eMedicine Specialties > Pediatrics: Surgery > General Surgery
Teratomas and Other Germ Cell Tumors: Treatment & Medication
Updated: May 29, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Surgical Care
In general, gross total resection of tumor is the goal. The tumor and involved adjacent structures should be resected en bloc, if this is possible and does not lead to disfigurement.
- Sacrococcygeal tumor
- Typically, the surgeon approaches this tumor through a posterior trans-sacral route. The coccyx must be resected en bloc with the tumor to minimize the risk of recurrence. Control and division of the middle sacral artery early in the procedure is advisable. If the sacrum or rectum is invaded by the tumor, complete resection may not be advisable at the initial operation. Treating these tumors with chemotherapy is reasonable, with resection after the maximum response is obtained.
- When the tumor extends high into the pelvis and abdomen, laparotomy or laparoscopy is required in addition to the posterior incision. Ascitic fluid should be collected or peritoneal washings obtained. The tumor may then be mobilized for removal from below or above, depending on the anatomy. Samples should be obtained in lymph nodes from the retroperitoneum. In tumors with a moderate pelvic component, laparoscopy may allow clip placement in the middle sacral artery and mobilization of the pelvic portion of the tumor.
- Cowles et al (2006) reported preoperative embolization of the major vessels that supply a large teratoma followed by radiofrequency ablation of the zone between normal tissue and tumor.13 Damage to the nerves supplying the leg has been reported with prenatal radiofrequency ablation.
- Ovarian tumor
- Open resection is the preferred approach to these tumors. Typically, laparoscopy requires morcellation of the tumor in a bag. The consequent destruction of the tumor capsule prevents pathological staging; thus, patients must be treated as stage II. Ascites or peritoneal washings should be undergo cytologic analysis. The entire peritoneal cavity should be inspected. Any suspicious implants should be sampled or resected. Gliomatosis peritonei does not worsen the stage of a tumor, but all implants must have mature glial tissue. Immature tissue suggests metastatic disease and requires more intensive therapy. The omentum must be inspected. If disease is possible (eg, adherence, nodules, implants), the affected area should be resected at this time.
- Ipsilateral oophorectomy or salpingo-oophorectomy should be performed. Uninvolved fallopian tubes should be preserved if possible. In cases of mature teratoma, the contralateral ovary should be inspected. If it appears normal, it should be left alone. Bilateral malignant tumors require bilateral oophorectomy, but hysterectomy is unnecessary for germ cell tumors. Some authors advocate ovary-sparing resection of mature teratomas. This is not always possible.
- Samples of suspicious and involved lymph nodes should be obtained. Random bilateral sampling is no longer required because it did not have an impact on survival in the last Intergroup study.14
- Testicular tumor
- Testicular teratomas may be treated with local resection in prepubertal patients. The tumor should be removed with a small rim of normal testicle. If the testicular tissue shows signs of pubertal change, radical inguinal orchiectomy should be performed.
- In all malignant cases, radical inguinal orchiectomy should be performed with high ligation of the spermatic cord. For very large tumors, the incision may be enlarged by extending the medial portion of the incision downward into the upper scrotum. Transscrotal resection with intact capsule is now treated as a stage I tumor, provided the cord structures are completely removed and are uninvolved. If trans-scrotal biopsy was performed prior to resection, the stage is at least stage II. Because most of these preadolescent tumors are responsive to chemotherapy, hemiscrotectomy is rarely necessary.
- If images do not reveal lymph node enlargement, sampling of ipsilateral retroperitoneal lymph nodes is not required. When images show positive findings of nodal enlargement of 2-4 cm, perform a biopsy of the enlarged nodes. Nodes larger than 4 cm diameter are treated as stage III metastatic disease and do not require biopsy. Tumor debulking is no longer recommended.
- Mediastinal tumor
- The approach to the resection may be via median sternotomy or lateral thoracotomy. Small lesions have been resected by using video-assisted thoracic surgery (VATS). Large lesions may cause airway compromise and require intubation and care in the intensive care unit. Many of these large tumors are best managed with initial biopsy, neoadjuvant chemotherapy, and delayed complete resection.
- Adherent nonvital structures such as the pericardium and thymus should be removed en bloc with the tumor. Lymph nodes should be sampled
- Neck tumor
- These lesions present special surgical challenges. In large congenital lesions, the airway may be compromised, and intubation may be difficult. The ex utero intrapartum treatment (EXIT) procedure, in which a cesarean delivery is performed and the neonate remains attached to the placenta, may allow enough time for bronchoscopic airway placement.
- Resection should be total but not at the expense of vital structures. A staged procedure is acceptable in this circumstance. Complete resection may then be possible after chemotherapy.
- Recurrent disease
- Recurrent disease must be surgically staged. The extent of disease is an important prognostic factor. Surgically resectable recurrent disease has a far more favorable prognosis than unresectable disease. The best prognosis exists when complete surgical resection is accompanied by high intensity chemotherapy with autologous stem cell rescue.
- Additionally, recurrent disease may have a different tissue type than that of the original tumor. PNET, for example, is a frequent component of germ cell tumors that may not respond to bleomycin, etoposide, and cisplatin (BEP)–type therapy.
- Metastatic disease: When these tumors are metastatic, initial chemotherapy may lead to resolution of metastatic disease. When it does not, residual disease may be necrotic tumor, mature teratoma, persistent malignant disease, or combinations of the above. No current radiologic test reliably distinguishes between these possibilities. Surgical biopsy may help guide therapy. Resection is recommended when possible.
Consultations
Psychological support is important for both the patient and the family after any diagnosis of cancer. For older patients, fertility issues, as well as issues of sexual identity, may also be important.
Diet
Maintaining adequate nutrition is often difficult during chemotherapy. Additionally, intestinal obstruction may be a consequence of an abdominal tumor. Nutritional supplements or parenteral nutrition may be necessary. In cases other than those involving frank obstruction, enteral tube feeding has proven useful.
Medication
Since the introduction of platinum-based therapy for this disease, the survival rate has improved considerably. First-line therapy includes the use of cisplatin, etoposide, and bleomycin. Survival with carboplatin containing regimens has not been as favorable. For low risk tumors (testicular stage II, and ovarian stage I and II) 4 cycles of BEP has a survival rate of 94-100%. For high risk tumors (stage III and IV testicular and ovarian tumors and stage I-IV extragonadal tumors) high-dose BEP has better overall survival at the cost of some increase in toxicity.
Salvage therapy typically consists of a combination of paclitaxel, ifosfamide, carboplatin, etoposide, and vinblastine or vincristine plus peripheral blood stem cell (PBSC) transplantation. Gemcitabine has been used as salvage therapy in a phase 2 protocol.
Kollmannsberger et al (2003) reported improved 2-year survival with a second course of high-dose chemotherapy with stem cell rescue and complete surgical resection in high-risk patients who failed initial ablative chemotherapy and autologous stem cell transplant.15
Antineoplastic agents
Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (ie, phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2). Finally, a mitotic cell division occurs (ie, phase M). Cell division rates vary for different tumors.
Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, while others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.
Current protocols use these agents in combinations that exploit differences in growth and recovery between tumors and normal tissues.
Bleomycin (Blenoxane)
Glycopeptide antibiotic that inhibits DNA synthesis. For palliation in the management of several neoplasms.
Adult
0.25-0.5 U/kg (10-20 U/m2) IV/IM/SC 1-2 times qwk; reconstitute the 15-U vial with 1-5 mL of sterile water or 0.9% NaCl for injection
Pediatric
15 mg/m2 IV has been administered in several pediatric chemotherapy trials
May decrease plasma levels of digoxin and phenytoin; cisplatin may increase bleomycin toxicity when administered systemically
Documented hypersensitivity; significant renal function impairment; compromised pulmonary function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal impairment; possibly secreted in breast milk; may cause mutagenesis and pulmonary toxicity (10%); idiosyncratic reactions similar to anaphylaxis (1%) may occur; monitor for adverse effects during and after treatment; vaso-occlusive phenomenon with distal necrosis of digits; permanent damage to nail matrix may occur
Etoposide (Toposar, VePesid)
Inhibits topoisomerase II and causes DNA strand breakage, which arrests cell proliferation in the late S or early G2 portion of the cell cycle.
Adult
100 mg/m2 IV on days 1-5
Pediatric
100 mg/m2 IV over 1 h in 250 mL/m2 of 0.9% NaCl has been administered in several pediatric chemotherapy trials
May prolong the effects of warfarin and increase the clearance of methotrexate; cyclosporine and etoposide have additive effects in the cytotoxicity of tumor cells
Documented hypersensitivity; IT administration (may cause death)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Bleeding and severe myelosuppression may occur
Vinblastine (Velban)
Inhibits microtubule formation, which, in turn, disrupts the formation of the mitotic spindle, causing cell proliferation to arrest at metaphase.
Adult
4-20 mg/m2 (0.1-0.5 mg/kg) IV q7-10d or a 5-d continuous IV infusion of 1.4-1.8 mg/m2/d or 0.1-0.5 mg/kg/wk
Pediatric
0.11 mg/kg/d (or 3 mg/m2) IV over 1 h for 2 d has been used in pediatric clinical trials
Phenytoin plasma levels may be reduced when administered concomitantly; with mitomycin, vinblastine toxicity may significantly increase
Documented hypersensitivity; bone marrow suppression; IT administration (may result in death)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in impaired liver function and neurotoxicity; closely monitor patients receiving mitomycin C for shortness of breath and bronchospasm
Cisplatin (Platinol)
Inhibits DNA synthesis and, thus, cell proliferation by causing DNA cross-linking and denaturation of the double helix.
Adult
20-120 mg/m2 IV q3-4wk
Pediatric
20 mg/m2 IV qd for 5 consecutive days has been administered in pediatric clinical trials
40 mg/m2 IV qd for 5 consecutive days has been administered in one pediatric trial; it had substantial toxicity despite administration with increased mannitol dose and vigorous hydration to limit renal toxicity
Increases toxicity of bleomycin and ethacrynic acid
Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Adequately hydrate before and 24 h after dose to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, nausea, and vomiting may occur
Carboplatin (Paraplatin)
Analog of cisplatin. Has same efficacy as cisplatin but with a better toxicity profile. Dose is based on the following formula: total dose (mg) = (target AUC) X (GFR + 25), where AUC is the area under plasma concentration-time curve expressed in mg/mL/min, and GFR is expressed in mL/min.
Adult
360 mg/m2 IV q3wk as monotherapy or 300 mg/m2 q4wk as combination therapy
Pediatric
600 mg/m2 IV on day 2 of therapy, or the following formula has been used in clinical trials: 6 X (uncorrected GFR + [15 X surface area])
Nephrotoxicity increases with aminoglycosides and other nephrotoxic drugs
Documented hypersensitivity; bone marrow suppression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor bone marrow function
Paclitaxel (Taxol)
Mechanisms of action are tubulin polymerization and microtubule stabilization.
Adult
175 mg/m2 IV over 3 h q3wk or 135 mg/m2 IV over 24 h q3wk
Pediatric
200 mg/m2 IV infused over 24 hours has been used in pediatric trials
Coadministration with cisplatin may further increase myelosuppression
Documented hypersensitivity to paclitaxel or polyoxyethylated castor oil; peripheral neuropathy; bone marrow suppression; liver failure; severe cardiac disease
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Premedicate with steroids and H1 and H2 blockers to decrease risk of hypersensitivity reactions; myelosuppression, alopecia, arthralgia/myalgias, and cardiac arrhythmia may occur
Ifosfamide (Ifex)
Inhibits DNA and protein synthesis and, thus, cell proliferation by causing DNA cross-linking and denaturation of the double helix.
Adult
50 mg/kg/d IV over 30 min or 700-2000 mg/m2/d for 5 d
Alternatively, 700-900 mg/m2/d for 5 d IVP and repeat q3-4wk
Pediatric
1-2 g/m2 IV with mesna has been used in pediatric trials
Phenobarbital, phenytoin, chloral hydrate, and other drugs that induce CYP3A activity may increase clearance; may increase INR when coadministered with warfarin
Documented hypersensitivity; depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause hemorrhagic cystitis (administer with mesna) and severe myelosuppression; caution in renal function impairment or compromised bone marrow reserve
Gemcitabine (Gemzar)
Cytidine analog. After it is intracellularly metabolized to become an active nucleotide, it inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA.
This drug has been shown to have activity in a phase 2 trial against relapsed germ cell tumors.
Adult
1000 mg/m2 once weekly for as long as 7 wk or until toxic effects not tolerated; follow with 1 wk rest and subsequent cycles of once weekly infusion for 3 consecutive wk q4wk
Pediatric
1.2 g/m2 IV infused over 30 min on days 1, 8, and 15 of 28-d cycles has been used in pediatric trials
May increase INR when coadministered with warfarin
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause myelosuppression (particularly thrombocytopenia); toxicities include flulike syndrome, LFT abnormality, maculopapular rash, pruritus, nausea, vomiting, dyspnea, hematuria, proteinuria, and hemolytic uremic syndrome; IV infusions administered over >60 min are associated with more adverse effects
Vincristine (Vincasar PFS, Oncovin)
Mechanism of action is uncertain. May involve a decrease in reticuloendothelial cell function or an increase in platelet production. However, neither of these mechanisms fully explains the effect in TTP and HUS.
Adult
2 mg IV injection
Pediatric
1.4 mg/m2 IV injection; not to exceed 2 mg/dose
Acute pulmonary reaction may occur when taken concurrently with mitomycin-C; asparaginase, CYP3A4 inhibitors (eg, itraconazole, quinupristin/dalfopristin, sertraline, ritonavir), colony-stimulating factors (eg, sargramostim, filgrastim), or nifedipine increase toxicity; CYP3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, rifampin) may decrease effects
Documented hypersensitivity; IT administration (may be fatal)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in severe cardiopulmonary disease, hepatic impairment (adjust dose), or preexisting neuromuscular dysfunction
Antibiotic agents
Trimethoprim and sulfamethoxazole (TMP-SMZ) is indicated for prophylaxis of Pneumocystis carinii infection.
Trimethoprim and sulfamethoxazole (Septra, Bactrim)
Dihydrofolate reductase inhibitor that prevents tetrahydrofolic acid production in bacteria. Active in vitro against a broad range of gram-positive and gram-negative bacteria, including uropathogens (eg, Enterobacteriaceae species, Staphylococcus saprophyticus). Resistance is usually mediated by decreased cell permeability or alterations in amount or structure of dihydrofolate reductase. Demonstrates synergy with sulfonamides, potentiating inhibition of bacterial tetrahydrofolate production.
Adult
160 mg TMP/800 mg SMZ PO q12h on 3 sequential days qwk during chemotherapy
Pediatric
75 mg/m2 (based on TMP component) bid on 3 sequential days per wk during chemotherapy
May increase PT when used with warfarin (perform coagulation tests and adjust dose); coadministration with dapsone may increase blood levels of both; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use in pregnancy near term (increases risk of kernicterus and hemolytic anemia in neonate); discontinue at first appearance of skin rash or adverse reaction; frequently obtain CBC counts; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer 5-15 mg/d leucovorin); caution in folate deficiency (eg, elderly patients, those with chronic alcoholism or malabsorption syndrome, those receiving anticonvulsant therapy); hemolysis may occur in G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation
Uroprotective antidotes
Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide and cyclophosphamide. In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity.
Mesna (Mesnex)
Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.
Adult
Dose depends on ifosfamide or cyclophosphamide dose; typically 60-100% of the antineoplastic agent used; may be administered as an initial bolus followed by continuous or intermittent IV infusions prior to and after chemotherapy
Pediatric
Administer as in adults
May increase warfarin affect, adjust dose according to INR target
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor morning urine for hematuria prior to ifosfamide or cyclophosphamide dose; common adverse effects include hypotension, headache, GI toxicity, and limb pain
Antiemetic agents
Antiemetics should be administered before, during, and for 6 hours after chemotherapy. Antineoplastic-induced vomiting is stimulated through the chemoreceptor trigger zone (CTZ), which then stimulates the vomiting center (VC) in the brain. Increased activity of the central neurotransmitters dopamine in CTZ or acetylcholine in VC appears to be a major mediator for inducing vomiting. After the administration of antineoplastic agents, serotonin (5-HT) is released from enterochromaffin cells in the GI tract. With serotonin release and subsequent binding to 5-HT3-receptors, vagal neurons are stimulated; they transmit signals to the VC, resulting in nausea and vomiting.
Antineoplastic agents may cause nausea and vomiting so intolerable that patients may refuse further treatment. Some antineoplastic agents are more emetogenic than others. Prophylaxis with antiemetic agents prior to and after cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.
Ondansetron (Zofran)
Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. Prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and complete-body radiotherapy.
Adult
8 mg PO 1-2 h before radiotherapy and 8 mg bid for chemotherapy prophylaxis
Alternatively, three 0.15-mg/kg IV doses or 32 mg IV once
Pediatric
4-11 years: 4 mg PO 30 min before chemotherapy; may repeat q8h for 2 doses
>11 years: Administer as in adults
Potential for CYP450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) to change half-life and clearance, but dose adjustment not usually required
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
For prevention of nausea and vomiting, not for rescue of nausea and vomiting
More on Teratomas and Other Germ Cell Tumors |
| Overview: Teratomas and Other Germ Cell Tumors |
| Differential Diagnoses & Workup: Teratomas and Other Germ Cell Tumors |
 Treatment & Medication: Teratomas and Other Germ Cell Tumors |
| Follow-up: Teratomas and Other Germ Cell Tumors |
| Multimedia: Teratomas and Other Germ Cell Tumors |
| References |
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Further Reading
Keywords
teratomas, germ cell tumors, solid neoplasms, dermoid, sacrococcygeal teratoma, seminoma, dysgerminoma, yolk sac tumor, endodermal sinus tumor, choriocarcinoma, embryonal carcinoma, gonadoblastoma, primitive neuroectodermal tumor, PNET, ovarian teratoma, congestive heart failure, cervical teratomas, dysgerminoma, high-output cardiac failure, placentomegaly, hydrocele, cryptorchidism, hernia, pyloric stenosis, intersex anomalies, gonadoblastoma, carcinoma in situ
