Laboratory Studies
In patients with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS), a baseline CBC count with differential provides parameters before therapy and is useful in evaluating for involvement of the bone marrow.
Chemical tests to assess renal function and creatinine clearance provide baseline parameters before chemotherapy is given and further testing is performed.
Liver function testing provides baseline parameters before chemotherapy and is helpful in evaluating for hepatic involvement.
Imaging Studies
Primary site imaging:
Plain radiography of the involved areas may be useful in the initial evaluation of a mass, depending on its location and suspected involvement of bony structures.
CT and MRI are used to determine the size of the mass and the extent of local involvement and impingement on adjacent structures. CT and MRI also help in defining options for surgical resection. Contrast-enhanced studies are most helpful. Abdominal CT scanning is important for assessing abdominal primary lesions and to determine hepatic involvement.
Staging imaging:
For NRSTSs with a predisposition for lymphatic spread (including epithelioid sarcoma and synovial sarcoma), imaging of draining lymph nodes should be performed, preferably with MRI.
A non-contrast chest CT is generally preferred over chest plain radiography to evaluate for pulmonary metastatic disease. When feasible these studies should be performed prior to general anesthesia as atelectasis can make interpretation more difficult.
Radionucleotide bone scanning is necessary to rule out bony involvement.
The roles of positive emission tomography (PET)-CT and of18 F-fluorodeoxyglucose (FDG) PET to image NRSTS in children have not been well established. However, PET-CT may prove beneficial in distinguishing normal from pathologic processes, in the initial staging of a sarcoma, in monitoring responses to therapy, and in detecting recurrences. [46, 47]
Other Tests
A cardiologist may need to be consulted to perform cardiac ECG and echocardiography in patients who will receive anthracycline-based chemotherapy or radiation therapy to the chest.
Testing of renal glomerular filtration or creatinine clearance may be necessary before renal-toxic chemotherapy agents (eg, cisplatin, ifosfamide) are administered.
Procedures
Carefully planned and executed biopsy of the mass lesion is required for diagnosis.
Whatever technique is used, adequate tissue must be obtained to allow for histology, immunostaining, and other studies including cytogenetics, fluorescent in situ hybridization (FISH), and molecular pathology.
If possible, the biopsy should be accomplished in a manner that does not compromise the possibility for later local surgical control of the tumor. The definitive surgical procedure should be delayed until after the biopsy because neoadjuvant chemotherapy, radiation therapy, or both may be needed.
Fine-needle aspiration is not recommended as this procedure may often yield insufficient diagnostic material.
Percutaneous image-guided core needle biopsy may be feasible and the preferred procedure for obtaining diagnostic material in many cases. However, this should be performed by a skilled interventional radiologist. [48]
An open procedure is required if core-needle biopsy yields nondiagnostic pathologic material. A surgeon with expertise in oncologic surgery should perform this procedure. The surgeon's specific discipline depends on the location of the mass. Minimally invasive surgical techniques using fiberoptic surgical procedures may be appropriate in certain biopsy situations. The best approach for small lesions in accessible areas may be excisional biopsy. Large masses involving critical organs or structures may require incisional biopsy for diagnosis.
Sentinel lymph node biopsy in the diagnosis and staging evaluation of NRSTS is controversial. For NRSTS with predilection for lymphatic metastases we recommend MRI of regional draining lymph nodes and biopsy if concern for metastatic spread on imaging.
Consider long-term venous access. In cases where adjuvant and/or neoadjuvant chemotherapy is planned, placement of an implanted or externalized central venous catheter is useful for monitoring laboratory results and for delivering chemotherapy and supportive care.
Routine bilateral bone marrow aspirates and biopsy is not recommended in the standard staging of children with NRSTS due to the unlikelihood of bone marrow metastatic spread. However, we recommend examination of the bone marrow if there are unexplained cytopenias or other findings that raise the clinical suspicion for bone marrow involvement. In children, these procedures are best performed in the posterior iliac crests.
These tests should be accomplished in conjunction with another procedure requiring sedation, if possible.
If there is a high clinical suspicion for central nervous system involvement (e.g. parameningeal tumors or tumors involving the CNS), lumbar puncture may be considered to rule out contamination of the cerebrospinal fluid (CSF) with tumor cells though not routinely performed.
Histologic Findings
Diagnosis of an NRSTS can be confirmed only with biopsy of the mass. Diagnosis of a specific tumor depends on the mesenchymal and/or support tissue it most closely represents. Immunostaining, electron microscopy, cytogenetic analysis, and tests for molecular markers of genetic rearrangements may all be used for final diagnosis, depending on the differentiation of the specific tumor. Many of the NRSTSs are characterized by chromosomal translocations that lead to a fusion of two genes. The resultant fusion gene can be detected by FISH, polymerase chain reaction (PCR)-based techniques, and newer next generation DNA/RNA sequencing diagnostic platforms. NRSTSs possess a wide range of histologic features.
A tumor is classified as low-grade or high-grade on the basis of its potential to metastasize. Low-grade lesions are unlikely to metastasize. Certain types of tumors are arbitrarily considered high grade; examples are synovial cell sarcomas and malignant peripheral nerve sheath tumors. Malignant and metastatic potential are based on the degree of anaplasia and mitotic activity the tumor specimen exhibits.
Staging
No staging system is validated for NRSTSs in children. Two systems are currently in use: the surgicopathologic grouping system used by the Intergroup Rhabdomyosarcoma Study (IRS), which is based on the amount of tumor remaining after initial surgery, and the American Joint Commission for Cancer (AJCC) staging system for Soft Tissue Sarcomas. [49] This is the staging system that is being used in the current COG trial for NRSTS.
Table. American Joint Commission for Cancer Staging (Tumor, Node, and Metastases [TNM] System) (Open Table in a new window)
|
Primary Tumor |
Regional Lymph Nodes |
Distant Metastasis |
Histologic Grade |
Stage I |
Any tumor size, superficial or deep |
N0 |
M0 |
G1 or G2 |
Stage II |
T1a (tumor < 5 cm, superficial) |
N0 |
M0 |
G3 |
T1b (tumor < 5 cm, deep) |
N0 |
M0 |
G3 |
|
T2a (tumor >5 cm, superficial) |
N0 |
M0 |
G3 |
|
Stage III |
T2b (tumor >5 cm, deep) |
N0 |
M0 |
G3 |
Stage IV |
Any tumor size, superficial or deep |
N1 |
M0 or M1 |
G1, G2, or G3 |
Any tumor size, superficial or deep |
N0 or N1 |
M1 |
G1, G2, or G3 |
G1 = well differentiated; G2 = moderately differentiated; G3 = poorly differentiated; M0 = no distant mets; M1 = distant mets; N0 = no regional LN mets; N1 = regional LN mets
Intergroup Rhabdomyosarcoma Study (IRS) groups staging is as follows:
-
Group I - Complete resection with negative margins
-
Group II - Microscopic residual disease after resection
-
Group III - Incomplete resection or biopsy with gross residual tumor
-
Group IV - Metastatic disease present at time of diagnosis
-
COG-ARST0332 experimental design schema.
Tables
|
Primary Tumor |
Regional Lymph Nodes |
Distant Metastasis |
Histologic Grade |
Stage I |
Any tumor size, superficial or deep |
N0 |
M0 |
G1 or G2 |
Stage II |
T1a (tumor < 5 cm, superficial) |
N0 |
M0 |
G3 |
T1b (tumor < 5 cm, deep) |
N0 |
M0 |
G3 |
|
T2a (tumor >5 cm, superficial) |
N0 |
M0 |
G3 |
|
Stage III |
T2b (tumor >5 cm, deep) |
N0 |
M0 |
G3 |
Stage IV |
Any tumor size, superficial or deep |
N1 |
M0 or M1 |
G1, G2, or G3 |
Any tumor size, superficial or deep |
N0 or N1 |
M1 |
G1, G2, or G3 |
Risk group |
Tumor characteristics |
Treatment |
|||
Tumor Grade |
Tumor Size |
Tumor Stage |
Upfront Surgical Resectability |
||
Low |
Low |
Any |
Localized |
Gross resection (with negative or positive microscopic margins) |
Surgery + observation |
| Low | High |
< 5 cm |
Localized |
Gross resection with negative microscopic margins |
Surgery + observation |
| Low | High |
< 5 cm |
Localized |
Gross resection with positive microscopic margins |
Surgery + adjuvant radiation therapy |
Intermediate |
High |
>5 cm |
Localized |
Gross resection |
Surgery + adjuvant radiation therapy + adjuvant chemotherapy |
| Intermediate | High |
Any |
Localized |
Unresectable or Planned delayed surgical resection due to high grade, size >5 cm, and anticipate gross resection only possible with positive microscopic margins |
Neoadjuvant chemotherapy + surgery + adjuvant chemotherapy with or without radiation therapy |
High |
Low |
Any |
Metastatic |
Gross resection |
Surgery + observation |
| High | High |
Any |
Metastatic |
Gross resection |
Surgery + adjuvant radiation therapy + chemotherapy |
| High | High |
Any |
Metastatic |
Unresected |
Neoadjuvant chemotherapy + surgery + adjuvant chemotherapy with or without radiation therapy |
