Benign and Malignant cysts and tumors of the ovary Dr . Hayder Al Shamma’a

objectives Refer to your previous knowledge regarding anatomy and embryology of the ovaries recognize the epidemiology, risk actors and etiology of ovarian cancer Become familiar with the types of ovarian tumors Appreciate the danger of ovarian tumors Understand the effect of hormonally active ovarian tumors Be able to differentiate ovarian mass from other abdominal and pelvic masses Able to diagnose the possible complications of ovarian mass recognize the symptoms and signs suggesting malignant ovarian tumors Know the principles of treatment, surgery, chemotherapy, radiotherapy Be able to diagnose ovarian mass early and referral of suspicious cases for further evaluation

Introduction The ovaries give rise to a wide varieties of tumors and cysts more than any organ in the body This gives number of problems regarding classification, diagnosis and treatment The picture is more confused by the occurrence of functional and physiological cysts ( difficult to differentiate them from neoplastic cysts

Ovarian cysts and tumors can affect all age groups They are often asymptomatic even the malignant tumors (danger of delay diagnosis)

Embryology of the ovaries

Classification of ovarian tumors Many types of classifications According to histopathology **Can determine prognosis **Type of chemotherapy **Method of treatment

WHO Classification 1 - Epithelial tumors 75% a) serous (benign , borderline , malignant ) b) mucinous c ) endometrioid d) clear cell e) Brenner f) mixed g) unclassified

2- Sex cord tumors 5-10% a) granulosa stromal cell tumor i- granulosa ii- thecoma iii- fibroma b) androblastoma (Sertoli – Leydig ) c) gynandroblastoma (Sertoli – granulosa)

3-Germ cell tumors 15-20% a) teratoma b) dysgerminoma c) choriocarcinoma d) endodermal sinus tumor e) embryonal carcinoma f) polyembryoma g) mixed

4- metastatic tumors 5% a) Krukenberg tumor b) lymphoma 5- Others

Serov classification I : Epithelial II: Sex cord III: Lipid cell IV: Germ cell V: Gonadoblastoma VI: Soft tissue tumors non specific to ovaries VII: Unclassified VIII: Secondary ovarian tumors IX : Tumor like conditions

Tumor like conditions Follicular cyst Corpus luteum cyst Theca-lutein cyst Polycystic disease Endometriomatous cyst Inflamatory others

Epithelial tumors serous tumors 40% of all tumors are serous Benign (serous cystadenoma) Moderate size single Lucullus smooth outline, lining may contain papilliferous processes , contain clear serous fluid , 50% bilateral Histopathology:- epithelial lining of single colomnar or cuboidal with cilia ( like Fallopian tube)

Malignant (serous cystadenocarcinoma) It is the most common type of ovarian cancer May be cystic or solid or combination (solid with cystic component) Lined by fine papilliferous processes which may perforate the cyst wall and spread to peritoneal cavity, tubes, uterus Calcium deposition may occur psammoma bodies 50% bilateral

Mucinous cystadenoma Unilateral ,multilocular cyst It may reach enormous size Smooth outline Filled with jelly like mucin Lined by tall columnar cells with dark nuclei similar to cervical glands 5-10% tendency for malignant ransformattion

Spontaneous perforation may cause seedling of benign or low malignant cells in the peritoneal cavity causing ascitis of gelatinous fluid (pseudomyxoma peritonei) cusing cachexia and then death usually after several laparotomies Malignant (mucinous cystadenocarcinoma) Is relatively chemo and radio resistant

Endometrioid tumor Usually malignant (benign are rare) Solid cystic tumor often contain hemorrhagic area Lining is similar to proliferative endometrium with glans Some time associated with endometrial cancer

Brenner tumor Unilateral , solid 5-15 cm It is usually borderline malignant Histopathology :- transitional epithelial cells imbeded in a fibrous tissue stroma

Germ cell tumors These are tumors derived from totipotent cells (has the potential to differentiate to all types of tissues) ie, can differentiates to embryonal cell line or extra-embryonal cell line (chorionic cells)

a) teratoma Mature teratoma (dermoid cyst) Benign cystic It is the commonest ovarian cyst seen in young women It affect 2nd and 3rd decade of life 20% bilateral It is a smooth unilocular cyst filled with sebum with a hump of tissue at one side called mammillary process The hump contain variable types of tissues , bone , teeth, cartilage, skin, sebaceous glands , hair which project inside the cavity

The cyst usually lie in the vesicouerine pouch It contain tissue of endoderm , mesoderm and ectoderm It may contain thyroid tissue causing thyrotoxicosis called stroma ovarii

b) Immature teratoma Usually solid Unilateral Usually malignant ( benign solid teratoma is rare) Affect 2nd decade of life

b) dysgerminoma Lobulated solid tumor soft in consistancy Yellow creamy color 10 – 20 % bilateral Highly radio and chemosensitve Histopathology:- large polyhedral cells contain glycogen

c) Choriocarcinoma (non gestational ) Tumor consist of trophoblastic tissue Secret hCG

Sex cord tumors a) granulosa cell tumor Occur at any age Unilateral lobulated solid or partly cystic yellow color Low grade malignancy (borderline malignant) Histology:-granulosa cells which sometimes form micro-follicles called Call – Exner bodies Usually secret estrogen Rarely secret testosterone

b) theca cell tumor Firm yellow tumor Usually benign Usually secret estrogen rarely androgens

C) fibroma Benign tumor lobulated solid hard white mass Highly mobile Benign tumor Associated with ascitis and some time pleural effusion Meig’s syndrome

d) androblastoma Sertoli and Leidig cells Form seminephrous tubules like a testis but without spermatozoa Secret testosterone

Secondary ovarian tumors Metastasis from other organs uterus, stomach, colon, breast Krukenberg tumor Bilateral solid masses of adenocarcinoma with signet ring cells contain mucin which push the nucleus to the periphery of the cell The tumor may become larger than the primary site

Etiology of ovarian tumors Unknown Environmental high fat diet low fiber diet , vit A talcum powder caffeine ? asbestos? radiation ? viral infection mumps, rubella, influenza ??

Etiology of ovarian tumors Hormonal effect pregnancy, breast feeding, OCCP, are protective against ovarian cancer nulliparity, drugs for ovulation induction, early menarche , late menopause , are risks for ov. Cancer Tubal ligation, hysterectomy , protective! endometriosis increase risks

Etiology of ovarian tumors Genetic factors Site specific ovarian cancer (autosomal dominant) Hereditary breast-ovarian cancer syndrome Lynch syndrome II hereditary non polyposis colonic cancer (HNPCC)

Epidemiology More in industrialized countries 35% of genital tract malignancy More than 50% mortality Most epithelial cancer in postmenopausal women The disease usually asymptomatic and at presentation it is usually extended beyond the ovaries and involve adjacent organs

Spread of ovarian tumors Local infiltration to near organs by perforating the capsule and gain attachment to the omentum, broad ligament, bowel, uterus, etc…. Transperitonial spread through seedling Lymphatic spread to para-aortic lymph nodes to thoracic duct to left supraclavicular Hematological spread (uncommon)

staging Is the determination of the extent of the disease on preoperative clinical exam, investigation . But the final staging is surgical FIGO staging Stage I ( limited to the ovaries ) Stage II ( pelvic extension ) Stage III (intraperitonial metastasis ) Stage IV ( distant metastasis )

Clinical features of ovarian tumors

Age incidence :- with exception of germ cell and sex cord tumors , most ovarian tumor occurs at age 40-60 years.

Symptoms of ovarian cysts and tumors Asymptomatic:-many ovarian masses discovered accidentally during routine antenatal care or during routine exam at medical or surgical clinics

2. Pain:- pain is unusual symptom of uncomplicated neoplasm but it could occur in the following situation Metastasis to sacral plexus cause sacral root pain and dull aching back pain In cases of complicated cyst ( rupture, hemorrhage, twist, impaction and infection) cause acute abdominal pain (acute abdomen)

3. Abdominal enlargement 4 3. Abdominal enlargement 4. Pressure symptoms a) bowel :- indigestion, loss of appetite, vomiting ,constipation b) bladder:- frequency , retention of urine c) venous plexus :- varicose veins of the vulva , lower limbs , hemorrhoids

5. Menstrual cycle :- neither benign nor malignant tumor affect the menstrual cycle and the cycle usually remain regular even in the presence of malignant tumor , …except when the tumor is hormonally active (rare)

Tumors secrete estrogen child → precocious puberty adult → menstrual irregularity old → post menopausal bleeding Tumors secrete androgens child → heterosexual precocious puberty adult → defeminization (breast atrophy, amenorrhea ) then → musculinization (deep voice, hirsutism, enlarged clitoris, muscular )

Physical signs of ovarian tumor/cyst Small pelvic ovarian tumor:- Lying in the pelvis , not palpable abdominally and only palpable by vaginal examination It felt as a smooth mobile mass behind the uterus and to the side , the uterus can be separated from the mass Some time the mass may be felt anterior to the uterus suggest dermoid cyst or torsion

2. Big ovarian tumor:- rise up from the pelvis To the abdomen, it has a tendency to lie in the midline just under the abdominal wall pushing the bowl up and to the side

Differential diagnosis of small pelvic ovarian tumor tubo-ovarian abscess (bilateral, fixed, pyrexia, painful ). Broad ligament cyst(unilateral , pushing the uterus to the other side, painless, fixed Pedunculated fibroid (difficult to differentiate) Chronic ectopic Pelvic kidney (posterior fixed mass, ivp is diagnostic )

Differential diagnosis of large ovarian tumor Full bladder ( voiding or catheterization → disappear) Fecal mass ( elongated, indentation, defecation change shape and site) Ascitis ( resonant at the center dull at the periphery ) Fibroid (firm, move with the uterus, if pedunculated difficult to differentiate) Pregnancy (central mass, characteristic consistency , fetal parts and fetal heart auscultation ) Gross obesity ( distended abdomen , no mss can be felt ) Large hydrosalpinx Enlarged spleen Flatulence Mesenteric cyst (feel whole cyst , move only in one plane perpendicular to the root of mesentery )

Complication of ovarian cyst/tumor Torsion:- twist of the cyst with the ovary on its pedicle obstructing venous blood flow causing congestion, hemorrhage inside the cyst , pain, then obstruction of arterial blood causing necrosis Occur in moderate size cyst, when there is no adhesions Large cysts , presence of adhesions are unlikely to twist

Diagnosis :- colicky abdominal pain intermittent then continuous vomiting, tender adnexial mass Treatment emergency laparotomy/laparoscopy

2.Rupture :- either spontaneous or traumatic Spontaneous in large tumor rapidly growing with necrosis of the wall Traumatic during pv exam or blow to the abdomen The symptoms and signs depend on the content of the cyst If clear non irritant material →no symptoms (only diagnosed when sudden disappearance of cyst on u/s follow up if irritant as blood or sebum →acute abdomen Treatment :- laparotomy/laparoscopy

3. Hemorrhage:-may occur inside a cyst causing rapid enlargement and acute abdominal pain Treatment :- laparotomy/laparoscopy

4. Impaction:- the cyst grow and remain in the pelvis and press on the bladder neck and rectum causing abdominal pain , retention of urine , constipation Treatment :- laparotomy/laparoscopy 5. Infection :- from nearby structure like appendix, diverticulum, cause pelvic abscess Treatment:- laparotomy/laparoscopy

Investigation of ovarian cyst/tumor Ultrasound +Doppler ( is the main investigation ) 2. radiology:- a) may show calcifications, teeth, b) CXR preoperative investigation c) IVP d) CT scan MRI 3. Paracentesis cytology of ascitis (do not puncture the cyst) 4. OGD , colonoscopy 5. Tumor markers ( CA125 for ep. Cancer and hCG, CEA , AFP, for germ cell tumors)

Clinical features suggesting malignancy Age :- childhood tumors are usually malignant, in adults chance of malignancy increase with increasing age Pain :- dull aching pain and sacral root pain suggest malignancy Rapid growth Solid or solid/cystic Bilateral Ascitis Leg edema Fixation Vulvar varices Metastasis *** indicates malignancy

Treatment of ovarian cyst/tumor Determine whether functional or neoplastic , and if neoplastic whether benign or malignant Calculate the Risk of Malignancy Index ( RMI ) By measure CA 125 u/ml x US score x menopausal score US score = (0 ,1, 3 ) for each of the following feature , one point multilocular, bilateral, solid area, metastasis, ascitis (0 for no US score, 1 for one US finding , 3 for 2 or more points) Premenopause 1 , postmenopause 3

Example :- 25 years old , bilateral simple ovarian cyst, CA 125 = 20 u/ml RMI = 20 x 1 x 1 = 20 → low risk ( cutoff value 200 ) Example 55 years , solid bilateral tumor , CA 125 = 90 u/ml RMI = 90 x 3 x 3 = 810 high risk malignancy

Treatment of functional cyst Functional cyst in asymptomatic woman ,(unilateral, simple cyst, thin wall, no ascitis less than 7 cm ) follow up for 6 weeks Functional cyst will disappear

Treatment of ovarian neoplasm Mainly surgical Laparoscopy for benign ( low risk ) Laparotomy for malignant (high risk )

Treatment of benign ovarian cyst Below age of 45 years treated by cystectomy for small cyst oopherectomy for large cysts Above age 45 years TAH + BSO

Treatment of malignant ovarian tumor Staging +treatment Stage I and II TAH + BSO + omentectomy + para aortic lymphadenectomy + biopsy from diaphragm For stage III and IV surgical staging + cytoreduction + chemo/radio therapy

Terminal care Ascitis :- repeated aspiration, some times local chemotherapy Intestinal obstruction:- subacute obstruction treated conservatively , surgical treatment indicated if the disease limited to a small segment of the bowel Pain :- pain relief is an essential part of care and it is the least thing to do to the patient

Tumor like conditions Follicular cyst :- very common When small not regarded as abnormal Thin walled cyst lined by granulosa cells Contain clear fluid Rarely exceeds 5 cm Asymptomatic secret estrogen May cause endometrial hyperplasia Occur when Graafian folicle not ovulate

Corpus luteum cyst:- Bleeding inside corpus luteum Increase it’s life span Secret progesterone Delay menstruation Some time painful Misdiagnosed as ectopic

Theca lutein – graulosa lutein cysts Bilateral Occur when excessive stimulation of the ovaries by gonadotrophins From H- mole secret hCG From Clomiphene treatment or FSH Disappear when gonadotrophins stoped

Ovarian tumors in pregnancy Occur in 1/1000 pregnancy 5% malignant 10% functional 85% benign , dermoid and cystadenoma

Management Malignant → treat irrespective to pregnancy Benign → treat in 2nd trimester

Thank you