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Malignant disease of the ovary

Dr. Pamudri M. Basnayake


Introduction
• 2nd most common gynaecological malignancy
• Major cause of death from gynaecological
cancer
• If detected in early stage, had an excellent
prognosis
• Most women present in the advanced stage
• Screening has not been shown to be effective
• Few advances in the development of targeted
treatments for advanced disease
Incidence
• Life time risk in the general population is 1.4% (1
in 70)
• Mean age of presentation 64 years
• Prevalent in higher income nations
• White women have the highest incidence , Asian
women has a lower incidence
• Rare in young women, 3% under 35 yrs
• Large proportion of O/C may originate in the
fallopian tube rather than in the ovarian surface.
• Genetic has an impact
• Women with hereditary cancer present early,
with mean age of 54 years
Classification of ovarian cancer
• Primary cancers; Epithelial (80%), sex cord
stromal, germ cell tumours
• Common site for mets
• Krukenberg tumours are metastasis associated
with primary cancer of the colon, stomach and
breast
Histological classification of ovarian cancers

Histological type Examples


Epithelial ovarian tumours (80%) High grade serous
Endometrioid
Clear cell
Mucinous
Low grade serious (borderline)
Sex cord stromal tumours (10%) Granulosa cell
Sertoli leydig
Gynandroblastoma
Germ cell tumours (10%) Dysgerminoma
Endodermal sinus(egg yolk)
Teratoma
Choriocarcinoma
Mixed
Metastatic (krukenberg)
Epithelial ovarian cancers
• Includes a heterogeneous group of tumours of different
histological subtypes and aetiologies that affect the ovary,
fallopian tube and peritoneum
• Can be benign, malignant or borderline
• 10% are classified as BOTs
• Well differentiated
• Some features of malignancy
• Nuclear pleomorphism, cellular atypia
• Do not invade the basement membrane
• BOTs spread to abdominopelvic structures – peritoneum,
omentum
• Do not often recur after initial surgery
• Majority of BOTs are serious tumours
• Mucinous BOTs may actually arise from appendicaecal
carcinomas of low malignant potential and can be associated
with pseudomyxoma peritoneii
• High grade serious carcinomas account for 75% of all
epithelial ovarian cancers.
• Mucious and endometrioid tumours are less common, (10%)
followed by clear cell carcinomas
• High grade tumours are characterized;
– Concentric rings of calcifications – pasmmoma bodies
• Mucinous carcinomas;
– Large multiloculated tumours
– associated with pseudomyxoma peritoneii
• Endometrioid carcinomas
– similar in histological appearance to endometrial
cancer
– associated with endometriosis in 10% of cases
– Well differentiated
– Better survival than high grade serous carcinomas
• Clear cell carcinomas can also arise from
endometriosis, characterized histologically by
clear cells, much like renal cancer
Aetiology and risk factors
High grade pelvic serous carcinomas
• Present w/ advanced disease
• Involves peritoneal surface, fallopian tube and ovary
• Often impossible to find the anatomical site of origin
• Women with BRCA mutations w/ prophylactic bilateral
salpingo oophorectomy suggest a fallopian tubal
precursor lesion for high grade pelvic serious tumours.
– These are serous tubal intraepithelial carcinoma (STIC)
lesions
• + p53 mutations
• 50% have BRCA mutations
Endometrioid, mucinous, clear cell, borderline and low grade
serious ovarian carcinomas
• Cysts or the ovarian surface epithelium and endometriosis give
rise to these neoplasms
• These are ovarian in origin
• Endometrioid and clear cell cancers are associated with
endometriosis
• KRAS, PTEN,BRAF and ARID1A mutations are involved rather
than TP53
• BRCA mutation carrier status is a risk factor for high grade serious
ovarian cancer
• Most are sporadic and risk relate to reproductive factors and
hormone treatment, contraceptive use, ovulation and pregnancy
• Excess gonadotrophic secretion cause cancer by oestrogen
stimulated epithelial proliferation and malignant transformation
Risk factors of ovarian cancer
Genetic factors in ovarian cancer

• 10-15% predisposition
• BRCA1,BRCA2 and Lynch syndrome have an increased
life time risk of epithelial ovarian cancer
• Most common hereditary cancer is breast ovarian
cancer syndrome (BRCA) – 90%
– Mutation ins BRCA1 (80% ) and BRCA2 in 15 %
• Lynch syndrome is hereditary non polyposis colorectal
cancer
– Associated with endometrial cancer
• There are adenocarcinomas
• Present in later stages with exception of Lynch
syndrome
Preventing ovarian cancer
Screening
• TVUSS and CA125 measurement shows no
improvement in survival in women with
familial predisposition
– BRCA mutation carrier status develop rapidly and
present in later stage before dxed by screen

– Read the ten teachers


Clinical features
• 66% present in stage 3 – difficult dx due to non-
specific symptoms
• Bloating/ inc abdominal girth
• Persistent abd and pelvic pain
• Difficulty eating
• Early satiety
• Change in bowel habit, urinary symptoms, back
ache, irregular bleeding and fatigue
• Palpation of a fixed hard mass arsing from pelvis
• Presence of ascites – most likely of ovarian cancer
• DDX of palpable pelvic mass;
– Non epithelial ovarian cancer
– Tubo ovarian abscess
– Endometriomas
– Fibroids
• 20% of adenexal masses in premenopausal women
are found to be malignant
• 50% of adenexal masses in postmenopausal women
are malignant
• Chest exam for pleural fluid and the neck of groin for
enlarged nodes
Diagnosis and investigations
• TVUSS – initial imaging modality of choice
• Mass ; size, consistency, presence of solid elements,
bilaterality,
• Check for ascites, extraovarian ds, peritoneal
thickening, omental deposits
• Measure tumour markers
• CA125 non specific marker, elevated in over 80% of
epithelial ovarian tumours
• Also elevated in conditions like, pregnancy,
endometriosis, alcoholic liver disease
• Risk of Malignancy Index – RMI triage pelvic masses
into low, intermediate and high risk malignancy
– Based on menopausal state, pelvic USS, CA125 level
• CT / MRI; intermediate and high risk malignancy
– CT; extrapelvic assessment and stagin
– MRI; to assess tissue planes and operability
• Pre-op workup; x ray, ECG,FBC, U&E, LFTs
• + ascites or pleural effusion – paracentesis or
pleural aspiration may be required
– cytology of the aspirate
• If dx is uncertain – primary chemotherapy is
considered; advanced ds – surgery
• Biopsy
– Laparoscopically or US/ct guided biopsy
– Omentum is a good site for biopsy
Management
• Surgery
• Necessary for dx, staging and tx of epithelial
ovarian cancer
• Vertical incision – gain access to all areas of
abdomen
• Ascites or peritoneal washings are sampled
• Total abdominal hysterectomy and BSO
performed along with an omentectomy
• Lymph node resection is important
particularly with stage 1 tumours
• Unilateral salpingo oophorectomy, omentectomy,
peritoneal biopsies and sparing surgery,
peritoneal biopsies and pelvic/para –aortic node
dissection
– For Young patients w/ early stage disease wishing for
conservative fertility sparing surgery
– Endometrial sampling is send to exclude a
synchronous tumour
– Also in borderline tumours
• Primary chemotherapy is offered for patients
unwilling or unfit for surgery
• If responds for chemo, interval surgery carried
out after three cycles
– Reduce postop morbidity, no influence on survival
• Second look surgery – planned laparotomy at
the end of chemotherapy
– No survival benefit
– Not a standard management outside clinical trials
• The role of chemo in stage 1c is uncertain but
postop chemo is offered for all other stages of
epithelial ovarian cancer
Chemotherapy
• Can be given as a primary tx; as an adjunct following surgery or for relapse
of disease
• can be used to prolong clinical remission and survival or for palliation
• First line tx; combination of a platinum with paclitaxel
• Given on out pt basis, 3 weeks apart for six cycles
• Platinum compounds most effective in ovarian cancers
• Arrest cell replication – cross links in DNA
• Carboplatin – main platinum compound used, less renal toxicity causes less
nausea than cisplatin, equally effective , dose calculated according to the
GFR
• Paclitaxol- prevents replication and cell division Steroids given due to high
sensitivity reactions;
– Peripheral neuropathy s/e, neutropenia and myalgia, loss of body hair
• Bevacizumab, monoclonal antibody against vascular endothelial growth
factor, inhibits angiogenesis
– Improve recurrences
– s/e; HN, delayed wound healing, GI perforation arterial thromboembolic events
– Not a first line tx for primary tumour due to cost but used for recurrences
• Following chemotherapy; CT scan to assess
response to tx
• Follow up; clx examination CA125 measurement
• Treating isolated rising CA125 levels does not
improve survival
• When recurs treatment is largely palliative
• If the duration of remission is more than 6
months, carboplatin may be used or taxol,
topotecan or liposomal doxyrubicin can be given
Read prognosis in the book
Primary peritoneal carcinoma
• High grade pelvic serious carcinoma
• Histologically indistinct from tumours arising
from the Fallopian tube or ovary
• Criteria for dx;
– Normal sized or slightly bulky ovaries
– More extra- ovarian disease than ovarian disease
– Low volume peritoneal disease
• Clx behaviour, prognosis and tx is same as for
other high grade pelvic serous carcinomas
• Primary chemotherapy is used as surgical
debulking is difficult
Sex cord stromal tumours
• 10% of ovarian tumours ; 90% of all functional tumours
• Low malignant potential w/ a good long term prognosis
• Some morbidity + from oestrogen and androgen
producing tumours
– Oestrogen producing; granulosa, theca, sertoli
– Androgen producing; sertoli-Leydig or steroid cell
• Results; precocious puberty, abnormal menstrual
bleeding, increased risk of endometrial cancer
• Peak incidence ; age of menopause
• Juvenile granulosa cell tumour; most common subtype;
girls <10 years age, causes precocious puberty
• Granulosa cell tumours – most common subtype, 70%
of sex cord stromal tumours
Clinical features;
• Irregular menstruation
• Postmenopausal bleeding
• Precocious puberty
• Most - unilateral ovarian masses; upto 15cm
• Solid with areas of haemorrhage, cut surface be yellow due
to high level of steroid production
• Granulosa cell tumours – large pelvic mass or with pain due
to torsion/ haemorrhage
• Granulosa cell tumours produce inhibin, used for follow up
surveillance, levels rise prior to clx detection of recurrence
• Sertoli- leydig cell – androgen in over 50%
– + pelvic mass and signs of virilisation
– Amenorrhoea, deep voice, hirsutism
– Occasionally produce oestrogen and rarely renin causing
hypertension
• Tx;
• Based on age and wish to preserve fertility
• Young pt; unilateral salpino-oophorectomy,
endometrial sampling and staging sufficient
• Older group full surgical staging is
recommended
• Granulosa cell tumour can recur many years
after initial presentation
• Long term follow up required
• Surgery – mainstay of tx
• No effective chemotherapy regime
Germ cell tumours
• Mainly in young women
• 10% of ovarian tumours
• Derived from primordial germ cells w/in the ovary ; contains any cell type
• Mx mainly fertility preserving surgery and chemotherapy
• Most common Sx; pelvic mass
• 10% w/ torsion or haemorrhage
• Some present during pregnancy
• 70% are stage 1
• Spread by lymphatics or blood borne
• Dysgerminonmas – 50% of all cell tumours
– Bilateral in 20% of cases and occasionally secrete hCG
• Endodermal sinus yolk sac tumours – 2nd most common germ cell tumour;
15%
– Rarely bilateral, secrete AFP
– Large solid mass – causes acute sx w/ torsion or tupture
– Spread of endometrial sinus tumours is a late event and is usually to the lungs
• Immature teratomas – 15-20% of malignant germ
cell tumours and 1% from all teratomas
• Classified; mature and immature – grading of
neural tissue present
• 1/3 secrete AFP
• Occasional malignant transformation in a mature
teratoma; most common cell type to transform –
epithelium; usually squamous cell carcinoma
• Non-gestational choriocarcinomas are very rare
– Usually presents in young girls
– Irregular bleeding and very high levels of hCG
Clinical features
• Young woman with lard solid ovarian mass
that is rapidly growing
• Tumour markers elevated .....??
• MRI – check morphology
• CT – abdomen, assess liver and lymph nodes
• CXR – exclude pulmonary metastasis
Tx;
• Fertility sparing tx preferred
• Exploratory laparotomy is performed to remove the
tumour and assess contra-lateral spread to other ovary
• If + cyst – remove
• Inspection of the abdominal cavity is required w/
peritoneal biopsies and sampling of any enlarged pelvic
or para –aortic nodes formed
• Post op chemo depend on the stage
• Stage 1 dysgeminomas and low grade teratomas are
treated by surgery alone
• For the remainder – chemo
• Combination of bleomycin, etopodise and cisplatin -3
to 4 tx, 3 weeks apart