Soft Tissue Tumors in Children and Adolescents:
A Morphologic Pattern Oriented Approach with Molecular and Genetic Correlations
Section 1 -
Cheryl M. Coffin, M.D.
David M. Parham, M.D.
Childhood cancer, though rare, is the leading cause of death from disease in children 1 to 15 years
old in the United States. About 10,000 new cases of childhood cancer are diagnosed annually and soft
tissue sarcomas account for 7%. The most common soft tissue sarcomas are rhabdomyosarcoma and Ewing
sarcoma, which together comprise 70% of pediatric soft tissue sarcomas. In the past 30 years, the 5-year
survival rate for pediatric soft tissue sarcomas has improved. Histologic subtypes with prognostic
significance have been identified and clinical staging and histologic grading systems have been refined.
Tumor-related chromosomal and molecular genetic abnormalities, some with prognostic significance, have
been discovered. Manifestations of cancer family syndromes in childhood are now recognized. Treatments
are being developed to match risk status, and new trait treatments will target molecular genetic
abnormalities. Late treatment effects remain a challenge, with the risk of second malignant neoplasms
many years after completion of chemotherapy and radiation therapy. Pathologists have contributed
significantly to clinical, diagnostic, and therapeutic advances.
Among the solid tumors of childhood, soft tissue tumors are a large, challenging, and complex group.
Although most soft tissue masses are benign, soft tissue sarcomas as a group rank 5th in
frequency among childhood cancers. For benign lesions it is important to avoid over-treatment and in
some instances to evaluate margins to assess the risk of recurrence. Also, some benign soft tissue
neoplasms have important syndromic and genetic implications for the patient and the family. Among the
malignant soft tissue tumors, approximately 95% of patients are treated on protocols. Intermediate soft
tissue tumors with a risk of local recurrence or very low frequency of metastasis continue to be the
focus of studies.
Thoughtful evaluation of the fresh tumor specimen is essential for appropriate specimen handling,
triage for diagnostic and prognostic studies, and collection of information with clinical, therapeutic,
prognostic, and genetic importance. In addition to formalin-fixed paraffin-embedded tissue for routine
histopathology and immunohistochemistry, samples can be taken from the fresh specimen for cytogenetic and
molecular genetic studies, DNA and RNA preparation, flow cytometry, electron microscopy, and research
protocols. Different types of specimens ranging from needle biopsies to open incisional biopsies to
various types of resections have distinct advantages and disadvantages in terms of the information that
can be gleaned from the specimen. When presented with a soft tissue lesion in a young patient, the
pathologist must consider differential diagnosis, specimen handling, and the optimal way to gather the
most information for potential diagnostic, prognostic, and therapeutic uses.
Although morphology remains the central basis for tumor diagnosis the importance of cytogenetic and
molecular genetic abnormalities in the biologic development, classification, progression, and prognosis
of tumors has increased greatly in recent years. Knowing when and how to use cytogenetic and molecular
genetic studies in combination with conventional morphologic and immunohistochemical techniques is now
integral to practice.
This presentation focuses on examples of pediatric soft tissue tumors from the broad morphologic
categories of small round cell tumors and spindle cell tumors. These cases illustrate the clinical
findings, pathologic criteria, use of ancillary diagnostic techniques, molecular and cytogenetic
correlations, and differential diagnoses for this challenging group of neoplasms.
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