Pediatric Teratomas and Other Germ Cell Tumors Workup

Updated: Jul 31, 2019
  • Author: E Stanton Adkins, III, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
  • Print
Workup

Laboratory Studies

When a germ cell malignancy is suspected, tumor markers should be assessed prior to surgery. If the diagnosis is made after resection, marker studies should be performed as soon as possible thereafter. When tumor marker findings are positive, they should be monitored before each cycle of chemotherapy to determine the response to therapy and check for relapse.

Alpha-fetoprotein (AFP) is present in tumors with the following histologic features:

  • Fetal liver or endodermal sinus tumor elements
  • Embryonic carcinoma
  • Endodermal sinus tumor
  • Teratoma

Beta–human chorionic gonadotropin (β-HCG) is present in tumors with the following histologic features:

  • Embryonal carcinoma
  • Choriocarcinoma
  • Teratoma

The lactate dehydrogenase (LDH) isoenzyme LDH-1 is present in many tumors with the histologic features of an endodermal sinus tumor.

Once the diagnosis has been histologically confirmed, and if chemotherapy is needed, the following tests should be performed:

  • Complete blood count (CBC), differential, and platelet count
  • Glomerular filtration rate (GFR) or creatinine clearance rate - These are used to establish baseline renal function prior to platinum-based chemotherapy
  • Uric acid levels - These are used are used to assess the added risk from tumor lysis
  • Liver function tests - These include assessment of bilirubin, alkaline phosphatase, alanine aminotransferase, total protein, and albumin levels; they are used to assess possible metastases and determine baseline results prior to chemotherapy
  • Electrolytes, calcium, and magnesium levels - These should be monitored daily during chemotherapy, and deficiencies should be treated with supplements or changes in intravenous therapy
Next:

Imaging Studies

Diagnostic imaging is an essential part of initial staging, monitoring the response to therapy, and detecting relapse. Different modalities are appropriate at different points in the therapeutic course.

Chest radiography may be used at diagnosis to detect metastasis.

Computed tomography (CT) of the abdomen and pelvis is essential for the staging of abdominal and pelvic tumors at presentation. [32] Follow-up studies may be performed after the third course of chemotherapy, at the conclusion of induction therapy, and at the conclusion of maintenance therapy to monitor the response. CT is needed at relapse to determine the extent and location of the disease.

Magnetic resonance imaging (MRI) of the abdomen and pelvis may be substituted for CT. [32] If so, it should be used throughout therapy to maintain consistency in imaging studies. Yamaoka et al reported that among ovarian teratomas, mature tumors had imaging appearances typical of sebaceous fluid, whereas immature teratomas had multiple foci of fat as well as simple fluid-containing cysts. [33] MRI has also been used to characterize cardiac tumors. [34]

At diagnosis, chest CT is necessary to evaluate the presence and extent of metastatic disease that originates in the abdomen or pelvis. If a thoracic primary tumor is present, CT is used to assess the location and extent of the primary disease.

Bone scanning is a nuclear medicine test that is used to detect metastatic disease. It should be performed at presentation, as well as after the third course of chemotherapy, at the conclusion of induction therapy, and at the conclusion of maintenance therapy.

The remaining tests are optional and may be used as the clinical situation dictates.

CT or MRI of the brain should be performed whenever brain metastases are suspected.

Ultrasonography (US) of the abdomen and pelvis may aid in the detection of ovarian tumor spread and in monitoring certain masses without the risk of ionizing radiation. Testicular US may be useful for detecting microliths in testes contralateral to known tumors. These findings signify a high likelihood of neoplasia in situ.

Fluorodeoxyglucose (FDG) positron emission tomography (PET) appears to be most useful in the detection of relapse because other modalities cannot be used to detect the activity of the disease. The presence of elevated tumor marker levels, without the depiction of new disease on CT or MRI, is an indication for FDG-PET.

Previous
Next:

Other Tests

Pulmonary function studies, including diffusing capacity tests, are used to establish baseline function and determine the risk of bleomycin toxicity.

Brainstem auditory evoked responses (BAERs) or audiograms are assessed, depending on the patient's age, to establish baseline values prior to platinum-based chemotherapy.

Because germ cell tumors may be associated with chromosomal abnormalities (eg, Klinefelter syndrome [23] and mediastinal germ cell tumors), genetic screening is advisable in many cases. [35]

Previous
Next:

Histologic Findings

With mature teratoma, sampling of the entire tumor is necessary to ensure that no immature neural elements or occult foci of malignancy are present. The pathologist should evaluate the tumor at 1-cm intervals.

Histologic findings may include the following:

  • Immature teratoma - Grade 1, one low-power immature region per slide; grade 2, immaturity in four or fewer low-power fields per slide; grade 3, immaturity in more than four low-power fields per slide
  • Gliomatosis peritonei - These must be thoroughly evaluated at biopsy; if all glial elements are mature, no added risk is present
  • Germinoma, dysgerminoma, or seminoma - Sheets of polygonal cells separated by fibrous bands; stains with placental alkaline phosphatase in more than 80% of cases
  • Yolk sac tumor and endodermal sinus tumor - Most common malignancy within a teratoma; infiltrative tumor composed of pseudopapillary, reticular, solid, or vitelline cellular patterns
  • Choriocarcinoma - Syncytiotrophoblasts and cytotrophoblasts are present; heterozygosity is often absent
  • Embryonal carcinoma - Grossly smooth with cystic necrosis; anaplasia, mitotic figures, hemorrhage, necrosis; lack of Schiller-Duval bodies

Differentiation of the various subtypes of testicular germ cell tumors may be facilitated by immunohistochemical testing for molecular markers such as Aurora B, GPR30, Nek2, HMGA1, HMGA2, and others. [36] Such markers could represent also useful novel molecular targets for antineoplastic strategies.

Previous
Next:

Staging

Staging of these tumors depends on the organ of origin.

Ovarian tumors are staged according to two different systems. The International Federation of Gynecology and Obstetrics/American Joint Committee on Cancer (FIGO/AJCC) staging system [37] was initially developed for use in adults, and it is most relevant for epithelial malignancies. The Children's Oncology Group (COG) system is specific to germ cell tumors; it was developed specifically for pediatric tumors.

Testicular tumors are staged and treated according to a COG-specific system. Boys who have achieved sexual maturity have tumors that are staged and treated according to adult protocols.

FIGO/AJCC staging

In FIGO/AJCC stage I ovarian cancers, growth is limited to the ovaries or fallopian tubes. Subcategories are as follows:

  • IA - Limited to the inside of one ovary or the inside of one fallopian tube, with no tumor on the external surface; no cancer cells in ascites or abdominal/pelvic washings
  • IB - Limited to the insides of both ovaries or fallopian tubes, with no tumor on the external surfaces; no cancer cells in ascites or abdominal/pelvic washings
  • IC - Stage IA or IB with any of the following: (1) capsule around the tumor broken during surgery (stage IC1); (2) cancer on the outer surface of at least one ovary or fallopian tube, or capsule ruptured before surgery (stage IC2); (3) cancer cells found in ascites or abdominal/pelvic washings (stage IC3)

In stage II, cancer is in one or both ovaries or fallopian tubes and has spread to other pelvic organs, or there is primary peritoneal cancer; there is no spread to nearby lymph nodes (N0) or to distant sites (M0). Stage II may be subcategorized as follows:

  • IIA - The cancer has spread to or has invaded (grown into) the uterus or the fallopian tubes, or the ovaries
  • IIB - The cancer is on the outer surface of or has grown into other nearby pelvic organs such as the bladder, the sigmoid colon, or the rectum

In stage III, tumor involves one or both ovaries or fallopian tubes, with spread or growth into other organs and lymph nodes but with no distant metastases (M0). It may be subcategorized as follows:

  • IIIA1 - Cancer is in one or both ovaries or fallopian tubes, or there is primary peritoneal cancer (T1) and it may have spread or grown into nearby pelvic organs; spread is to retroperitoneal lymph nodes only
  • IIIA2 - Cancer is in one or both ovaries or fallopian tubes, or there is primary peritoneal cancer and it has spread or grown into organs outside the pelvis; no cancer is visible to the naked eye in the abdomen (outside the pelvis), but tiny deposits are found in the abdominal lining on laboratory examination; there is possible spread to retroperitoneal lymph nodes
  • IIIB - Cancer is in one or both ovaries or fallopian tubes, or there is primary peritoneal cancer and it has spread or grown into extrapelvic organs; cancer deposits of cancer are large enough to be visible but ≤ 2 cm across; there is possible spread to retroperitoneal lymph nodes but no spread to the inside of the liver or spleen or to distant sites
  • IIIC - The cancer is in one or both ovaries or fallopian tubes, or there is primary peritoneal cancer and it has spread or grown into extrapelvic organs; cancer deposits of cancer are >2 cm across and may be on the outside of the liver or spleen; there is possible spread to retroperitoneal lymph nodes but no spread to the inside of the liver or spleen or to distant sites

In stage IV, growth involves one or both ovaries or fallopian tubes, with lymph node spread and distant metastases. Subcategories are as follows:

  • IVA - Cancer cells are in the fluid around the lungs, with no other areas of cancer spread (eg, liver, spleen, intestine, or extra-abdominal lymph nodes)
  • IVB - Cancer has spread to the inside of the spleen or liver, to lymph nodes other than retroperitoneal, or to other organs or tissues outside the peritoneal cavity (eg, lungs or bones)

COG staging

In the COG system, ovarian tumors are staged as follows:

  • Stage I - Tumor is limited to one or both ovaries; peritoneal fluid and washings are negative for tumor; no clinical, radiographic, or histologic evidence of disease is present beyond the ovaries; tumor marker levels return to the reference range after an appropriate postsurgical half-life decline; the presence of gliomatosis peritonei does not worsen the stage
  • Stage II - Microscopic residual or positive lymph nodes (< 2 cm as measured by pathologist) are present; peritoneal fluid or washings are negative for malignant cells; tumor markers are positive or negative
  • Stage III - Lymph node or nodes with malignant metastatic nodule (>2 cm as measured by a pathologist) are present; gross residual or biopsy only; contiguous visceral involvement (omentum, intestine, or bladder) is observed; peritoneal washings are positive for malignant cells; tumor markers are positive or negative
  • Stage IV - Distant metastases, including liver metastases, are present

Testicular tumors are staged as follows:

  • Stage I - Limited to testis; tumor markers normal after appropriate half-life decline
  • Stage II - Transscrotal orchiectomy; microscopic disease in scrotum or high in spermatic cord (< 5 cm from proximal end); retroperitoneal lymph node involvement (< 2 cm); increased tumor marker levels after appropriate half-life decline
  • Stage III - Retroperitoneal lymph node involvement (>2 cm); no visceral or extra-abdominal involvement
  • Stage IV - Distant metastases; liver metastases

Extragonadal germ cell tumors are staged as follows:

  • Stage I - Complete resection at any site; en-bloc coccygectomy for sacrococcygeal site; normal tumor margins; tumor marker levels normal or elevated
  • Stage II - Microscopic residual disease; lymph nodes normal; tumor marker levels normal or elevated
  • Stage III - Gross residual disease or biopsy only; retroperitoneal nodes normal or involved with metastatic disease; tumor marker levels normal or elevated
  • Stage IV - Distant metastases, including those to the liver

The COG has proposed modifying their risk classification system to more accurately reflect current knowledge of pediatric germ cell tumors. Those modifications are being tested in current protocols. Treatment groups will undoubtedly be revised as more knowledge is obtained.

As more is learned about the molecular biology of these tumors, risk stratification is likely to be based less on the site of origin or tumor type and more on the molecular abnormalities of each specific tumor.

Previous