2: any positive LN, can be pelvic, para aortic, inguinal

Stage 4

Distant metastasis or tumor in the liver parenchyma

Stage 3 and 4 are called Advanced stage disease