Notes #4: Ovarian Pathology

Ovary produces a wide variety of neoplasms, both benign and malignant. Cannot definitively separate all benign lesions from all malignant, but ultrasound is one of the best ways of screening the ovary. Widespread ovarian screening by ultrasound is recommended by some, but not proven cost-effective due to rarity of disease.

Ovarian Screening Rationale:
Access risk factors; follow hi-risk with Ca125, pelvic exams, and ultrasounds

Ovarian Cancer:
3rd most common gynecologic malignancy, but highest mortality due to late diagnosis.
Asymptomatic: Palpable ovary, GI symptoms and/or backache as tumor enlarges.

5 year survival:
overall 20-30% survival, low # due to late diagnoses (65-70% have mets at diagnosis)
Survival if detected at Stage 1 -- 80-90% five year survival

Incidence:
30-70 per 100,000 women; approximately 21,000 new cases per year in U.S.
Age 30 ---- 0.3 per 1000 women
Age 70 ---- 0.7 per 1000 women
Lifetime Risk ---- approximately 1 per 1000 women (assumes you live to be 100)

Risk Factors:
Family hx. of breast, ovarian, or colon cancer
Nulliparity
Infertility or treatment with infertility drugs
Late menopause or early menarche
Uninterrupted ovulation (pregnancy and BCP reduce risk)

Descriptive terms utilized in describing ovarian masses:
(from Transvaginal Sonography by Timor-Tritsch and Rottem

Septations:
structures which cross a liquid phase as echogenic bridges measuring 0.5 mm to more than 1 cm.

Papillae:
echogenic formations protruding into the liquid phase, measuring from 5 mm to 2 cm but not occupying more than 25% of the space of the mass.

Daughter Cysts:
embracing semicircular echogenic structures protruding into the liquid phase. The distance between the ends of the cyst is less than 1 cm, and they should not have interstructural contingency.

Loculations:
embracing semicircular or circular echogenic structures protruding into the sonolucent content with interstructural contingency or measuring more than 1 cm between the two ends in case of a solitary structure.

Liquid Phase: (not illustrated)
intratumor sonolucency or low-level echogenicity or completely sonolucent.
(He is including low level endometriomas in this definition.)

Solid Lesion:
echogenic formation occupying more than 25% of the space of the mass. (He is including complex masses in this definition if more than 25% of the structure is solid.)

Functional/Physiologic Ovarian Cysts and Complications:

Follicular Cysts:
overdistention of follicles which have failed to rupture
unilateral and common
may be multiple
1-10 cm.
simple cysts, may have thin septations

Theca Lutein Cysts:
relate to high levels of B-HCG
bilateral
multiloculated with thin walls
3 - 20 cm. -- Largest of the functional cysts
Associated with trophoblastic disease or Ovarian hyperstimulation due to infertility drugs
Corpus Luteum:
unilateral
less common in normal cycle than follicular cysts but tend to be larger and more symptomatic
Prone to hemorrhage
Under 3 cm. normal cycle
May reach 3-5 cm. size during pregnancy
Resolves by 16 weeks gestation -- (regresses at 10 weeks)

Corpus luteal Cyst:
results from hemorrhage into corpus luteum
also called hemorrhagic cyst
septations, complexities common
May mimic many other pelvic masses in appearance
Often symptomatic
Polycystic Ovary Disease:
Chronic anovulation associated with imbalance of LH, FSH --- (Triad of Stein Leventhal one form of spectrum) - - incidence may be as high as 15% reproductive age women
Stein-Leventhal Syndrome - Endocrine disorder associated with obesity, infertility, hirsutism, oligomenorrhea, and polycystic ovaries
Enlarged ovaries bilaterally
Multiple small cysts 2-6 mm. on both ovaries -- more than 5 each ovary used as dfn. by some
Approximately 1/4 will appear to have nl. ovaries --- see small follicular cysts transvaginally

Ovarian Torsion:
Partial or complete rotation of ovarian pedicle
May occur with normal ovaries
Most common with cysts, hyperstimulation -- associated with ovarian masses or enlargement
Severe pelvic pain, nausea, vomiting
Subject to hemorrhage
Occurs more often on right than on left
Absent intraparenchymal arterial flow -- may be documented with Doppler
May see enlarged, edematous ovary but visual changes uncommon


Non-ovarian Adnexal Masses:

Tuboovarian Abscesses:

Endometriomas:

Pelvic Varices:

Parasitic or Pedunculated Leiomyomas:

Paraovarian Cyst:
Arise from broad ligament between uterus and ovary
No changes with hormonal cycle
Extraovarian --- 2 to 20 cm. in size, often mistaken for ovarian cyst
Common --- by some account for 10% adnexal masses

Peritoneal Inclusion Cysts:
Inclusion Cysts most common when status post - pelvic surgery
Fluid becomes walled off between layers of peritoneum
Extraovarian

Neoplastic Ovarian Masses:

Over 400 different varieties of tumors named, others arise in individual women
approximately 80% benign, others borderline or malignant

Classification by cell type:

Epithelial Tumors:
most common source of ovarian neoplasms
60%-70% of all ovarian neoplasms
arise from surface epithelium (germinal matrix)
Examples: cystadenomas, cystadenofibroma (Brenner's tumor), endometroid tumor

Stromal Tumors (also sex-cord stromal):
arise from central echogenic stroma
Fibromas which are primarily fiber
Hilus and lipoid tumors and thecomas which are primarily fat
Virilizing tumors such as Arrhenoblastoma, Sertoli-Leydig tumors which produce male hormone
Granulosa cell, theca cell tumors - estrogenic

Germ Cell Tumors:
Arise from follicles or cells surrounding it
May produce estrogen
Examples: dermoid tumor, teratoma, dysgerminoma, endodermal sinus (yolk sac) tumor


Epithelial Neoplasms:

Serous Cystadenoma:
account for 30% ovarian neoplasms
20% bilateral

Serous Cystadenocarcinoma:
account for 40% ovarian Ca
50% bilateral
Papillary projections and septae common

Mucinous Cystadenoma:
account for 20% ovarian neoplasms
less than 5% bilateral

Mucinous cystadenocarcinoma:
account 10% ovarian Ca
25% bilateral

Pseudomysoma Peritonei - intraperitoneal spread of mucin-secreting cell due to rupture or penetration of tumor capsule. Appearance similar to ascites, but with debris and septations in the intraperitoneal fluid. Occurs most often with mucinouscystadenocarinoma, may also occur in cystadenocarcinoma.

Endometroid Tumor:
account for 20% ovarian Ca
second most common type ovarian malignancy
30% -50% bilateral
may be seen in association with endometrial carcinoma

Brenner Tumor:
Uncommon, rarely malignant
May be found with cystic neoplasm on ipsilateral ovary

Germ Cell Neoplasms:

Dermoid Cyst / Benign Teratoma:
10% - 15% bilateral
Dermoid contains ectodermal tissue (teeth, hair, glandular tissue, fluid (both serous and oily sebaceous)
Teratoma contains ectoderm, mesoderm, and endoderm - totipotential with regard to cell type
Typically small <10cm.
Appearances:
Cystic --- least common appearance
Cyst with debris and clumps of highly echogenic material
Cyst with fluid / fluid levels -- apparent septae that moves with patient position and gravity
Iceberg or Polar cap -- echogenic structure with shadowing below, no posterior wall seen
Solid Lesion with cystic components
100% solid mass, very echogenic

Struma Ovarii - benign teratoma in which thyroid tissue predominates: causes hormonal related symptoms


Malignant Teratomas:
less than 1% of all teratomas
occur most commonly before age 20
highly aggressive tumors
Dysgerminoma:
Solid, malignant germ cell tumor
1% - 2% primary ovarian neoplasms (3%-5% malignancies)
most common solid ovarian mass in pregnancy
occur primarily in younger women
15% bilateral

Sex-Cord Stromal Tumors:

Ovarian Fibroma:
Account for 4% ovarian neoplasms
Similar to thecomas or Brenner's tumor in sonographic appearance, but not hormonally active
Benign, unilateral
Meig's Syndrome (fibroma, ascites, pleural effusion)

Granulosa cell tumors:
Sex cord-Stromal tumor
5% bilateral
low malignancy potential
most common estrogen active tumor

Thecoma or Theca cell tumor or thecofibromas:
Unilateral, almost always benign
Account for less than 1% ovarian neoplasms
Estrogen producing tumor

Sertoli-Leydig Cell Tumor (Androblastoma):
Rare, less than 0.5% ovarian neoplasms
Unilateral
10% - 20% malignant
Masculinization symptoms
Appearance similar to graulosa cell tumors

Metastatic Tumors of the Ovary:
Most common origin breast and gastrointestinal tract
Krukenberg tumor metastatic tumor from GI tract with mucin- producing cells
Usually bilateral masses

Distinquishing Benign from Malignant Ovarian Tumors:

Morpologic Scoring by Characteristics:

Internal Echo Pattern
Sonolucent
Low Echogenicity
Low Echogenicity with echogenic core
Mixed Echogenicity
High Echogenicity


Septations
No Septa
Thin septa (<3mm)
Thick septa (>3mm)
Inner Wall Structure: Wall Excrescences
Smooth
Irregularities < 3mm.
Papillae >3mm.
Not applicable, solid lesion
Wall Thickness
Thin (< 3mm.)
Thick (>3mm.)
Not applicable, solid lesion

Other Morphologic Features associated with malignancy:

Size: Larger size neoplasms (> 10 cm.), except simple cysts, are more likely malignant

Rapid growth consistent with malignancy:

Coexisting Ascites: (May be the result of liver disease or tuberculin PID or infection)

Liver and Spleen metastases

Pseudomyxoma Peritonei

Peritoneal Implants

Obstructive Uropathy

Bowel Adhesions - Clumps of bowel or fixed

Pelvic Doppler :

Resistivity index:
Peak Systolic Velocity - Peak End Diastolic Velocity / Peak Systolic Velocity
PSV - PEDV / PSV
Varies from 0 to 1
1 representing the greatest resistance to forward flow, least diastolic flow

Pulsatility index:
Peak systolic velocity - Peak End Diastolic Velocity / Mean Velocity
PSV - PEDV / mean
Varies from 0 to 10
Higher numbers represent higher resistance to flow, less diastolic flow
Normal ovaries have a PI that varies from 3.1 - 9.1, RI's 0.5-0.8

Low RI and PI seen in malignant tumors, during inflammation or infection, and with hormonal activity.

Measure 2-3 periperal vessels and internal vessels if present - record lowest resistance documented. In malignant masses, lowest resistance is in center of mass. May miss low resistance if measured at edge of the mass.

RI and PI of the ovarian and uterine vessels vary throughout the menstrual cycle. Gradually increase until mid-cycle, then drop during luteal phase. Low resistance or high velocity at mid-cycle associated with greater fertility that cycle.

Corpus Luteum cyst has low resistance flow.

Hormonal Replacement Therapy after menopause lowers RI and PI in pelvic vessels.

Overlap between malignant and benign masses especially with RI < 0.5

High resistance:
Normal ovaries during follicular phase
Fibroids neoplasms

Moderate resistance:
Normal Ovaries during luteal phase
Cystadenomas and most benign ovarian masses
Hemorrhagic Cysts

Low resistance:
Most Dermoids
Endometriomas
Rapidly growing benign masses

Lowest resistance:
Malignancies
Inflammatory / Infectious Masses
Strumi Ovarii and other metabolically active dermoids
Some metabolically active masses (Corpus luteum cyst, granuloma)

Waveform shape:
Neoplastic vessels often lack muscular intima and have numerous arteriovenous shunts.
Low resistance and increased diastolic flow.
Lack of muscular resistance in wall in neoplastic vessels gives unique, constant flow pattern
May not be seen when tumor small and hasn't developed its own internal vessels as yet