My Clinical Notes

• Most common lesions are benign cysts
• Intrinsic inflammations (oophoritis) are uncommon and are mostly associated with tubal inflammation

 

Non-neoplastic and functional cysts

 

• Cystic follicles are very common
• The originate from  unruptured Graafian follicles or follicles that have ruptured and immediately sealed

 

Follicular cysts

• Up to 2cm in diameter
• Filled with a clear serous fluid
• Granulosa cells may be visable if intraluminal pressure isn’t too great
• The outer thecal cells may be conspicuous with increased cytoplasm and a pale appearance
• Hyperthecosis may be associated with increased oestrogen production and endometrial abnormalities

 

Luteal cysts

• Normally present in the ovary
• Cells are lined by a rim of bright yellow luteal tissue containing luteninised granulosa cells
• Occassionally rupture and cause a peritoneal reaction
• When advance the combination of old haemorrhage and fibrosis may make them difficult to distinguish from endometrial cysts

 

Polycystic ovaries

• Affects 3-6% of women of reproductive age
• Associated with numerous cystic follicles and oligomenorrhoea
• May also be associated with anovulation, obesity, hirsituism and virilism
• Ovaries are normally twice the size with a smooth outer cortex and are studded with multiple subcortical cysts
• Histologically there is a thickened superficial cortex underneath which the follicular cysts are associated with hyperplasia of the theca interna

 

Stromal hyperthecosis

• Also called cortical stromal hyperplasia
• Disorder of the ovarian stroma most commonly seen in postmenopausal women
• Characterised by uniform enlargement of the ovary (up to 7cm)
• Ovaries are normally involved bilaterally
• Histologically consist of hypercellular stroma with luteinization of stromal cells which are visable as discrete nests with vacuolated cytoplasm
• Clinical features often resemble PCOS although virilisation may be more striking
• May be mimicked by the physiological condition, theca lutein hyperplasia of pregnancy, whereby thecal cells proliferate in response to pregnancy hormones resulting in expansion of the perifollicular zone. As this regresses the theca-lutein hyperplasia may become nodular

 

 

Ovarian tumours

 

• 80% of ovarian tumours are benign, mostly occurring in between age 20 -45
• Malignant tumours are more common between the ages of 45 to 60

 

Pathogenesis

• Risk factors
  • Nulliparity
  • Family history
  • Heritable mutations
• Reduced risk with taking the oral contraceptive pill
• Mutations in bit BRCA1 and BCRA2 increase the risk of ovarian cancer – mostly associated with cystadenocarcinomas
• 30% of ovarian adenomacarcinomas are associated with HER2/neu expression which is associated with poor prognosis
• Mutations in p53 are found in 50% of ovarian carcinomas

 

Classification

• Tumours of the ovary ultimately arise from one of three different ovarian components;
• The surface epithelium derived either from coelomic epithelium (from which the Mullerian epithelium is derived) or ectopic endometrial epithelium
• The germ cells
• Ovarian stroma which includes the sex cords, the forerunners of the endocrine tissue of the postnatal ovary

 

• Malignant tumours have generally spread before they become clinically evident
• Some of the tumours, particularly epithelial tumours tend to be bilateral

 

Common symptoms

• Abdominal pain and distension
• Urinary symptoms
• GI symptoms
• Vaginal bleeding

 

 

 

 

Tumours of the Mullerian Epithelium

 

• Accounts for most primary ovarian neoplasms
• Three major types
  • Serous
  • Endometrioid
  • Mucinous
• Components of the tumours may include;
  • Cystic areas – cystadenomas
  • Cystic and fibrous areas – cystadenomfibromas
  • Predominantly fibrous areas – adenofibromas
• Range from being benign to malignant
• On gross examination the risk of malignancy increases as a function of the amount of discernable solid epithelial growth

 

Serous tumours

 

• Common cystic neoplasms are lined with ciliated columnar epithelial cells
• Account for 30% of all ovarian tumours
• 75% are benign
• May present as intracystic or projecting from the ovarian surface
• Benign tumours typically present with a smooth glistening cyst wall with no epithelial thickening or with small papillary projections
• Bilaterality is common
• Borderline neoplasia doesn’t necessarily develop onto malignant neoplasia
• Unencapsualated tumours are more likely to extend to the peritoneal surface, this may effect prognosis
• Borderline tumours may extend to the peritoneal surface as non-invasive implants, remaining localised and causing no symptoms, or spread slowly possibly eventually causing intestinal obstruction
• Invasive implants may induce desmoplasia of the stroma and may form large masses with rapid clinical deterioration

 

Mucinous Tumours

 

• Account for 25% of all ovarian neoplasm
• More common in the middle of adult life
• 80% are borderline or benign
• resemble serous tumours although the cysts are more numerous and variable in size.
• The surface is rarely involved
• They are less frequently bilateral
• Tend to produce larger cystic masses
• They appear as multiloculated tumours filled with a stucky gelatinous fluid rich in glycoproteins
• Histologically, they are lined by columnar epithelium with apical mucin and the absence of cilia
• A condition associated with mucinous ovarian neoplasm is pseudomyxoma peritonei, whereby an ovarian tumour with extensive mucinous ascvites , implants on the peritoneal surface and develops adhesions
• If extensive this may result in intestinal obstruction and death
• Recent evidence points points to the presence of an extraovarian primary mucinous tumour with secondary ovarian and peritoneal spread
• Following bilateral presentation of mucinous tumour, non-ovarian tumours must be excluded

 

Endometrioid tumours

 

• Account for 20% of all ovarian cancers
• Most endometrioid tumours are carcinomas
• They are distinguished from serous and mucinous tumours by the presence of tubular glands resembling benign or malignant endometrium
• 15-20 are accompanied by endometrial carcinoma, but the relatively good prognosis in this case suggests they are from independent origin rather than metastatic spread
• grossly endometrioid carcinomas present as combined solid and cystic areas
• 40% involve both ovaries

 

Clinical course/detection/prevention of surface epithelial tumours

 

• All epithelial carcinomas produce similar clinical symptoms, lower abdominal pain and abdominal distension
• Other complaints are;
  • GI disturbance
  • Urinary frequency
  • Pelvic pressure
• Malignant forms may cause;
  • Progressive weakness
  • Weight loss
  • Cachexia
  • Ascites can occur if the tumour extends to seed the peritoneal cavity, the ascites will be filled with exfoliated tumour cells
• Peritoneal seeding produces a distinctive pattern, serosal surfaces are seeded diffusely with 0.1 to 0.5 cm nodules
• These surface implants rarely invade deeply into the organ parenchyma
• Regional lymph nodes are often involved
• Metastases may be found in the liver, lungs and GI tract
• In half of cases metastases can occur in the opposite ovary
• Poor survival rates as ovarian carcinoma is often not diagnosed until large or it has spread to other organs
• CA-125 is present in 80& of serous and endometrial carcinomas
• Osteopontin may be a new biochemical marker – expressed at slightly higher levels in ovarian cancer patients

 

• Fallopian tubal ligation and oral contraceptive pill reduce the risk
• OCP halves risk in patients with a strong family history

 

Germ cell tumours

 

• Constitute 15-0% of all ovarian tumours
• Most are benign cystic teratomas
• Remaining are found in children and young adults and have an aggressive malignant nature
• Difficult to diagnosis histologically as the closely resemble germ cell tumours in the male testes

 

Teratomas

 

• Can be divided into 3 categories;
  • Mature (benign)
  • Immature (malignant)
  • Monodermal or highly specialized

 

Mature (benign) teratomas

• Most are cystic and are known as dermoid cysts
• Presumably derived from the ectodermal differentiation of totipotential cells
• Usually present in young women
• May be bilateral
• Usually unilocular cysts containing hair and a thick sebaceous material
• Teeth may also be present
• Histologically cyst wall is composed of stratified epithelium with underlying sebaceous glands and hair follicles
• In most cases structures from other germ layers can be identified, such as cartilage, bone and thyroid tissue
• May be incorporated within the walls of a mucinous cystadenoma
• Around 1% may undergo malignant transformation of any of the component parts e.g. thyroid carcinoma, melanoma
• Karyotype of all benign ovarian teratomas is 46XX
• Suggested to be derived from the ovum after the first meiotic division

 

Monodermal teratomas

• Specialised teratomas, the most common of which are struma ovarii and carcinoid
• Struma ovarii is composed entirely of mature thyroid tissue and may hyperfunction causing hyperthyroidism
• Ovarian carcinoid, is presumably derived from intestinal epithelium, produces 5-HT and can cause carcinoid syndrome

 

Immature malignant teratomas

• Different from mature teratomas in that the tissue resembles that of the embryo/fetus rather than the adult
• Largely seen in prepubescent and young girls
• Grow rapidly and frequently penetrating the capsule with metastic spread
• Tumours are bulky and have a smooth external surface
• On section they have a solid structure and areas of haemorrhage and necrosis
• Hair, cartilage, bone and other calcifications may be present
• An important risk for extra ovarian spread is the histological grade which is based upon the proportion of tissue containing immature neuroepithelium 

 

Dysgerminoma

 

• Ovarian counterpart to the seminoma of the testes
• Accounts for 2% of all ovarian tumours
• Composed of large vesicular cells having a clear cytoplasm, well defined cell boundaries and a centrally placed regular nuclei
• Have no endocrine function although a few produce hCG and may have synctiotrophoblasts on histological examination
• All are malignant, but the degree of atypia varies so only 1/3 are aggressive
• Very radiosensitive
• Usually unilateral
• On histological examination, the dysgerminoma cells are dispersed in sheets or cords separated by scant fibrous stroma which is infiltrated by lymphocytes

 

Endodermal sinus (yolk sac) tumour

• Rare
• Derived from differentiation of malignant germ cells towards extraembryonic yolk sac structure
• Tumour is rich in alpha-fetoprotein and alpha1-antitrypsin
• Histologically has a glomerulus like appearance composed of a central blood vessel enveloped by germ cells within a space lined by germ cells (Schiller-Duval body)
• Tumours are generally unilateral but grow rapidly
• Mostly affects children and young women

 

Choriocarcinoma

• Commonly of placental origin
• Is also due to extraembryonic differentiation of malignant germ cell. However this can only be confirmed prior to puberty as after this time origin from an ectopic pregnancy cannot be discounted
• Most choriocarcinomas exist in combination with other germ cell tumours
• Primaries are aggressive and by the time of diagnosis have generally metastased to the lungs, bone, liver and other viscera
• May be diagnosed by the high levels of chorionic gonadotrophins
• Usually unresponsive to chemotherapy (in contrast to choriocarcinomas arising from the placenta)

 

Sex cord-stromal tumours

 

• Derived from the embryonic stroma which in turn is derived from the sex cords of the embryonic gonad
• As the undifferentiated gonadal mesochyme can produce structures for both sexes, either male Sertoli and Leydig cells or female granulosa or thecal cells, tumours can consist of any of these cell types
• Granulosa-theca cell tumours produce oestrogen and are feminising
• Leydig cell tumours produce androgens and are masculinizing

 

Granulosa-thecal cell tumours

• Composed entirely of granulosa cells or a combination of granulosa and thecal cells
• Account for 5% of all ovarian tumours
• Most occur postmenopausally
• Usually unilateral
• Histologically tumours which are hormonally active have a yellow colouration due to contained lipids
• Granulosa cell component can have different histological patterns, small cuboidal/polygonal cells may grow in sheets/strands
• The thecal component consist of clusters or cheets of cuboidal/polygonal cells
• The cells may be plumper with ample cytoplasm characteristic of luteinisation
• These tumours are of clinical importance for two reasons;
  • The potential to produce large amounts of oestrogen
  • Small hazard of malignancy in granulosa cell forms
• Functionally active tumours in prepubertal girls may produce precocious puberty
• In adults it may be associated with endometrial hyperplasia, cystic disease of the breast and endometrial carcinoma
• Occasionally granulosa cell tumours may produce androgen which can masculinize the patient
• Tumours composed more of thecal cells are almost never malignant
• Inhibin may be a useful marker of granulosa cell tumours

 

Fibroma-thecomas

• Tumours which arise in the ovarian stroma from either fibroblasts (fibromas) or plump spindle cells with droplets (thecomas)
• Account for 5% of all ovarian tumours
• Mostly consist of a combination of both
• Fibromas are hormonally inactive but thecomas do produce hormones
• Unilateral and generally are solid, spherical or slightly lobulated encapsulated hard, grey-white masses covered by intact ovarian serosa
• As well as abdominal pain and distension, these tumours are associated with ascites and hydrothorax.
• The combination of the ovarian tumour, ascites and hydrothorax is called Meigs syndrome

 

Sertoli-Leydig cell tumours

• Commonly produce masculinisation or defeminisation
• Manifest by atrophy of breasts, amenorrheoa, sterility, hair loss or virilization with male distribution of hair, hypertrophy of the clitoris and voice changes
• Peak incidence is in the 2^nd and 3^rd decade
• Unilateral and resemble granulosa-thecal cell neoplasms

 

Metastatic tumours

 

• Most common are those of Mullerian origin;
  • Uterus
  • Fallopian tube
  • Contralateral ovary
  • Pelvic peritoneum
• Common extra-Mullerian primaries are;
  • Breast
  • Colon
  • Stomach
  • Biliary tract
  • Pancreas
  • Appendiceal  - pseudomyxoma peritonei
• Krukenberg tumour is characterised by bilateral masses composed of mucin producing signet ring cancer cells of gastric origin

This entry was posted on Wednesday, October 3rd, 2007 at 4:24 pm and is filed under Gynaecology/Obstetrics. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.