Ovarian cysts  are  quite often functional cystic spaces in the ovary.  But sometimes they could be endometriomas or if there are solid areas present, may harbour malignancy.  Current management principles of ovarian cysts are outlined below:

Asymptomatic unilateral cysts in the adolescent: If the clinical and ultrasonographic pictures are indicative of a simple ovarian cyst without any twist, it could be a functional cyst (e.g: follicular or corpus   luteum cyst) and could be left alone for 3 months. In the past, oral contraceptives were prescribed to reduce the size of the cysts, but recent studies have  shown that they may disappear even without any treatment (15). Persistence beyond 3 months points towards a simple serous cystadenoma. Simple serous  cystadenoma is a benign ovarian tumour. In a young unmarried girl a laparoscopic ovarian cystectomy is the treatment of choice .

Unilateral ovarian cysts in the adolesent with pain: If the patient   has persistent pain accompanied by autonomic symptoms like vomiting, one has to think in terms of a twist in the ovarian cyst. Identification   of the twisted vascular pedicle through ultrasonography is suggestive of ovarian torsion, and color Doppler sonography could be helpful in predicting the  viability of adnexal structures by depicting blood flow within the twisted vascular pedicle. A diagnosis of twisted ovarian cyst warrants surgery. During surgery, a bluish colour in the cyst on initial inspection is not confirmatory of gangrene in the ovary. In some cases, untwisting of the cyst may bring back vascularity to the ovary, which  may then regain its original colour (8). A cystectomy may now be done. In case the ovary  has undergone gangrene,   adnexectomy is the only option. Laparoscopic techniques if available are kindest to the patient in these circumstances. If the patient has symptoms of endometriosis like congestive dysmenorrhoea, an  endometrioma has to be suspected. In India, Ultrasonography in this age  group is usually done with transabdominal probes, which may be inadequate to distinguish a simple cyst from an  endometrioma. Endometriomas should  be managed by laparoscopic ovarian cystectomy and coagulation of any other endometriotic implants.

Unilateral unilocular simple ovarian cyst in the reproductive age group: In this age group, a vaginal sonography is possible, and in expert hands, a differentiation can be be made between a simple cyst and an endometrioma, the latter showing internal echoes. A simple cyst could be observed for 3 months. If it does not disappear,  the diagnosis of a benign ovarian neoplasm like serous or mucinous cystadenoma should be made.  If the patient has completed her family, salpingo-oophorectomy could be done on the affected side, instead of cystectomy.  Hysterectomy is a much more complicated procedure compared to ovarian cystectomy and is not warranted for treatment of benign neoplastic cysts. Endometriomas in this age group should be tackled taking in to consideration the findings in the rest of the abdomen. If there is extensive endometriosis in the pelvis, it may be prudent to do a hysterectomy with bilateral oophorectomy if the patient has completed her family. She should subsequently be put on hormone replacement therapy to prevent symptoms of oestrogen deficiency.

Ovarian cysts with  solid areas in the adolescent age group:

The presence of solid areas in the cyst makes the mass a complex mass.  Complex masses should alert one to the possibility of neoplasms, benign or malignant.  However, the mere presence of solid areas is not diagnostic of neoplasm. Complex cysts could be corpus luteum cyst, hemorrhagic cyst, ectopic pregnancy, ovarian torsion, tubo-ovarian abscess or appendiceal abscess,

endometrioma, or either benign or malignant neoplasm. Assuming that pregnancy, torsion, and infectious causes are excluded, a repeat sonogram should be performed after the next menses. Patients with pain may need to be scanned at a shorter interval. Hemorrhagic cysts can have a variable sonographic appearance that commonly changes over a period of days. If the mass decreases in size on ultrasound follow-up, it can continued to be followed. If the cyst persists for longer than two or three cycles, then neoplasm is more likely, and surgical evaluation is indicated. As with simple cysts, increase in size, pain, or mass effect should prompt earlier surgical intervention. Malignancy should be suspected on ultrasonography in some cases by observing the thickness of the capsule, shadowing, echogenecity, etc. Even if the ovarian cyst is palpable over the umbilicus, In the author’s experience, if an ovarian cyst is palpable above the umbilicus, unilocular and filled with clear fluid as shown on Ultrasound, it is possible to select a site on the abdomen where the cyst is looking tense and adjacent to the abdominal wall and put a needle in and aspirate the fluid through suction. Now it becomes easier to put in the laparoscope and salpingooophorectomy/cystectomy becomes possible.  In a large cyst, the thinner portion of the cyst is first excised. This makes it easier to delineate the ovarian wall from the cyst wall. A cystectomy can now be performed.  However, in a huge ovarian cyst, the functional ovarian tissue left behind after such a procedure is very less.

Unilateral cysts in the menopausal woman: If the cyst is only 3-5cm, she should have a serum CA-125 level done and a color doppler sonography done.    If CA–125 levels are less than 65IU and colour doppler is suggestive of a nonmalignant lesion, she could be followed up at 2,3,6,9, and 12 months and annually there after.  In cysts larger than this a unilateral salpingo-oophorectomy should be done, provided the CA125 levels and color doppler is suggestive of a nonmalignant lesion. An international multicenter study found that postmenopausal patients with an asymptomatic simple ovarian cyst 3-5 cm in diameter and a normal CA125 had a 0% risk of malignancy (6). CA125 is an antigenic determinant that is elevated in 80% of all patients with serous cystadenocarcinoma of the ovary but in only 50% of the patients with stage I disease. As a diagnostic aid, measurement of CA125 is most useful in postmenopausal patients with an ultrasonographically suspicious mass. In this setting, a level greater than 65 U/mL has been shown to have a positive predictive value of 97%. Color flow Doppler has been reported to be helpful in identifying malignancy. Computerized tomography (CT) does not have as good resolution of ovarian masses as ultrasound but does tell you a lot about the rest of the abdomen. Magnetic resonance imaging (MRI) is a little better at describing ovarian masses and, like CT, gives a good view of the entire abdomen; however, MRI is more costly. In summary, simple unilocular cysts are likely to be benign but should always be followed up with Ca- 125 levels. If it is greater than 65 U/ml, to be on the safe side the patient should be treated as ovarian malignancy. When CA125 levels are normal, the patients should be followed up.

Multilocular cysts:  Multilocular cysts as opposed to simple cysts need careful evaluation. Cysts >6cm should alert one to the possibility of malignancy.  The differential diagnosis of such a cyst in this age group should include an inflammatory tubo-ovarian mass, an endometrioma, a benign Teratoma (Dermoid) or even a hemorrhagic corpus luteum cyst..  In all these conditions a laparoscopic cystectomy/salpingo-oophorectomy is all that is needed. Here, it is useful to remember that CA-125 is elevated (>35mIU) in endometriomas, Pelvic infections, pregnancy and assossiated liver disease.  A markedly elevated Ca-125 (>200mIU) may make one strongly suspect malignancy and take a decision straight away in favour of a hysterectomy with bilateral salpingo-oophorectomy. A normal CA-125 level alone is not enough to rule out malignancy.  Quite often the diagnosis of borderline malignant ovarian tumour is made presumptively at the time of surgery on seeing the excrescences on the tumour, adhesions etc, confirmation being made only after histopathology. Thus in a patient with multilocular cysts, a colour doppler scanning and testing of serum for tumour markers might help in preoperatively detecting malignancy, but even if preoperative evaluation does not indicate malignancy a careful histopathology is mandatory postoperatively.

Ovarian cyst in pregnancy:  Traditionally, asymptomatic ovarian cysts >8cm should be removed only after 16 weeks as till then there is a possibility that the cyst is a corpus luteum cyst. Asymptomatic corpus luteal cysts disappear in second trimester.  But symptomatic cysts (Torsion, haemmorrhage, rupture) should be removed even in first trimester.Ultrasonographic cyst aspiration could be tried in selected cases.(20) In cases where cystectomy is done before 10 weeks, progesterone support should be given as the corpus luteum may have been removed.Progesterone suppositories are available in strengths of 100mg and 200mg. These could be given twice daily orally or vaginally.  Vaginal route is known to give better absorption rates.   One study has reported 6 cases of laparoscopic cystectomy for adnexal torsion without miscarriages, proving that in skilled hands laparoscopy is safe in 1st trimester(17).  The author also has done 2 laparoscopic ovarian cystectomies in first trimester of pregnancy with good maternal and fetal outcome.    Ovarian cysts getting impacted in the pouch of Douglas causing obstruction to labour in second stage could also be aspirated.

Risk factors for ovarian cancer: Family history of ovarian cancer is associated with increased risk of ovarian cancer.Family history of epithelial cancers are specially  associated with increased risk of ovarian cancer.  There are genetic markers, which can predict whether such an individual is at an increased risk of developing ovarian cancer. The most studied gene associated with ovarian cancer is the BRCA1 gene.  If relatives of patients who develop ovarian cancer are found to have this gene, they could undergo frequent surveillance for development of ovarian cancer.  If such individuals have to undergo hysterectomy, they should undergo a prophylactic bilateral oophorectomy as well. Similarly there are quite a few other genes also which have been found to be present in increased frequency in women with ovarian cancer. But, without further studies to confirm their usefuleness, it has not been found necessary to genetically screen the population as a whole to see who is at increased risk of ovarian cancer. These studies are as yet not available in India.

  Infertility and nulliparity is associated with increased risk of ovarian cancer.  The use of infertility drugs was suspected to increase the risk, but it has been found that it is infertility per se and not the use of ovulation inducing drugs that increases the risk of ovarian cancer.

The use of oral contraceptive pills, sterilization and gynaecological surgeries like hysterectomy has been found to be associated with a decreased risk of ovarian cancer.

Stages of Ovarian Cancer: Knowledge about the stages is necessary to make a decision on whether the surgical modality adopted for a particular tumour is adequate or if it is to be followed up with further treatment.

Stage I Growth limited to the ovaries

Stage IA Growth limited to one ovary; no ascites,No tumor on the external surfaces;capsules intact.

Stage IB Growth limited to both ovaries; noascites. No tumor on the external surfaces;capsules intact.

Stage IC Tumor either stage IA or IB, but with tumor on surface of one or both ovaries;or with capsule ruptured; or with ascitescontaining malignant cells; or with positive peritoneal washings.

Stage II Growth involving one or both ovaries,with pelvic extension.

Stage IIA Extension or metastases to the uterus or tubes.

Stage IIB Extension to other pelvic tissues.

Stage IIC * Tumor either IIA or IIB but on thesurface of one or both ovaries; or with capsule(s) ruptured;

.or with ascitescontaining malignant cells; or withpositive peritoneal washings.

Stage III Tumor involving one or both ovaries with peritoneal implants outside the pelvis or

Positive retroperitoneal or inguinal nodes;

 superficial liver metastasis equals stageIII;

tumor is limited to the true pelvis, but there is histologically proven malignant extension to small bowel or omentum

Stage IIIA Tumor grossly limited to the true pelviswith negative nodes but with Histologically confirmed microscopicseeding of abdominal peritoneal surfaces.

Stage IIIB Tumor involving one or both ovaries with histologically confined implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter;  nodes are negative

Stage IIIC Abdominal implants larger than 2 cm indiameter or positive retroperitoneal or inguinal nodes

Stage IV Growth involving one or both ovaries with distant metastases; if pleural effusion is present, there must be positive cytology to categorize as stage IV.

Benign tumours in adolescents: Breen and Maxson combined four series to demonstrate the shifting distribution of ovarian neoplasms by patient age. In young adolescents 10 to 14 years old, 72% of  ovarian neoplasms were germ cell; 8%, sex cord stromal; and 16%,epithelial tumours. Among the older adolescents 15 to 17 years old, 49% were germ cell; 16%,sex cord stromal, and 28%, epithelial.

Cystic teratomas: Cystic teratomas (Dermoids) are the most common benign tumour in this age group. Dermoids are benign germ cell tumours. They usually contain skin, teeth, bones, hair, and extremities. . On sonography, dermoid cysts often appear as complex cystic masses that contain solid elements that cause shadowing.  Laparoscopy or laparotomy can be used to remove dermoids by cystectomy in most patients or by oophorectomy when necessary. If the dermoid is larger than 6 cm or the patient has undergone multiple surgical procedures with adhesions, laparotomy is the preferred treatment approach..  Careful attention should be given to the other ovary because of the 12% rate for bilateral occurrence.  There is a 1-2% chance of malignant change in Dermoids, but this is unusual in this age group, being an occurence seen usually in the post-menopausal age group.

Germ Cell Malignancy :Germ cell tumors are the most common type of ovarian malignancy in adolescents. The median age at diagnosis for these tumors is 18 to 20 years. Unilateral salpingo-oophorectomy followed by platinum chemotherapy gives very good results, retaining the reproductive potential of the patient.

Dysgerminoma: It is the commonest germcell malignancy.In early cases unilateral salingo-oophorectomy followed by surveillance is all that is necessary.  In advanced cases, combination chemotherapy has to be added.

Other germ cell tumours: Other germ cell malignancies found in adolescents include immature teratoma, embryonal carcinoma, endodermal sinus tumor, gonadoblastoma, choriocarcinoma, and mixed germ cell tumors. Many of these tumors produce markers, as previously discussed, that may be useful for following response to therapy. Most patients should receive postoperative chemotherapy with bleomycin, etoposide, and cisplatin, with the exception of those with stage I, grade I immature teratoma, who can be followed with surveillance. The survival rate for these patients is not as good as those with dysgerminoma but is still excellent, especially for those with early stage disease with appropriate adjuvant chemotherapy.

Tumour markers in ovarian Ca in adolescent age group: Whenever a patient is suspected to have an ovarian malignancy, she should have the levels of tumour markers checked, both for diagnostic purposes and for following up the patient after surgery. The tumor marker, Cancer antigen 125(CA-125) is not as useful in adolescents as in menopausal patients. Elevation can be caused by a variety of processes that result in peritoneal irritation, such as endometriosis or PID, making the test nonspecific in this age group. Germ cell tumours are more common in this age group and the tumour markers specific to these tumours will be more useful in this age group.

Alpha-Fetoprotein can be made by endodermal sinus tumors, embryonal cell cancer, mixed germ cell malignancies, and rarely by immature teratomas. Serum beta-hCG can be found in nonpregnant patients with embryonal cell carcinoma and choriocarcinoma. Patients with dysgerminoma may have elevated lactate dehydrogenase levels. Tumor markers are most useful for following treatment response in patients diagnosed with ovarian malignancies.

Ovarian caner in the adult woman:

Epithelial tumours:

Benign epithelial tumors: Conservative surgery with the preservation of some ovarian tissue is enough in young women with benign epithelial tumors. This usually includes ovarian cystectomy or oophorectomy. In postmenopausal women a TAH/BSO can be considered to avoid future cancer risk.

Malignant epithelial tumours: Almost 85% of all ovarian malignancies are derived from ovarian epithelium, making epithelial malignancies the most commonly encountered ovarian cancer.  It could be borderline, or frankly malignant.  They include, Serous, mucinous, endometrioid, clear cell, Brenner-transitional cell, mixed mesodermal, and undifferentiated tumors.

Epithelial ovarian tumors of low malignant potential (borderline tumors):  In these tumours, there are atypical cells seen, but there is no stromal invasion.   In women who have completed their childbearing, a TAH/BSO/omentectomy is appropriate. 

Malignant epithelial ovarian tumour: Frank malignancy is suspecte

if the tumour is bilateral, adherent to adjacent organs has surface

excrescences,rupturedcapsule,ascites,peritoneal implants,haemmorrhage and necrosis,solid areas or intracystic papillations.  These tumours have to beremoved by cytoreductive surgery.  Cytoreductive surgery is the removal of as much of the tumor and its metastases as possible. It includes TAH, BSO, and complete omentectomy with resection of any metastatic lesions. In some patients, bowel resection and retroperitoneal lymphadenopathy are necessary to

obtain optimal cytoreduction. Optimal cytoreduction is achieved when the largest residual tumor mass measures less than 1.5 cm. This has to be followed up with chemotherapy. Sometimes the tumour appears inoperable at first laparotomy.  These patients are first given chemotherapy and when the tumour is more amenable to surgery, cytoreductive surgery should be attempted.

Germ cell tumours: Germ cell tumours include: dysgerminoma, endodermal sinus tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, teratoma, mixed forms, and gonadoblastoma. 

Benign germcell tumours:  These are Gonadoblastoma, Mature teratoma (Dermoid), & Struma ovarii. 

Malignant Germcell tumours: These include dysgerminoma, endodermal sinus tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, teratoma, mixed forms, and gonadoblastoma.

 In all these tumours, unilateral salpingo-oophorectomy and surgical exploration is all that is necessary in early stages.

Dysgerminoma: Usually the tumour does not go beyond Stage sugery and I can be stopped at unilateral salpingo-oophorectomy.  But if the stage has gone beyond Stage I, a cytoreductive surgery has to be done,with additional therapy.

Nondysgerminomatous malignancies: Unilateral tumors are the rule in nondysgerminomatous germ cell malignancies. Because of this, unilateral oophorectomy should be performed. This would preserve the contralateral ovary, as long as it appears normal, for hormone production and future childbearing potential. .  Cytoreductive surgery for advanced disease should be undertaken when possible. In patients needing to preserve childbearing function, unilateral salpingo-oophorectomy should be done followed by chemotherapy.  Normal menstruation is known to resume on stopping chemotherapy.  There is hardly any role for second look laparotomy for follow up of germcell tumours.  Measuring tumour markers may be enough for follow up.

Stromal cell tumours: These include Granulosa stromal cell tumor, Sertoli stromal cell tumor, sex cord tumor with annular tubules, Leydig cell tumor, lipid cell tumor, and gynandroblastoma.

Stage I and IA : If unilatateral salpingo-oophorectomy has been done at first surgery, that may be all that need be done.  It should be followed up with surveillance.  Granulosa tumours are usually indolent and if limited to the ovary, do not usually relapse. 

Stage IB onwards: If the patient has completed child bearing, TAH with BSO may be done.  Data are limited on treating patients with advanced or recurrent stromal tumors because of the rarity, multihistologic patterns, and indolent behavior of these tumors. Even less information is available regarding which patients should receive adjuvant therapy. However, use of chemotherapy and even radiotherapy has been described in a few studies for recurrent tumours. 

In summary,

Total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant chemotherapy should be considered in the following cases:

 Patients with stage I or II Epithelial tumours if any of the following are present:

Poorly differentiated disease (grade 3), tumor excrescences on the surface of the ovary, ascites, positive peritoneal cytology, or extraovarian disease.

Unilateral salpingo-oophorectomy may be enough for patients with with the following tumours:

Grade I, stage 1A Invasive epithelial tumors.

Borderline tumors.

Germ cell tumors.

Stromal cell tumors.

References:

1.     Abeloff: Evaluation of adnexal masses in adolescents. Clinical Oncology, 2nd Ed., Copyright © 2000 Churchill Livingstone,Inc.

2.     Ann N Y Ovarian malignancies in adolescence. Acad Sci 1997 Jun 17;816:338-46 

3.     Beretta P; Franchi M et al. Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation. Fertil Steril 1998 Dec;70(6):1176-80.

4.     Brooks SE. Preoperative evaluation of patients with suspected ovarian cancer. Gynecol Oncol. 1994;55(3 pt 2):580-590.

5.     Busacca M; Marana R Recurrence of ovarian endometrioma after laparoscopic excision. Am J Obstet Gynecol 1999 Mar;180(3 Pt 1):519-23

6.     Drake J. Diagnosis and management of the adnexal mass. Am Fam Physician. 1998;57:2471-2475.

7.     Flynn MK; Niloff JM Outpatient minilaparotomy for ovarian cysts. J Reprod Med   1999 May;44(5):399-404

8.     Gabriel oeslner,MD et al.,  Long term follow up of the twisted ischaemic adnexa managed by detorsion:Fertility and Sterility Vol.60  No6  December,1993.

9.     Goldstein SR. Conservative management of small postmenopausal cystic masses. Clin Obstet Gynecol.1993;35:395-401.

10.   Guerriero S; Mallarini G. et al. Transvaginal ultrasound and computed tomography combined with clinical parameters and CA-125 determinations in the differential diagnosis of persistent ovarian cysts in premenopausal women. Ultrasound Obstet Gynecol 1997 May;9(5):339-43.

11.   Hutton.J. Gynaecological disease(Nonmalignant). :  High RiskPregnancy Management Options. Ed.David K.James,Philip J.Steer. sec.edition. W.B.Saunders.

12.   Laurel.W.R. The Ovary : Ryan: Kistner’s Gynecology & Women’s Health, Seventh Edition, 1999       Mosby, Inc.

13.   Lee EJ; Kwon HC. Diagnosis of ovarian torsion with color Doppler sonography: depiction of twisted vascular pedicle. J Ultrasound Med 1998 Feb;17(2):83-9

14.   Lee EJ; Kwon HC,et al: Diagnosis of ovarian torsion with color Doppler sonography: depiction of twisted vascular pedicle.J Ultrasound Med 1998 Feb;17(2):83-9.

15.   Linda Van Lee,“Clinical presentation of adnexal masses”  at 48th annual meeting of American College of Obstetricians and Gynecologists, San Fransisco,May 2000.

16.   Major T; Borsos A; Lampe L; Juhasz B Ovarian malignancies in childhood and adolescence.      Eur J Obstet Gynecol Reprod Biol 1995 Nov;63(1):65-8

17.   Morice P; Louis-Sylvestre C Laparoscopy for adnexal torsion in pregnant women.Reprod Med 1997 Jul;42(7):435-9

18.   Schutter EM, Kenemans P, Sohn C, et al. Diagnostic value of pelvic examination, ultrasound, and serum CA125 in postmenopausal women with a pelvic mass. An international multicenter study. Cancer. 1994;74:1398-1406.

19.   Stark JE; Siegel MJ Ovarian torsion in prepubertal and pubertal girls: sonographic findings. Am J Roentgenol 1994 Dec;163(6):1479-82.

20.   Troiano RN; Taylor KJ . Sonographically guided therapeutic aspiration of benign-appearing ovarian cysts and endometriomas.  Am J Roentgenol 1998 Dec;171(6):1601-5.Volume 46 • Number 3 • June 1999

21.   Walter H. Gotlieb MD, PhDa ., et al. CA 125 measurement and ultrasonography in borderline tumors of the ovary. Am J Obstet Gynecol 2000;183:541-6.

22.   Zanetta G; Lissoni A. et al., Role of puncture and aspiration in expectant management of simple ovarian cysts: a randomised study. BMJ 1996 Nov 2;313(7065):1110-3.