MALIGNANT OVARIAN TUMOURS

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• MALIGNANT OVARIAN TUMOURS
• Prof.Osman Donia

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• 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  

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• I. EPITHELIAL OVARIAN CANCER

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• 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.

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• 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.
  

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• 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).

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

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• 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

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• MALIGNANT GERM CELL TUMOURS

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

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• 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

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• 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.

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• 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.

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• 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.

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• 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

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• 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.

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• 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

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• MALIGNANT SEX-CORD STROMAL TUMOURS

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• 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.

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• 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

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• 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.

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PATTERNS OF SPREAD OF OVARIAN CANCER

• Primary methods of spread of ovarian cancer are
• Direct extension
• Lymphatic spread
• Transcoelomic spread
• Haematogenous spread

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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.

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

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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.

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• 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.

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• 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.

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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.

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• 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).

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• 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).

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• 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).

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• 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.

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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.

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• 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).

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• 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

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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.

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• 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.

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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.

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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.

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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
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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.

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• 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).

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

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• 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.

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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).

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• 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.

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• 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).

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• 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.

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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.

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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).

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• 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