1. Pelvic Mass in the Female Patient
Differentials and Workup
David C Murphy, D.O.
IOA Summer Conference
French Lick, Indiana
August 2017

2. ~ 20% will develop a pelvic mass sometime in their lives
5-10% lifetime risk of surgery
Occurs from fetus to elderly
Asymptomatic 25 – 40 : 7.8%
Asymptomatic postmenopausal: 2.5%

3. Clinical approach Determine most likely etiology Anatomic location Age
Reproductive status
Features of urgent conditions are fairly specific
Malignancy must be excluded for any mass not clearly benign

4. Anatomic location Ovarian Fallopian tube Paratubal or paraovarian
Tuboovarian abscess
Broad ligament leiomyoma
Ov: physiologic cysts, benign neoplasms, cancer or metastatic disease
Ft: ectopic pr, hydrosalpinx, cancer

5. Age and reproductive status
Children and adolescents:adnexal torsion or ovarian malignancy (10-20%)
Premenopausal women: most masses are benign
Pregnant: ectopic pregnancy, luteomas, corpus luteum, theca lutein cysts
Postmenopausal: excluding malignancy is main priority
Germ cell tumors~35% -v- 20% in adults. Prem: incidence of ov cancer increases w age /100,000 age 20-29, v /100,000 age PM: avg dx is 63 in US

6. General evaluation Medical history: pelvic pain or pressure
Physical exam: size, consistency, mobility, abdominal distention, ascites
Imaging studies: pelvic ultrasound, MRI
Lab evaluation: pregnancy test, cbc, tumor markers
Characteristics: onset, location, duration, constant/intermittent, other associations. Adnexal mass and bleeding ?ectopic, hx of fever and vaginal discharge-TOA, persistent serosanguinous discharge without fever-fallopian tube cancer, Infertility- endometrioma or hydrosalpinx

7. Evaluation of urgent conditions
First trimester bleeding or pain
Acute pelvic or abdominal pain
Adnexal torsion
Ruptured or hemorrhagic ovarian cyst
Fever : TOA, periappendicial abscess, diverticular abscess

8. Evaluation of malignancy
Ovarian cancer- most common histiologic type is epithelial ovarian cancer
High grade serous EOC, fallopian tube and peritoneal carcinomas are considered a single clinical entity.
Metastatic disease from another primary- gastric and breast most common
Likelihood of malignancy depends on imaging findings, age/menopausal status, risk factors, lab results
No minimally invasive biopsy technique- would upgrade tumor
Family history of ovarian, breast, uterine, or colon cancer
High grade serous EOC, fallopian tube and peritoneal cancers are considered a single clinical entity

9. Evaluation- continued
Pelvic ultrasound is first line-sensitivity 86-91%, specificity 68-83%
MRI
Additional studies may be necessary to evaluate for metastasis
Serum markers
Surgical evaluation allows a definitive histiologic diagnosis
Patients with a complex adnexal mass, findings suggestive of metastatic EOC, fallopian tube or peritoneal carcinoma, or laboratory testing suggestive of ovarian cancer should be referred to a gynecologic oncologist.

10. Differential diagnosis of adnexal mass

11. A consensus paper from the Society of Radiologists in Ultrasound in 2010 indicated that transvaginal ultrasound, supplemented by transabdominal ultrasound, was the best technique for imaging and characterizing an adnexal cyst.

12. Pics ov anatomy and origins of ovarian tumors
Most common neoplasms are epithelial. Ovarian germ cell tumors are derived from primordial germ cells. Ovarian sex cord-stromal tumors derive from stem cells that would normally give rise to supporting epithelial cells, including ovarian stroma and follicles.

14. Fetuses, children, and adolescents
Pelvic mass in newborn is most likely a physiologic cyst, but can include GU disorders, GI tract disorders, or miscellaneous
Neonatal to puberty- physiologic cysts are uncommon because gonadotropin ovarian stimulation decreases in infancy and rises with puberty. Ovarian neoplasms <1% of tumors in this age group
Menarche – 18: simple and complex cysts common. <5% of ovarian cancers
However: ovarian cancer is the most common gynecologic malignancy in women<25. Germ cell tumors ½ - 2/3 , compared to 20% in adults
In girls younger than 9, approximately 80% of ovarian neoplasms are malignant
Peak age for germ cell tumors between

15. Premenopausal women
Many adnexal masses stimulated by hormones, including physiologic cysts, endometriomas, and leiomyomas

16. Prevalence of specific adnexal mass pathologies- IOTA n=4848
International Ovarian Tumor Analysis group

17. Follicular cysts appear smooth, thin-walled and unilocular
Follicular cysts appear smooth, thin-walled and unilocular. Simple cysts < 3 cm are considered physiologic. Generally < 10 cm
Corpus luteal can be simple, or complex, containing internal debris, and thick walls. Can be up to 8 cm, and generally resolve spontaneously

18. Theca lutein cysts are a result of overstimulation from high human chorionic gonadotropin. Gestational trophoblastic disease, multiple gestation, ovarian hyperstimulation, or pregnancy complicated by fetal hydrops.
May cause maternal virilization, hyperemesis gravidarum, preeclampsia or thyroid dysfunction.

19. Polycystic Ovarian Syndrome (PCOS)- enlarged ovaries with multiple small follicular cysts. Classic phenotype is obese, hirsute and anovulatory.
Treated to manage abnormal uterine bleeding, infertility, insulin resistance, obesity, and hirsutism.

20. Ectopic pregnancy is suggested by history of a missed menses, abdominopelvic pain, and vaginal bleeding.

21. Endometriosis is often associated with pelvic pain, dysmenorrhea and dysparunia.
Chocolate cyst- complex mass typically containing homogenous internal echoes.
Ground glass

22. Leiomyoma- benign neoplasm of smooth muscle origin.
Clinically apparent in 25% of reproductive age women.
Depending on size and location, patients present with c/o pelvic pressure, pain, menorrhagia, and/or dysmenorrhea

23. Tubo-ovarian abscess- inflammatory mass involving the fallopian tube, ovary, and occasionally adjacent pelvic organs
Characteristically presents with abdominopelvic pain, fever, purulent cervical discharge, and cervical motion tenderness.

24. Hydrosalpinx should be suspected when a dilated, tubular cystic structure is seen adjacent to the ovary
Often have incomplete septations

25. Serous or mucinous cystadenoma- among most common benign ovarian neoplasms. Thin-walled, uni- or multi-locular, and can range from 5 – 20 cm.
Mucinous occur less frequently, are more likely to be multilocular, are larger, and tend to be unilateral.
Many are assymptomatic and found incidentally on exam. Benign-appearing masses that are persistently symptomatic should be removed.

26. Mature cystic teratoma(dermoid) is a benign germ cell tumor and is the most common ovarian neoplasm in the 2nd and 3rd decades.
Contain elements to all three germ layers: ectodermal, mesodermal and endodermal
Ec- skin, hair, follicles and sebaceous glands, Me- muscle, urinary, En- lung, GI. Bilateral in % of patients

27. Malignant neoplasms Incidence in adnexal mass ranges from 6 – 11%
Most are partially cystic and derive from epithelial cell
Germ cell tumors 2nd most common in women < 30, rare afterwards
Krukenberg tumor- metastatic to ovary from another primary site, classically GI tract or breast
At least 30% of ovarian masses in women >50 are malignant. Nonmalignant etiologies include many of those seen in reproductive age
KT: gastric adenocarcinoma, especially at the pylorus,
most common

28. Risk factors for ovarian cancer

29. Estimated cancer risks brca1 and brca2

30. Estimated Cancer Risks (cont)

31. Lynch syndrome cancer risk

32. Epithelial neoplasms Accounts for 90%
High grade serous carcinoma 70 – 80 %
Endometroid carcinoma 10%
Clear cell carcinomas 10 %
Mucinous carcinoma 3 %
Low-grade serous carcinoma < 5%
Different subtypes also differ in risk factors and clinical behavior
High-grade tubal intraepithelial neoplasia/carcinoma is typically seen either associated with an ovarian or tubal mass or as a pathology result after risk-reducing SO in a patient with a BRCA mutation
Average age of diagnosis is ~ 60
Vague GI symptoms

33. Represent 70% of ovarian neoplasms in 10 – 30 year olds
Germ cell tumor
Malignant degeneration of a teratoma, is the most common germ cell tumor in postmenopausal women
Represent 70% of ovarian neoplasms in 10 – 30 year olds
Sex cord-stromal tumors
~ 1.2% of primary ovarian cancers
Avg age of diagnosis ~ 50
Often comprised of cells that produce ovarian hormones (estrogens, androgens)
Meigs syndrome: adnexal mass, ascites, pleural effusions. The prevelance of a simple unilocular cyst in postmenopausal women ranges from 2.5 – 18 %

34. Ultrasound differentiation
Determine whether the mass is almost certainly benign or whether the mass has some reasonable chance of being malignant.
Masses may be physiologic or pathologic
Gray-scale gives a 2 dimensional display of anatomy
Doppler look for presence or absence of flow in solid areas or septations
Combine with pertinent clinical information
Expertise of sonologist influences the likelihood of a correct diagnosis
Most physiologic masses are cystic.

35. Steps in characterizing a mass
1:Is it a simple cyst?
2: Is there a physiologic process that can account for potentially confusing findings?
3: Are there characteristics of specific entities?
4: Follow-up ultrasound or additional testing

36. 10 simple rules
M1 Irregular solid tumor M2 presence of ascites M3 At least 4 papillary structures M4 Irregular multilocular solid tumor with largest diameter > 100 mm M5 Very strong blood flow (color score 4)
B1 Unilocular B2 Presence of solid components where the largest solid component has a largest diameter < 7 mm B3 Presence of acoustic shadows B4 Smooth multilocular tumor with largest diameter < 100 mm B5 No blood flow(color score 1)
If one or more M-rules apply in the absence of a B-rule, the mass is classified as malignant. If one or more B-rules apply in the absence of an M-rule, the mass is classified as benign. If both rules, or no rules, the mass cannot be classified
International Ovarian Tumor Analysis (IOTA)group

37. Serum biomarkers CA 125 HE4 OVA1 Risk of Malignancy Algorithm (ROMA)
The United States National Institutes of Health defines a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic response to therapeutic intervention”.
Currently no serum biomarker is both sensitive and specific

38. Markers secreted by germ cell and sex cord-stromal tumors of the ovary

39. CA 125 1983 Most widely used biomarker
Large transmembrane glycoprotein derived from coelomic and mullerian epithelia
CA 125: <35U/ml
CA 125 II: <20 U/ml
Number on benign processes that can cause elevation
C- pericardium, pleura, peritoneum M- fallopian, endometrial, endocervical

40. Human epididymIs protein 4 (HE4)
2008
Monitoring for recurrent or progressive disease in patients with EOC
Antigen that is overexpressed in serous and endometroid ovarian carcinoma
Reference range is <150 pM

41. Carcinoembryonic antigen (cea)
Protein normally found in embryonic or fetal tissue
In adults- mucinous cancers associated with the GI tract or ovary
Also associated with breast, pancreas, thyroid and lung
Benign elevations- smoking, mucinous cystadenoma of ov or appendix, cholecystitis, cirrhosis, diverticulitis, inflammatory bowel disease, pancreatitis and pulmonary infections
Nonsmokers: <3.8 mcg/L
Smokers: <5.5 mcg/L

42. Cancer antigen 19-9
mucin protein that may be elevated in EOC
Used primarily to monitor disease response, or recurrence
Gastric, pancreatic, gallbladder, cholangiocarcinoma and adenocarcinoma of the ampulla of Vater
Investigational biomarkers
Osteopontin, mesothelin, lysophosphatidic acid, haptoglobin, transthyretin, apolipoprotein A1, serum C-reactive protein, and OVX1

43. Ova 1
2009
includes 5 serum biomarkers- CA 125 II, beta 2 microglobulin, transferrin, transthyretin, apolipoprotein A1
Ovarian malignancy risk index score
Premenopausal women Low < 5.0, High >5.0
Postmenopausal women Low <4.4, High >4.4
Affected by elevated triglycerides or rheumatoid factor levels

44. overa 2016 as a second generation multivariate index assay
CA 125 II, HE4, apolipoprotein A1, FSH and transferrin
Low risk < 5.0
High risk > 5.0

45. Risk of malignancy algorithm
2011
Includes CA 125 and HE4 to determine likelihood of malignancy in women undergoing surgery for an adnexal mass
Also uses two separate logistic regression algorithms, depending on menopausal status
Premenopausal: high risk of malignancy > 13.1%
Postmenopausal: high risk of malignancy > 27.7%

46. Risk of malignancy index
Used primarily in UK
Combines menopausal status, CA 125 and pelvic ultrasound
RMI I = U x M x CA 125
U- multi-locular cyst, solid areas, metastasis, ascites, bilat masses 3= 2-5 points
M- 1 for pre and 3 for post

47. Referral to gyn-onc: acog guidelines
Premenopausal (refer if any present)
Very elevated CA 125 level
Ascites
Evidence of abdominal or distant metastasis
Postmenopausal (refer if any present)
Elevated CA 125 level
Ascites
Nodular or fixed pelvic mass
Evidence of abdominal or distant metastasis
Committee Opinion No. 477

48. references
Ultrasound differentiation of benign versus malignant adnexal masses. (n.d.). Retrieved June 02, 2017, from
Differential diagnosis of the adnexal mass. (n.d.). Retrieved June 02, 2017, from
Approach to the patient with an adnexal mass. (n.d.). Retrieved June 02, 2017, from
Serum biomarkers for evaluation of an adnexal mass for epithelial carcinoma of the ovary, fallopian tube, or peritoneum. (n.d.). Retrieved June 02, 2017, from

49. References
Diagnosis and Management of the Adnexal Mass. (n.d.). Retrieved June 01, 2017, from
(n.d.). Retrieved June & july, 2017, from
Kaunitz, A., M.D. (2016, November 30). How to Apply New Guidelines for Evaluating Adnexal Mass. Retrieved July 20, 2017, from