Benign epithelial and borderline ovarian tumors (Borderline ovarian tumors…
Benign epithelial and borderline ovarian tumors
functional ovarian cysts
inflammatory tumors of ovaries
nonmalignant tumors (epithelial and nonepithelial)
borderline ovarian tumors
malignant ovarian tumors (epithelial and nonepithelial)
Most frequently they are asymptomatic
Patients with symptoms can complain to pain in the abdomen or in thepelvis, or syndromes caused by pressure on the surrounding organs (constipation, urgency incontinence and frequent miction).
The torsion of an ovarian cysts presents typically as an acute abdominal pain with nausea and vomiting, positive peritoneal
symptoms. This is an urgency requiring surgical intervention.
Adnexal masses present a diagnostic dilemma; the differential diagnosis is extensive, and most masses are benign.
without histopathologic tissue diagnosis, a definitive diagnosis is generally precluded. Diagnosis is not performed by transabdominal or transvaginal biopsy of lesions – the risk of disseminating a malignancy is too high.
Diagnosis of ovarian tumors is based on the probability of malignant events using clinical, radiological, and laboratory information.
ELEMENTS OF ASSESSMENT OF RISK OF CANCER
Medical interview- age of the patient (benign process is higher in women of reproductive age, prepubertal girls and postmenopausal women increases the risk of a malignant neoplastic), cancers in medical history
Ultrasound TV, TA / TK /NMR
laboratory tests of tumor markers, inflammatory parameters, assessment of BRCA mutations, mutant genes
RISK OF MALIGNANCY
BRCA gene mutation test should be particularly recommended for women who:
Have had at least 2 cases of breast cancer or breast and ovarian cancer in the family (three generations back), especially before the age of 50
Have had themselves or have had relatives with ovarian cancer (regardless of age)
have experienced atypical disease (bilateral, early, breast cancer in a related man)
have relatives with prostate cancer, larynx or melanoma,
have had benign lesions such as breast or ovarian cysts
Have a family of individuals who have been diagnosed with the BRCA1 or BRCA2 gene mutation.
IMAGING – USG CT MRI
For evaluation of ovarian tumor morphology in pre-diagnosis, adequate examination is an ultrasound vaginal ultrasonography (if necessary rectal) - high resolution image. TK or NMR is performed in case of significant malignancy in case of evaluation of tumor lesions outside the ovaries (also for evaluation of possible primary tumors: Krukenberg tumors).
The following masses pose the greatest concern in ultrasound (including borderline malignancy):
Those that have solid components
Those that have papillary grows inside
Those that have thick septs
Cancer antigen 125 (CA-125)
expressed by tissues derived from coelomic and müllerian epithelia, and levels are elevated in at least 80% of females with advanced epithelial ovarian cancers.
single-point CA-125 measurements are limited by both a lack of sensitivity (low in early-stage malignancy) and specificity (it is produced by many other nonmalignant conditions).
CA-125 is elevated in approximately 80% of all women with ovarian cancer. In stage I disease, the sensitivity of this biomarker is approximately 50%, which rises to 90% in patients with advanced disease.
it can also be elevated in many other conditions, including gynecologic etiologies such as endometriosis, and pregnancy, and nongynecologic conditions such as gastroenteritis, pancreatitis, cirrhosis, and congestive heart failure.
The most effective tool in the differentiation between benign and
malignant ovarian epithelial cancer was combination of Ca125 and HE4
(sensitivity 94.4% at 75% specificity)
In the clinical practice, the algorithm of Risk of Malignancy Algorithm
(ROMA) is taken into account Ca125, He4 and female menopausal status.
CRP, PROKALCYTONIN, LEUCOCYTOSIS – for evaluation of inflammatory states.
no possibilty of hormonal treatment of functional cysts, Benign cysts or borderline ovarian tumors.
Hormonal contraception causes cessation of ovulation and decreases the risk of new functional cysts to form.
The Basic surgical treatment is enucleation of the tumor or resection of the whole ovary – the decision depends on the risk of malignancy and the age of the patient (pregnancy plans).
In high risk patients we are obliged to plan a radical surgical procedure (patient’s concent, intraoperative examinatinon, surgical time, experience of the surgeon).
Surgical procedures performed in the pelvis might influence future fertility (abdominal adhesions). On the other hand, even asymptomatic tumors might be early staged ovarian cancers, that requires urgent intervention. With the mentioned criteria of malignancy a adequate surgical qualification can be made (removal of the whole ovary with the Fallopian tube or enucleation of the tumor). It also prevents a situation when the capsule of the tumor ruptures in malignant tumors, which avoids cancer dissemination.
In postmenopausal women the resection of the whole tumor with the ovary is the basic surgery (ovary with the tumor and Fallopian tube, even with the contrlateral adnexa).
Functional ovarian cysts
normal functioning ovary produces a follicular cyst 6-7 times each year.
In most cases, these functional cysts are self-limiting and resolve within the duration of a normal menstrual cycle.
Their size usually does not exceed 3cm.
In such situations there are no indications for surgical treatment.
The indication for surgical treatment is "torsion of ovarian cyst" associated with severe pain and general symptoms, "acute abdomen" symptoms.
In rare situations, a cyst persists longer or becomes enlarged- indicated surgical treatment. At this point, it represents a pathological adnexal mass.
FOLLICLE CYST (result from nonrupture of the dominant mature follicle)
CORPUS LUTEUM CYST (persistant corpus luteum transforms into a cyst and does not regress after 14 days and causes menstrual delay)
HEMORRHAGIC OVARIAN CYST (mainly result from intracystic hemorrhage)
THECA-LUTEIN CYST (is produced by the high concentration of hCG;accompanied with hydatidiform mole, chorioncarcinoma, during Clomiphen therapy; usually size >30cm; they regress when levels of bHCG fall)
LUTEIN CYST (reaction to HCG which stimulates tecalutein cells to proliferate; often associated with multiple pregnancies; it can contribute to virilization in women or formation of fetal organ in the featus)
Polycystic ovarian syndrome ( PCOS )
the most common cystic structures found in healthy ovaries
occur during all stages of life, from the fetal stage to the postmenopausal period.
result from either nonrupture of the dominant mature follicle or failure of an immature follicle to undergo the normal process of atresia
many follicle cysts lose the ability to produce estrogen
the cysts are thin walled and unilocular, usually ranging from several millimeters to 8 cm in diameter (average, 2 cm).
Corpus luteum cyst
persistant corpus luteum cyst
hemorrhagic ovarian cyst - mainly result from intracystic hemorrhage
may tend to rupture with intraperitoneal bleeding, especially in patients on anticoagulant therapy.
Generally, no treatment is required, and many of these cysts resolve spontaneously within 6-12 weeks.
In rare situations (eg, torsion, rupture and hemorrhage), operative intervention may be needed to treat these cystic masses.
Theca lutein cysts
produce elevated leves of hCG
seen in patients with
During clomiphen therapy
Rarely in normal pregnancy
Usually disapear spontaneously following
termination of the molar pregnancy,
treatment of chorioncarcinoma
Discontinuation of fertility therapy
Surgery is reserved for complications such torsion or hemorrhage
Benign ovarian tumors
most common, about 60% of epithelial tumors, resembles the oviduct epithelium, is about 10 cm in size;
The most common form - cystadenoma, cystadenoma papillare serosum); have smooth, white or transparent pouch with a smooth inner surface and are filled with bright serum
most commonly seen in women in their forties and fifties,
bilateral in 15-20% of cases.
unilocular or multilocular; have a smooth lining surface;
contain thin, clear, yellow fluid.
Epithelium similar to the cervical epithelium; they grow slowly and can reach considerable proportions causing enlarged abdominal circumference, characterized by the presence of thin, easily cracking septums, filled with gelatinous mucus content; increased risk of rupture, with resultant myxoma peritonei
most common in the third to fifth decades of life
generally multilocular,usually smooth walled; true papillae are rare compared with the serous variety
can grow quite large, measuring up to 30 cm; patients often present with ovarian torsion
the larger-sized varieties are associated with an increased risk of rupture, with resultant pseudomyxoma peritonei
ENDOMETRIOID TYPE- resembles the endometrium; clinical and macroscopic images are similar to serous cysts, ultrasonal tumors with irregular shapes, thick capsule, filled with fluid content with increased echogenicity
Transitional cell ( Brenner ) tumor- 1.5% -2.5% ovarian tumors, solid, fibrous tumor composed of cells resembling urinary bladder transition epithelium; often have estrogenic activity; may coexist with the Meigs syndrome
MIXED TUMOR- is recognized when each of the tumor components represents at least 10% of the tumor, the most common are serous mucous or serous-endometrial tumors
Sex – cord Stromal – gonadal
Functional: granulosal-tecal (producing estrogen), Sertoli-Leydig (producing androgens), gynadroblastoma
Fibroma (hormonally nonactive)
is the most common benign ovarian neoplasm
small, unilateral tumors,
arise from the ovarian cortical stroma
occur most commonly in women of postmenopausal age.
Hilus cell tumor
Dermoid cyst – mature teratoma (with ectodermal, endodermal
and mezodermal tissues)
consists of differentiated tissue from all 3 germ layers
contain organic structures, such as thyroid, bronchial, and central nervous system tissue. In dermoid cysts, ectodermal structures such as hair, teeth, and skin predominate
Mixed - cystadenofibroma
for women of childbearing age:
simple excision of the tumor
simple unilateral oophorectomy via laparoscopy or laparotomy is adequate provided the contralateral ovary appears grossly normal
for women of perimenopausal age:
total abdominal hysterectomy and bilateral salpingo-oophorectomy ( TAH + BSO )
Borderline ovarian tumors
2 major histologic tumor subtypes are serous and mucinous, with serous being more common. Rarely, there is an endometrial subtype and a Brenner tumor.
Borderline tumors make up approximately 15% of all epithelial ovarian tumors.
The mean age of occurrence is approximately 10 years younger than that of women with frankly malignant ovarian cancer.
Low fertility index (nulliparity and low pregnancy rate)
Hormonal contraception reduces the risk
Increased incidence in patients treated for infertility with stimulating ovulation regiments (clomifen, IVF)
Positive family history does not influence the incidence of BOT
As opposed to its true malignant counterpart, epithelial ovarian carcinoma, borderline ovarian cancer is often found at an early stage.
increases the risk of malignant transformation and incidence of ovarian cancer.
The risk of BOT recurrence is about 8%
Current guidelines include biopsy specimens of the pelvic peritoneum (cul-de-sac, pelvic wall, and bladder peritoneum), abdominal peritoneum (paracolic gutters and diaphragmatic surfaces), omentum, intestinal serosa and mesentery.
Borderline tumors are correctly diagnosed 58-86% of the time by frozen section, depending on the experience of the pathologist and the site of the operation (eg, tertiary care vs community hospital).
CA-125 levels are not shown to aid in the diagnosis or follow-up care of patients with borderline tumors.
The rate of detection of intratumoral blood flow in borderline tumors (90%) is similar to that of malignant neoplasms (92%). The resistance and pulsatility indexes are also significantly reduced in carcinoma and borderline ovarian tumors compared with those of benign tumors.
Computed tomography (CT) scanning should be considered preoperatively to identify possible foci of metastasis.
Histology and Cytology
According to Dietel and Hauptmann, the histology of borderline tumors is characterized by the following features:
Epithelial multilayering of more than 4 cell layers
Mild nuclear atypia
Increase in nuclear/cytoplasmic ratio
Slight to complex branching of epithelial papillae and pseudopapillae
No destructive stromal invasion - A major component in differentiating
malignant from borderline tumors
Mucinous tumors look similar to their benign counterparts, having large, multilocular cysts with smooth surfaces.
Microinvasive invasion is possible - stromal infiltration does not exceed 5mm; there is no adverse effect of microinvasion on prognosis.
majority of BOT is discovered in I FIGO stage (only in the ovary) – in the rest the metastasis is seen as formation of implants.
Peritoneal implants are described as invasive or noninvasive. They are usually single tumors on the surface of the peritoneum but it is possible to find larger tumors.
Noninvasive implants are glandular or papillary proliferations with cell detachments. Psammoma bodies, cellular atypia, and desmoplastic fibrosis are observed in some instances.
The accepted initial treatment of borderline ovarian tumors is surgical removal of the tumor and the performance of biopsies (multiple biopsy of the peritoneum, omentectomy – as in ovarian cancer).
hysterectomy and contralateral oophorectomy are not necessary (if the ovary appears normal) if the patient wishes to preserve fertility.
In the case of cystectomy (and BOT is discoved in the definite histopathological examination) it is recommended to perform a second surgery to remove the remaining ovary and the staging procedure (or remove the uterus – as written below).
It is possible to preserve the ovary that had the BOT but this increases the risk of recurrence in this ovary (or formation of a low grade ovarian cancer). This procedure is reserved to situations when the patients do not agree for a second surgery (eg. Planning pregnancy).
If the patient is beyond childbearing age, then hysterectomy is a reasonable option. Removal of a normal, contralateral ovary should be based on existing data regarding ovarian physiology.
If no normal adjacent tissue is present, oophorectomy or salpingo- oophorectomy should be performed. If the contralateral ovary is normal in appearance, a biopsy should not be performed on the adjacent ovary because of the risk of destruction (if fertility is an issue).
BOT without or with implants after proper staging do not require any additional treatment – require only observation.
The general consensus is that borderline tumors with noninvasive
implants do not require any further therapy and should be observed.
Some authors recommend chemotherapy in BOT with invasive implants
due worse prognosis. However, the benefits are still under discussion.