Ovarian tumor

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Ovarian tumor

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• Ovarian tumor is one of the most common
  tumors of the female generative system. Little
  progress has been made in identifying precursory
  or in situ stages of these lesions. The 5-year
  survival rate for all stages is still
  35-38little better than 35 years ago.

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Table 1 Histology of ovarian tumors (WHO,
1972)

• (3) Embryonal carcinoma(4)
  Polyembryoma(5) Choriocarcinoma(6) Teratoma
  Immature Mature(a) Solid (b)
  Cystic Monodermal and highly specialized(a)
  Struma ovarii (b) Carcinoid (c)
  Others(7) Mixed germ cell tumors
• Gonadoblastoma
• Non-ovarian specific soft tissue tumor (sarcoma,
  fibrosarcoma, lymphosarcoma)
• Unclassified tumor
• Metastatic tumor
• Tumor like condition Follicle cysts, lutein
  cysts, and so on
•  

1. Epithelial ovarian tumors(1) Serous(2)
   Mucinous(3) Endometrioid(4) Clear cell(5)
   Brenner(6) Mixed epithelial(7)
   Undifferentiated
2. Gonadal sex cord stromal tumor
   (1) Granulosa stromal cell tumor
   Granulosa cell tumor Thecoma-fibroma
   tumor (a) Theca cell tumor (b) Fibroma(2)
   Sertoli leydig cell tumor (androblastoma)(3)
   Gynandroblastoma
3. Lipid (lipoid) cell tumor
4. Ovarian germ cell tumors(1) Dysgerminoma(2)
   Endodermal sinus tumor (yolk-sac tumor)

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• Epethelial tumors account for more than 5070 of
  all primary ovarian neoplasia and more than
  85-90 of ovarian malignant tumors.
• Ovarian germ cell tumors account for 20-40 of
  ovarian tumors. They include dysgerminoma,
  embryonal carcinoma, teratoma, endodermal sinus
  tumour, choriocarcinoma , and so on.

5

• Sex cord stromal tumors account for about 5 of
  all ovarian tumors. These tumors are potentially
  functional, that is, producing hormones, so we
  call them ovarian functional tumors.
• Metastatic tumors account for 5-10 of ovarian
  tumors. The primary sites are commonly
  gastrointestinal tract, breast, genital organs.

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High risk factors

• 1. The factors of heredity and family
• 2. Environmental factors
• 3. Endocrine factors

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?Pathophysiology?

• 1. Epithelial tumors
• ?Epithelial ovarian tumors present at an average
  age of 30-60 years.
• ?Cellular proliferation, atypia, and the presence
  of stromal invasion are the histologic criteria
  used to classify malignant potential.

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SEROUS CYSTADENOMA

• BENIGN TUMORs
• ?comprises approximately 25 of benign ovarian
  neoplasms.
• ? divided 2 categories, simple and papillary.
• ? Psammoma bodies (small irregular
  calcifications) are characteristic of serous
  tumors.

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BORDERLINE SEROUS CYSTADENOMA

• papillary formation
• good differentiation
• lack of stromal invasion

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SEROUS CYSTADENOCARCINOMA

• external papillary excrescences covered by
  stratified epithelium (usually over 4-5 layers)
• nuclear atypia
• occasional mitotic figures and stromal invision

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MUCINOUS CYSTADENOMA

• BENIGN TUMORs
• ? Account for approximately 20 of benign ovarian
  neoplasms
• ? Generally unilateral, rounded or ovoid, smooth,
  grayish-white
• ? Cut section reveals the multilocular cysts
  strikingly filled with a viscous and tremellose
  mucin.
• ? The rate of malignant alteration is 5-10.

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BORDERLINE MUCINOUS CYSTADENOMA

• The tumor generally is rather large.
• Microscopically, cellular stratification occurs.
• No stromal invasion
• Cellular atypia may be mild to moderate and a
  moderate number of mitoses may be present.

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MYXOMA PERITONEI

• the progressive accumulation of mucin witnin the
  abdomen
• arise from either a mucinous ovarian tumor or
  from a mucocele of the appendix
• account for approximately 2-5 of mucinous
  cystadenomas
• tumor cells secrete mucin
• rare cellular atypier and mitotic activity

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MUCINOUS CYSTADENOCARCINOMAS

• account for 10 of ovarian malignant neoplasms.
• Cut section reveals the multilocular cysts filled
  with a turbid or bloody mucin.
• Microscopically, glands are crowded and stroma
  are rather few. Stromal invasion and cellular
  atypia may occur strikingly.
• In contrast to serous cystadenocarcinoma, this
  tumor has a more favorable prognosis.

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OVARIAN ENDOMETRIOID TUMOR

• The malignant kinds of these neoplasms are
  endometrioid carcinomas, account for 10-24 of
  primary ovarian malignant neoplasms.
• The histologic type are adenocarcinoma or
  adenoacanthoma, as in uterine carcinomas.
• Endometrial cancer found in the uterus and ovary
  commonly represents multifocal and not metastatic
  disease.

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OVARIAN GERM CELL TUMOR

• They are found in the gonad or at any site from
  which the germ cell arises or to which it
  migrates.
• This tumor occurs principally in young
  females-60-90 in prepuberal and only 4 in
  postmenopausal women.
• Germ cell tumors may contain germ cells as the
  predominant component.

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TERATOMA

• Teratoma is one of the most fascinating of all
  neoplasms.
• This tumor may contain tissues of ectoderm,
  endoderm, and mesoderm.

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MATURE TERATOMA

• Mature teratoma is the most common tumor of
  ovary.
• This tumor often occurs in patients 20-40 years
  old.
• Cut section reveals the unilocular cysts
  strikingly filled with adipose and hair,
  sometimes with bone and teeth.

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• Special varieties of teratoma may produce unusual
  symptoms.
• Malignant change in a primarily benign cystic
  teratoma is uncommon.
• Any tissues may occur malignant change to form
  every kind of malignant tumors.
• The epithelium of scolex easily occur malignant
  change.

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IMMATURE TERATOMA

• The tumor commonly occurs during the early
  reproductive years.
• The degree of malignance is bases on the
  proportion of immature tissues, the cellular
  differentiation, and the neuroepithelium content.
  
• Maturation at a secondary site has even
  occurred in some instances.

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DYSGERMINOMA

• Occurs principally in young females.
• Comprises approxmately 5 of all malignant
  ovarian neoplasms.
• Radiation therapy is very effective in this
  tumor.
• The 5-year survival rate is 90.

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ENDODERMAL SINUS TUMOR

• Occurs principally in young female.
• The biologic marker is alpha-fetoprotein (AFP).
• The survival time has been prolonged by
  combination chemotherapy and surgery.

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OVARIAN GONADAL SEX CORD STROMAL TUMOR
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GRANULOSA STROMAL CELL TUMOR

• GRANULOSA CELL TUMOR
• Found in all age groups and associated with
  pseudoprecocious puberty.
• Early breast development , menstrual
  disorder, postmenopausal vaginal bleeding make up
  the characteristic symptom.

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• Laboratory studies demonstrate an increase in the
  numbers of mature epithelial cells in the vaginal
  cytologic specimen, elevated urinary and serum
  estrogen levels, and variant degrees of
  endometrial proliferation.
• The characteristic cell is the round or slightly
  ovoid granulosa cell with its dark nucleus.
• Mitoses are common, and the ovumlike Call-Exner
  bodies are classic.

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THECA CELL TUMOR

• This tumor offen exists with granulosa cell
  tumor.
• The classic cell is short spindle, with abundant
  cytoplasm.
• The endometrium offen becomes proliferative, and
  postmenopausal vaginal bleeding may occur.
• The prognosis is better than that of other
  ovarian carcinomas.

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FIBROMA

• These tumors account for about 2-5 of all
  ovarian tumors.
• These solid ovarian tumors may be associated with
  Meigs syndrome.

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SERTOLI LEYDIG CELL TUMORS

• also be called androblastoma
• often affect females beneath the ages of 40 years
• usually be luteinized, simulating the classic
  pattern of the testes and producing steroids
• generally benign, may produce the masculinization
• The 5-year survival rate is 70-90.

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OVARIAN METASTATIC TUMORS

• Krukenbergs tumor

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PATTERNS OF SPREAD

• At the time of diagnosis, over 70 of patients
  with epithelial carcinomas have metastased
  outside the pelvis.

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The most common location of metastases
Peritoneum 85
Omentum 70
Contralateral ovary 70
Liver 35
Pleura 33
Lung 25
Uterus 20
Vagina 15
Bone 15
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STAGING

• The extent of the disease determines the stage
  and the appropriate form of management.

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Table 2. FIGO stages for primary carcinoma of
the ovary (1985)
?Growth limited to the ovaries ?A Growth limited to one ovary no ascites present containing malignant cells no tumor on the external surface capsule intact ?B Growth limited to both ovaries no ascites present containing malignant cells no tumor on the external surface capsule intact ?C Tumor either stage ?A or?B, but with tumor on the surface of one or both ovaries or with ruptured capsule or with ascites containing malignant cells or with positive peritoneal washings ? Growth involving one or both ovaries, with pelvic extension ?A Extention and/or metastases to the uterus and/or tubes ?B Extention to other pelvic tissues ?C Tumor either stage ?A or ?B, but with tumor on the surface of one or both ovaries or with capsule(s) ruptured or with ascites present containing malignant cells or with positive peritoneal washings ? Tumor involving one or both ovaries, with peritoneal implants outside the pelvic and/or positive retroperitoneal or inguinal nodes superficial liver metastasis equals stage ?. Tumor is limited to the true pelvis, but with histologically proven malignant extention to small bowel or omentum ?A Tumor grossly limited to the true pelvis, with negative nodes but with histologcally confirmed microscopic seeding of abdominal peritoneal surfaces ?B Tumor involving one or both ovaries, with histologically confirmed inplants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter nodes are negtive ?C Abdominal inplants greater than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes ? Growth invoving one or both ovaries with distant metastases. If pleural effusion is present, there must be positive cytologic findings to allot a case to stage ? parenchymal liver metastasis equals stage ?
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CLINICAL FIDINGS
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1. BENIGN OVARIAN TUMORS

• These tumors are generally asymptomatic and are
  found on routine pelvic examination.
• On physical examination the most common signs of
  an ovarian tumor include an adnexal mass (or
  masses), an abdominal mass.
• If the tumors are large enough, they may produce
  pelvic pain, urinary retention or frequency
  micturition, rectal discomfort, and bowel
  obstruction, no ascites.

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2. MALIGNANT OVARIAN TUMORS

• The evaluation includes a carful history and
  complete physical examination in addition to a
  pelvic examination.
• Most neoplastic ovarian tumors produce few
  symptoms.
• On physical examination the most common signs
  include an adnexal mass (or masses), an abdominal
  mass ascites, or evidence of metastasis.
• When interpreting an adnexal mass,it must be
  remembered that any palpable ovarian mass in a
  premenarcheal or postmenopausal woman is abnomal.

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DIAGNOSIS

• Although most ovarian tumors have not
  special symptoms, they may be diagnosed by
  patitnts age, careful histories and complete
  physical examination in addition to a pelvic
  examination.

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1. CELLULAR ANALASIS

• Ascites or peritoneal washing is of greatest
  value when the process appears to be early or to
  be unilateral.
• If there is clear extension of malignancy to
  peritoneal surfaces, if there is omental tumor
  extension, or if the entire tumor cannot be
  removed, the peritoneal washing are less value.

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2. FINE-NEEDLE PARACENTESIS

• Routine paracentesis to obtain samples
  for cellular analysis is not recommended but may
  be useful in the diagnosis of advanced or
  inoperable diseases.

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3. OTHER ACCESSORY EXAMINATIONS

• Ultrasonography (endovaginal ultrasound) and
  computed tomography are accurate techniques.
• A laparotomy at least for histological purposes
  is mandatory.
• CA125 is the best known marker for ovarian
  cancer.
• In young patients, serum ßhuman chorionic
  gonadotrophin (ß-hCG) , a-fetoprotein (AFP)
  titres should be determined.

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?DIFFERENTIAL GIAGNOSIS?

• 1. Benign ovarian tumors and malignant ovarian
  tumors See table 3

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Table 3. Benign ovarian tumors and malignant
ovarian tumors
Content Benign Malignant
History Long, growth slowly Short, growth rapidly
Sign Generally unilateral, active, cystic, smooth, no ascites Generally bilateral, fixed, solid or semisolid, nodular or lobulated, often with bloody ascites containing malignant cells
General physical condition Good Cachexia present
Ultrasound Opaque dark area of fluid, with interval band, edge clearly Opaque dark area of fluid with light beam or sport, edge not clearly
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• 2. DIFFERENTIAL DIAGNOSIS OF BENIGN OVARIAN
  TUMORS

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(1) OVARIAN TUMOR LIKE CONDITION

• Follicle cysts and lutein cysts are the most
  common.
• Indeed, in a normally menstruating woman any
  adnexal mass larger than 5cm should be concidered
  suspect if it persists for more than 6 weeks.

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(2) SALPINGO-OOPHORY CYSTS

• These are inflammation cysts and often produce
  infertility.

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(3) LEIOMYOMA

• Leiomyomas are generally multiple, linked with
  uterine, often associated with a menstrual
  abnormality.
• On physical examination, the tumor moves when
  corpus uteri and cervix move.

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(4) UTERINE PREGNANCY

• The careful menstrual history, the HCH
  study, and untrasonography scane may be useful to
  differentiate the two conditions.

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(5) ASCITES

• The patient often has history of hepatic disease,
  or cardiac disease.
• When the patient lies down, the shape of her
  abdomen likes as frog-belly.
• Percussion note is tympany in the middle abdomen,
  dullness in the lateral abdomen. The shifting
  dullness is positive.

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3. DIFFERENTIAL DIAGNOSIS OF MALIGNANT OVARIAN
TUMORS
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(1) ENDOMETRIOSIS

• The lesion generally produces progressive
  dysmenorrhea, hypermenorrhea, premenstrual
  irregular vaginal bleeding, and so on.
• Ultrasound, laparoscopy are the promising
  adjuvant examination.
• Laparotomy should be performed if ovarian
  neoplasms cannot be ruled out.

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(2) PELVIC INFLAMMATION OF CONNECTIV TISSUE

• The patient may have history of abortion or
  puerperal inflammation.
• Use of antibiotic may remit symptoms, and make
  the mass or masses small or disappear.

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(3) TUBERCULOUS PERITONITIS

• The lesions often occur in young or infertility
  women, generally have history of lung
  tuberculosis, often produce leanness, asthenia,
  low fever, night sweat, anorexia, infrequent
  menstruation or amenorrhea.
• Ultimately the dignosis of this lesion depends on
  surgical exploration.

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(4) EXTRA-GENERATIVE TRACT TUMORS

• Ovarian malignant neoplasms must be
  differentiated from retroperitoneal masses,
  rectal cancer or sigmoid cancer.
• Untrasound, barium enema, intravenous
  pyelography may assist in establishing the
  diagnosis.

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(5) METASTATIC OVARIAN TUMORS

• The metastatic ovarian neoplasms should
  be suspect if the adnexal mass or masses were
  bilateral, median large, kedney shape, active and
  solid.
• The patient has gastrointestinal
  symptoms, history of gastrointestinal cncer, and
  breast cancer.

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?COMPLICATION?

• Complications include pediculotorsion,
  capsule ruptured, inflammation, and malignant
  transformation. They may produce pelvic pain or
  abdominal pain, fever, ascities, abdominal mass
  or masses, and so on.

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?TREATMENT?

• 1. BENIGN TUMORS
• Operation should be performed while the diagnosis
  is established.
• The extent of surgery depends on the patients
  age, the patients desire of childbearing, and
  contralateral ovary.
• Frozen section should be used at the time of
  surgery.

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2. MALIGNANT TUMORS

• (1) SURGERY
• Surgery is usually performed to establish the
  type, histologic grading, and stage of the tumor.
  
• In certain early or borderline cases, surgery may
  also be curative, and in nearly all cases it is a
  major part of therapy.
• At the time of surgery, peritoneal fluid or
  peritoneal washing should be aspirated for
  cytologic analysis.
• A second-look operation is indicated when an
  inoperable tumor responds so remarkably to
  adjunctive therapy that surgery becomes feasible.

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(2) CHEMOTHERAPY

• Since the introduction of cisplatin-based
  combinations in the 1980s, the outcome of
  treatment has improved markedly.
• Generally, a pulse therapy regimen ie, 5 days
  of therapy per month for 6-8 courses, has been
  the most commonly accepted program.
• Some new drugs (hexamethylmelamine, cisplatin,
  Carboplatin, adriamycin) are the promising
  chemotherapeutic agents.
• It must be appreciated that these agents are
  toxic, and the combinations are more noxious than
  the single agents.(Table 4)

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Table 4. Toxicity of chemotherapeutic agents
System Drug
Hepatic toxicity Methotrexate (esprcially chronic low-dose)
Renal toxicity Methotrexate (esprcially high-dose), Cisplatin
Myelosuppressive toxicity Many agents
Peripheral neuropathy Vincristine, Hexamethylmelamine
Ototoxicity Cisplatin
Pulmonary toxicity Bleomycin, Methotrexate, Cyclophosphamide
Cardiac toxicity Doxorubicin (acute or cumulative)
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(3) RADIOTHERAPY

• Radiation therapy was the prime therapeutic
  modality for many years, but inability to deliver
  effective dosages to the upper abdomen without
  damaging the liver or kidneys limited its
  usefulness.
• Because of the availability of a multitude of
  chemotherapeutic agents, chemotherapy has
  recently replaced radiation.

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?PREGNOSIS?

• The grade of tumor differentiation and FIGO
  substage are most likely the strongest factors
  predicting for recurrence in early stage.
• In the advanced stages, prior to treatment,
  performance status, FIGO classification,
  differentiation grade, size of the residual
  tumor, presence or absence of ascites, and cell
  type all influence the survival outcome.