Unexplained adnexal mass

An adnexal mass is a swelling arising from or near the ovary, fallopian tube or broad ligament, found on examination or imaging.

Most are benign functional cysts or mature teratomas, but a minority are malignant or borderline tumours, and some are urgent (torsion, ectopic pregnancy, tubo ovarian abscess).

The main clinical point is to exclude pregnancy and acute pathology, classify the mass by ultrasound morphology, age and menopausal status, add tumour markers where indicated, and direct women with a high risk of malignancy to gynaecological oncology before surgery.

Clinical relevance. Ovarian cancer is often diagnosed late. Surgery by an oncology team improves survival, and inappropriate cyst drainage or rupture at surgery worsens stage and outcome.

Anatomy. The adnexa include the ovaries, fallopian tubes, ovarian and tubal ligaments and the broad ligament. Masses may arise from the ovary (functional, epithelial, germ cell, sex cord stromal), tube (hydrosalpinx, pyosalpinx, ectopic pregnancy, tubal cancer), paraovarian tissue (paraovarian and paratubal cysts), or adjacent organs (appendix, bowel, uterus, retroperitoneum).

Mechanisms. Functional cysts result from failed follicle rupture or persistent corpus luteum. Neoplasms arise from epithelium, germ cells or stroma. Inflammatory masses result from infection and endometriosis. Metastasis from gastrointestinal, breast and endometrial tumours also occurs.

Classification. By morphology on ultrasound: simple (unilocular, anechoic, thin walled), unilocular with echoes (haemorrhagic cyst, endometrioma, dermoid), multilocular, multilocular solid, and solid.

By origin: ovarian or non ovarian. By risk: low, intermediate or high risk of malignancy.

Key distinctions. A simple unilocular cyst of any size is nearly always benign. A cyst with ground glass echoes suggests endometrioma, and one with echogenic fat, hair and acoustic shadowing suggests a mature teratoma. Solid components with blood flow, irregular papillary projections, ascites and bilateral involvement suggest malignancy. Sudden severe pain suggests torsion or rupture.

History

• Symptoms: pelvic or abdominal pain (acute or chronic), bloating, early satiety, abdominal distension, urinary frequency, constipation, dyspareunia, menstrual change, postmenopausal bleeding, weight loss, fatigue.
• Acute pain with vomiting (torsion), fever and discharge (pelvic inflammatory disease), amenorrhoea and bleeding (ectopic pregnancy).
• Menopausal status, menstrual pattern, parity, fertility treatment (ovarian stimulation), hormonal therapy, tamoxifen.
• Family history of ovarian, breast, endometrial or colorectal cancer (BRCA1 and BRCA2, Lynch syndrome), previous cancer.
• Previous pelvic surgery, endometriosis, pelvic infection, ovarian cysts and their course.
• Symptoms of hormonal activity: virilisation (androgen secreting tumour), abnormal bleeding or precocious puberty (oestrogen secreting tumour), hyperthyroidism (struma ovarii).
• Gastrointestinal symptoms, haematuria, respiratory symptoms.
• Region specific: genital tuberculosis, schistosomiasis, hydatid disease.

Examination

• Vital signs, BMI, performance status, pallor, supraclavicular and inguinal nodes.
• Breast examination when metastasis or hormone effect is possible.
• Abdomen: mass size, consistency, mobility, tenderness, guarding (torsion, rupture), ascites (shifting dullness), hepatomegaly, umbilical nodule, omental mass.
• Chest: pleural effusion.
• Speculum and bimanual and rectovaginal examination: adnexal mass size, tenderness, mobility, fixed or nodular pouch of Douglas, uterine size, cervical abnormality.
• Signs of androgen excess (hirsutism, clitoromegaly) or oestrogen excess.

Red flags

• Sudden severe unilateral pain with vomiting (torsion).
• Haemodynamic instability, shoulder tip pain or positive pregnancy test (ruptured ectopic pregnancy, haemorrhagic cyst).
• Fever, rigors and cervical motion tenderness (tubo ovarian abscess).
• Persistent bloating, early satiety, pelvic or abdominal pain, urinary urgency, ascites, weight loss in a woman over 50 years.
• Bilateral masses, solid components, irregular surface, fixed mass or nodular pouch of Douglas.
• Elevated CA 125 with suspicious ultrasound, or markedly elevated markers in a young woman (germ cell tumour).
• Rapid growth, a mass over 10 cm, or a postmenopausal mass.
• Virilisation or precocious puberty.
• Family history of BRCA, Lynch syndrome or breast or ovarian cancer.
• Pleural effusion or umbilical nodule.

Special groups. Pregnancy: most are corpus luteum cysts or dermoids; torsion risk is highest in the first trimester and after cyst enlargement. Girls and adolescents: germ cell tumours and torsion are more frequent. Postmenopausal women: higher risk of malignancy. Women on tamoxifen: functional cysts and endometrial pathology. Women with fertility treatment: ovarian hyperstimulation.

Organised by origin and nature. Each cause is common unless marked serious or uncommon. Functional and physiological

• Follicular cyst, corpus luteum cyst, haemorrhagic cyst.
• Theca lutein cysts (hCG excess in trophoblastic disease, multiple pregnancy, ovarian hyperstimulation).
• Luteoma of pregnancy.
• Polycystic ovarian morphology.

Benign neoplasms and endometriosis

• Mature cystic teratoma (dermoid).
• Serous and mucinous cystadenoma.
• Endometrioma.
• Fibroma, thecoma, Brenner tumour (Meigs syndrome with ascites and pleural effusion).
• Struma ovarii and benign sex cord stromal tumours.

Borderline and malignant ovarian tumours

• Serious: borderline serous and mucinous tumours.
• Serious: epithelial ovarian cancer (high grade serous, endometrioid, clear cell, mucinous, low grade serous).
• Serious: germ cell tumours (dysgerminoma, yolk sac tumour, immature teratoma, embryonal carcinoma, choriocarcinoma).
• Serious: sex cord stromal tumours (granulosa cell tumour, Sertoli Leydig cell tumour).
• Serious: metastatic tumours (Krukenberg tumour from stomach or colon, breast cancer, endometrial cancer, appendiceal tumour, lymphoma).
• Serious: primary fallopian tube cancer, primary peritoneal cancer.

Tubal and inflammatory

• Hydrosalpinx, pyosalpinx.
• Serious: tubo ovarian abscess.
• Serious: ectopic pregnancy.
• Genital tuberculosis, schistosomiasis.
• Pelvic inflammatory disease with phlegmon.
• Adhesions and peritoneal inclusion cyst.

Paraovarian and uterine

• Paraovarian, paratubal and mesonephric cysts.
• Pedunculated or broad ligament fibroid.
• Uterine anomalies (non communicating rudimentary horn).
• Serious: uterine sarcoma with adnexal extension.
• Serious: ovarian torsion (with any mass).

Non gynaecological

• Appendiceal mucocele, appendiceal abscess or tumour.
• Diverticular abscess, Crohn disease mass, faecal loading.
• Pelvic kidney, ureteric dilatation, bladder diverticulum, urachal cyst.
• Retroperitoneal tumour, lymphocele, peritoneal cyst, hernia, hydatid cyst.
• Pelvic haematoma or abscess after surgery, ovarian remnant syndrome.
• Rare: cystic lymphangioma, neurogenic tumours.

Stepwise reasoning

1. Exclude pregnancy and acute surgical causes (ectopic pregnancy, torsion, abscess, rupture).
2. Characterise the mass with transvaginal and transabdominal ultrasound, and score it using validated ultrasound rules or a risk model.
3. Calculate a risk of malignancy index in women who lack expert ultrasound, and add tumour markers by age and morphology.
4. Add MRI for indeterminate masses, CT for staging when malignancy is likely, and consider non ovarian sources.
5. Triage: observe, follow up, laparoscopic surgery by a gynaecologist, or surgery by gynaecological oncology.

First line tests

• Urine pregnancy test; serum beta hCG when positive.
• Full blood count, C reactive protein, urea, creatinine, electrolytes, liver function tests, coagulation screen if surgery is likely, group and save.
• Nucleic acid amplification tests for chlamydia, gonorrhoea, Trichomonas vaginalis and Mycoplasma genitalium when infection is suspected.
• Transvaginal ultrasound with colour Doppler: size, laterality, wall, septations, solid components and their size, papillary projections, acoustic shadowing, flow, ascites, peritoneal deposits, contralateral ovary, uterus and kidneys.
• Simple ultrasound rules, benign features: unilocular cyst, solid components under 7 mm, acoustic shadows, smooth multilocular tumour under 100 mm, no blood flow.
• Simple ultrasound rules, malignant features: irregular solid tumour, ascites, at least 4 papillary structures, irregular multilocular solid tumour of 100 mm or more, very strong blood flow.
• If only benign features are present the mass is benign; if only malignant features are present it is malignant. If neither or both are present the mass is indeterminate and needs expert review.
• Risk of malignancy index = ultrasound score x menopausal score x CA 125 (U/mL).
• Ultrasound score: 0 for no features, 1 for one feature, 3 for two or more of multilocular cyst, solid areas, bilateral lesions, ascites, intra abdominal metastases. Menopausal score: 1 premenopausal, 3 postmenopausal.
• An index of 200 or more indicates high risk and needs referral to gynaecological oncology.

Tumour markers

• CA 125: raised in most epithelial ovarian cancers but also in menstruation, pregnancy, endometriosis, fibroids, pelvic inflammatory disease, liver disease, heart failure, ascites and other cancers; less useful in premenopausal women. Use for women over 50 and for indeterminate masses.
• HE4 and risk of ovarian malignancy algorithm where available (improves specificity in premenopausal women).
• Girls and women under 40 with a complex solid mass: alpha fetoprotein, beta hCG and lactate dehydrogenase (germ cell tumour); inhibin and anti Müllerian hormone (granulosa cell tumour); testosterone, androstenedione and dehydroepiandrosterone sulphate (androgen secreting tumours).
• CEA and CA 19-9 for mucinous masses or suspected gastrointestinal metastasis.
• Thyroid function for suspected struma ovarii.

Imaging and procedures

• MRI pelvis with contrast for indeterminate masses (solid components that enhance suggest malignancy; fat signal suppresses in dermoid; shading in endometrioma).
• CT chest, abdomen and pelvis for suspected malignancy and staging (peritoneal disease, nodes, liver, omentum, pleural effusion); PET CT for selected cases.
• Colonoscopy and gastroscopy when metastasis from the gastrointestinal tract is possible (mucinous masses, bowel symptoms).
• Ascitic or pleural fluid cytology when present (not percutaneous aspiration of an ovarian mass).
• Diagnostic laparoscopy for torsion, tubo ovarian abscess or unclear findings.
• Image directed biopsy of omental or peritoneal disease before neoadjuvant chemotherapy.
• Genetic testing (BRCA1 and BRCA2, mismatch repair genes) in confirmed epithelial ovarian cancer.

Limitations. Ultrasound accuracy depends on operator experience. Frozen section may be unreliable for mucinous and borderline tumours. CA 125 has poor sensitivity for early disease and for mucinous and germ cell tumours. Dermoid and endometrioma can appear complex. Aspiration of an ovarian mass for diagnosis is not advised because of recurrence and the risk of spread.

Immediate steps. Resuscitate unstable women with intravenous access, crystalloid in 250 to 500 mL aliquots, blood and early senior review. Treat torsion with urgent laparoscopy and preserve the ovary. Treat ectopic pregnancy, ruptured cyst with haemodynamic compromise, and tubo ovarian abscess by the same day gynaecology team. Provide analgesia.

Analgesia. Paracetamol 1 g orally or intravenously every 4 to 6 hours, maximum 4 g daily (3 g daily with chronic alcohol use, malnutrition or hepatic impairment; 15 mg/kg each dose under 50 kg). Ibuprofen 400 mg orally every 6 to 8 hours with food, maximum 2.4 g daily; avoid in peptic ulcer, renal impairment, heart failure and NSAID sensitive asthma, and when surgery is likely. Morphine 2 to 5 mg intravenously every 5 to 10 minutes, titrated, for severe pain, reducing the dose in older adults and renal impairment.

Simple cysts

• Premenopausal: under 5 cm need no follow up; 5 to 7 cm need repeat ultrasound in 3 to 6 months, then yearly while present; over 7 cm need MRI or surgical review.
• Postmenopausal: unilocular cysts under 5 cm with a normal CA 125 need repeat ultrasound at 4 to 6 months, then yearly for up to 2 years if stable (evidence for the follow up schedule is limited); larger or complex cysts need referral.
• Hormonal suppression (combined oral contraceptive) does not hasten resolution of functional cysts.

Haemorrhagic cyst. Analgesia and observation, with repeat scan in 6 to 12 weeks. Surgery for haemodynamic instability or falling haemoglobin.

Endometrioma. Hormonal suppression (dienogest 2 mg orally once daily, or combined oral contraceptive) for pain; laparoscopic excision of the cyst wall (rather than drainage) when large (over 5 cm), symptomatic, growing, or with infertility, with counselling on effect on ovarian reserve. Suspicious features in postmenopausal women need oncology review.

Mature cystic teratoma. Laparoscopic cystectomy for symptomatic or large masses (over 5 to 6 cm) or growth on follow up, preserving ovarian tissue; observation for small asymptomatic masses with yearly ultrasound.

Serous and mucinous cystadenoma. Laparoscopic cystectomy or oophorectomy depending on age, size and fertility; send for histology.

Tubo ovarian abscess and pelvic inflammatory disease. Admit for severe illness. Give ceftriaxone 2 g intravenously once daily, doxycycline 100 mg orally or intravenously twice daily, and metronidazole 500 mg intravenously every 8 hours. Change to oral therapy after 24 hours of improvement to complete 14 days (oral: doxycycline 100 mg twice daily and metronidazole 400 mg twice daily).

Drainage under ultrasound or CT control, or laparoscopy, for abscess over 7 cm or no response after 48 to 72 hours. Remove an intrauterine device if there is no response at 72 hours. Treat partners and test for HIV, syphilis and hepatitis B.

Ectopic pregnancy.

Stable, unruptured, no foetal cardiac activity, mass under 35 mm and beta hCG under 5000 IU/L: methotrexate 50 mg/m2 body surface area intramuscularly as a single dose. Give a second dose if beta hCG falls by less than 15% between day 4 and day 7.

Before methotrexate, check full blood count, renal and liver function. Avoid NSAIDs, folic acid, alcohol and live vaccines. It is contraindicated in breastfeeding, active infection and severe renal, hepatic or haematological disease.

Unstable or ruptured: laparoscopic salpingectomy or laparotomy. Give anti D immunoglobulin 250 IU intramuscularly within 72 hours to rhesus negative women.

Torsion. Urgent laparoscopy for detorsion, preserving the ovary even when it looks dusky; oophoropexy and cystectomy as indicated.

Suspected or confirmed malignancy

• Refer to gynaecological oncology within 2 weeks (same day when unstable). Avoid cyst rupture and drainage. Laparoscopic surgery by oncology teams for selected stage I disease, with specimen retrieval in a bag.
• Surgery: peritoneal washings, total hysterectomy and bilateral salpingo oophorectomy, omentectomy, peritoneal biopsies, lymph node assessment as indicated; fertility sparing surgery (unilateral salpingo oophorectomy with staging) for young women with early disease. Advanced disease: primary debulking or neoadjuvant chemotherapy followed by interval debulking.
• Chemotherapy (specialist): carboplatin AUC 5 to 6 intravenously (dose calculated from glomerular filtration rate) with paclitaxel 175 mg/m2 intravenously over 3 hours every 21 days for 6 cycles.
• Before each cycle check full blood count, renal function, liver function and neuropathy. Premedicate against hypersensitivity; reduce for neutropenia and renal impairment.
• Maintenance therapy for BRCA mutated or homologous recombination deficient tumours is specialist.
• Germ cell tumours: fertility sparing surgery and chemotherapy with bleomycin, etoposide and cisplatin by specialist teams.
• Borderline tumours: conservative or radical surgery depending on fertility wishes.

Special groups. Pregnancy: most masses are physiological and are observed with ultrasound; surgery in the second trimester for torsion, rupture, suspicion of malignancy or very large masses (over 10 cm). Girls: paediatric surgical and oncology review; ovarian sparing surgery.

Postmenopausal women: low threshold for oncology referral.

Monitoring. Repeat ultrasound as planned, track symptoms and CA 125 trends in suspicious masses. After surgery, review histology at a multidisciplinary meeting within 2 weeks. After cancer treatment, follow up every 3 months for 2 years with examination and CA 125.

Referral and escalation. Refer urgently within 2 weeks to gynaecological oncology for a risk of malignancy index of 200 or more, an indeterminate mass with malignant features, ascites with a pelvic mass, or a markedly raised marker. Refer to the on call team the same day for torsion, ruptured ectopic pregnancy, or tubo ovarian abscess. Refer to genetics for BRCA or Lynch syndrome.

Admission criteria. Haemodynamic instability, suspected torsion, ectopic pregnancy, tubo ovarian abscess, uncontrolled pain, bowel obstruction from a mass, and large ascites or pleural effusion. Discharge and follow up. Women with benign masses go home with a written plan, scan date and indication for urgent return. Women with suspected cancer have a named oncology contact.

Safety netting. Return for sudden severe pain, vomiting, fainting, fever, heavy bleeding, rapid abdominal swelling, breathlessness, persistent bloating or early satiety.