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MALIGNANT OVARIAN TUMOURS

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Title: MALIGNANT OVARIAN TUMOURS


1
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2
  • MALIGNANT OVARIAN TUMOURS
  • Prof.Osman Donia

3
  • Malignant epithelial tumours
  • Serous adenocarcinoma
  • Mucinous adenocarcinoma
  • Endometrioid adenocarcinoma
  • undifferentiated adenocarcinoma
  • Malignant germ cell tumours
  • Dysgerminoma
  • Endodermal sinus tumour
  • Choriocarcinoma
  • Solid teratoma
  • Malignant sex cord stromal tumours
  • Granulosa cell tumour
  • Sertoli-Leydig cell tumour  

4
  • I. EPITHELIAL OVARIAN CANCER

5
  • Incidence
  • Primary ovarian epithelial cancer forms 60-70 of
    all ovarian tumours.
  • 90 of all ovarian malignancies.
  • It is the third common malignancy of female
    genital organs.

6
  • Aetiology
  • Possible factors include
  • Reproductive factor
  • Nulliparous or infertile women are more liable
    to develop it.
  • 2. Hereditary 'Genetic' factor
  • 5- 10 of epithelial ovarian cancer occur in
    women with hereditary predisposition.
  • A particular feature of familial cancer is that
    it tends to occur at a younger age.
  • Hereditary predisposition is due to a defective
    gene in their families, which is tumour
    suppression gene BRCA, BRCA2 .i.e. gene mutation.

7
  • Three types of familial ovarian cancer are
    identified
  • Site specific ovarian cancer syndrome (15)
  • Hereditary breast / ovarian cancer syndrome (75)
  • Hereditary non polyposis colorectal cancer
    syndrome with endometrial, breast, or ovarian
    cancer (10).

8
  • Risk factors for epithelial cancer
  • Age
  • Nulliparity infertility
  • White race
  • Prior history of endometrial or breast cancer
  • Family history of ovarian cancer

9
  • PATHOLOGY OF PRIMARY EPITHELIAL OVARIAN CANCER
  • Macroscopic appearance
  • Usually solid but may be partially cystic
    partially solid.
  • Unilateral or bilateral
  • The size is extremely variable
  • The substance of the tumour is the seat of
    extensive haemorrhage and necrosis.

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  • Microscopic picture It is an Adenocarcinoma
  • Which might be either
  • Serous cystadenocarcinoma
  • Mucinous cystadenocarcinoma.
  • Endometrioid cystadenocarcinoma.
  • Which could be either
  • a. Well differentiated (Gr I)
  • b. Moderately differentiated (Gr II)
  • c. Undifferentiated (Gr III)
  • N.B. Border line epithelial tumours

12
  • MALIGNANT GERM CELL TUMOURS

13
  • The incidence of germ cell tumours is only 20-30
    of all ovarian tumours.
  • Five per cent of germ cell tumours are malignant.

14
  • Classification of malignant germ cell tumours
  • Dysgerminoma
  • Endodermal sinus tumour (yolk sac tumour)
  • Choriocarcinoma
  • Malignant teratoma
  • Benign cystic teratoma with malignant
    transformation
  • Malignant solid teratoma

15
  • Special Features of Germ Cell Tumours
  • They differ from epithelial ovarian cancer by the
    following points
  • Lower age incidence
  • The commonest tumours of abnormal gonads and in
    sex chromatin negative females.
  • tend to grow rapidly resulting in pelvic pain and
    pressure symptoms occurring early tend to grow
    rapidly resulting in pelvic pain and pressure
    symptoms occurring early.

16
  • Most tumours produce substances in the
    circulation that can be used as tumour markers
  • Dysgerminoma alkaline phosphatase lactic acid
    dehydrogenase.
  • Endodermal sinus tumour alpha feto proteins.
  • Choriocarcinoma hCG
  • Radiosensitive, chemotherapy in some of them
    gives excellent results in stage Ia.
  • Conservative surgery in the form of
    salpingoopherectomy is the first line of
    treatment.

17
  • Dysgerminoma
  • The commonest malignant germ cell tumour
    accounting for about 30-40 of all malignant germ
    cell tumours.
  • Represents 1-3 of all ovarian tumours.
  • Tends to occur at a younger age (10-20 years).
  • May secrete alkaline phosphatase and lactic acid
    dehydrogenase.

18
  • Pathology
  • Solid ovarian tumour, usually of small or
    moderate size
  • Bilateral in only 10 of cases.
  • Greyish with lobulated surface with tendency to
    haemorrhage and necrosis.

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  • Microscopically
  • Consists of gem cells arranged in alveoli or
    nests separated by fibrous tissue septa heavily
    infiltrated with lymphocytes.
  • Cells are round, large, with abundant cytoplasm
    and a large irregular nucleus.
  • Treatment
  • Surgery
  • Unilateral salpingoophorectomy,
  • TAHBSO
  • Radiotherapy

21
  • B) Endodermal Sinus Tumour EST
  • Prevalent in a young age (median age of 16-18
    years).
  • Most EST secrete alpha-fetoproteins that are used
    as a tumour marker.
  • Pathology
  • Small solid tumours which are almost always
    unilateral.

22
  • Microscopically
  • EST have a characteristic microscopic picture
    Shiller-Duval bodies. These are cystic spaces in
    which projects a glomerulous-like structure with
    a central vascular core.
  • Treatment
  • Surgery
  • unilateral salpingoophorectomy
  • TAHBSO
  • Chemotherapy the tumour is chemosensitive

23
  • MALIGNANT SEX-CORD STROMAL TUMOURS

24
  • Sex-cord stromal tumours may arise from non-
    functioning or functioning stroma of the ovary.
  • Functioning sexcord tumours may be
  • Estrogenic as granulosa cell tumour.
  • Androgenic as Sertoli-leydig cell tumours
  • Both estrogenic and androgenic effect (very
    rare) as in Gynandroblastoma.
  • Non- functioning stroma may very rarely give rise
    to fibrosarcoma of the ovary.

25
  • A) Granulosa Cell Tumours
  • Usually unilateral, solid, yellow or yellow-grey
    in colour.
  • Some are functioning secreting oestrogen, while
    most appear to secrete inhibin.
  • Associated with endometrial carcinoma in 5-10 of
    cases, and with endometrial hyperplasia in 25-50
    of cases.
  • They may cause irregular bleeding or precocious
    puberty (before puberty), menstrual
    irregularities or post menopausal bleeding.

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  • Microscopically
  • The tumour is formed of granulosa cells arranged
    in different patterns. Call-Exner bodies are
    pathognomonic, but are present in only 50 of
    cases. These are cystic spaces surrounded by
    granulosa cells arranged in a rosette-like shape.
  • Treatment
  • Unilateral salpingoophorectmy
  • TAH BSO
  • No place for irradiation or chemotherapy

28
  • B) Sertoli-Leydig Cell Tumours
  • They are very rare representing lt 0.2 of all
    ovarian tumours.
  • They are usually small, unilateral, solid
    tumours, of low grade malignancy.
  • Many are functioning producing androgens.
  • Treatment Either unilateral salpingoopherectmy
    if the patient is young or TAHBSO.

29
PATTERNS OF SPREAD OF OVARIAN CANCER
  • Primary methods of spread of ovarian cancer are
  • Direct extension
  • Lymphatic spread
  • Transcoelomic spread
  • Haematogenous spread

30
Metastatic Ovarian Cancer
  • Metastatic ovarian cancer forms about 5-6 of all
    ovarian tumours. The primary may be
  • Genital tumours From the endometrium, cervix,
    tube, and contralateral ovary.
  • Extragenital tumours From the stomach, colon,
    breast, biliary tract, and thyroid gland.

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Krukenberg Tumour
  • It accounts of 30-40 of metastatic cancer to the
    ovary.
  • The primary is usually in the pylorus, less
    commonly in colon, breast or biliary tract.
  • They are bilateral solid ovarian tumour retaining
    the shape of the ovary.
  • The main interest is in its histogenesis, the
    most acceptable theory is that malignant cells
    reached both ovaries by retrograde lymphatic
    spread.

33
  • Prognosis
  • Bad, most patients die within one year because
    most of the lesions are not discovered until the
    primary disease is advanced.

34
CLINICAL PICTURE OF PRIMARY MALIGNANT OVARIAN
TUMOURS
  • This is a disease of late decade of life 5565
    years of age in the majority of cases.
  • It is more common in industrial countries.
  • SYMPTOMS
  • Early stage disease are mostly asymptomatic.
  • may be associated with non specific GIT symptoms
    in the form of dyspepsia, indigestion, and
    anorexia. Pressure symptoms as urinary frequency,
    and constipation may be present, with or without
    pelvic pain.

35
  • Late stage disease may present with
  • Abdominal pain and cachexia, abdominal swelling.
  • Abnormal uterine bleeding, and especially
    postmemnopausal bleeding.
  • Rarely ascites may be the first clinical
    presentation.

36
  • PHYSICAL SIGNS
  • The most important physical sign is the palpation
    of a pelvic mass.
  • If the patient is lucky this pelvic mass is
    discovered during routine pelvic examination.
  • In late cases a pelviabdominal fixed solid mass
    is felt.
  • Bilateral solid fixed masses are always
    suspicious of malignant ovarian tumour.

37
CLINICAL FEATURES SUGGESTING MALIGNANCY INOVARIAN
TUMOURS
  • A) History
  • Age, especially extremes of age (before puberty,
    or gt 40-60 years).
  • Rapid growth of the tumour.
  • Pain and loss of weight are always late symptoms.
  • Post menopausal bleeding and symptoms of
    virilisation, are suspicious.

38
  • B) General examination
  • Malignant Cachexia (with marked and rapid weight
    loss and dehydration)
  • Palpable supraclavicular lymph nodes especially
    on the left side, (Virchows glands).
  • Pleural effusion, however it may be present in
    Meigs syndrome.
  • Associated breast mass, on breast examination
  • Unilateral leg edema (unilateral pressure by
    tumour with venous and lymphatic obstruction).

39
  • C) Abdominal Examination
  • Inspection Abdominal enlargement, over lying
    skin showing peau dorange.
  • Palpation Tumour which is solid (or partially
    solid), fixed especially if bilateral.
  • Percussion Presence of ascites (except with
    ovarian fibroma in Meigs syndrome).

40
  • D) Pelvic examination
  • Nodules in Douglas pouch in the presence of a non
    tender adnexal mass.
  • Bilateral, especially if solid adnexal masses are
    very presumptive.
  • Fixed pelvic masses especially if amalgamated
    with pelvic organs (frozen pelvis).

41
  • At Laparotomy
  • Ascites, especially if altered blood stained
    ascites.
  • Bilaterality, fixation, and invasion of the
    capsule.
  • Extracystic papillae, and adhesions to
    surrounding structures.
  • Peritoneal nodules or secondary deposits in
    omentum, intestine or liver
  • Variable consistency with a cut section of the
    tumour shows haemorrhage and necrosis.

42
SPECIAL INVESTIGATIONS FOR OVARIAN CANCER
  • Pelvic ultrasound
  • Endometrial curettage
  • Chest X-Ray
  • Plain X-Ray abdomen
  • Barium meal and/or enema
  • Upper and/or lower G.I. Endoscopy
  • I.V.P.
  • Paracentesis.
  • CT MRI.

43
  • Tumour markers
  • CA 125 (n lt 35 u/ml)
  • This the most important marker used.
  • However it may be elevated in some benign
    conditions as endometriosis and chocolate cysts.
  • It can be used also to monitor response to
    chemotherapy (decreasing levels denote good
    response).
  • Other markers include serum B-hCG
    (choriocarcinoma), alpha fetoprotein (EST), serum
    alkaline phosphatase, and lactic acid
    dehydrogenase (dysgerminoma).

44
  • SCREENING for Ovarian Cancer
  • Routine yearly pelvic examination in
    premenopausal and postmenopausal women.
  • Periodic TVS coupled with a serum CA-125 in those
    with an enlarged ovary

45
DIFFERENTIAL DIAGNOSIS of ovarian masses
  • Pelvic masses as
  • adnexal masses.
  • uterine enlargement (myomata pregnancy).
  • colonic masses.
  • retroperitoneal masses (pelvic kidney,
    retroperitoneal sarcoma, ...)
  • Abdominal masses as
  • liver or pancreatic tumour.
  • tense ascites.

46
  • EXPLORATORY LAPAROTOMY IN OVARIAN CANCER
  • The final diagnosis of ovarian cancer can only
    be made at exploratory laparotomy, which will
    serve not only for diagnosis but also for
    surgical staging and primary surgical treatment.

47
STAGING OF OVARIAN CANCER
  • Clinical staging
  • For a malignant ovarian tumour will always
  • be short of important items that will affect
  • the prognosis and line of treatment, surgical
  • staging is therefore the only standard
  • method.

48
Surgical staging of primary ovarian cancer
  • entails a mid line subumbilical suprapubic
  • exploratory laparotomy in which the following is
  • performed
  • Exploration of the pelvic and peritoneal cavity
  • Aspiration of any fluid in cul de sac (ascites),
    or perform peritoneal washings for Cytology.
  • Performing an infracolic omentectomy.
  • Pelvic and paraaortic lymph node sampling
  • Resection of any visible enlarged nodules or
    masses.

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  • The complete procedure will then be a TAH BSO (or
    debulking of the malignant tumour), omentectomy,
    lymph node sampling or resection, removal of any
    pelvic or extrapelvic tumour masses gt2.0 cm, and
    cytology to peritoneal fluid.

51
FIGO surgical staging for primary epithelial
ovarian carcinoma
Stage FIGO definition (simplified)
Stage I Growth limited to ovaries
Ia Growth limited to one ovary No ascites No tumour on external surfaces capsule intact
Ib Growth limited to both ovaries No ascites no tumour on external surfaces capsule intact
52
FIGO surgical staging for primary epithelial
ovarian carcinoma (ctd)
Ic


Stages Ia, or Ib with tumour on surface of one or both ovaries, capsule ruptured, or presence of ascites containing malignant cells or ve peritoneal washings
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FIGO surgical staging for primary epithelial
ovarian carcinoma (ctd)
Stage II Growth involving one or both ovaries with pelvic extension to
IIa uterus and tubes
IIb other pelvic tissues
IIc stages IIa, or IIb with tumour on surface of one or both ovaries, capsule ruptured, or presence of ascites containing malignant cells or ve peritoneal washings
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FIGO surgical staging for primary epithelial
ovarian carcinoma (ctd)
Stage III  Growth involving one or both ovaries with peritoneal implants outside the pelvis or positive retroperitoneal or inguinal nodes
IIIa tumour grossly limited to the true pelvis with ve nodes
IIIb tumour with implants lt 2.0 cm on abdominal peritoneal surface. Nodes are -ve
IIIc tumour with implants gt 2.0 cm or Nodes are ve N.B. superficial liver metastases is included in stage III c.
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FIGO surgical staging for primary epithelial
ovarian carcinoma (ctd)
Stage IV Growth involving one or both ovaries with distant metastases.
If pleural effusion is present there must be ve cytology to allot a case to stage IV. Parenchymal liver metastasis equals stage IV.
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SURGICAL TREATMENT OF OVARIAN CANCER
  • A) Early stage Ovarian Cancer
  • TAH BSO and infracolic omentectomy is the
    standard treatment for patients with disease
    limited to the ovary (no gross evidence for
    extension beyond the ovaries Stage I-IIa).
    Surgical staging is completed via peritoneal
    wash, and lymph node sampling, for microscopic
    assessment of the extent of the disease.

61
  • Occasionally, unilateral salpingo-oophorectomy
    may be done in selected cases of stage Ia disease
    (tumour confined to one ovary, with capsule
    intact, and ve peritoneal cytology), only when
    the patient is young and fertility is desired.
    Such conditions are mostly met with in some early
    epithelial tumours (border line tumours), but
    more commonly with malignant germ cell tumours
    (dysgerminoma and EST), and malignant sex cord
    stromal tumours (granulosa and Sertoli Leydig
    cell tumours).

62
  • B) Advanced stage Ovarian Cancer
  • Primary Cytoreductive surgery (initial Debulking)
  • Interval Debulking
  • Radical oophorectomy

63
  • Second-look Surgery in ovarian cancer
  • Second look laparotomy or laparoscopy, have been
    advocated to asses residual tumour within the
    abdominal cavity after primary surgery and
    chemotherapy, to decide on further adjuvant
    therapy needed.
  • Nowadays modern imaging technique, as spiral CT
    MRI, together with serum CA125 tests have
    largely nullified the need for second look
    surgery. At the present state its only place is
    when a tumour marker is rising apart from
    negative imaging for tumour residues.

64
CHEMOTHERAPY IN OVARIAN CANCER
  • Chemotherapy whether single or multiple agents
  • has a major role in the management of ovarian
  • cancer especially in advanced disease, and mostly
  • with epithelial ovarian cancer
  • Early stage disease It has a limited place only
    with poor prognostic factors as Poorly
    differentiated tumours, ruptured capsule, or ve
    peritoneal wash (even in stage I cases).

65
  • Advanced stage disease Chemotherapy is indicated
    in all cases of stage II-IV disease.
  • All cases after primary cytoreductive debulking
    surgery
  • Palliative therapy in patients with irresectable
    tumours, or patients with recurrent disease.

66
  • Types of chemotherapy used
  • Chemotherapy is usually recommended as soon as
    possible after surgery, and is given for five or
    six cycles at 3-4 weekly intervals.
  • The most frequently used chemotherapeutic agents
    include Cisplatin or Carboplatin alone or in
    combination with Paclitaxel (Taxol).

67
  • Toxicity from chemotherapy
  • Chemotherapeutic agents are highly toxic at
    therapeutic doses, and therefore need close
    monitoring during treatment cycles. Toxicity
    includes nausea, vomiting, myalgia and
    arthralgia. In severe cases renal damage,
    peripheral neuropathy, hearing loss, dehydration
    and electrolyte imbalance may occur.

68
RADIATION THERAPY IN OVARIAN CANCER
  • Radiation therapy has little place in epithelial
  • ovarian cancer. It may be used as an
  • adjuvant therapy following cytoreductive
  • surgery in patients who refuse or are not
  • good candidate for chemotherapy. Two main forms
    are used
  • Intraperitoneal radioactive colloids
  • Whole external beam abdominal radiation.

69
PROGNOSIS IN OVARIAN CANCER
  • The prognosis depends upon
  • Histopathological type of ovarian cancer
    (epithelial or non epithelial ovarian cancer)
  • Stage of ovarian malignancy the best prognosis
    is in stage Ia
  • Optimal versus Suboptimal surgery (TAH BSO
    omentectomy, versus debulking)
  • Histology and grading of the tumour. Well
    differentiated tumours carry best prognosis,
    while poorly differentiated and clear cell
    carcinomas carry the worst prognosis.
  • Response of the tumour to adjuvant therapy
    (chemotherapy irradiation).

70
  • The 5-year survival rate in epithelial ovarian
    cancer is as follows
  • In stage I 85-90
  • In stage II 80
  • In stage III 15-20
  • In stage IV 5

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  • Thank you
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