This document provides an overview of extragonadal germ cell tumors (EGGCTs), which develop outside of the ovaries or testicles. Key points include: 1) EGGCTs most commonly occur in the mediastinum, intracranial region, retroperitoneum, and sacrococcygeal area. Common histologies include seminoma, nonseminomatous tumors, teratoma, and mixed germ cell tumors. 2) Presenting symptoms vary based on location but may include chest pain, neurological deficits, or abdominal masses. Diagnosis involves tumor markers, imaging, and biopsy. 3) Treatment approaches also vary by location and histology but commonly involve

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2. Extragonadal Germ Cell
Tumors
Dr. Md. Nazmus Sakib
MD (Oncology) Resident
Phase-A
Session: March,2020
Dhaka Medical College

3. Introduction
Germ cell tumor
• Germ cell tumors (GTCs) arise by the malignant transformation
of primordial germ cells.
• Germ cell tumors most often develop in the ovary or testicle-
Gonadal GCTs
• Infrequently GCTs may develop outside of the ovaries or
testicle- Extragonadal germ cell tumor (EGGCT)

4. Germ cell tumors in male
• Testicular cancers are the most common malignant neoplasm
affecting men aged 15 to 35 years.
• Approximately 90% of testicular cancers are germ cell tumors.

5. Mixed
Nonseminomatous
• Embryonal carcinoma
• Yolk sac tumor
• Trophoblastic tumors
•Choriocarcinoma
• Teratoma
Seminomatous
• Seminoma
• Spermatocytic seminoma
GCTs classification (Testicular)

6. Ovarian GCTs classification (WHO)
Dysgerminoma
Yolk sac tumor
Embryonal carcinoma
Choriocarcinoma
Teratoma
Mixed germ cell tumor

7. Extragonadal GCTs
• Extragonadal germ cell tumors occur much more commonly in males
than in females and are usually seen in young adult.
• They are aggressive neoplasms and can arise virtually anywhere, but
typically the site of origin is in the midline from the cranium (pineal
gland) to the presacral area, corresponding to the embryologic
urogenital ridge, presumably from aberrantly migrated germ cells.

8. EGGCTs…
• The diagnosis can be difficult and should be considered in
any patient with a poorly defined epithelial malignancy,
particularly young individuals with midline masses.

9. GCTs
Gonadal
Extragonadal
1-5%
Mediastinal
Intracranial
Retroperitoneal
Sacrococcygeal

10. Sites

11. Mediastinal germ cell
(MGC) tumors
• Mediastinal germ cell (MGC) neoplasms account for only 2% to 5% of
all germinal tumors.
• 50% to 70% of all extragonadal tumors.
• Most commonly seen in the anterior mediastinum
• They can occur at any age but most commonly occur between 20 and
40 years of age
• MGC tumors are most commonly diagnosed in the third decade of
life, but patients as old as 60 years of age have been reported.

12. MGC tumors..
• MGC tumors are broadly classified as benign or malignant.
• Benign
• Mature teratomas
• Mixed teratomas with an immature component
• Malignant
• Seminomas (dysgerminomas) and
• Nonseminomatous tumors

13. MGCTs
Teratoma
• Teratomas contain elements from all three germ cell layers
with a predominance of the ectodermal component in most
tumors, including the skin, hair, sweat glands, sebaceous
glands, and teeth.
• The mesoderm is represented by fat, smooth muscle, bone,
and cartilage.
• Respiratory and intestinal epithelium are often both seen as
the endodermal component.

14. Teratoma..
• Teratomas may be solid or cystic in appearance and are often
referred to as dermoid cysts if unilocular.
• Most mediastinal teratomas are composed of mature ectodermal,
mesodermal, and endodermal elements and exhibit a benign
course.
• Immature teratomas, which phenotypically appear as malignant
ectodermal, mesodermal, or endodermal tumors, behave
aggressively and generally are not responsive to therapy

15. Seminoma
• Seminomas uncommonly may exist in a pure form, but any
elevation of serum AFP levels indicates the presence
of at least a small element of nonseminomatous tumor.

16. .
Nonseminomatous Tumors
• Mediastinal nonseminomatous germ cell tumors are most commonly
found in the anterior mediastinum.
• Nonseminomatous tumors include embryonal
carcinomas, choriocarcinomas, yolk sac tumors, and immature
teratomas.
• Non–germ cell malignant components may be
present or even predominate in immature teratoma, including
adenocarcinoma, squamous cell carcinoma, smallcell undifferentiated
carcinoma, neuroblastoma, rhabdomyosarcoma, or other sarcomas

17. • Karyotypic abnormalities, particularly the 47,XXY pattern of Klinefelter
syndrome, have been found in up to 20%
of patients.
• 85% to 95% have systemic disease at the time of diagnosis.
• Common metastatic sites include the lungs, pleura, lymph nodes, the
liver, and, less commonly, bone.

18. Diagnosis
• CF
– May be asymptomatic (teratoma)
– Chest pain, dyspnea, cough, fever, or
– complaints from compression or invasion of adjacent mediastinal structures
– Seminomas typically grow slowly and metastasize later than
nonseminomatous
– Symptoms are usually related to their effects on the surrounding mediastinal
structures
– Pulmonary and other intrathoracic metastases are present in 60%
to 70% of patients, whereas extrathoracic metastases usually involve bone

19. Tumor markers
• β-hCG and AFP
• AFP (60% to 80%), β-hCG (30% to 50%), or
both are elevated in 80% to 85% of nonseminomatous germ
cell tumors.
• Patients with pure seminoma
– May have low levels of β-hCG, but AFP is not detected unless a
nonseminomatous component also exists

20. • Patients with benign teratomas have normal markers.
• The presence of isochromosome 12p is diagnostic of a germ
cell malignancy, even in the absence of elevated serum
markers.

21. Chest radiographs
• MGC tumors typically are detected by standard chest radiographs,
which are abnormal in 95% of cases.
• Most masses are noted in the anterior mediastinum, but 3% to 8%
of tumors arise within the posterior mediastinum.
• Chest CT scans
– large inhomogeneous masses containing areas of hemorrhage and
necrosis
– the extent of disease
– the relationship to surrounding structures, and
– the presence of cystic areas and calcification within the tumor

22. 38-year-old man with primary mediastinal yolk sac tumor. Contrast-
enhanced chest CT scan shows bulky anterior mediastinal mass with large
central unenhancing necrotic region and peripheral heterogeneously
enhancing solid component.
48-year-old man with primary mediastinal seminoma. Contrast-enhanced
axial CT image through chest shows large well-defined homogeneous soft-
tissue density mass with minimal contrast enhancement in posterior
mediastinum, partially surrounding thoracic aorta

23. • Abdominal imaging should be performed to assess for liver metastases.
• Careful examination of the testes, including a testicular ultrasound,
should always be performed
• The diagnosis of nonseminomatous germ cell tumors in young males with
anterior mediastinal masses and elevated serum tumor markers (AFP and
β-hCG) may be made without a tissue biopsy, and treatment may be
initated .

24. • If a tissue confirmation is necessary, a core needle biopsy
with cytological staining for tumor markers usually is
adequate.
• Rarely, an open biopsy via an anterior mediastinotomy
approach is necessary.

25. Management of MGC tumors
• MGC tumors are not formally staged according to the AJCC
staging system but can be characterized as
– localized,
– locally advanced, and
– metastatic.
• Due to the lack of a staging system, these tumors will be
discussed by histologic subtype

26. Tx of Teratoma
• Treatment of a mature mediastinal teratoma consists of complete
surgical resection, which results in excellent long-term cure rates.
• If adherent to surrounding structures, necessitating resection of
the pericardium, pleura, or the lung.
• Radiotherapy and chemotherapy play no role in the management
of this tumor.
• If the tumor is not completely resectable neoadjuvant
chemotherapy with cisplatin-based combination chemotherapy
(four cycles of cisplatin, etoposide, and bleomycin or vinblastine,
ifosfamide, and cisplatin) may be considered.

27. Seminoma
• Seminomas are extremely radiosensitive tumors, and for many
years, high-dose mediastinal radiation was used as the definitive
therapy, resulting in long-term survival rates of 60% to 80%.
• Radiation therapy in the extragonadal seminoma, including
recommendations for mediastinal and bilateral supraclavicular
fields as well as for doses of 35 to 45 Gy.

28. • In case of bulky, extensive, and locally invasive disease, requiring
large radiotherapy portals that would result in excessive irradiation
of surrounding the normal lung, heart, and other structures
• Currently, due to these limitations, only an isolated mediastinal
seminoma with minimal disease is managed with radiotherapy
alone.
• Instead, the use of cisplatin-based combination chemotherapy,
which was previously used only in advanced
gonadal seminoma, is now used as first-line therapy.

29. • All patients (localized, locally advanced, and visceral
metastatic) should be treated with curative intent.
• Locally advanced and bulky disease should be treated initially
with
– cisplatin-based combination chemotherapy, which is most often four
cycles of cisplatin and etoposide
– with or without supradiaphragmatic radiotherapy.

30. • Patients with distant metastases should undergo chemotherapy
alone as the initial treatment.
• Salvage chemotherapy (vinblastine, ifosfamide, and cisplatin)
may be required for persistent or recurrent disease.
• In addition, surgical debulking of large tumors has not been
shown to be of benefit in improving local control or survival .

31. Nonseminomatous Germ Cell Tumors
• The mainstay of treatment of nonseminomatous germ cell tumors
is cisplatin-based chemotherapy.
• Overall complete remission rates of 40% to 64% were obtained in
most series.
• Patients with relapsing mediastinal nonseminomatous germ cell
tumors have poor prognosis

32. Intracranial GCTs
• Very rare tumors of the adolescent and young adult.
• Intracranial germ cell tumors (ICGCTs) are localized preferentially
to the pineal and suprasellar regions.
• Although germinomas (60% of intracranial germ cell tumors) have
a predilection for the suprasellar region
• Embryonal carcinomas, yolk-sac tumors, and choriocarcinomas
mainly occur in the pineal region.
• Occasionally are found in other areas such as the basal ganglia,
ventricles, cerebral hemispheres, and spinal cord.

33. Classification
Germinoma
Embryonal carcinoma
Yolk sac tumor
Choriocarcinoma
Teratoma
• Mature teratoma
• Immature teratoma
• Teratoma with malignant transformation
Mixed germ cell tumor

34. CF
• Patients with pineal tumors present with headache, nausea,
and vomiting because of increased intracranial pressure; they
require early ventriculoperitoneal (VP) shunting.
• Deterioration of intellectual functions, gait abnormalities with
frequent falls, and sphincteric incontinence are common.
• Choreic movements and ataxia of the limbs with spastic
weakness appear in later stages of Parinaud syndrome.

35. • In suprasellar tumors, precocious pseudopuberty, diabetes
insipidus with or without anterior pituitary dysfunctions (eg,
adrenocorticotropic hormone [ACTH] deficiency), central
hypothyroidism, growth hormone (GH) deficiency, and
hypogonadism may be seen.
• Decreased visual acuity, visual field defect, diplopia, obesity,
psychosis, and obsessive-compulsive symptoms have also
been reported.

36. Markers
• α-Fetoprotein (elevated in yolk sac tumors) and human chorionic
gonadotropin-β (elevated in choriocarcinoma and, to a modest
extent, in germinoma) are generally secreted by
these tumors.
• Mature teratomas do not have elevated tumor markers.
• The levels of β-hCG in the cerebrospinal fluid of patients with
primary intracranial germ cell tumors (ICGCT) are elevated more
frequently than in the plasma.

37. Imaging
• On CT, these lesions are hyperdense.
• On MRI, the mass is hypointense on T2-weighted sequences
(due to the high cellularity of the mass) and shows
enhancement with gadolinium.
• Calcification and fat may be seen in
teratomas or mixed malignant germ cell tumors.
• Germinomas tend to surround a calcified pineal gland

38. • Fig. —26-year-old man with primary
intracranial mixed seminoma and embryonal
carcinoma in pineal region. Contrast-
enhanced axial CT scan of head shows
enhancing mass (straight arrow) containing
calcification (curved arrow) and causing
hydrocephalus (arrowheads).

39. Mx of ICGCT
• Determination of histology, tumor markers, and extent of
disease is critical for the optimal management of pineal region
tumors.
• The prognosis varies depending on the histologic type, the size
of the tumor, and the extent of disease at presentation.

40. Surgery
• There is no role for cytoreductive surgery in the treatment of
germinoma, which requires only a biopsy from the neurosurgeon
followed by-
– radiation, chemotherapy, or both.
• Resection is important when tumors are radioresistant or when
an excision may be curative (e.g., as in teratomas)
• Importance of surgery is to obtain tissue when a diagnosis cannot
be made from serum tumor markers, CSF tumor markers or by
imaging.

41. RT
• The standard treatment for intracranial germ cell tumors has been
radiotherapy, either alone (germinomas) or in combination with
chemotherapy (nongerminomatous germ cell tumors).
• Radiation therapy varies in intensity from
– craniospinal irradiation (CSI) with boost (the most intense),
– to whole brain irradiation with boost,
– ventricular irradiation with boost, and
– focal irradiation alone (the least intense).

42. Chemotherapy
• Germinomas are chemosensitive and responsive to cisplatin,
carboplatin, ifosfamide, cyclophosphamide, bleomycin, and
etoposide.
• The chemotherapy response rate high, approximately half of the
patients developed recurrent disease, suggesting that a
multimodal therapeutic approach of surgery, chemotherapy, and
radiotherapy is necessary.

43. Retroperitoneal germ cell tumors
• Retroperitoneal germ cell tumors
(RGCTs) represent 10% of all
malignant primary retroperitoneal
tumors.
• Many patients with retroperitoneal
germ cell tumors present late, after
their tumors have reached large
dimensions.
• Presenting symptoms are abdominal
mass with or without pain,
backache, and weight loss.
CT showed necrotic retroperitoneal mass (white dot)
partially encasing aorta (curved arrow) and displacing
inferior vena cava (straight arrow). Multiple liver
metastases (arrowheads) are seen. Histopathology
revealed 70% embryonal carcinoma and 30% yolk sac
tumor.

44. • Primary chemotherapy with four cycles of bleomycin, etoposide,
and cisplatin (BEP) is recommended for both seminomas and
nonseminomas, with excision of residual mass in nonseminomas.
• Nichols recommends primary abdominal radiotherapy for patients
with small-volume retroperitoneal seminomas (abdominal mass < 5
cm) and chemotherapy for patients with larger volume disease
(abdominal mass > 10 cm).
• Patients with intermediate disease may be treated with either
modality