Extragonadal Germ Cell Tumors Follow-up

Updated: Apr 16, 2015
  • Author: Kush Sachdeva, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Further Outpatient Care

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  • Detection of late recurrences (>2 y after treatment discontinuation), development of testicular tumors several years after the initial diagnosis of extragonadal germ cell tumors (EGGCTs), and treatment-related complications justify prolonged periods of follow-up care with clinical evaluation, tumor markers, and imaging studies.
  • In children (and probably in adults) with intracranial germ cell tumors (ICGCTs), obtain baseline intelligence quotient (IQ) and achievement tests before starting radiotherapy. Perform follow-up intellectual assessments at 1 year after completion of radiation, then at 2, 3, and 5 years, and if any intellectual deterioration is noted. Evaluate hearing if intellectual deterioration occurs. Evaluation of thyroid, corticotropin, gonadotropin, prolactin, and GH functions is obtained before and regularly after radiation therapy.


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  • Growing teratoma syndrome is the increase in tumor size during or after chemotherapy for mediastinal germ cell tumors (MGCT) or retroperitoneal germ cell tumors (RGCT) and only mature teratoma at histologic analysis of the resected tumor specimen. [25] Mature teratoma component is present in the majority of the primary tumors (86%). The major risk factor for this complication is the completeness of the surgical resection of the primary tumor because it was seen in only 4% of the patients who underwent complete resection compared to 83% of those patients who had partial resection. Complete surgical resection is the treatment of choice.
  • Rupture of a mature teratoma as a result of the digestive enzymes secreted by intestinal mucosa or pancreatic tissue into the bronchi or lung may result in hemoptysis [26] or expectoration of hair or sebum. Rupture into the pleura or pericardium leads to pericardial or pleural effusion.
  • Teratoma with malignant transformation is a rare complication of mediastinal germ cell tumors. The most common transformations are different kinds of sarcomas, glioblastomas, nephroblastomas, neuroblastomas, adenocarcinomas, and hematologic malignancies.
  • The incidence of hematologic malignancies in patients with nonseminomatous mediastinal germ cell tumors (NS-MGCTs) is 200- to 300-fold higher than in matched controls.
    • The median time from the diagnosis of the germ cell tumors (GCTs) to the diagnosis of the hematologic malignancy is 6 months (range 0-47 mo). Acute myelogenous leukemia and myelodysplasia with megakaryocyte lineage abnormalities are the most common disorders.
    • Patients present with pancytopenia, isolated thrombocytopenia, splenomegaly, and/or hepatomegaly. Flushing and syncope are suggestive of systemic mastocytosis, another unusual hematologic malignancy complicating mediastinal germ cell tumors.
    • The clinical course is very aggressive, with a median survival of 5 months. Predictors of the subsequent occurrence of leukemia are mediastinal localization of the germ cell tumors and endodermal sinus tumor and teratocarcinoma histologic types. Bone marrow biopsy should not be delayed if cytopenia persists or recurs after the initial chemotherapy period.
  • Chemotherapy-related complications may be immediate or delayed.
    • Nausea and vomiting became less common with the advent of 5-hydroxytryptamine 3 (5-HT3) antagonists. Postcisplatin delayed emesis is better treated by oral administration of metoclopramide, benzodiazepine, and dexamethasone for 2-4 days.
    • A certain degree of cisplatin-related nephrotoxicity is almost always present and is cumulative. Hypomagnesemia is common, requiring supplementation for prolonged periods in some patients.
    • Arthralgias, myalgias, peripheral neuropathy, and paralytic ileus are common toxic effects of vinblastine. However, since replacement of vinblastine with etoposide in first-line therapy began, these complications are no longer seen. Auditory toxicity with reduced high-tone hearing may be seen after cisplatin. It rarely requires hearing aids.
    • Neutropenic fever and severe thrombocytopenia are relatively uncommon with etoposide and cisplatin (EP) as first-line chemotherapy. The addition of bleomycin and salvage chemotherapy results in significant increase of these complications (50%), requiring the prophylactic use of hematopoietic growth factors after the first episode of neutropenic fever.
    • Pulmonary toxicity from bleomycin is unpredictable and rare (10% of treated patients) and is dose- and age-dependent (rate is higher in patients >70 y and after a cumulative dose >1200 IU or 400 mg). The progression to pulmonary fibrosis is uncommon and occasionally fatal (1%). Although carbon monoxide diffusing capacity may not predict clinically significant lung damage, its use was recommended along with chest x-ray as a screening test in patients treated with bleomycin. If radiographic changes or a decrease of diffusing capacity of lung for carbon monoxide (DLCO) greater than 30% is detected, discontinue the drug.
    • Raynaud phenomenon and, to a lesser degree, stroke and myocardial infarction were reported after use of bleomycin.
    • Accelerated coronary artery disease is a well-recognized complication of mediastinal radiotherapy.
    • Infertility is seen in as many as 50% of patients after chemotherapy. Standard bilateral retroperitoneal lymph node dissection almost always is associated with retrograde ejaculation. Nerve-dissecting, nerve-avoiding, and posterior approaches decrease, but do not abolish, this adverse effect.
    • The frequency of etoposide-related secondary leukemia is dose dependent. It is seen in less than 0.5% of patients who received a total dose less than 2000 mg/m2 and in about 6% of those who received more than 3000 mg/m2. Abnormalities of chromosome band 11q23 are very common in this setting. Latency period varies from 2-4 years. The incidence of gastrointestinal malignancies, especially gastric cancers, and soft-tissue sarcomas is increased slightly after combined radiation and chemotherapy. Latency period is about 10 years or more.
    • Weijl et al reported a high rate of thromboembolic events (8.4%) during chemotherapy in 179 patients with germ cell tumors. Liver metastases and high-dose corticosteroids were identified as risk factors for these complications. [27]
  • With the achievement of prolonged survival for patients with intracranial germ cell tumors (ICGCTs), researchers became increasingly aware of long-term effects of cranial radiation on intellectual and endocrine functions.
    • These complications are correlated with the total dose and fraction sizes of irradiation and are correlated conversely to the patient's age at the time of treatment. Concomitant chemotherapy increases the risk of toxicity.
    • Verbal IQs and reading skills are affected to a lesser degree than performance IQs or mathematic ability. Personality changes include anxiety, depression, lability, belligerence, hypersexuality, reduced attention span, memory problems, and reduced reasoning ability.
    • GH deficiency with growth retardation and hypothyroidism are much more common than gonadotropin and corticotropin deficiencies.
    • Leukoencephalopathy, hearing loss, and second malignancies (20-y cumulative probability of about 12% for the latter) are increased after cranial irradiation.


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  • Analysis of available data on 5862 patients with germ cell tumors (GCTs) resulted in development of a classification system by the International Germ Cell Collaborative Group (IGCCG). [28] This system categorizes tumors based on histologic type (seminomas have better prognosis than nonseminomas), localization of metastases (retroperitoneal and testicular portend better prognosis than mediastinal and intracranial germ cell tumors), and initial levels of serum AFP, bhCG, and LDH (the higher the tumor markers the worse the effect on survival).
  • Nonseminoma
    • Good prognosis is indicated by all of the following:
      • Testis/retroperitoneal primary
      • No nonpulmonary visceral metastases
      • Good markers - AFP < 1000 ng/mL, bhCG < 1000 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%
  • 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.
  • Ganjoo analyzed the data from 75 patients treated at Indiana University for nonseminomatous mediastinal germ cell tumors (NS-MGCTs) with chemotherapy followed by surgery. Tumor marker elevation prior to or after chemotherapy was not found to be an independent prognostic variable for survival. However, the presence of visceral metastases and especially postchemotherapy pathology were the most important predictors of survival. [29]
  • The Institut Gustave-Roussy prognostic model based on tumor marker levels was not able to classify their group of 38 patients treated for nonseminomatous germ cell tumors accurately. The use of etoposide seemed not to make any difference in survival. Although patients who were able to receive dose-intensive chemotherapy fared better, this did not reach statistical significance. Extrapulmonary metastases remained the sole significant parameter in long-term survival.
  • Patients with mediastinal germ cell tumors (MGCTs) have a poor prognosis owing to at least the following 3 factors: mediastinal germ cell tumors are not as sensitive as other germ cell tumors to chemotherapy, bulky disease increases the risk of poor outcome in the short term owing to respiratory failure, and hematologic malignancies are linked to a very unfavorable prognosis.

Patient Education

For excellent patient education resources, see eMedicineHealth's patient education article Tailbone (Coccyx) Injury.