YJPSU-58827; No of Pages 9

Journal of Pediatric Surgery xxx (xxxx) xxx–xxx

Contents lists available at ScienceDirect

Journal of Pediatric Surgery

journal homepage: www.elsevier.com/locate/jpedsurg

Review Article

Ovarian masses in the child and adolescent: An American Pediatric

Surgical Association Outcomes and Evidence-Based Practice Committee
systematic review
Elizabeth J. Renaud a,⁎, Stig Sømme b, Saleem Islam c, Danielle B. Cameron d, Robert L. Gates e,
Regan F Williams e, Tim Jancelewicz e, Tolulope A Oyetunji f, Julia Grabowski g, Karen A. Diefenbach h,
Robert Baird i, Meghan A. Arnold j, Dave R. Lal k, Julia Shelton l, Yigit S. Guner m, Ankush Gosain n,
Akemi L Kawaguchi o, Robert L. Ricca p, Adam B. Goldin r, Roshni Dasgupta q
a
Division of Pediatric Surgery, Department of Surgery, Warren Alpert Medical School at Brown University, Hasbro Children's Hospital, 2 Dudley Street, Suite 190, Providence, RI 02905
b
Division of Pediatric Surgery, Children's Hospital of Colorado, University of Colorado, Aurora, CO
c
Division of Pediatric Surgery, University of Florida, Gainesville, FL
d
Department of Surgery, Boston Children's Hospital, Boston, MA
e
Division of Pediatric Surgery, University of Tennessee Health Science Center, Memphis, TN
f
University of Missouri-Kansas City School of Medicine, Department of Surgery, Children's Mercy Hospitals and Clinics, Kansas City, MO
g
Division of Pediatric Surgery, Ann and Robert H. Lurie Children's Hospital, Northwestern University, Chicago, IL
h
Department of Pediatric Surgery; Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH
i
Department of Pediatric General and Thoracic Surgery, The Montreal Children's Hospital, McGill University Health Centre
j
Department of Surgery, Section of Pediatric Surgery, University of Michigan, Ann Arbor, MI
k
Division of Pediatric Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI
l
Division of Pediatric Surgery, Department of Surgery, University of Iowa Stead Family Children's Hospital, Iowa City, IA
m
Department of Surgery, University of California Irvine and, Division of Pediatric General and Thoracic Surgery, Children's Hospital of Orange County
n
Division of Pediatric Surgery, University of Tennessee Health Science Center, Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, TN
o
Department of Pediatric Surgery, Mc Govern School of Medicine at the University of Texas HSC at Houston, Houston, TX
p
Department of Pediatric Surgery, Naval Medical Center Portsmouth, Portsmouth, VA
q
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Medical Center, Cincinnati, OH
r
Department of Pediatric General and Thoracic Surgery, Seattle Children's Hospital, Seattle, WA

a r t i c l e i n f o a b s t r a c t

Article history: Background: The treatment of ovarian masses in pediatric patients should balance appropriate surgical manage-
Received 26 September 2017 ment with the preservation of future reproductive capability. Preoperative estimation of malignant potential is
Received in revised form 13 August 2018 essential to planning an optimal surgical strategy.
Accepted 29 August 2018 Methods: The American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee drafted
Available online xxxx
three consensus-based questions regarding the evaluation and treatment of ovarian masses in pediatric patients.
A search of PubMed, the Cochrane Library, and Web of Science was performed and Preferred Reporting Items for
Key words:
Ovarian mass
Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify articles for review.
Pediatric Results: Preoperative tumor markers, ultrasound malignancy indices, and the presence or absence of the ovarian
Adolescent crescent sign on imaging can help estimate malignant potential prior to surgical resection. Frozen section also
Diagnosis plays a role in operative strategy. Surgical staging is useful for directing chemotherapy and for prognostication.
Management Both unilateral oophorectomy and cystectomy have been used successfully for germ cell and borderline ovarian
tumors, although cystectomy may be associated with higher rates of local recurrence.
Conclusions: Malignant potential of ovarian masses can be estimated preoperatively, and fertility-sparing tech-
niques may be appropriate depending on the type of tumor. This review provides recommendations based on
a critical evaluation of recent literature.
Type of study: Systematic review of level 1–4 studies.
Level of evidence: Level 1–4 (mainly 3–4).
© 2018 Published by Elsevier Inc.

⁎ Corresponding author. Tel.: +1 901 258 4201.

E-mail address: elizabeth_renaud@brown.edu (E.J. Renaud).

https://doi.org/10.1016/j.jpedsurg.2018.08.058
0022-3468/© 2018 Published by Elsevier Inc.

Please cite this article as: Renaud EJ, et al, Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and
Evidence-Based Practice Commit..., J Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.08.058
2 E.J. Renaud et al. / Journal of Pediatric Surgery xxx (xxxx) xxx–xxx

Contents

1. Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

1.1. Research questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
1.2. Search methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
1.3. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
1.4. Review process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2. Pediatric ovarian tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.1.1. Which patients with benign-appearing ovarian lesions are candidates for ovarian preservation? . . . . . . . . . . . . . . . . . . 0
2.2. Tumor size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.3. Tumor characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.3.1. Screening for malignancy: scoring systems and the “ovarian crescent sign”. . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.3.2. Torsion and malignancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.3.3. Borderline ovarian tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3. Recommendation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3.1. Which patients with benign-appearing ovarian lesions are candidates for ovarian preservation? Screening for malignancy . . . . . . . . . . 0
3.1.1. Screening for malignancy, role of frozen section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
4. Recommendation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
4.1. Which patients with benign-appearing ovarian lesions are candidates for ovarian preservation? Role of frozen section . . . . . . . . . . . . 0
5. Surgical staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
5.1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
5.1.1. In what situations are formal staging procedures or more extensive resections (e.g. omentectomy, lymph node dissection) warranted? 0
6. Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
6.1. In what situations are formal staging procedures or more extensive resections (e.g. omentectomy, lymph node dissection) warranted? . . . . 0
6.1.1. Germ cell tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
6.1.2. Epithelial and borderline neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
7. Ovarian preservation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
7.1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
7.1.1. Is ovarian preservation safe in the setting of suspected malignant disease? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
8. Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
8.1. Is contralateral ovarian preservation safe in the setting of suspected malignant disease? Conservative surgery . . . . . . . . . . . . . . . . 0
8.1.1. Germ cell tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
8.1.2. Epithelial ovarian neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
8.1.3. Borderline ovarian tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
9. Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
9.1. Is ovarian preservation safe in the setting of suspected malignant disease? Cystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . 0
9.1.1. Germ cell tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
9.1.2. Borderline ovarian tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
10. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

Pediatric and adolescent patients who present with ovarian masses
pose multiple challenges for the surgical provider. In addition to
performing proper staging when malignancy is suspected, the surgeon
must weigh the risks and benefits of ovarian preservation and must
balance the best options for cure with those supporting future fertility
and hormonal health. Often, insufficient clinical information is available
preoperatively to assess malignant potential adequately. Preoperative
risk assessment of ovarian malignancy is essential to balance fertility pres-
ervation with more aggressive cancer treatment. Unilateral oophorectomy
in a patient with a nonmalignant mass may lead to future infertility; how-
ever, inadequate resection or staging in the setting of a malignancy may
place the patient at risk for unnecessary adjuvant therapy or recurrent dis-
ease. Surgeons treating patients with suspected malignant lesions must be
familiar with current guidelines and procedures for accurate staging in
order to best serve the patient for cure and preservation of fertility [1,2].
The goal of this systematic review was to evaluate the published literature
and derive recommendations regarding the preoperative evaluation and op-
erativemanagementofpediatricandadolescentpatientswithovarianmasses.
1. Materials and methods
1.1. Research questions
The members of the American Pediatric Surgical Association (APSA)
Outcomes and Evidence Based Practice (OEBP) Committee drafted and
iteratively refined the following three questions for this review:
(1) Which patients with benign-appearing ovarian lesions are
candidates for ovarian preservation? (2) In what situations are formal
staging procedures or more extensive resections (e.g. omentectomy,
lymph node dissection) warranted?; and (3) Is ovarian preservation
safe in the setting of suspected malignant disease?
This review was originally part of a larger project which also
included questions regarding ovarian torsion; the results of the review
for these additional research questions were published in a separate
study [3].
1.2. Search methods
An initial search of PubMed, the Cochrane Library, and Web of Sci-
ence was performed using the Medical Subject Headings (MeSH)
terms “ovary,” “ovarian,” “tumor,” “mass,” “malignancy,” “lesion,” and
“preservation.” Results were restricted to English language publications
of human subjects aged 0 to 18 years and to articles published from
1980 to July, 2015.
1.3. Study selection
The authors followed the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) guidelines to generate the final
list of articles used in this review [4]. Two authors (ER and RD)

Please cite this article as: Renaud EJ, et al, Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and
Evidence-Based Practice Commit..., J Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.08.058
 E.J. Renaud et al. / Journal of Pediatric Surgery xxx (xxxx) xxx–xxx 3

Records identified through

database search and removal
Identification
of duplicates
(n=536)

Records excluded if:

Screening Records screened -lack of relevance to study
(n=536) questions
-case study or opinion
(n=258)

Full-text articles assessed Full-text articles excluded

Eligibility
for eligibility if not relevant to study
(n=278) questions or of low
quality
(n=227)

Studies included in
Included qualitative synthesis
(n=51)

Question 1a Original search (5) Question 2 Question 3

Relevant studies + Snowballing (3) Relevant studies Relevant studies
n=13 n=12 n=25

Follow up Question 1b
search (6) Relevant studies
n=8

Question 1a
Final review
n=19

Fig. 1. Adapted from: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Met-Analyses: The PRISMA Statement.
PLoS Med 6(6): e1000097. Doi: https://doi.org/10.1371/journal.pmed1000097

independently reviewed abstracts and references and chose articles
pertinent to the study questions. Some studies with only adult
populations were chosen if they contained significant findings relevant
to tumors also seen in pediatric patients.
Titles without full text available were excluded from review.
Publications reviewed included prospective and retrospective clinical
studies as well as large case series and prior systematic reviews. Case
reports or opinion papers were excluded.
278 articles underwent full review. Bibliographies were searched for
additional titles. On final review, an additional online search was
performed to capture more recent articles. The final result was 64
articles which pertained to at least one of the three study questions
regarding ovarian masses. (Prisma chart, Fig. 1).
1.4. Review process
Articles were assessed for study design, patient population, sample
size, comparison and outcome measures, findings, and level of evidence
according to Oxford Centre for Evidence-Based Medicine (OCEBM)
guidelines (Table 1) [5].
2. Pediatric ovarian tumors
2.1. Background
Overall, pediatric and adolescent ovarian masses have a low likeli-
hood of malignancy. Approximately 1.5% of all childhood cancers are

Table 1
Oxford Centre for Evidence-based Medicine levels of evidence and grades of recommendation (Adapted from www.cebm.net) (RCT: Randomized Control Trial).

Level of Evidence Grade of Recommendation

I. Systematic Review of RCTs or RCT with a narrow confidence interval A. Consistent Level 1 studies
II. Cohort studies, low quality RCTs, outcomes research B. Consistent Level 2 or 3 studies or extrapolation from Level 1 studies
III. Case–control studies C. Level 4 studies or extrapolation from Level 2 or 3 studies
IV. Case series D. Level 5 evidence or inconsistent or inconclusive studies of any level
V. Expert Opinion

Please cite this article as: Renaud EJ, et al, Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and
Evidence-Based Practice Commit..., J Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.08.058
4 E.J. Renaud et al. / Journal of Pediatric Surgery xxx (xxxx) xxx–xxx
ovarian in origin; the reported frequency of malignancy found in pediat-
ric ovarian masses varies greatly but ranges from 4% to 22% [1,2,6,7],
with a malignancy incidence between 0.102 and 1.072 per 100,000
per year, depending on patient age [8]. In general, survival is high.
Germ cell tumors are the most common type of ovarian malignancy
found in the pediatric population. Epithelial tumors occur primarily in
adolescent patients and are mostly borderline or low malignant
potential; poorly differentiated epithelial tumors are rare [6,9].
2.1.1. Which patients with benign-appearing ovarian lesions are candidates
for ovarian preservation?
2.1.1.1. Screening for malignancy: signs, symptoms, patient characteristics.
Six studies (5 pediatric, 1 pediatric and adult) of level 4 evidence evalu-
ated the association between particular signs and symptoms with the
risk of malignancy in a newly diagnosed ovarian tumor; the results
were inconsistent. [8,10–14] Pediatric patients with ovarian masses
often present with nonspecific complaints. While four studies found
some association of malignancy with abdominal pain, distention, mass
on exam, or precocious puberty [8,10,13,14], two other studies found
no association between malignancy and presenting symptoms [11,12].
Therefore, symptomatology at presentation is not an accurate indicator
of the risk of preoperative malignancy.
2.1.1.2. Screening for malignancy: tumor markers. Different tumor
markers are associated with specific types of ovarian tumors: α-
fetoprotein (αFP), β-human chorionic gonadotropin (βHCG), and lac-
tate dehydrogenase (LDH) can be elevated in the presence of germ
cell tumors, while cancer antigen 125 (Ca-125) is elevated in epithelial
tumors. Estradiol and testosterone may be elevated in the presence of
sex cord tumors.
Three studies evaluated the use of tumor markers in preoperative
evaluation for malignancy [8,11,15]. These studies examined the predic-
tive discrimination of these markers as panels and not individually. A
prospective study of 53 patients 19 years and under with either germ
cell or epithelial tumors found that a positive result for any one of six
markers in a tumor marker panel (αFP, βHCG, LDH, Ca-125, estradiol,
and testosterone) had a 0.76 positive predictive value (PPV), 0.86 nega-
tive predictive value (NPV), and 0.83 accuracy for malignancy [15]. In
two retrospective studies of germ cell tumors, one found that elevations
of βHCG, αFP, and Ca-125 were associated with malignancy [8], and a
second noted a greater likelihood of malignancy with elevations of
αFP, βHCG, and LDH [11]. Therefore, tumor markers may be most useful
in the determination of malignancy when ordered as a standard panel
preoperatively.
2.1.1.3. Screening for malignancy: imaging characteristics. All studies
meeting inclusion criteria for this review evaluated ultrasound as the
primary imaging modality; there were no high quality studies which
evaluated CT or MRI.
2.2. Tumor size
Three studies found that tumor size was a helpful preoperative pre-
dictor of malignancy for pediatric patients [8,11,16]. Two retrospective
studies found that a larger diameter was associated with an increased
likelihood of malignancy [8,11]. In the first study (11% of tumors malig-
nant), a tumor diameter ≥ 8 cm had an odds ratio of 19 for malignancy
(95% CI, 4.42–81.69) [8]; in the second study (12% malignancy) a
diameter ≥ 10 cm had an odds ratio of 9.6 for malignancy (95% CI,
2.12–43.42) [11]. A third study noted that larger tumor volume (calcu-
lated with the “prolate ellipsoid formula” which measures the volume
of a nonuniform spheroid structure) was associated with malignant po-
tential. This method demonstrated that a cutoff of 184 mL had 100% sen-
sitivity, 54% specificity, NPV of 100% and PPV of 13% to rule out
malignancy [16].
Please cite this article as: Renaud EJ, et al, Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and
Evidence-Based Practice Commit..., J Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.08.058
2.3. Tumor characteristics
Three studies which evaluated tumor composition found that the
presence of solid components increased the odds of malignancy as
much as six fold [11,13,16]. Cystic appearance on ultrasound had a
high sensitivity (100%) for benign disease [16]. One study found that
solid tumors with a diameter of 9.0 cm or greater were malignant
69.2% of the time, and noted size as the most important indicator of
malignancy risk with solid lesions [13]. Therefore, the clinician's
suspicion for malignancy should increase in the presence of a solid,
large ovarian tumor.
2.3.1. Screening for malignancy: scoring systems and the “ovarian crescent
sign”
Ultrasound scoring systems which combine size and intrinsic mass
characteristics have been developed to increase the sensitivity, specific-
ity, and accuracy of ultrasound as a preoperative screening modality for
malignancy. Five studies evaluated ovarian scoring systems applicable
to a pediatric population (Table 2) [17–21]. In a retrospective study of
121 pediatric and adult patients, DePriest et al. described and validated
an ultrasound morphology index which included descriptions of the
volume, wall structure, and septations. By this index, an ovarian mass
with a score of ≥ 5 or more had a PPV of 0.45 for malignancy while
those with scores b5 were uniformly benign [17]. In 2003, Ueland
conducted a prospective study of adult patients and modified the
DePriest scoring system to focus on size and characteristics as a two
factor system. With this modification a score of ≥5 had a 0.981 sensitiv-
ity, 0.808 specificity, 0.409 PPV, and 0.997 NPV for malignancy [18]. In
an additional prospective study of 98 patients less than 20 years of age
with both epithelial and germ cell tumors, a Ueland index ≥ 7 had a
90% sensitivity, 94% specificity, and positive likelihood ratio of 35.870
for malignancy [19]. One final study of only pediatric patients developed
a pediatric risk of malignancy index. A combination of maximum diam-
eter of the largest solid component, the presence of enhancement of
flow in a septum or solid papillary projection, and the presence of sex
hormone-related symptoms predicted the presence of a benign or
nonbenign lesion with an accuracy of 96.4%. [20]. Unfortunately,
additional validation of this index showed poorer performance with
an accuracy of 82.1% and a PPV of 57.1% and NPV of 91.2%. [21]. There-
fore, as with other preoperative indicators, malignancy indices are a
helpful adjunct in preoperative risk stratification but do have limitations
and should be used with other assessment measures.
Another radiological indicator of malignancy is the ovarian crescent
sign (OCS). This finding said to be present (or “positive”), indicating a
benign lesion, when a rim of healthy ovarian tissue is seen on the ipsilat-
eral ovary in the presence of an ovarian mass. Two prospective adult
studies of mostly epithelial tumors demonstrated that the absence of
an OCS is associated with malignancy with a high sensitivity (96% and
100%) and a high specificity (92% and 93%) [22,23]. In the pediatric
literature, one prospective study found that the ovarian crescent sign
compared favorably with the Ueland index; OCS absence was 90%
sensitive and 72% specific for predicting malignancy [19]. It was less
predictive in premenarchal patients, who have smaller ovaries, and
also in the setting of ovarian torsion.
One final prospective study used both the Ueland index and the
ovarian crescent sign to develop a decision tree system for pediatric
patients [24]. If the index was 7 or more with no crescent sign, a mass
was classified as malignant; the system showed a 93% sensitivity, 97%
specificity, PPV of 85.7% and NPV of 98.9% for malignancy. The use of a
combination of radiologic findings and scoring systems appears to be
the safest means of screening for malignancy.
2.3.2. Torsion and malignancy
The overall rate of malignancy in torsed ovaries is low. Three recent
studies (2 retrospective, 1 prospective) have demonstrated a malig-
nancy rate of 3.5%–5.4% in torsed ovaries [24–26]. The study which
 E.J. Renaud et al. / Journal of Pediatric Surgery xxx (xxxx) xxx–xxx
Table 2
DePriest and Ueland indices17,18.
DePriest Index
Points Volume Cyst wall Structure Septa Structure
0 b10 cm3 Smooth b3 mm thickness No septa
1 10–50 cm3 Smooth N3 mm thickness Thin septa
b3 mm
2 N50–200 cm3 Papillary projections b3 mm Thick septa
3 mm–1 cm
3 3
3 N200–500 cm Papillary projections ≥3 mm Solid area
≥1 cm
3
4 N500 cm Predominantly solid Predominantly solid
5 N500 cm3
developed a decision tree for masses, referenced in the last section,
demonstrated that the tree was effective at distinguishing between
malignant and nonmalignant masses in patients that needed emergent
surgical treatment including those with torsion, and allowed for a
higher rate of preservation of ovarian tissue [24]. Therefore, while
malignancy may be present in a torsed ovary, the overall rate is low
and available ultrasound indexes can help estimate the likelihood of
malignancy preoperatively.
2.3.3. Borderline ovarian tumors
Borderline ovarian tumors (BOT) are epithelial tumors with
increased mitotic activity and nuclear atypia but generally without stro-
mal invasion. They share biochemical and radiological characteristics
with both benign and malignant tumors but present early in early
stage and have a good prognosis, and can be found in adolescent
patients [27]. As these tumors can be difficult to diagnose preopera-
tively, they should be in the differential diagnosis when preoperative
tests or scoring systems do not strongly favor a diagnosis of either a
benign or malignant lesion.
3. Recommendation
3.1. Which patients with benign-appearing ovarian lesions are candidates
for ovarian preservation? Screening for malignancy
Symptoms and signs are not reliable preoperative predictors of
malignancy.
Preoperative tumor markers, used as a panel and not individually,
may aid in predicting malignant potential.
Grade C, extrapolation from level 3 and 4 studies
Ultrasound malignancy indices such as the Ueland index and the
ovarian crescent sign are useful for distinguishing benign from malig-
nant lesions.
Grade B, consistent level 2 and 3 studies
3.1.1. Screening for malignancy, role of frozen section
Eight studies addressed the role of frozen section in the intraoperative
diagnosis of ovarian malignancy [28–35]. Most of these studies were of
level 3 or 4 evidence and focused primarily on adult patients and on epi-
thelial tumors. In 6 studies reporting tumor histology, 43.4%–56% were ep-
ithelial [28–33]. The accuracy of frozen section for a combination of tumor
histology types was 92% to 97.1% [29–33]. For BOT, underdiagnosis could
occur; frozen section for BOT had a sensitivity of 60% to 71% and an accu-
racy of 55% to 78.6% [28–30,32]. This finding was supported by the single
pediatric-only study (b20 years of age) of borderline ovarian tumors in
which the rate of agreement between permanent and frozen section was
only 55.1% [34]. Pure cystic nature and size N 17 cm in diameter decreased
frozen section accuracy owing to sampling error [29,35]. Mucinous tumors
also increased sampling error owing to larger size and increased heteroge-
neity, as single mucinous lesions could contain benign, borderline, and ma-
lignant areas [28,30].
Please cite this article as: Renaud EJ, et al, Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and
Evidence-Based Practice Commit..., J Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.08.058
5
Ueland Index
Volume Tumor Structure
b10 cm3 Smooth wall,
sonolucent
10–50 cm3 Smooth wall, diffuse echogenicity
N50–100 cm3 Wall thickening,
b3 mm fine septa
N100–200 cm Papillary projection
≥3 mm
N200–500 cm3 Complex, predominantly solid
Complex, solid and cystic areas with extratumoral fluid
4. Recommendation
4.1. Which patients with benign-appearing ovarian lesions are candidates
for ovarian preservation? Role of frozen section
Studies in adults demonstrate that frozen section can accurately
distinguish benign from malignant tumors; data in the pediatric popula-
tion are limited. Frozen section is less accurate for borderline ovarian
tumors, large tumors, purely cystic lesions, and those of mucinous
histology, and should be used with caution for these masses.
Grade C recommendations, level 3 and 4 studies
5. Surgical staging
5.1. Background
Current guidelines for surgical staging of adult epithelial tumors are
derived from the International Federation of Gynecology and Obstetrics
(FIGO) [36,37]. In addition to intact tumor removal, optimal staging
practice includes the
“assessment of peritoneal fluid volume, and fluid cytology…biopsies
should be taken from the pelvic side walls, cul-de-sac, and paracolic gut-
ters. The infra-diaphragmatic surface should be evaluated by cytology or
biopsy. Bowel serosa and mesentery should be evaluated for tumor. The
infra-colic omentum should be removed…Pelvic and para-aortic lymph
node sampling is part of surgical staging.”
This protocol allows for the preservation of the uterus and the con-
tralateral ovary in the case of a young patient with early disease who
wishes to preserve reproductive potential [36,37].
The current surgical staging procedure for pediatric ovarian germ
cell tumors has been outlined by the Children's Oncology Group
(COG). These guidelines recommend:
“(1) Collection of ascites or washings on entering the peritoneal cav-
ity; (2) examination of the peritoneal surfaces with biopsy or excision of
any nodules; (3) examination and palpation of lymph nodes in the
retroperitoneum with sampling of any firm or enlarged nodes;
(4) inspection and palpation of the omentum with removal of any
adherent or abnormal areas noted; (5) inspection and palpation of the
opposite ovary with biopsy of any abnormal areas; and (6) complete
resection of the tumor-containing ovary with sparing of the fallopian
tube if not involved.” [9]
5.1.1. In what situations are formal staging procedures or more extensive
resections (e.g. omentectomy, lymph node dissection) warranted?
5.1.1.1. Germ cell tumors. Four articles of level 3 and 4 evidence quality
addressed the role of formal staging for germ cell tumors [9,38–40].
Three studies including adult and pediatric patients concluded that con-
servative surgery, defined as preservation of the contralateral ovary and
the uterus, yielded outcomes similar to more radical resections. Overall,
recurrences were low, occurred in the setting of both radical surgery
6 E.J. Renaud et al. / Journal of Pediatric Surgery xxx (xxxx) xxx–xxx
and contralateral preservation, and were generally salvageable with ei-
ther additional surgery or chemotherapy. [38–40] In an additional study
of pediatric patients with germ cell tumors, the Pediatric Intergroup, a
combination of Pediatric Oncology Group and Children's Cancer Study
Group, evaluated the outcomes of 131 patients between 1.4 and
20 years of age with ovarian germ cell tumors [9]. Only 3 patients
underwent an initial exploration according to the traditional FIGO stag-
ing. This study reported excellent survival for all stages of disease with
the use of conservative surgery in combination with platinum based che-
motherapy. It was concluded, therefore, that survival appeared to have
been unaffected by deviations from traditional surgical guidelines. This
paper was the basis for the current COG surgical staging guidelines [9].
Based on the above, the use of more conservative surgery, in partic-
ular contralateral ovarian preservation, appears safe in the treatment of
germ cell tumors. However, tumor biology and appropriate use of
chemotherapy have a direct effect on recurrence, and adherence to
staging recommendations aids in directing adjuvant therapy and deter-
mining prognosis.
5.1.1.2. Epithelial neoplasms. Only two studies in pediatric patients
addressed the extent of initial surgery for the treatment of epithelial
neoplasms [6,41]. The paucity of reports is likely owing to the rarity of
malignant epithelial ovarian lesions in patients less than 18 years of
age. The first study, a retrospective review of 69 epithelial neoplasms
(4.7% malignant, 37.5% of low malignant potential), found an overall
low recurrence rate and argued that pathological diagnosis should be
definitively established before proceeding to extensive resection. [6]. A
second study evaluated whether the COG germ cell tumor guidelines
could be applied to all pediatric ovarian tumors, regardless of histology.
This study included 424 patients less than 19 years of age, of whom 46
had malignancies (11%), and evaluated surgeon adherence to current
COG staging practices. The results demonstrated that COG germ cell
tumor staging guidelines were followed in only 24% of cases. This cohort
experienced two recurrences and four deaths; all were in individuals
who had undergone complete staging at their original procedure. The
authors concluded that a worse outcome was associated with inherent
tumor biology and not secondary to protocol deviation [41].
5.1.1.3. Borderline ovarian tumors. Although BOT have some properties
similar to malignant lesions, these tumors may not require extensive
staging procedures. Six articles of level 3 evidence addressed the need
for extensive surgery in borderline ovarian tumors; five of these
included adolescent patients [42–47]. The definitions of a “complete”
staging procedure varied among the studies and, therefore, limited
their comparability. The studies also reported conflicting results in
terms of recurrence: three [42–44] noted an increase in recurrence
with incomplete staging, while two showed no difference [45,46]. In
all studies relapse did not affect overall survival. The presence of malig-
nant transformation in a recurrence was associated with age greater
than 40 years at initial presentation and not completeness of staging
[43]. Restaging surgery after initial incomplete staging did not affect
recurrence or survival [45,46]. All studies recommended against biopsy
of the contralateral ovary in the absence of a visible abnormality owing
to the low likelihood of detecting occult disease [42–47].
6. Recommendations
6.1. In what situations are formal staging procedures or more extensive
resections (e.g. omentectomy, lymph node dissection) warranted?
6.1.1. Germ cell tumors
Providers should adhere to the COG guidelines when conducting and
reporting a staging procedure for patients with suspected germ cell
malignancy.
Grade C, consistent level 3 and 4 studies.
Please cite this article as: Renaud EJ, et al, Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and
Evidence-Based Practice Commit..., J Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.08.058
6.1.2. Epithelial and borderline neoplasms
There is a lack of literature regarding staging protocols for epithelial
malignancies in the pediatric population. Current pediatric staging re-
flects recommendations for adults, although COG staging practices rather
than more extensive FIGO standards may be sufficient for pediatric pa-
tients with low grade tumors and BOT. Patients who are incompletely
staged at the time of diagnosis should be followed closely for recurrence.
Grade C, extrapolations from level 3 studies.
7. Ovarian preservation
7.1. Background
The primary goal of surgery for a malignant mass is cure. However,
owing to the age and expected lengthy disease-free survival of many pe-
diatric and adolescent patients with ovarian tumors, the potential for
fertility as well as future hormonal health must also be considered in
their care. In terms of fertility, unilateral oophorectomy may have neg-
ative effects on later oocyte production and may result in earlier meno-
pause. Large cohort studies from Norway and Japan of women
previously undergoing unilateral oophorectomy demonstrate a ten-
dency towards earlier menopause and premature ovarian failure
[48,49]. Earlier menopause may also affect the overall health of a patient
in terms of earlier cardiovascular disease, osteoporosis, and other effects
of aging [50,51]. Concerns such as these have resulted in a focus on safe
strategies which preserve fertility by retaining the contralateral
undiseased ovary or possibly the affected ovary itself without
compromising the oncologic completeness of the tumor resection.
7.1.1. Is ovarian preservation safe in the setting of suspected malignant
disease?
7.1.1.1. Contralateral ovarian conservation, germ cell tumor. This review
found five articles of level 3 or 4 evidence quality which addressed con-
tralateral ovarian preservation for germ cell tumors; all articles included
at least some pediatric patients in their study populations [39,52–55].
These studies agreed that for lower stage disease, preservation of the
uterus and contralateral ovary did not increase the rate of recurrence
or affect prognosis [39,52–55]. Unilateral oophorectomy can also be
performed with more advanced disease: two studies demonstrated
that recurrence was higher with advanced disease whether or not bilat-
eral oophorectomy was performed [53,55]. Three studies which re-
ported the outcome of intraoperative contralateral ovarian biopsy
found that no biopsy of a normal-appearing ovary revealed occult dis-
ease [52,53,55]. Therefore, the sacrifice or biopsy of a normal appearing
contralateral ovary is not necessary during operations for germ cell
tumors.
7.1.1.2. Contralateral ovarian conservation, epithelial ovarian neoplasm.
Four studies of level 3 and 4 evidence addressed fertility-conserving
procedures in the setting of epithelial neoplasms [12,56–58]. Only one
study exclusively examined patients younger than 21 years of age
[12]. This report was a case series of 19 patients treated at a single insti-
tution; the patients had a combination of low malignant potential and
more invasive tumors. Of those with invasive carcinoma, 4 underwent
unilateral salpingo-ophorectomy with staging only; none developed a
recurrence. Of the 5 who underwent hysterectomy with bilateral
salpingo-oophorectomy, two died of their disease. Both had small cell,
anaplastic tumors which are known to portend a poorer prognosis [12].
The three other studies included some pediatric patients. In two of
these studies, recurrences occurred in the contralateral ovary, but over-
all recurrence was low (7/31 and 2/56) [56,57]. Most recurrences were
in patients with initial tumors of stage greater than I. None of the three
studies recommended attempting contralateral ovarian preservation in
patients who presented with greater than stage I disease [57,58], and
one study did not recommend contralateral conservation for tumors
 E.J. Renaud et al. / Journal of Pediatric Surgery xxx (xxxx) xxx–xxx
over stage Ia [56]. Therefore, contralateral conservation may be safe for
low stage epithelial neoplasms.
7.1.1.3. Contralateral ovarian conservation, borderline ovarian tumor. Two
concerns exist regarding ovarian preservation in the setting of BOT: the
risk of recurrence in the remaining ovary, and the risk of that recurrence
as an invasive tumor. Four articles of level 3 evidence, including 3 with
adolescent patients, compared outcomes between patients undergoing
radical or fertility-preserving (unilateral oophorectomy) procedures
[43,47,59,60]. Recurrence after radical surgery ranged from 0% to 4.9%
among all studies; recurrence after fertility preserving procedures
ranged from 5.1% to 7.7% [43,47,59,60]. The most common site of recur-
rence for those undergoing unilateral oophorectomy was in the contra-
lateral retained ovary. Three studies reported stage as a risk factor
associated with recurrence [43,47,60], and one reported that the
fertility-preserving approach was a negative predictive factor on multi-
variable analysis [43]. However, all of the studies reported no difference
in overall survival between groups, despite the higher rate of recurrence
in some studies. Recurrences of BOT were generally effectively treated
with a second surgery, which in some cases was again ovary-preserving.
The frequency of invasive cancer at the time of recurrence varied by
study. The study by Boran [59], which included some adolescent pa-
tients, found no invasive disease at the time of recurrence. In the study
by Park of 360 patients [47], there were 18 recurrences, 5 of which
consisted of an invasive cancer. Four of these were in patients who had
undergone radical surgery. In the study by Song [60], there were 4 recur-
rences with invasive cancer with one death from disease. Overall, the
likelihood of recurrence of BOT as an invasive cancer was low.
8. Recommendations
8.1. Is contralateral ovarian preservation safe in the setting of suspected
malignant disease? Conservative surgery
8.1.1. Germ cell tumors
Conservation of the contralateral ovary and the uterus is safe in the
setting of germ cell tumors if postoperative chemotherapy guidelines
are followed, and may therefore be considered in this subset of patients.
Grade C, consistent level 4 studies.
8.1.2. Epithelial ovarian neoplasms
As there is limited literature regarding contralateral ovarian presen-
tation in pediatric patients with epithelial ovarian neoplasms, treatment
should follow adult guidelines; contralateral ovarian preservation may
be appropriate for low stage tumors.
8.1.3. Borderline ovarian tumor
Patients undergoing unilateral oophorectomy for borderline ovarian
tumor are at higher risk for recurrence; these recurrences may be sal-
vaged without an effect on overall survival. Unilateral oophorectomy
may therefore be considered for these patients with caution and with
close follow up.
Grade C, extrapolation from level 3 studies.
8.1.3.1. Cystectomy, germ cell. The risk of metachronous ovarian tumors in
patients with germ cell tumors varies from 5% to 15% among studies;
therefore, even patients undergoing unilateral oophorectomy may still
be at risk of later sterility if a new mass arises in the contralateral organ.
Cystectomy can help reduce this risk. Five articles addressed the use of
cystectomy in the setting of a germ cell tumor [14,40,61–63]. One study
of 31 benign ovarian teratomas found in pediatric patients and treated
with cystectomy or unilateral oophorectomy demonstrated five recur-
rences. Four were in the contralateral ovaries of patient who had under-
gone unilateral oophorectomy and one in the ipsilateral ovary of a
patient who had undergone cystectomy. All recurrences were benign ter-
atomas without malignant transformation [61].
Please cite this article as: Renaud EJ, et al, Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and
Evidence-Based Practice Commit..., J Pediatr Surg (2018), https://doi.org/10.1016/j.jpedsurg.2018.08.058
7
The other four studies of both pediatric and adult patients included an
array of germ cell tumors, including immature teratoma, dysgerminoma,
endodermal sinus tumor, yolk sac tumor, and mixed germ cell tumor
[14,40,62,63]. Three studies were level 4 evidence, and one was level 3.
In three series, while only a small number in each study underwent
cystectomy, there were no recurrences. Most patients underwent chemo-
therapy in addition to cystectomy. The authors concluded that
cystectomy was an option in the setting of adjuvant chemotherapy, al-
though they could not comment on cystectomy as monotherapy
[14,40,62]. The only retrospective comparative study demonstrated that
only use of nonplatinum based chemotherapy and AFP N1000 were asso-
ciated with increased relapse. The extent of surgery was included in this
analysis and was not found to be associated with recurrence [63].
8.1.3.2. Cystectomy, borderline ovarian tumor. Patients presenting with
BOTs are often younger than those presenting with epithelial neoplasms
and tend to have more favorable long term outcomes. Preservation of
fertility has, therefore, become a focus for this lower risk group. In addi-
tion, as the risk of synchronous or metachronous tumors ranges from
20% to 40%, patients undergoing unilateral oophorectomy may still be
at risk for future sterility [64].
Eight studies explored the potential of cystectomy as a treatment for
borderline ovarian tumors [43,59,64–69]. Two articles, an initial report
and a follow up, evaluated a randomized control study (Level 1) of
cystectomy for adult patients presenting with bilateral borderline ovar-
ian tumors. The first study randomized patients to unilateral salpingo-
oophorectomy (USO) with contralateral cystectomy or bilateral
cystectomy and found no statistically significant difference in the rate
of recurrence between the two groups (58.8% in the bilateral
cystectomy group vs. 60% in the USO with cystectomy group). Patients
undergoing bilateral cystectomy did have a shorter time to recurrence
[64]. The follow up study confirmed these findings [65]. All recurrences
were in the ovaries that had undergone cystectomy; however, none
were invasive cancer. These patients were treated with repeat surgical
resection. In addition, there was an improvement in fertility in the bilat-
eral cystectomy group compared to the USO with cystectomy group.
This improvement was reflected in a significantly shorter time to con-
ceive, higher cumulative pregnancy rate, and persistently stable follicle
stimulating hormone (FSH) levels for those undergoing bilateral
cystectomy, while those undergoing USO with cystectomy demon-
strated increases in FSH during the first two years after surgery [64].
In the remaining studies, all of level 3 or 4 evidence, recurrence after
cystectomy ranged from 15% to 36.3%, in contrast to recurrence after
USO which ranged from 2.4% to 15.1% [59,66]. Of those studies reporting
site, all recurrences were in retained ovarian tissue, whether ipsilateral
or contralateral [59,67,68]. One database study reported a 30% rate of
malignant transformation in recurrences; this study did not specify
the type of initial operation [42]. In evaluating factors related to recur-
rence, two articles included cystectomy in their analysis and did not
find an association [68,69]. One study recommended that cystectomy be
performed only if a margin of normal ovarian tissue was visible [59];
this recommendation was supported by the finding of another study
that involvement of the resection margin and removal of more than one
cyst from an ovary were associated with persistence or recurrence [68].
All articles recommended that if cystectomy was chosen as a treatment
modality, patients must have close follow up with appropriate surveil-
lance and aggressive treatment of any suspected recurrence [59,64–69].
9. Recommendations
9.1. Is ovarian preservation safe in the setting of suspected malignant dis-
ease? Cystectomy
9.1.1. Germ cell tumors
While there is limited literature evaluating cystectomy for germ cell
tumors, it is likely safe for benign teratomas depending on size of lesion
8 E.J. Renaud et al. / Journal of Pediatric Surgery xxx (xxxx) xxx–xxx

Ovarian Mass

Imaging: composition

solid
purely cystic
Tumor marker panel: FP, HCG,
LDH, Ca125, estradiol, testosterone
Any marker positive

8 cm diameter < 8 cm diameter

>185 cc volume
Imaging: Size Low likelihood of
Suspicion for
Malignancy
Malignancy
7 <7
Imaging: Ueland Index

Ovarian
absent present
Preservation
Ovarian Crescent
Intraoperative
Sign
Frozen Section

Benign Borderline Malignant

Ovarian Review Staging

Preservation suspicion
Tumor resection with
Possible +/- Ovarian Ipsilateral
cystectomy Preservation oophorectomy

Fig. 2. Ovarian Mass Decision Pathway.

and ovary. Cystectomy alone in the setting of immature or malignant
germ cell tumors is not supported by the current literature, and is not
considered standard of care even when utilizing platinum based
chemotherapy.
Grade C, extrapolations from level 4 studies.
9.1.2. Borderline ovarian tumors
The risk of recurrence is higher after cystectomy than after conserva-
tive surgery for BOT. Recurrence can be salvaged with additional sur-
gery with a limited effect on survival. Cystectomy may therefore be
considered when treating these patients.
Grade B, consistent level 3 and 4 studies.
10. Conclusions
can greatly increase a patient's likelihood of cure. Preservation of future
fertility may be possible in cases of malignant tumors, but this option
must be evaluated on an individual basis with close follow up owing
to a higher risk of recurrence. Further research regarding the best surgi-
cal management of these tumors may benefit from a prospective evalu-
ation of outcomes according to tumor histology, stage, and method of
treatment. Overall, physicians treating ovarian malignancies in children
can be optimistic in counseling patients and families about the possibil-
ity of long term survival and potential for future fertility.
Acknowledgments
The authors would like to thank Elizabeth Irish MLS, AHIP for her as-
sistance with the searches required for this review.

Malignant ovarian masses are rare but treatable tumors in children
and adolescents. Although the literature for this patient population re-
garding their management is limited by the lack of prospective and ran-
domized trials and the dependence on retrospective studies, this review
found that some preoperative indicators, including select ultrasound
characteristics and a panel of tumor markers, can guide the surgeon
when evaluating the preoperative likelihood of malignancy (Ovarian
Mass Decision Pathway, Fig. 2). In the setting of malignancy, proper
staging determines the need for subsequent adjunctive therapy which
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