PGI Joezelle Salunga

Module 6: Benign Gynecologic Tumors

Assessment: 32/F Gravida 1 Para 1 (1-0-0-1) Adnexal mass probably ovarian new growth

Pertinent Positive Pertinent Negative

Palpable mass No associated urinary symptoms: no dysuria, no hematuria, no incontinence, no

- 3 year history nocturia, no frequency
- Size: initially tennis ball No dyspareunia
(~6.5-7cm) → 12 x 12 cm on No post-coital bleeding
PE
- Location: right lower PE:
quadrant Inspection: grossly normal external genitalia
Speculum examination: clean-looking cervix, no erosions, no nodulations
- PE: cystic, movable, Bimanual examination: cervix close, uterus not enlarged, there is no cervical
nontender motion tenderness, no mass or tenderness at the left adnexa

GUIDE QUESTIONS:

1. What are your differential diagnosis?

Most adnexal masses are detected incidentally on physical examination or at the time of pelvic imaging.

An abdominal or pelvic mass may be attributed to multitudes of conditions. Considering the presentation of the patient—
with a long term palpable mass, and no other associated symptoms, as well as the physical examination, differential
diagnoses for this case would revolve around adnexal masses, more specifically ovarian masses.

Adnexal masses (mass of the ovary, fallopian tube, or surrounding connective tissues) may be found in females of all
ages, fetuses to the elderly, and there is a wide variety of types of masses. The principal goals of the evaluation are to
address acute conditions (eg, ectopic pregnancy, ovarian torsion, tubo-ovarian abscess), to determine whether a mass is
malignant, and the likelihood of spontaneous resolution.

Initial conditions we should consider upon encountering an adnexal mass are those that require immediate attention;
these include ectopic pregnancy, adnexal torsion, a ruptured ovarian cyst with hemorrhage, or a tubo-ovarian abscess.
However, as we have mentioned, this patient did not present with any associated symptoms.

The different conditions considered for an adnexal mass are summarized in the following table:

GYNECOLOGIC: GYNECOLOGIC: GYNECOLOGIC: NONGYNECOLOGIC

OVARIAN TUBAL EXTRAOVARIAN

Functional cyst Ectopic Paraovarian cyst Constipation

Corpus luteal cyst pregnancy Paratubal cyst Appendiceal abscess
Luteoma of pregnancy Hydrosalpinx Uterine leiomyoma Diverticular abscess
Polycystic ovaries (pedunculated or Pelvic abscess
Endometrioma cervical) Bladder diverticulum
Benign
Cystadenoma Tubo-ovarian abscess Ureteral diverticulum
Benign ovarian germ Pelvic kidney
cell tumor Peritoneal cyst
Benign sex cord Nerve sheath tumor
stromal tumor
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Epithelial carcinoma Epithelial Metastatic endometrial Appendiceal neoplasm
Epithelial borderline carcinoma carcinoma Bowel neoplasm
neoplasm Serous tubal Metastasis
Malignant Germ cell tumor intraepithelial Retroperitoneal sarcoma
Metastatic cancer neoplasia
Sex-cord/stromal tumor

Physical examination findings may suggest whether the ovarian mass is benign or malignant. Physical examination
findings obtained from this patient highly suggest a benign mass, if compared from the following criteria:
Benign ovarian mass Malignant ovarian mass

Cystic, non-tender* Large, solid, nodular

Movable Fixed

Unilateral Bilateral

No ascites With associated ascites

In addition, differential diagnosis can be narrowed depending on the stage of the woman’s reproductive life. The great
majority of adnexal masses occur in reproductive-age patients (including postmenarchal adolescents), and most of these
masses are benign. This is because the pathogenesis of many benign adnexal masses is associated with reproductive
function. Many other types of adnexal masses are associated with the menstrual cycle or reproductive hormones (eg,
follicular cysts, endometriomas) and are common findings found in this patient population.

BENIGN LESIONS

Signs and Symptoms Gross Features Diagnosis

Follicular · Usually asymptomatic · 2.5 or 3 cm to 15 cm in size · Ultrasound: thin-

Cyst · If (+) symptoms: abnormal menses, · Solitary or multiple walled, unilocular,
tenesmus, transient pelvic tenderness, deep · Translucent, thin-walled, and are filled anechoic
dyspareunia, and AUB with watery, clear to straw-colored
· If large cyst: (+) vague, dull sensation or fluid
heaviness in the pelvis

Corpus · Asymptomatic · 3-10 cm in size · Ultrasound: thin-

Luteum Cyst · If (+) symptoms: dull, unilateral lower · Corpus luteum hemorrhagicum: most walled, unilocular,
abdominal pain; (+) direct and rebound prone to rupture → results to pooling of mixed
tenderness due to peritoneal irritation; blood echoes/haziness
adnexal tenderness (hemorrhage in
· Halban’s Triad: delay in normal period, cyst)
unilateral pelvic pain, tender adnexal mass · TVS color flow
mapping: “ring of
fire”

MALIGNANT CONDITIONS

NON-EPITHELIAL OVARIAN TUMORS

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Germ Cell · Rapidly growing mass (palpable) · Adnexal mass ≥2cm
Tumors · Subacute pain due to distention, in premenarcheal
hemorrhage, necrosis girls, ≥8cm in
· Pressure symptoms premenopausal
· Menstrual irregularities women
· Abdominal distention (ascites) · hCG, AFP titers,
· Palpable adnexal mass CBC, liver function
· Signs of ascites, pleural effusion, tests
organomegaly (e.g. dyspnea) · Chest X-Ray,
karyotype
· Preoperative CT
scan, MRI

Dysgermino · Most common malignant tumor of the · Large, round, ovoid or polygonal · Adnexal mass ≥2cm in
ma germ cell type(30-40%) cells, with abundant, clear, and very premenarcheal girls,
· Usually confined to one ovary pale staining cytoplasm ≥8cm in
· Large and irregular nuclei with premenopausal
prominent nucleoli; mitotic figures women
seen · hCG, AFP titers, CBC,
liver function tests
· Chest X-Ray,
karyotype
· Preoperative CT scan,
MRI

Immature · TERATOMA (Generalities) · Immature (fetal) tissues from all · X-ray, ultrasound →
Teratoma o The second most common germ cell three germ cell layers calcifications
malignancy · Immature neural elements are · NO TUMOR
o Usually unilateral common and may correlate with MARKERS
o Grow rapidly, causes pain early outcome

Mature · Most common benign non-epithelial CA · X-ray, Ultrasound to

Teratoma · Contains elements from all germ cell detect calcifications,
layers no tumor markers

Yolk Sac · Third most frequent malignant germ cell · Presence of endodermal sinus or · UTZ: Large,
Tumors tumor of the ovary SCHILLER DUVAL BODIES predominantly cystic
· Peak at 19 yo · Cystic spaces lined with a layer of mass, measuring 20
· Abdominal/pelvic pain flattened or irregular endothelium to 30 cms in greatest
· Unilateral into which projects a glomerulus tuft diameter
· Secretes AFP with central vascular core · Large, solid, soft
· Contains clear, glassy cytoplasm tissue components
· Rosette formation surrounds with low level echoes
vascular core intermixed with
numerous septations
· AFP

Embryonal · Least differentiated germ cell tumor · hCG

Carcinoma · Lack of syncitiotrophoblast and
cytotrophoblast
· Secretes estrogen
· <20 yo

Polyembryo · Very young, premenarcheal girls with · AFP & hCG

ma pseudopuberty

SEX-CORD TUMORS

Granulosa · Low grade malignancy · Smooth, lobulated · CALL-EXNER BODIES: · Inhibin

Stromal Cell · Post-menopausal surface, granular round or ovoid cells with
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Tumors · Secretes estrogen and frequently scant cytoplasm and may
· Unilateral trabeculated; yellow assume small clusters or
· Pre-pubertal: sexual or gray-yellow rosette formation around
pseudoprecocity a central cavity
· Reproductive age: · The typical “coffee
irregular menses bean” nuclei are difficult
· Postmenopausal: AUB to see
· Hemoperitoneum · Nucleus is compact
“sunflower”

Fibroma · Most common benign · Heavy, solid, well-

solid neoplasm of the encapsulated,
ovary grayish-white
· Very slow growing · Cut: White or
· Pressure and abdominal yellow-white solid
enlargement tissue with whorled
· Meig’s syndrome: Ovarian appearance
fibroma + Ascites
· Hydrothorax

Serroli- · 3rd-4th decades of life

Leydig · Virilization
Tumor · Low-grade malignancies

Uncommon Ovarian Cancers

· Metastatic Tumors: Ovaries and vagina: most common site of metastasis to female genital tract
· Krukenberg: See below.

Krukenberg · Usually bilateral · Composed of mucin filled,

Tumor · Most common in the SIGNET RING cells with
stomach thickening on tip

2. What laboratory and ancillary procedures will you request and rationale for each?

The type of mass is determined with pelvic imaging, use of biomarkers, and/or surgical exploration and pathologic
evaluation.

High frequency, gray scale transvaginal ultrasonography (TVS) is, to date, the common diagnostic test used to evaluate
the adnexal tumors. The images can approximate the gross appearance of the tumor. Other advantages to its use are:
availability, cost-effectiveness, and good patient tolerability. Compared to the other imaging modalities, TVS is superior,
justifying its routine use. Ultrasound findings should always be correlated to the physical findings so that a refined
differential diagnosis could be made.

The sonographic approach to the evaluation of adnexal masses is based upon the ability to evaluate the likelihood of
malignancy and also to recognize masses that are consistent with a normal physiologic structure or a benign neoplasm.
To accomplish this, the sonologist must take into consideration normal and abnormal anatomy and physiology, clinical
information, and ultrasound techniques, and they must set appropriate diagnostic thresholds to help guide further
management.

The International Ovarian Tumour Analysis (IOTA) group set simple rules to assign benignity or malignancy to a mass.
The rules include five to predict malignancy (M-rules) and five to predict a benign mass (B-rules):

B-rules M-rules

B1. Unilocular cyst M1. Irregular solid tumor

B2. Presence of solid components, where the largest solid M2. Ascites
component is less than 7 mm in largest diameter M3. At least four papillary structures
B3. Acoustic shadows M4. Irregular multilocular-solid tumor with a largest
B4. Smooth multilocular tumor less than 100 mm in largest diameter of at least 100 mm.
diameter M5. Very high color score using color Doppler
B5. No detectable blood flow at Doppler examination
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Rule 1: If one or more M features are present in absence of B features, the mass is classified as malignant
Rule 2: If one or more B features are present in absence of M features, the mass is classified as benign
Rule 3: If both M features and B features are present, or if no B or M features are present, the result is inconclusive and a
second stage test is recommended

In addition, in an attempt to identify ovarian cancer, other morphologic scoring systems were developed:
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Sassone Scoring Lerner Scoring

Additional tumor marker testing may be useful if a less common ovarian histopathology is suspected. Levels of β-hCG, L-
lactate dehydrogenase, and alpha-fetoprotein may be elevated in the presence of certain malignant germ cell tumors.
Granulosa cell tumors produce estrogen and inhibin and should be suspected in women with a solid pelvic mass and
irregular or postmenopausal bleeding.

The following serum biomarker results may differentiate Ovarian Germ Cell Tumors:
B-hCG AFP LDH CA 125

Dysgerminoma + - + -

Endodermal Sinus Tumor - + - -

Choriocarcinoma + - - -

Immature Teratoma - + + +

Embryonal Carcinoma + + - -

These biomarker panels are not recommended for use in the initial evaluation of an adnexal mass, but may be helpful in
assessing which women would benefit from referral to a gynecologic oncologist.

Serum CA 125 is most useful when non-mucinous epithelial cancers are present, but it is not of value in distinguishing
other ovarian cancer categories. The value of elevated CA 125 is in distinguishing malignant ovarian mass among post-
menopausal women. In premenopausal women, we measure a serum CA 125 only if the ultrasound appearance of a
mass raises sufficient suspicion of malignancy to warrant a repeat ultrasound or surgical evaluation.

Serum HE4 together with CA 125 increases PPV of ovarian malignancy. It is more sensitive alone in non-mucinous
epithelial cancers and endometrial cancers. It is also useful in differential diagnosis and monitoring after treatment but not
for screening purposes

Carcinoembryonic antigen (CEA) is a protein normally found in embryonic or fetal tissue. In adults, CEA may be
elevated in malignancies that produce the protein, particularly mucinous cancers associated with the gastrointestinal tract
or ovary. The ratio of CA 125 to CEA has diagnostic implications. Among women undergoing pelvic mass evaluations,
when CEA levels were >5 ng/mL, 68% were found to have nonovarian malignancies. In those with a CA 125/CEA ratio
>25, a primary ovarian cancer was found in 82%.

Cancer antigen 19-9 (CA 19-9) is a mucin protein that may be elevated in ovarian cancer but is used sparingly in ovarian
cancer management. CA 19-9 is used primarily to monitor disease response to therapy or detect cancer recurrence in
patients with a documented gastric cancer, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, or
adenocarcinoma of the ampulla of Vater.
3. Transvaginal ultrasound was done. What is your proposed management for the case?
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ULTRASOUND
CERVIX 2.17 x 2.78 x 2.44 cm
UTERUS 5.83 x 4.82 x 5.01 cm
ENDOMETRIUM 1.4 cm; hyperechoic
RIGHT OVARY Not visualized
LEFT OVARY 3.3 x 2.69 x 3.08 cm.
OTHERS Within the right adnexa is a unilocular, cystic mass measuring 13.2 x 12.8 x 12.1 cm, with
hyperechoic lines and dots within. Capsule is smooth measures 0.2 cm.
IMPRESSION Average sized anteverted uterus,
Secretory phase endometrium.
Right adnexal mass probably ovarian, probably benign.
Normal sized left ovary.

Observation is recommended when the morphology of the adnexal mass on ultrasonography suggests benign disease or
when morphology is less certain but there is a compelling reason to avoid surgical intervention. Observation in the
asymptomatic woman may be justified when the evaluation shows a normal CA 125 level in the absence of transvaginal
ultrasound findings suspicious for cancer.

With rare exception, simple cysts up to 10 cm in diameter on transvaginal ultrasonography performed by experienced
ultrasonographers are likely benign and may be safely monitored using repeat imaging without surgical intervention.
However, with cysts ≥ 10 cm, because of the substantial risk of malignancy, torsion, or labor obstruction, surgical removal
is reasonable.

Surgical intervention is also warranted for symptomatic masses or for suspected malignancy based on the results of
radiologic imaging, serum marker testing, or both. However, some women for whom surgical intervention would normally
be considered are at substantial risk of perioperative morbidity and mortality, such as women of very advanced age or
with multiple comorbidities. In such instances, repeat imaging often is safer than immediate operative intervention,
although the ideal interval for repeat imaging has not been determined.

Minimally invasive procedures are the preferred route of surgery for presumed benign adnexal masses. Laparoscopic
management of ovarian cysts has been the treatment method for the past years. Laparoscopy has shown the same
outcomes but has its advantages over laparotomy in terms of operative time, cosmetic purposes, and decreased cost of
hospital stay. However, there have been results of more spillage and rupture in laparoscopic cystectomies compared to
adnexectomy. Some authors advocate the use of frozen section after diagnostic laparoscopic adnexectomy to avoid
laparotomy particularly for postmenopausal women with complex masses on ultrasound.

Regardless of the approach employed, fertility preservation should be a priority when managing masses in adolescents
and premenopausal women who have not completed child-bearing. Even in women who present with large ovarian cysts
of 10 cm or greater, it is possible to save normal portions of the ovary and remove the cyst laparoscopically.

Cystectomy is the procedure of choice in premenopausal women where normal ovarian tissue is still appreciated.
Unilateral oophorectomy or salpingo-oophorectomy (adnexectomy) is indicated in patients in whom ovarian tissue
cannot be preserved, and when there is involvement of the fallopian tube particularly in large-sized masses. The extent of
surgery usually depends on the diagnosis, patient’s age, and the patient’s desire for ovarian function. The patient should
be informed of the risks of bilaterality which is approximately 2-3% in benign mucinous tumors, 15% for mature cystic
teratomas, and as hgh as 25% for benign serous tumors.

4. Intraoperatively, cut section of the specimen is as

follows. What is your diagnosis?
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With the presence of several different types of tissue (such as hair, muscle, teeth, or bone), the presented cut section is
characteristic of a teratoma. Teratomas are the most common type of germ cell tumor. Most, but not all, teratomas are
benign. The component tissues in a teratoma range from immature to well-differentiated and are foreign to the anatomic
site in which they are found.

Teratomas are divided into four categories: mature (cystic or solid, benign), immature (malignant), malignant due to a
component of another somatic malignant neoplasm, and monodermal or highly specialized.

Macroscopic appearance Clinical Presentation Histopathology

Mature teratoma Benign cystic teratomas is a multicystic Most women with dermoid cysts are Mature cystic teratomas contain
(dermoid cysts) mass that contains hair, teeth, and/or skin asymptomatic. If present, symptoms mature tissue of ectodermal (eg,
that is mixed into sebaceous, thick, sticky, depend upon the size of the mass. skin, hair follicles, sebaceous
and often foul-smelling material. Torsion is not uncommon. Rupture of glands), mesodermal (eg, muscle,
dermoid cysts with spillage of urinary), and endodermal origin
A solid prominence (Rokitansky sebaceous material into the abdominal (eg, lung, gastrointestinal). The
protuberance) is located at the junction cavity can occur, but is uncommon. mechanism by which these cysts
between the teratoma and normal ovarian Shock and hemorrhage are the develop is possibly by failure of
tissue. The greatest cellular variety is immediate sequelae of rupture; a meiosis II or from a premeiotic cell
found in the area of this junction, which marked granulomatous reaction in which meiosis I has failed. They
should therefore be examined carefully by (chemical peritonitis) may subsequently may be bilateral in 10 to 17% of
the pathologist to exclude immature/ develop and lead to formation of dense cases.
malignant components. adhesions.

Immature teratoma Of similar gross appearance with mature The clinical presentation is similar to These neoplasms are typically
also called malignant teratoma, and may only be differentiated that of other OGCTs (incidentally composed of tissue from the three
teratoma, histologically discovered adnexal mass, abdominal germ cell layers: ectoderm,
teratoblastoma, or enlargement or pain). In some cases, mesoderm, and endoderm,
embryonal teratoma alpha fetoprotein (AFP) or lactate arranged in a haphazard manner.
dehydrogenase (LDH) may be elevated. Histologically, there are varying
amounts of immature tissue, most
frequently with neural
differentiation, although immature
stromal elements can also be
present.

Struma ovarii Teratoma predominantly composed of The secretion of thyroid hormones It is often associated with a mature
mature thyroid tissue results in clinical hyperthyroidism in 25 cystic teratoma and rarely with a
to 35 percent of patients. cystadenoma.

Carcinoid Primary ovarian carcinoid neoplasms are Some carcinoid neoplasms secrete
neoplasms usually unilateral, localized to the ovary, bioactive polypeptides and amines,
and indistinguishable histologically from producing a constellation of symptoms,
metastasis. They have similar predominantly flushing and diarrhea.
appearances to those that arise in any Carcinoid syndrome develops in
other site (eg, gastrointestinal or approximately one-third of cases, and it
respiratory). They are comprised of nests can develop without hepatic metastases
and cords of relatively bland cells (uniform due to direct venous drainage from the
cells without nuclear atypia) with endocrine ovary into the systemic circulation.
features and a fine vascular network.

Ovarian cystectomy is suggested in order to make a definitive diagnosis, preserve ovarian tissue, and avoid potential
problems such as torsion, rupture, or development of malignant components. For women who have completed
childbearing, salpingo-oophorectomy is also acceptable treatment. Benign cystic teratomas do not recur if surgically
resected. Dermoid cysts may be removed via either laparoscopy or laparotomy. With either approach, the abdomen
should be copiously irrigated to avoid a chemical peritonitis from spillage of the sebaceous cyst fluid.

5. How will you differentiate benign from malignant tumors according to:

Benign Tumors Malignant Tumors

Possible symptoms: increase in abdominal size, abdominal bloating, abdominal/pelvic pain,

History indigestion, inability to eat normally, urinary frequency/incontinence, constipation, back pain, fatigue

Slow growing Fast growing

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Usually asymptomatic Only 5% are asymptomatic. Around 70% have
Symptoms usually due to compression of the symptoms 3 months prior to diagnosis while 30%
surrounding structure, or hormone over have symptoms 6 months prior
production Tends to metastasize
Often lead to death

Physical Cystic, non-tender Large, solid, nodular

Examination Movable Fixed
Unilateral Bilateral
No associated ascites With associated ascites

Laboratory Serum CA 125 < 30 U/mL Serum CA 125 > 30 U/mL

Ultrasound B1. Unilocular cyst M1. Irregular solid tumor

B2. Presence of solid components, where the M2. Ascites
largest solid component is less than 7 mm in M3. At least four papillary structures
largest diameter M4. Irregular multilocular-solid tumor with a largest
B3. Acoustic shadows diameter of at least 100 mm.
B4. Smooth multilocular tumor less than 100 M5. Very high color score using color Doppler
mm in largest diameter
B5. No detectable blood flow at Doppler
examination

Intraoperatively Smooth edge, encapsulated Not encapsulated

Does not invade surrounding tissue Invades and destroys surrounding tissue

Histologically Cells are well-differentiated Cells are poorly-differentiated

Looks like tissue of origin Does not look like tissue of origin
Anaplastic

Reference:

Cunningham, F. G., Leveno, K. J., Bloom, S. L., Spong, C. Y., Dashe, J. S., Hoffman, B. L., . . . Sheffield, J. S.
(2018). Williams Obstetrics (25th edition.). New York: McGraw-Hill Education.

Gershenson, David M. (2020). Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and
diagnosis. UpToDate. Retrieved August 2020.

Lobo RA, Gershenson DM, Lentz GM, Valea FA editors (2017); Comprehensive Gynecology 7th edition.

POGS (2010). Clinical Practice Guidelines (CPG) on Myoma and Adnexal Masses, First Edition.

Timmerman, D. et. al (2000). Terms, Definitions, and Measurements to describe sonographic features of adnexal
tumors : a consensus opinion from the International Ovarian Tumor Analysis (IOTA).

Ueland, F., Li, A.J. (2020). Serum biomarkers for evaluation of an adnexal mass for epithelial carcinoma of the
ovary, fallopian tube, or peritoneum. UpToDate. Retrieved August 2020.