Keywords
mature teratoma - dermoid cyst - ovarian tumor - ovarian tissue cryopreservation -
fertility
New Insights and the Importance for the Pediatric Surgeon
The potential for metachronous contralateral should be considered at index operation
and a decision made regarding resectional strategy. Ovarian tissue cryopreservation
should be discussed in a multidisciplinary setting and with careful consideration
of the risks and benefits guided by best available evidence.
Introduction
Mature teratoma is the most common benign ovarian tumor affecting children.[1] Arising in multiple germinal layers, mature ovarian teratomas are characterized
by the presence of ectopic tissue and display a preponderance for ectodermal proliferation.[2] Treatment requires surgical excision, either ovarian sparing or by oophorectomy.[3] Though complete resection is associated with a good prognosis there remains a risk
of metachronous contralateral disease, the magnitude of which is uncertain (reported
at 4–23% in several European studies[4]
[5]
[6]). Girls with mature ovarian teratoma in the United Kingdom undergo regular postoperative
surveillance with ultrasound scan to identify contralateral metachronous disease.[3] If this occurs then infertility is an inevitable sequel when bilateral oophorectomy
is required. While ovarian-sparing surgery would likely preserve fertility in these
rare cases, it may not be possible. This could be due to concern of a malignant tumor
prior to excision, prompting oophorectomy as a safe oncological procedure, or due
to it being impossible to identify any macroscopically normal ovarian tissue at the
time of surgery. Indeed, oophorectomy is the recommended treatment for any ovarian
mass for which the diagnosis is uncertain.[7]
For children with cancer, the U.K. National Institute for Health and Care Excellence
advises considering options for fertility preservation before treatment is started.[8] The only method available for prepubertal girls is ovarian tissue cryopreservation
(OTC).[9] This involves retrieval of ovarian tissue (by ovarian biopsy or oophorectomy) which
is then frozen. If the patient is rendered infertile by their oncological disease
or its treatment (chemo-/radiotherapy, bone marrow transplant, or surgery) and later
wishes to attempt a biological pregnancy, the tissue can be thawed and autotransplanted
into the ovarian medulla or an adjacent peritoneal window.
Evidence concerning the efficacy and morbidity of OTC in prepubertal girls is limited.
For girls with certain types of cancer and those undergoing bilateral oophorectomy
for other reasons, however, it offers the only hope of fertility preservation. We
present a case of oophorectomy and OTC for the treatment of metachronous bilateral
mature ovarian teratoma in a prepubertal girl. The challenges which have emerged following
analysis of the case are discussed.
Case Report
A premenarchal 11-year-old girl presenting with abdominal pain was found to have a
left iliac fossa mass. Ultrasonography demonstrated a 7.3-cm left adnexal mass with
a central cystic component and peripheral rim of soft tissue ([Fig. 1]), associated with a small volume of free fluid in the pelvis. Alpha-fetoprotein,
human chorionic gonadotropin, CA-125, and lactate dehydrogenase were normal.
Fig. 1 Ultrasonography demonstrating a sagittal view of suspected left adnexal mass. Laparoscopy
confirmed that the tumor was in fact associated with the right ovary.
Contrary to preoperative clinical and radiological findings, laparoscopy identified
a right ovarian mass comprising cystic and solid components with no normal ovarian
tissue visible ([Fig. 2]). The reason for discrepancy between pre- and intraoperative findings was not clear,
other than that the anatomy was distorted by the presence of the large mass. Inspection
of the left ovary, left fallopian tube, and uterus revealed no abnormality and no
other intra-abdominal pathology was evident. The mass was delivered through a muscle-sparing
Pfannenstiel incision and excised, with presumed en masse resection of the right ovary.
Histopathology demonstrated a completely excised mature ovarian teratoma with no malignant
features. There was no normal ovarian tissue visible on microscopy, save for a small
amount of hemorrhagic and edematous ovarian stroma. Given the risk of metachronous
disease, annual follow-up was arranged with pelvic ultrasonography at each appointment.
Fig. 2 Laparoscopic view of the right-sided mature ovarian teratoma.
At follow-up 1 year after surgery, routine ultrasound revealed a 1.7-cm area of increased
echogenicity concerning for calcification in the left ovary. Magnetic resonance imaging
demonstrated a multicystic left adnexal lesion containing fat ([Figs. 3] and [4]). Tumor markers were again normal. The patient received multidisciplinary input
from consultants in pediatric oncology, pediatric surgery, and reproductive medicine
alongside a fertility counselor. A decision was made to attempt ovarian-sparing excision
of the tumor to preserve fertility. It was, however, agreed preoperatively that OTC
would be performed if oophorectomy became necessary.
Fig. 3 Magnetic resonance imaging (MRI) demonstrating an axial view of the metachronous
left ovarian teratoma preoperatively.
Fig. 4 Magnetic resonance imaging (MRI) demonstrating a sagittal view of the metachronous
left ovarian teratoma preoperatively.
At laparoscopy, the left ovary appeared pathological but intra-abdominal inspection
was otherwise normal. The previous Pfannenstiel incision was reopened and the left
adnexal structures were delivered through the wound. The tumor's limits were difficult
to discern, with no macroscopically normal ovarian tissue visible, therefore oophorectomy
was performed. Following resection, the specimen was dissected ex vivo and a sample
of apparently normal ovarian tissue was sent for cryopreservation. Histopathology
demonstrated a mature ovarian teratoma with clear margins and no malignant characteristics.
Multidisciplinary care continued postoperatively. There were no oncological or surgical
concerns and hormone replacement therapy was commenced. The patient received counseling
and was reviewed by a dietitian as her weight remained static during a 6-month period
postsurgery. She continues to be followed up by a general pediatrician and pediatric
endocrinologist. Her frozen sample of ovarian tissue is now stored securely and will
be made available if she wishes to attempt pregnancy at a later date.
Discussion
We have described a case of bilateral metachronous oophorectomy and OTC to treat metachronous
bilateral mature ovarian teratoma in a prepubertal girl. This is a rare condition,
but has been reported in up to 23% of girls with mature ovarian teratoma.[4]
[5]
[6] The case highlights important challenges for those caring for girls with this pathology.
It is believed that the ideal method of fertility preservation in children with mature
ovarian teratoma is to perform ovarian-sparing tumor excision to preserve healthy
ovarian tissue. The desire to preserve fertility must, however, be balanced against
the need to perform an oncologically safe resection. Adherence to the principles of
oncological surgery entails complete tumor dissection, staging, and avoiding tumor
spillage.[10] In cases of suspected mature ovarian teratoma, the surgeon must still respect these
principles as the true nature of the disease cannot be known until histopathological
examination has been performed. In their series of children with mature ovarian teratoma,
Chabaud-Williamson et al demonstrated complete resection in all cases of ovarian-sparing
surgery (n = 10).[5] They recommended that this technique be reserved for tumors suspected to be localized
mature ovarian teratoma. This view is supported by recent guidance from the Children's
Cancer and Leukaemia Group, which states that an attempt at ovarian-sparing resection
is acceptable if mature teratoma is strongly suspected.[3] In addition, a clear plane of dissection between tumor and normal ovary must be
visible intraoperatively.[11] In this case, ovarian-sparing surgery was not possible for either side. This resulted
in the unfortunate position of a girl rendered infertile following surgical treatment
of what ultimately was found to be benign disease.
For situations such as this, OTC represents the only option for a future biological
pregnancy. However, the sparsity of evidence concerning the efficacy and safety of
prepubertal OTC presents a challenge to those considering its undertaking. Limited
reports exist regarding the efficacy of OTC when tissue has been harvested prepubertally,
although this is a rapidly developing field. Two cases of successful pregnancy have
been reported following prepubertal OTC[12]
[13] and induction of puberty has been reported following autotransplantation of prepubertally
cryopreserved ovarian tissue.[14]
[15] While generally a safe procedure, harvesting of ovarian tissue may require additional
surgery with the inherent associated risks. Due consideration of these risks should
be made in particular in cases where laparoscopy would otherwise not be required and
the risk of gonadal failure (usually related to treatment of oncological or hematological
disease) may be difficult to quantify.[16] There is currently no standardization of service provision for OTC in prepubertal
girls in the U.K. At our center, it is considered in individual cases at high risk
of infertility secondary to treatment for benign or malignant disease.
In conclusion, the possibility of metachronous contralateral disease necessitating
bilateral oophorectomy should be considered in all children with mature ovarian teratoma.
Ovarian-sparing surgery should be considered at index operation, and regular ultrasound
surveillance should be undertaken. The efficacy of prepubertal OTC remains uncertain
and it is important to engage full multidisciplinary team discussion prior to its
undertaking. Informed consent regarding resectional strategy and OTC mandates full
disclosure of the associated benefits and risks, guided by the best available evidence.
