Germ Cell Tumor By Mohamed Bayoumy, M'D'

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Germ Cell TumorByMohamed Bayoumy, M.D.
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Primordial germ cells originate in the yolk sac
endoderm and migrate around the hindgut to the
genital ridge on the posterior abdominal wall.
Aberrant migration accounts for the occurrence
of GCT in midline sites.
Normal Fetal Yolk Sac
Germ Cell production
Primordial Germ Cell
Migration
Normal
Abnormal
Cell Death
Gonads
Neoplastic Cell
Supressed differentiation
Differentiation
Embryonic Extra-embryonic
Germinoma (Seminoma) (Dysgerminoma)
Embryonal Carcinoma Mature or Immature
Teratoma
Choriocarcinoma Yolk Sac Tumor (EST)
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Mature Teratomas (Recommendations)

• Surgical Resection the treatment of choice.
• In sacrococcygeal tumors the entire coccyx
  should be removed.
• (Med Pediatr Oncol 31(1) 8-15, 1998)

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Management of Immature Teratomas(Recommendations)

• The experience with immature teratomas in the
  recent CCG/POG Intergroup Study strongly supports
  using complete resection only, followed by close
  observation of serum tumor markers and diagnostic
  imaging.

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Management of Immature Teratomas(Recommendations)

• Those patients unable to undergo complete
  resection should be offered chemotherapy
• 4 cycles.
• Cisplatin 20 mg/m2 x 5 days combined with
  etoposide 100 mg/m2 and bleomycin 15 IU/m2.
• Another 2 cycles of the same chemotherapy for
  persistent high tumor marker and/or residual
  tumor by diagnostic imaging.
• (Am J Surg Pathol 22(9) 1115-24, 1998)
• (Am J Obstet Gynecol 181(2) 353-8, 1999)
• (J Clin Oncol 17(7) 2137-43, 1999)

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Pediatric Oncology Group/Childrens Cancer Group
Staging of Testicular Tumors
Stage
Extent of Disease I Limited to
Testis completely resected by the high inguinal
orchiectomy with no spill no
clinical, radiologic, or histologic evidence of
disease beyond the testes tumor
markers normal after appropriate postsurgical
half-life decline patients
with normal or unknown markers at diagnosis
must have a negative ipsilateral
retroperitoneal node dissection to confirm
stage I. II Trans-scrotal
orchiectomy with gross spill of the tumor
microscopic disease in scrotum or
high in spermatic cord (lt5 cm from proximal end)
retroperitoneal lymph node
involvement (lt2cm) increased tumor marker
after appropiate half-life. III
Rettroperitoneal lymph node involvement
(gt2cm) no visceral or
extra-abdominal involvement. IV
Distant metastases, including liver.
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Childrens Oncology Group Staging of Ovarian GCT
Stage Extent of Disease I
Limited to ovary or ovaries peritoneal
washing negative for malignant
cells no clinical, radiographic, or
histologic evidence of disease
beyond the ovaries tumor markers normal after
appropriate half-life
decline the presence of gliomatosis peritonei
doesnt upstage the patient. II
Microscopic residual or positive lymph nodes
(lt2cm as measured by
pathologist peritoneal washings negative for
malignant cells tumor
markers positive or negative the presence of
gliomatosis peritonei does
upstage the patient. III Lymph node
with malignant metastatic nodule (gt2cm as
measured by pathologist
gross residual or biopsy only contiguous
visceral involvement
(omentum, intestine, bladder) peritoneal
washings positive for
malignant cells tumor markers positive or
negative. IV Distant metastases,
including liver.
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Childrens Oncology Group Staging of Extragonadal
Extracranial GCT
Stage Extent of Disease I
Complete resection at any site, coccygectomy for
sacrococcygeal tumors
negative tumor margins tumor markers positive or
negative. II Microscopic
residual disease after resection negative lymph
nodes tumor markers
positive or negative. III Gross
residual disease or biopsy only retroperitoneal
nodes negative or
positive tumor markers positive or negative.
IV Distant metastases, including
liver.
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Recommendations

• Pre-therapy evaluation
• Complete history.
• Physical examination.
• Laboratory evaluation complete blood count
  with differential, electrolytes, renal profile,
  hepatic profile, and tumor marker studies (?FP
  and ?HCG).
• Audiogram or brain auditory evoked responses.
• CT scan or MRI of the primary tumor.
• CT scan chest, abdomen, and pelvis.
• Assessment of renal function utilizing
  radioisotope glomerular filtration rate
  creatinine clearance is unreliable in patients
  receiving chemotherapy.
• Bone scan if there is evidence of metastases at
  other sites.

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Recommendations

• POG9049/CCG8882 Intergroup Study
• This study support the stratification of
  children with malignant GCT into three groups
  (low, intermediate, and high-risk) based on their
  primary site and disease stage.
• The low-risk group - patients with stage I
  testicular tumors, ovarian tumors, and
  extragonadal tumors.
• The intermediate-risk group patients with
  stage II-IV gonadal tumors and stage II
  extragonadal tumors.
• The high-risk group patients with advanced
  (stage III-IV) extragonadal tumors.

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Recommendations

• Low-risk group
• Stage I testicular tumors good outcome with
  surgical resection (radical inguinal orchiectomy)
  .
• (A Pediatric Intergroup report (POG9048/CCG8891).
  Proc Am Soc Clin Oncol 16511a,1997)
• Stage I ovarian and extragonadal tumors good
  outcome with surgical resection.
• (J Clin Oncol 17 2137-2143, 1999)
• Recurrent disease salvageable with slandered
  cisplatin, etoposide and bleomycin with 3-year
  EFS 100.

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Recommendations

• Low-risk Group
• Even with normalization of AFP, patients with
  stage I disease must be observed cautiously,
  because 20 to 40 of false-negative measurements
  have been identified and retroperitoneal nodal
  disease has occurred before elevation of AFP.
• Follow-up recommendations
• Monthly follow-up of markers for two years is
  mandatory.
• P.E. every 2 months.
• Patients with no or unknown markers at
  diagnosis, P.E. and abdominal ultrasound should
  be done every 2 months for 2 years.

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Recommendations

• Intermediate-risk group
• 3-year EFS of 90 with standard-dose PEB.
• 4 cycles of PEB.
• Surgery pre or post chemo.
• (A pediatric Intergroup trial (POG9049/CCG8882).
  Pro Am Soc Clin Oncol 17525, 1998)
• Follow up recommendations are the same as
  low-risk group.

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Recommendations

• High-risk group
• A large proportion of these patients are likely
  to have initial biopsy followed by a definitive
  surgical excision after maximal chemotherapy
  effect.
• 4 courses of standard PEB.
• Definite surgical procedure after receiving
  induction chemotherapy complete vs. partial
  resection.
• Pathological evaluation of the resected mass
  fibrotic or necrotic tumor (pathologic CR) vs.
  viable malignant tumor.
• Tumor markers (post chemotherapy and surgery)
  normal vs. elevated.

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Recommendations

• High-risk Group
• Patients with residual active disease after
  second-look surgery will receive two further
  courses of PEB.
• Patients in clinical CR after six courses of
  therapy will electively stop therapy.
• Patients with progressive disease, no response,
  and partial response will receive 4 courses of
  vinblastine, ifosfamide, and cisplatin.
• There is a randomized trial currently going for
  the high risk group using amifostine as a
  cytoprotective agent with HD-PEB to evaluate
  whether the use of amifostine can reduce the
  toxicities of HD-PEB.