Transcript Mediastinal germ cell tumors

‫الدكتور‬
‫ُم َح َّمد يحيى كوي َفاتية‬
‫اختصاصي في طب األورام ومعالجتها‬
‫‪ Oncologist‬ألمانيـا‬
‫طبيب في قسم األورام – مستشفى زاهي أزرق‬
Question For Cancer Patient:
1)Are we sure of the diagnosis?
2) What is the stage of disease?
3)Can this patient be cured?
4)If can’t be cured, How can we help the patient the
most?
5)Can this patient participate in clinical trial?
Case Report
Male, 31 years old, smoker came on 5.4.2007 suffered
from Chest pain and dyspnea.
Biopsy from Mediastinal mass with CT guided :
small cell carcinoma.
Chest CT
Chest X-ray:
Radiology:
CT Chest : huge mass in mediastinum measured about
15 cm
CT Abdomen, Pelvis: normal
CT Brain : normal.
Differentional Diagnosis of Mediastinal :
Germ cell tumors
Thymic tumors
Mesenchymal tumors
Lymphomas
Neurogenic tumors
Extra gonadal Germ Cell Tumor Carcinoma Syndrome :
1) It occurs in young men( younger than 50 years)
2) The tumors are located predominantly in the
medline ( Mediastinum, Retroperitoneum)
3) History of rapid tumor growth, the symptom interval
is short fewer than 3 months
4) Serum levels of BCGH , AFP are elevated
5) Good Response to Chemotherapy
Labor:
BHCG: 0,46 normal
AFP < 1000 diluted 10 times 27000
LDH: 882,3
CEA: 3,82
Testis examine was normal
Pathology: AFP: positive CK positive
Diagnosis:
Extragonadal Germ Cell Tumor Carcinoma : Stage I or II
Mediastinal primary tumor
AFP: >1000 = 27000
: poor prognosis according to
International Germ Cell Cancer Collaborative
Group
Plane: curable Cancer.
Extra gonadal Germ Cell Tumor Carcinoma : poor prognosis
Chemotherapy: 4xBEP doses.
salvage (VIP) etoposide, ifosfamide, and cisplatin If the
serum tumor markers remain elevated
If the CT scan shows residual disease without tumor marker
elevation, perform surgical resection.
Additional postoperative chemotherapy is given if the patient
is found to have viable tumors
Treatment:
From 15.5.2007 till 6.8.2007 he was taking three cycles
BEP, and two cycles EP chemotherapy
After the second cycle AFP was 71.7
the third
was 19.3
fourth
was 12.3
On 19.8.2007, mass was executed through lung
Pathology: Necrosis, Fibrosis, and a little bit tumor cells.
Chest CT : Case after operation no Mass.
On 30.8.2007 AFP 2.17 normal
From 1.9.2007 till 22.10.2007 he took another three cycles EP .
After the last cycle AFP was 1.81 normal
19.9.2010 AFP: 1.94
Extragonadal Germ Cell Tumors
Introduction
(EGGCTs) are rare tumors that predominantly affect young males.
The only known risk factor for (EGGCTs) is Klinefelter syndrome(47XXY), which is associated with
mediastinal nonseminomatous germ cell tumors.
They are characterized by their location on the midline from the pineal gland to the coccyx.
In (EGGCTs), no evidence of a primary malignancy is present in either the testes or ovaries by
radiologic imaging or physical examination.
(EGGCTs) produce a rich symptomatology and may reach large volumes if they arise in silent areas.
Histologically, they mirror their gonadal counterparts with which they share the same
chemosensitivity and radiosensitivity.
Modern approaches to diagnosis and treatment can result in high rates of long-term survival and
even cure.
Frequency :
In United States (EGGCTs) represent 5-10% of all germ cell tumor (GCTs), predominantly
affect young males
Seminomas account for 30-40% of these tumors, and nonseminomatous germ cell tumors
(NS-GCTs) account for 60-70%.
Nonseminomatous germ cell tumors include yolk-sac tumors, embryonal carcinomas,
choriocarcinomas, teratomas, and nonteratomatous combined germ cell tumors.
Pathology of postchemotherapy residual masses reveals necrosis in 24%, teratoma in 45%,
sarcoma in 5%, and viable germ cell cancer in 26%.
Sex
In children, (EGGCTs) occur equally in males and females.
In adults, more than 90% of (EGGCTs) occur in males.
Clinical
Symptoms vary depending on the site and the size of the tumor. Those arising in nonvital organs can reach large
sizes before becoming symptomatic.
Mediastinal germ cell tumors
The mediastinum is the most common site of (EGGCTs) 50-70%
Retroperitoneal germ cell tumors
The second most common site of (EGGCTs) (30-40%), (RGCTs) represent 10% of all malignant primary
retroperitoneal tumors.
Often patients with retroperitoneal germ cell tumors present late, after their tumors have reached large
dimensions.
symptoms are abdominal mass with or without pain, backache, and weight loss.
Intracranial germ cell tumors
(ICGCTs) are localized preferentially to the pineal and suprasellar regions.
Pineal tumors present with headache, nausea, and vomiting because of increased intracranial pressure;
they require early ventriculoperitoneal (VP) shunting.
Sacrococcygeal germ cell tumors
In the literature to date, 17 cases have been reported. Pain and bowel habit change are the main symptoms.
Mediastinal germ cell tumors:
Mediastinal germ cell tumors account for 10-15% of adult anterior mediastinal tumors.
Mature teratomas represent 60-70% of mediastinal germ cell tumors.
Malignant mediastinal germ cell tumors (30-40%) are divided between seminomas
(40%) and nonseminomatous germ cell tumors (60%)..
Although their incidence peaks in the third decade, several cases have been reported
in patients older than 60 years.
Patients may present with chest pain (39%), dyspnea (29%), cough (22%), weight
loss (19%), superior vena cava syndrome (12%), Nausea (6%), fever (6%),
postobstructive pneumonia, weight loss, night sweats, dysphagia, shoulder or
arm pain, vocal cord paralysis, and hoarseness.
Mediastinal germ cell tumors:
In one third of patients the anterior mediastinal mass is an incidental finding of
a routine chest radiograph (in most of these cases, a benign tumor is found).
Metastases to locoregional lymph nodes or to distant sites, such as the lungs,
liver, or bone, may be present in 20-50% of cases on presentation.
Mature teratoma rupture, teratoma with malignant transformation, and
hematologic malignancies may complicate mediastinal germ cell tumors
Growing teratoma syndrome is the increase in tumor size during or after
chemotherapy, surgical resection is the treatment of choice.
Extragonadal germ cell cancer syndrome:
Midline fast-growing tumors (eg, of the mediastinum,
retroperitoneum) occur in young males. Histologically,
these tumors are poorly differentiated carcinomas with
atypical features.
The germ cell origin of these tumors is suggested by the
typical abnormalities of chromosome 12 and the
elevation of beta human chorionic gonadotropin
(bhCG) and/or alpha-fetoprotein (AFP).
Laboratory Studies
Tumor markers provide diagnostic, staging, and prognostic information. Check these levels before and then at
regular intervals after therapy.
Choriocarcinoma, embryonal carcinoma, and a minority of seminomas (<10%) produce bhCG
Serum AFP elevations are seen in yolk-sac tumors and embryonal carcinoma.
AFP, bhCG, or both are elevated in approximately 85% of extragonadal nonseminomatous germ cell tumors.
Small increases in serum beta-hCG can be seen in up to 50% of patients with disseminated seminoma.
(LDH) is a nonspecific marker. Its level correlates well with the tumor burden and with the number of i(12p) copies.
Tumor marker elevation in the appropriate clinical setting makes the diagnosis of germ cell tumors highly likely.
Chemotherapy can be initiated in these cases without tissue diagnosis if a need for immediate treatment is
present
Cytogenetic analysis of patients with mediastinal germ cell tumors (MGCTs) reveals trisomy 8 in 16% of cases and
Klinefelter syndrome (XXY) in 14-20% of cases. However, the most common karyotype abnormality is i(12p),
present in 38% of patients. The presence of this abnormality helps identify midline germ cell tumors presenting
as poorly differentiated carcinomas with atypical features.
Imaging Studies:
Testicular ultrasound: This should be ordered to rule out a gonadal primary site.
CT scan of the chest, abdomen, and pelvis
Mature teratomas appear as heterogeneous cystic, well-defined, anterior mediastinal masses
with walls of different thicknesses. Calcifications are present in approximately one quarter,
with a bone or a tooth rarely identifiable. The combination of fluid, soft tissue, calcium,
and/or fat attenuation in an anterior mediastinal mass is highly specific for mature teratoma.
Seminomas present as bulky, lobulated, homogeneous, anterior mediastinal masses.
Although invasion of adjacent organs is uncommon, metastases to regional lymph nodes and
bone can be seen. Calcifications are rare.
Nonseminomatous mediastinal germ cell tumors (NS-MGCTs) appear as irregular, anterior
mediastinal masses, often with extensive, central heterogeneous areas of low attenuation
caused by necrosis, hemorrhage, and/or cyst formation. Adjacent organ involvement and
metastases to regional lymph nodes as well as to distant sites may occur.
positron emission tomography (PET- CT Scan)
Studies have suggested that PET may be more sensitive
than CT, disease smaller than 0.5 cm was not detected.
In patients with nonseminomatous germ cell tumors
(NSGCT), PET has not been consistently able to
identify residual viable malignant germ cell tumors
(GCTs) and also does not detect teratoma.
One study has shown that PET is useful in the detection
of residual viable seminoma in patients with masses
larger than 3 cm in diameter after chemotherapy
Staging
Clinical staging of mediastinal germ cell tumors (MGCT)
Stage I - Well-circumscribed tumor with or without focal
adhesions to the pleura or pericardium but without
microscopic evidence of invasion into adjacent organ
Stage II - Tumor confined to the mediastinum with macroscopic
and/or microscopic evidence of infiltration into adjacent
structures
Stage III - Tumor with metastases
Stage IIIA - With metastases to intrathoracic organs
Stage IIIB - With extrathoracic metastases
Treatment
Treatment modality is determined by the site and the histologic type of the
primary tumor.
Mature teratomas are relatively insensitive to both chemotherapy and radiation
therapy therefore surgery is the only treatment for teratomas
seminoma of the mediastinum:
Treatment with 4 cycles of bleomycin, etoposide, and cisplatin (BEP) is the current
standard of care. Radiotherapy can be used after chemotherapy in bulky
mediastinal seminomas.14
In nonseminomatous mediastinal germ cell tumors (NS-MGCT), 4 cycles of (BEP)
also are recommended. If the serum tumor markers remain elevated, give
salvage chemotherapy etoposide, ifosfamide, and cisplatin (VIP), . If the CT
scan shows residual disease without tumor marker elevation, perform surgical
resection, Additional postoperative chemotherapy is given if the patient is
found to have viable tumors.
Prognosis
Classification system by the International Germ Cell Collaborative Group (IGCCG).
Nonseminoma :
Good prognosis is indicated by all of the following:
Testis/retroperitoneal primary
No nonpulmonary visceral metastases
Good markers - AFP <1000 ng/mL, bhCG <10000 IU/L, and LDH <1.5 X upper limit of normal (N)
Includes 56% of nonseminomas, which have a 5-year progression-free survival rate (PFS) of 89% and 5-year
survival rate of 92%
Intermediate prognosis is indicated by all of the following:
Testis/retroperitoneal primary
No nonpulmonary visceral metastases
Any of AFP >1000 and <10,000 ng/mL, bhCG >5000 and <50,000 IU/L, or LDH >1.5 X N and <10 X N
Includes 28% of nonseminomas, which have a 5-year PFS of 75% and 5-year survival rate of 92%
Poor prognosis is indicated by any of the following:
Mediastinal primary
Nonpulmonary visceral metastases
Poor markers - Any of AFP >10,000 ng/mL, bhCG >50,000 IU/L, or LDH >10 X N
Includes 16% of nonseminomas, which have a 5-year PFS of 41% and 5-year survival rate of 48%
Prognosis
Classification system by the International Germ Cell Collaborative Group (IGCCG).
Seminoma
Good prognosis is indicated by the following:
Any primary site
No nonpulmonary visceral metastases
Normal AFP, any bhCG, any LDH
Includes 90% of seminomas, which have a 5-year PFS of 92% and 5-year survival rate of 88%
Intermediate prognosis is indicated by the following:
Any primary site
Nonpulmonary visceral metastases
Normal AFP, any bhCG, any LDH
Includes 10% of seminomas, which have a 5-year PFS of 67% and 5-year survival rate of 72%
Poor prognosis: No patients are classified as having poor prognosis.
Follow-up:
Detection of late recurrences (>2 y after treatment
discontinuation)
development of testicular tumors several years after the
initial diagnosis of (EGGCTs)
treatment-related complications justify prolonged
periods of follow-up care with clinical evaluation, tumor
markers, and imaging studies.
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