14.6.1 Macroscopic Aspects

•Gray–white tumor with various necrotic, hemorrhagic, or cystic parts

•Glistening, moist appearance on sectioning

•Tumors are capable of extensive growth in the medullary cavity of bones, with or without cortical invasion

•Early invasion of periosteal soft tissue is frequently seen

•Often the extraskeletal part is more prominent than the bone tumor

14.6.2 Microscopic Aspects

•Typical small, blue round-cell tumor

•Proliferation of undifferentiated mesenchymal cells, usually in solid, cellular broad sheets

•Monomorphous appearance of tumor cells

•Round cells with scant cytoplasm, high ratio of nuclear to cytoplasmic material, basophilic nucleus, which is central

•Chromatin is homogeneous, with fine granularity and one to three nucleoli

•Often a biphasic pattern with light and dark cells; the latter represent tumor cells undergoing apoptosis

•Sometimes rosette-like structures may be formed by tumor cells (less than 20% in ES, more than 20% in PNET), and termed as Homer-Wright rosettes

•Ultrastructure may be particularly helpful in identifying neuroectodermal differentiation

14.6.3 Immunohistochemistry

•Periodic acid-Schiff (PAS), reaction staining for glycogen is positive

•Expression of CD99 (MIC2) in approximately 90% of ES and PNET:

–Important for differential diagnosis

–Codes for a membrane protein (p30/32)

–Not specific for tumors of the EFT

•Vimentin-staining test results in 80–90% of cases are positive

•Neuron-specific enolase test results are positive

•S-100, Leu-7, HNK-1, and other proteins

14.7Clinical Manifestations

•Related to the sites of the disease

•Painful, palpable mass

•Fever (in approximately 20%)

•Anemia, leukocytosis, increased sedimentation rate

•Pathological fracture occurs in approximately 10% of cases

•Symptoms caused by metastases (e.g., decreased muscular strength in legs or bowel and bladder dysfunction can be due to spinal cord compression)

14.8Metastases

•Based on the identification of the typical genetic translocation found in EFT, early metastatic spread of tumor cells causing micrometastases is often observed

•Macroscopically visible metastases are present in 20–30% of patients with EFT

•Hematogenous route is most frequent pattern of spread: lungs, then bone and bone marrow

•Rarely seen in lymph nodes, liver, or central nervous system

•Askin tumors, that is, Ewing sarcoma of the chest wall, may invade the adjacent pleural space with subsequent pleural effusion (cytology of the material may be diagnostic)

14.9Evaluation

•Optimal management of the patient requires a multidisciplinary team (pediatric oncologists, orthopedic surgeons, pathologists, and radiologists)

•Laboratory findings:

–Complete blood count

–Tumor lysis parameters, electrolytes, kidney and liver parameters, lactate dehydrogenase

–Consider vanillylmandelic acid and homovanillic acid to rule out neuroblastoma, blood sedimentation rate, and C-reactive protein

•Radiology:

–Primary site: conventional X-rays (periosteal reaction, “onion-skin phenomenon,” represents layers of periosteum due to de novo bone formation)

–Metastases: radionuclide scan of skeleton with X-rays or MRI scans of affected areas, chest X-ray, chest CT, bone marrow aspiration (cytology and molecular biology). PET/CT is becoming more accepted as an imaging modality to determine the extent of disease

•Open biopsy

14.10 Differential Diagnosis

•Osteomyelitis (20% of patients with EFT have fever)

•EFT rarely represents a diagnostic problem because of immunohistochemistry and molecular biology characteristics

•Small, blue round-cell tumors