Germ cell tumors (GCT) constitute less than 3% of all ovarian cancers. These tumors occur predominantly in children and women under 30 years of age. The immature ovarian teratoma is the third commonest of the germ cell tumors following dysgerminoma and endodermal sinus tumor. The growing teratoma syndrome (GTS) is an extremely rare metastatic complication of a malignant germ cell tumor. The finding of a growing solid mass (or masses) during or after chemotherapy treatment for GCT of the ovary should raise the possibility of the growing teratoma syndrome. These lesions should be resected to confirm the diagnosis, to exclude malignancy, to relieve a possible pressure on adjacent organs and to prevent a possibility of malignant transformation in future.

1. Growing teratoma syndrome - Case report
and review of literature

2. Review Article
Growing teratoma syndrome e Case report
and review of literature
Ruquaya Mir a
, Sandeep Kaul b,*
, V.P. Singh a
a
Sr. Consultant, Surgical Oncology Indraprastha Apollo Hospital, India
b
Surgical Oncology Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India
a r t i c l e i n f o
Article history:
Received 11 July 2014
Accepted 31 October 2014
Available online xxx
Keywords:
Growing teratoma syndrome
Non-seminatous germ cell tumors
Immature teratoma
a b s t r a c t
Germ cell tumors (GCT) constitute less than 3% of all ovarian cancers. These tumors occur
predominantly in children and women under 30 years of age. The immature ovarian
teratoma is the third commonest of the germ cell tumors following dysgerminoma and
endodermal sinus tumor. The growing teratoma syndrome (GTS) is an extremely rare
metastatic complication of a malignant germ cell tumor. The finding of a growing solid
mass (or masses) during or after chemotherapy treatment for GCT of the ovary should raise
the possibility of the growing teratoma syndrome. These lesions should be resected to
confirm the diagnosis, to exclude malignancy, to relieve a possible pressure on adjacent
organs and to prevent a possibility of malignant transformation in future.
Copyright © 2014, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Case history
A 16/yr female resident of Uzbekistan presented to our hos-
pital in 2013 with a diagnosis of immature teratoma for which
she had underwent a trans-abdominal hysterectomy with
bilateral salphingo-ophorectomy in 2010 in Uzbekistan fol-
lowed by 3 cycles of standard BEP chemotherapy. Presently
she had progressive abdominal distension which had started
while patient was still receiving chemotherapy. She had oc-
casional complaints of abdominal pain, vomiting and con-
stipation but had good appetite and maintained good health.
On general physical examination, her vitals were stable but
pallor was present. There was a vertical midline scar
extending from the xiphoid to pubic symphisis. Per abdominal
examination revealed a large lobulated palpable non-tender
mobile mass filling whole of the abdomen with overlying
skin stretched, visible veins were present with flow from
below upwards upon eliciting Harvey's sign. Lab in-
vestigations revealed Hb-10.6 g/dl, TLC 12,800 cumm3
, DLC
N86L9M5, ESR-36 mm/1st hr, PCV 32.1%, Platelet Count-
196,000, PTI 13.5 s, aPTT 30.6 s, INR 1.3, S-Urea-19 mg/dl, S-
Creatinine-1.3 mg/dl,LDH-332 IU/L, aFP-0.66 IU/ml, HCG <2 IU/
ml. Contrast enhanced computerized tomogram of the chest
and abdomen revealed a large complex solid/cystic mass in
the abdomen and pelvis 40 Â 21 Â 25 cm, occupying most of
the right side of the abdominal cavity with specks of calcifi-
cation, displacing small bowel and pancreas. The right lobe of
the liver was distorted and scalloped by the mass, bilateral
ureters revealed hydroureters. The right hemi-diaphragm was
elevated with right lower lobe and rest of lung fields were
clear. After informed consent patient underwent an
* Corresponding author.
E-mail addresses: drsandeepkaul@yahoo.com, drsandeepkaul@gmail.com (S. Kaul).
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/apme
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Please cite this article in press as: Mir R, et al., Growing teratoma syndrome e Case report and review of literature, Apollo
Medicine (2014), http://dx.doi.org/10.1016/j.apme.2014.10.004
http://dx.doi.org/10.1016/j.apme.2014.10.004
0976-0016/Copyright © 2014, Indraprastha Medical Corporation Ltd. All rights reserved.

3. exploratory laparotomy. The intra-operative findings revealed
minimal ascites, extensive peritoneal disease, a large multi-
lobulated tumor in the pelvis, abdomen and right sub-
diaphragmatic region closely abutting segment V, VI and VII of
right lobe of liver.
Multiple well encapsulated lesions were present. The right
lobe of the liver was adherent to the upper abdominal mass
without any parenchymal infiltaration. Optimal cytoreduction
with peritonectomy was done. The significant intra-operative
events were intra-operative hypotension/hypovolemia, on
tumor mobilization and IVC compression, iatrogenic dia-
phragmatic tear which was repaired primarily with 1.0 pro-
lene. Intra-operatively 4 units of PRC and 2 units of FFP were
transfused. The patient had an uneventful post-op recovery
and was discharged on 7th post-operative day. Though the
patient has not come for follow-up but relatives have
informed us that she is doing well and is asymptomatic.
2. Histopathology report
The tissue show orderly arrangement and are represented by
cystic spaces lined variably by gastrointestinal type epithe-
lium, respiratory epithelium, and keratinized stratified squa-
mous epithelium cuffed by thick layer of smooth muscle;
lobules of mature adipose tissue; plates of hyaline cartilage
and mature lamellar bone; lobules of seromucinous glands
and gastric fundic gland; cells; blood vessels and skin ap-
pendages. Islands of primitive neuroepithelium or immature
tissues are not identified in multiple sections examined.
Evidence of somatic malignancy arising within this tumor
not seen. Histology picture with normal tumor markers con-
firms diagnosis of GTS (Fig. 1, Fig. 2, Fig. 3).
3. Discussion
The growing teratoma syndrome (GTS) is an extremely rare
metastatic complication of a malignant germ cell tumor (GCT)
described for the first time by Logothetis et al.1
The syndrome
is defined as a detection of an enlarged mass during or after
chemotherapy treatment for GCT. The histology of the lesion
is of mature teratoma with no malignant elements. The syn-
drome appears in 1.9e7.6% of the patients after treatment for
testicular non-seminomatous germ cell tumor (NSGCT).2
Logothetis coined this phenomenon the “growing teratoma
syndrome” (GTS). According to his original description, three
criteria are required for the definition of the GTS. First,
normalization of previously elevated tumor markers (aFP or
bHCG). Second, enlargement of the primary tumor & third,
only mature teratoma elements in pathologic examination.
All these criteria should be met after or during chemotherapy
treatment of NSGCT.
GTS is much less common after ovarian GCT. Kattan et al3
were the first to use the term “growing teratoma syndrome” in
woman. The patient had a recurrent mature teratoma im-
plants during chemotherapy treatment for metastatic malig-
nant teratoma of the ovary.
One large series from a single institution, MD Anderson
Cancer Center,4
and the two large series from the Gynecologic
Oncology Group5,6
reported the presence of Mature teratoma
(MT) from the second e look operation for GCT in 13/52 pa-
tients, 10/76 patients, and 21/108 patients, respectively, with
an overall incidence of 17.8%.
Teratoma is a tumor whose components are derived from
more than one germ cell layer. Mature teratoma (MT) is
composed of well-differentiated elements, whereas immature
teratoma is only partially differentiated and is in this respect
akin to foetal tissue. These are distinct entities in the WHO
classification. MT is classified as a benign entity and is resis-
tant to primary chemotherapy. Surgical resection is the
standard treatment for these patients. MT is the only
component found during GTS. As immature teratoma is
considered by some authors to be a malignant NSGCT, its
presence in growing masses should not be equated with GTS.
The pathogenesis of the GTS is still a subject of contro-
versy. Two basically distinct mechanisms are currently under
consideration: malignant cell differentiation into MT or se-
lective chemotherapy-induced destruction of components
other than MT. The demonstration that malignant germ cells
can differentiate into MT could support the first hypothesis.
However, several arguments support the model according to
which chemotherapy kills malignant cells during concomi-
tant enlargement of MT.
Fig. 1 e 10X nodules of mature glial tissue separated by
fibrous septae.
Fig. 2 e 10X admixture of plates of hyaline cartilage mature
adipose tissue and stratified squamous epithelium.
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e42
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4. It has been suggested that the presence of MT in residual
masses after chemotherapy for NSGCT is predictive of a late
recurrence containing MT. These finding advocate complete
surgical resection of post chemotherapy residual masses
containing MT. Moreover, close surveillance by CT scan is
probably justified for patients at risk as it permits early
detection of GTS. This early detection is associated with a high
rate of complete resection.
Despite the fact that serum tumor marker levels usually
normalize in these patients during chemotherapy, there is a
demonstrated growth of these metastatic tumors on radio-
logical imaging, prompting the genitourinary medical oncol-
ogist and/or urologist to consider the clinical diagnosis of GTS.
The treatment of choice for GTS is complete surgical excision.
Because GTS consists predominantly of chemo-refractory
teratomatous elements, late diagnosis of GTS could result in
significant symptomatology as well as make the surgical
excision more technically challenging. Most previous studies
have reported excellent treatment related outcomes with the
surgical excision of GTS.7,8
If this tumor is not excised, it may eventually give rise to
serious complications such as severe renal obstruction, biliary
and duodenal obstruction, or vena cava compression.9
More-
over, it may exhibit dedifferentiation to become malignant
germ cell tumors as reported in one patient by Deleo et al.10
It
may even coexist with the development of nongerm cell tu-
mors such as adenocarcinomas11
or sarcomas.12
Otherwise, as
demonstrated by some authors, histologically mature, tera-
toma may present a benign appearance but genomically may
be malignant.13
Patients with surgically unresectable GTS of
the testis have been described in the literature. Tonkin et al14
reported a patient with abdominal GTS in whom the disease
was proven inoperable due to mesenteric involvement. This
patient had controllable disease for 8 years while on inter-
feron, but he subsequently developed acute myeloid leukemia
and died within a few months. Similarly, van der Gaast et al15
described a long-lasting stabilization with interferon in a pa-
tient who had a retroperitoneal relapse after 2 subsequent
surgical resections of an abdominal growing teratoma. Jeffery
et al16
also reported 2 cases of incomplete resection out of 13
GTS. One of them was doing well with stable retro rural dis-
ease 21 months following surgery, while the other died of
uncontrollable aortic hemorrhage 48 h after surgery for
growing teratoma relapse.
MT has been reported to possess a malignant potential,
including transformation into malignant NSGCT, sarcoma,
squamous cell carcinoma, adenocarcinoma, carcinoid tu-
mors15,17,18
and primitive neuroectodermal tumor (PNET).
Transformation of MT into malignant NSGCT might be either
due to an intrinsic biological potential or to small malignant
NSGCT foci overlooked by the pathologist and associated with
MT in post chemotherapy residual masses.
It is difficult to predict the growing potential of the GTS.
Long-term stabilization of GTS, has previously been reported
but no spontaneous disease regression. Cytokines, growth
factors and steroid hormones have been put forward as
possibly instrumental in the biological regulation of these
successive periods of enlargements and stabilization. The
clinical responses and stabilizations obtained with a-inter-
feron reported in the literature16,19
and indirectly argue in
favor of cytokine-mediated regulation of the GTS. GTS
generally grows at the initial site and at the site of metastasis.
It is well known that MT has a propensity to metastasis which
is quite paradoxical given its benign phenotype.
On the basis of our review of literature, we have observed
that GTS of the ovary can present from the age of 5e38 years,
with a mean age of 20 years. The primary tumor was either a
pure immature teratoma or a mixed germ cell tumor of the
ovary. The first round of GTS nodules can appear anywhere
from the commencement of chemotherapy until 2 years, and
at an average of 8 months.
Malignant transformation of mature ovarian teratoma is a
well-known phenomenon and malignancies of all 3 embryo-
logic lineages can develop.20
It is not clear what drives this
process. Two of the largest studies on record examined
mature cystic ovarian teratomas as a general group, and re-
ported the rate of secondary malignancies to be 1.4% and
0.17%, respectively.21
Both studies showed that the patients
who present with secondary malignancies arising from
mature teratomas of the ovary are at least 15 years older than
the average patient with mature cystic teratoma, and have
tumors of a larger size. On the basis of this data, one can
extrapolate that secondary malignancies may develop in
masses of GTS of the ovary, and especially in those that have
been left in the patient for many years.
Patients should be followed up closely since relapses with
teratoma or carcinoma may occur in as many as 19% of pa-
tients and as late as 20 years (Loehrer et al, 1988).22
Post-operative adjuvant chemotherapy or radiation ther-
apy which had been used after GTS resection in a few reported
cases,5
is not appropriate for this benign lesion. Interferon was
also reported to have modest effect because it could only
temporarily stabilize or slightly reduce the size of the residual
tumor masses.4
Conflicts of interest
All authors have none to declare.
Fig. 3 e 10x admixed lobules of mature fat tissue and
nodules of mature glial tissue along with cystic space lined
by keratinized stratified squamous epithelium.
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e4 3
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