Germ cell tumour

1. Management of Germ cell tumors
in Pediatric patients
P R E S E N T E R – D R . M U R A L A S A I R O H I T H R E D D Y
M O D E R AT O R S – D R . R A N J A N I R A M M O H A N
D R . S R U J A N A S K U S H TA G I

2. Introduction
Germ cell tumors (GCT) arise
from primordial germ cells and
vary widely in their clinical
behavior, histology, and locations.
The majority of GCTs will develop
in the gonads or along the midline
structures of the body.
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3. Embryology
Primordial germ cells originate in
the epiblast, migrate through the
primitive streak, and by the 3rd
week reside among endoderm
cells in the wall of the yolk sac
close to the allantois.
During the 4th week, they migrate
along the dorsal mesentery of the
hindgut, arriving at the primitive
gonads at the beginning of the 5th
week and invading the genital
ridges in the 6th week.
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4. Epidemiology
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Pediatric GCTs are rare
Incidence of 11.7 and 6.7 per million, among
boys and girls, respectively.
Account for 3% of tumors in children <15
14% of tumors among children and young
adults between 15 and 19 years
Benign, Mature teratomas are the most
common histology

5. Conditions associated with increased risk of developing
GCTs
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Males with
Cryptorchidism or
Klinefelter’s syndrome
– Increased risk for
developing Testicular
and Mediastinal GCTs
Females with Turner’s
syndrome – Increased
risk for Ovarian GCTs
Patients with Gonadal
dysgenesis – Increased
risk for
Gonadoblastoma in
streak gonads.

6. Classification
Primordial Germ
cells
No
differentiation
Seminom
a
Dysgerminom
a
Germinom
a
Extra-
embryonic
Yolk sac
tumor
Choriocarcinoma
Embryonic
Embryonal
carcinoma
Somatic
Mature
teratoma
Immature
teratoma
Normal
differentiation
Normal
gametes
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7. 2 / 2 5 / 2 0 2 4 S A M P L E F O O T E R T E X T 7
Benign GCT - Mature teratomas
Malignant –
• Germinomatous
• Seminoma
• Dysgerminoma
• Germinoma
• Nongerminomatous
• Yolk sac tumor
• Choriocarcinoma
• Embryonal carcinoma
• Gonadoblastoma
• Mixed GCTs

8. Tumor markers
If elevated, tumor markers are useful
to monitor response to treatment and
for post treatment surveillance
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Alpha fetoprotein (AFP) is
elevated in patients with
Yolk sac tumors
Embryonal carcinoma
Beta hCG is elevated in
patients with
Choriocarcinoma
Embryonal carcinoma
Lactate dehydrogenase is
elevated in patients with
germinomatous tumors

9. Staging
Pediatric GCTs are staged according to the COG (Children’s oncology group) system
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10. Stage
I
Testis - Complete resection via orchidectomy. Lymph
nodes negative
Ovary - Limited to Ovary (with negative evaluation of
peritoneum), no evidence of extraovarian disease
Extragonadal - Complete resection at any site with
negative margins (including coccygectomy for
sacrococcygeal teratomas)
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11. Stage
II
1.Testis - Trans-scrotal biopsy performed, microscopic
disease in scrotum or cord, failure of tumour markers to
normalize
Ovary - Microscopic residual disease, peritoneal
evaluation negative, failure of tumour markers to
normalize
Extragonadal - Microscopic residual disease with
negative lymph nodes, failure of tumour markers to
normalize
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12. Stage
III
1.Testis - Retroperitoneal lymph node involvement without
2.visceral or extra-abdominal involvement
Ovary - Lymph node involvement, metastatic nodule, gross
residual disease, or biopsy only, contiguous visceral involvement
(omentum, bladder, intestine), peritoneal evaluation positive
Extragonadal - Lymph node involvement, gross residual disease,
biopsy only
Stage
IV
Distant metastasis
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13. Risk groups
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14. Medical therapy
• Platinum based chemotherapy serves as the backbone for medical treatment of Pediatric and Adult
GCTs.
• Bleomycin, Etoposide and Cisplatin is the standard regimen for Adult GCTs
• The same regimen is used for pediatric GCTs, with a reduced dose of Bleomycin (Commonly
referred to as PEb)
• Carboplatin may be preferred to Cisplatin leading to reduced toxicity with similar event free survival
and overall survival rates
• In Stage I gonadal GCTs, Surgery and observation alone is sufficient. In case of relapse,
chemotherapy alone nearly always will suffice.
• For stage I malignant gonadal GCTs, PEb is recommended for Intermediate and Poor risk GCTs
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15. • Medical therapy for IT is controversial.
• PEB was administered for adult ovarian ITs (Grade 2 and 3) since higher rates of relapse was
noted among women who did not receive chemotherapy
• For pediatric ITs, outcomes are excellent without chemotherapy. It is generally accepted among
pediatric practitioners that ITs are largely unresponsive to chemotherapy.
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16. • PEB :
Day 1 – Cisplatin 35 mg/m2 IV infusion over 1 hour + Etoposide 120 mg/m2 IV over 1 hour
Day 2 – Same as Day 1
Day 3 – Same as Day 1 + Bleomycin 15 mg/m2 IV over 30 minutes
Ensure pre and post hydration with 125 mL/m2 of N/2 saline with Cisplatin
• JEB : used as an alternative, especially in cases with deranged renal functions
Day 1 – Etoposide 120 mg/m2 in 5% dextrose-normal saline over 1 hour
Day 2 - Etoposide as above + Carboplatin 600 mg/m2
Day 3 – Etoposide as above + Bleomycin 15 mg/m2 IV over 30 minutes
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17. • As Bleomycin toxicity is enhanced in patients with renal impairment (GFR <60/min/1.73m2), it
should be avoided and replaced with Vincristine 1.5 mg/m2 IV bolus on Day 3. Once renal
impairment improves, Bleomycin can be reintroduced.
• For children < 6 months of age, the dose should be reduced to 50% of the calculated and for those
between 6 months and 1 year, it should be 75% of the calculated in both PEB and JEB regimen.
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18. General principles –
Surgical
Management
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Key for both Treatment and Staging
For the initial work-up , USG, CT or MRI are useful for imaging the
primary tumor.
Abdominal CT or MRI is essential for evaluating intraperitoneal
spread and/or retroperitoneal lymphadenopathy in Ovarian,
Testicular, Sacrococcygeal and Retroperitoneal GCTs.
Chest imaging for Pulmonary metastasis.
Upfront surgical resection for all GCTs is preferable if feasible and
expected morbidity is minimal
For unresectable tumors or if
resection would be associated
with unacceptable morbidity:
Pre-operative biopsy
Establishment of venous access for
chemotherapy

19. Ovarian GCTs
1. Mature teratoma :
Most teratomas are cystic (mature cystic teratoma; dermoid cyst) and are composed of mature
differentiated elements including tissue of ectodermal (eg, skin, hair follicles, sebaceous glands),
mesodermal (eg, muscle, urinary), and endodermal (eg, lung, gastrointestinal) origin
A solid prominence (Rokitansky protuberance) is located at the junction between the teratoma and normal
ovarian tissue. The greatest cellular variety is found in the area of this junction, which should therefore be
examined carefully by the pathologist to exclude immature/malignant components.
2. Immature teratoma :
Immature teratomas (also called malignant teratoma, teratoblastoma, or embryonal teratoma) comprise
less than 1 percent of ovarian teratomas and are most common in the first two decades of life
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20. 3. Monodermal highly specialized teratomas – Ex : Struma ovarii, Carcinoid neoplasms
4. Dysgerminomas –
They account for 33 percent of malignant OGCTs. The majority of cases arise in adolescents and
young females. The growth of dysgerminomas is usually rapid and as a result, patients often present
with abdominal enlargement and pain due to rupture with hemoperitoneum or torsion.
5. Yolk sac tumors –
These neoplasms usually occur in young females, the median age at presentation is 23 years and
one-third of patients are premenarchal. Tumor growth can be very rapid and aggressive with
extensive intraperitoneal dissemination.
6. Embryonal carcinoma
7. Choriocarcinoma –
Nongestational choriocarcinoma is a rare and highly malignant type of OGCT. A choriocarcinoma of
ovarian origin derives from an extraembryonic differentiation of malignant germ cells. All
choriocarcinomas produce hCG, which may cause isosexual precocity in young girls and irregular
vaginal bleeding of uterine origin. Serum levels of hCG are useful for monitoring response to
treatment.
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21. Surgical management of Pediatric Ovarian GCTs
• Optimal surgery – Complete resection of the tumor without rupture or spillage and Complete peritoneal
staging.
• Rupture of tumor will result in upstaging of the disease and may require addition of chemotherapy
• If complete resection requires the removal of any organ other than ipsilateral ovary or fallopian tube, a
biopsy should be performed and resection should be postponed until after the administration of NACT.
• Malignant GCTs – Resection, via ipsilateral oophorectomy, Fallopian tube can be preserved if
uninvolved.
• If MT is suspected, with negative tumor markers, Ovarian sparing approach should be pursued. In ~8-
10% cases metachronous lesions can occur in contralateral ovary.
• If ovarian sparing surgery is performed and a diagnosis of IT is made, completion oophorectomy is
recommended.
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22. • Complete intraperitoneal staging is vital. If not done, stage I can’t be assigned and chemotherapy
would be necessary when it otherwise may have been omitted.
• Peritoneal fluid/washings should be sent for cytology.
• Uterus and contralateral adnexa should be examined, suspicious lesions biopsied.
• Normal appearing ovary need not be biopsied.
• For bilateral tumors, resection can be pursued if ovarian parenchyma can be spared. Otherwise,
Biopsy and NACT is recommended.
• Omentum and peritoneal surfaces should be examined and biopsied/resected if suspicious lesions
are present.
• Retroperitoneal lymph nodes should be visualized and palpated. Abnormal appearing, firm or
enlarged nodes should be removed. Sampling of normal appearing nodes is not indicated.
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23. Prognosis
• For stage I malignant ovarian GCTs – event free survival of just 52%, but nearly all patients who
experience relapse were later salvaged with chemotherapy – resulting in an overall survival of 96%
• For advanced stage ovarian malignant GCTs – Overall survival after Surgery and Chemotherapy is
between 85-100%, especially for pre-pubertal girls.
• Stage IV ovarian GCTs in girls >11 years, have an overall survival of 60%.
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24. Surgical management of Pediatric Testicular GCTs
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Malignant testicular GCTs –
Radical orchidectomy with high
ligation of the spermatic cord at
the level of Deep inguinal ring
via an inguinal incision.
MT in a young child – Testicular
sparing approach can be
considered. Orchidectomy is
recommended for Peripubertal
and Postpubertal males.
Scrotal approach is
discouraged.
Scrotal orchidectomy – with
intact resection of tumor and
testicle accomplished – will not
result in upstaging if the
remainder of the spermatic cord
is resected to the level of Deep
inguinal ring during a
subsequent procedure.
If tumor is present in the latter
specimen - the patient will be
upstaged to at least Stage II
If a trans-scrotal biopsy is
performed, the patient will be
upstaged to at least Stage II.
Completion Inguinal
Orchidectomy is recommended,
although hemiscrotectomy is not
needed.

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If the nodes are unchanged or enlarging – Biopsy is recommended.
If biopsy is negative – patient remains as Stage I.
If biopsy is positive or biopsy is not pursued – patient is
upstaged to Stage III and should receive
Chemotherapy.
Nodes 1-2 cm are considered indeterminate; For Stage I patients, follow up imaging in ~4-6 weeks is required.
CT/MRI abdomen and pelvis must be obtained to assess retroperitoneal lymphadenopathy, chest imaging for
pulmonary metastasis.
Nodes <1 cm in maximal diameter are considered
negative
Nodes >/= 2 cm are considered positive for metastatic
disease, designating the patient as having at least
Stage III disease.

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For pediatric patients
with testicular GCTs,
Nodal metastases
are effectively
treated with standard
chemotherapy.
For prepubertal boys
(<11 years) who
have completed
chemotherapy and
have the following,
resection of the mass
should be pursued.
Persistently elevated
tumor markers with a
residual mass
Negative tumor
markers and a mass
2 cm or more (or) one
that is growing 6 to 8
weeks after
completing therapy
Formal
retroperitoneal lymph
node dissection is
not recommended
For peripubertal or
postpubertal males
(>11 years) with a
residual mass in the
retroperitoneum at
the completion of
chemotherapy, with
or without
persistently elevated
tumor markers,
Retroperitoneal
lymph node
dissection with a
nerve sparing
template, is
recommended.

27. A 15 year old boy, presented with
complaints of a progressive left
scrotal swelling and scrotal pain.
On examination there was a
cystic left scrotal swelling, with an
impalpable left testis
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28. • He underwent a High inguinal orchidectomy.
• Histopathology -
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29. • Outcomes for pediatric patients treated for malignant testicular GCTs are generally excellent.
• Event free survival rates ranging from 48% to 95% for Stage I testicular GCTs
• Overall survival is ~100% i.e. even patients with relapse after surgery are highly salvageable with
addition of platinum based chemotherapy.
• Patients with more advanced stage testicular GCT – Overall survival ranges between 83-100%
depending on stage and age of the patient.
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30. Surgical management of Pediatric Extragonadal GCTs
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31. Sacrococcygeal GCTs
• Neonatal sacrococcygeal GCTs are more likely Teratomas and predominantly external in location.
• Those occurring later in childhood are more likely to be intrapelvic and malignant
• For suspected malignant SC GCTs, CT/MRI should be done to determine feasibility of resection
and optimal operative approach.
• It is important to assess involvement of the tumor with surrounding structures, including Neural
foramina, Rectum and Genitourinary structures on Pre-operative imaging. [Patients undergoing
treatment for SC GCTs exhibit high rates of long term bowel and bladder dysfunction]
• If the tumor can’t be safely separated from vital structures, Biopsy followed by administration of
NACT instead of upfront resection, must be done. This can facilitate a less morbid surgical
resection.
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32. Types of Sacrococcygeal GCTs
Altman classification -
• Type I – External
• Type II – Predominantly external
• Type III – Predominantly internal
• Type IV - Internal
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33. • The optimal surgical treatment for Neonatal SC GCTs involves intact removal of the tumor en bloc
with the coccyx while avoiding injury or resection of adjacent organs [Like Pelvic floor musculature],
to preserve future bowel, bladder and reproductive functions.
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34. 2 / 2 5 / 2 0 2 4 S A M P L E F O O T E R T E X T 34
A 11 days old
female baby was
brought by her
parents, with
complaints of a
swelling over
lower back since
birth
1
The swelling was
detected on
antenatal
screening and
hence the
mother
underwent LSCS
2
On examination
– Large 12 x 8
cm cystic
swelling noted
over left gluteal
region.
3

35. • Meticulous dissection is required to remove the
tumor
• For those with both internal and external
component, it may be necessary to work both in
the abdomen to control the blood supply, as well
as working on the perianal region
• The tumor usually displaces the anus and
rectum, therefore meticulously stay on the
capsule of the tumor
The baby underwent
Sacrococcygeal teratoma
excision with Removal of Coccyx.
The goal of the surgery is to
remove all of the tumor, to
remove the tailbone due to the
recurrence risk
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36. Mediastinal GCTs
• Primary Mediastinal GCTs are commonly large and involve critical structures.
• Thymus is commonly involved. [Hence removed with the tumor]
• Lesions with elevated tumor markers that seem to be unresectable should be biopsied [Image
guided, percutaneous core needle biopsy] and NACT administered if malignancy is confirmed.
[General anesthesia is contraindicated in patients with greater than 35-50% tracheal compression
on CT/MRI, PEFR of <50% predicted, or those with orthopnea. Alternative anesthetic strategies
required]
• Large lesions with Negative Tumor markers and features consistent with MT should be resected
primarily.
• In asymptomatic or minimally symptomatic patients, this can be done safely under GA through a
lateral thoracotomy or sternotomy.
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37. GCTs at other sites
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Extracranial GCTs may also arise from the retroperitoneum, vagina, head and neck etc.
Cervical GCTs in neonatal period – are often teratomas and require surgical resection. Airway compromise
is a critical concern, may require immediate postnatal airway securement.
Malignant retroperitoneal GCTs involve vital structures – Hence a biopsy and NACT administration is
required.
Intraperitoneal fluid/washings should be sent for cytology at the time of eventual resection. Retroperitoneal
lymph nodes and evidence of peritoneal spread should be assessed. Abnormal appearing nodes or
peritoneal implants should be excised and sent for biopsy.
Vaginal GCTs should be managed with the intent for Vaginal preservation with NACT given, to facilitate a
more limited, vagina-preserving resection.

38. A 1 month old male infant, was
brought by his parents with c/o
Progressive abdominal
distension and
breathlessness.
Per abdomen – Large mass
palpable in all quadrants
The infant underwent
exploratory laparotomy and
excision of the retroperitoneal
teratoma.
HPE -
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38

39. Surgical management of Metastatic disease
Multimodal therapy, including surgical resection of distant metastases is
encouraged [Associated with long term survival]
Surgical resection is then done for the remaining residual masses that are
more than 1 cm or when tumor markers remain elevated
Chemotherapy is given when metastatic disease is diagnosed initially.
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40. Refractory and Recurrent disease
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Surgical resection is the mainstay
Recurrent GCTs – Salvage chemotherapy + Resection of any residual
mass
Multiple regimens, including high dose chemotherapy with stem cell rescue
can be used
Biopsies revealing transformation to a somatic malignancy should be
treated with therapy apt for that histology

41. • Growing teratoma syndrome : When local or distant metastases from a GCT continue to
grow despite normalization of tumor markers with or without prior chemotherapy.
• Surgical resection is warranted for lesions that are growing/causing symptoms given the
lack of response to other therapies.
• For cases with diffuse peritoneal studding is encountered, aggressive cytoreductive
operations involving the stripping of peritoneal surfaces and the incorporation of HIPEC
are commonly performed for adult ovarian carcinomatosis.
• Among adult patients with growing teratoma syndrome – outcomes are good with
surgical resection, with majority of the patients achieving long term survival.
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42. Summary
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GCTs are quite responsive to treatment, including surgery and Chemotherapy
Proper technique for surgical resection and staging is critical to ensure favorable outcomes.
Tumor markers (AFP, Beta hCG, LDH) must be measured prior to treatment whenever a GCT is
suspected.
Rupture of tumors results in upstaging and must be avoided during operative resection.
Intra-op staging at the time of ovarian GCT resection is critical to ensure that an appropriate
stage is assigned to ensure the patient is not over or undertreated.
Orchidectomy with high ligation of the spermatic cord via an inguinal approach is the preferred
surgical approach to testicular GCTs. Transscrotal approach should be avoided.

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45. Thank you
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