Cytologic evaluation of the pleural fluid showed similar findings to the posterior mediastinal mass biopsy. The mass was contiguous to a left posterior rib lytic lesion. The FISH results confirmed EWS. EWS is the second most common malignant bone tumor of young adults and the most common for patients under the age 15 years. EWS is most common in the diaphysis of long bones, but can occur in any bone. There is a slight male predominance. The sarcoma is characterized by sheets of bland round cells, many of which are apoptotic giving the appearance of two cell populations, “light” and “dark” cells. The nuclei of these malignant cells are round with indentations and small nucleoli while their cytoplasm may contain glycogen vacuoles. The tumor may be associated with necrosis.
EWS is commonly associated with translations of the EWSR1 gene on chromosome 22, with t(11;22)(q24;q12) being the most common occurring in up to 85% of patients. This translocation involves fusion of the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. This resultant fusion protein is a combination of the DNA-binding portion of the ESWR1 gene and the transcription activation region of the FLI1 gene leading to unregulated transcription. Multiple types of this fusion have been identified with EWSR1 exons 1-7 fused to FLI1 exons 6-9 producing the most favorable prognosis. The second most common translocation t(21;22)(q22;q12) is a fusion between the EWSR1 gene and the ERG gene of chromosome 21, which occurs in up to 10% of tumors.
The differential for bone small round blue cell tumors in the pediatric population includes predominantly sarcomas, however, metastases including carcinoma (small cell), melanoma, and lymphoma should be excluded. The mediastinal location also brings up certain diagnoses. The mediastinum is broken into anterior, middle and posterior compartments. In the anterior mediastinum, thymic neoplasms and germ cell tumors should be considered. The middle mediastinum may be associated with lymphomas and metastatic carcinomas. The posterior mediastinum may give rise to neurogenic tumors. As this posterior mass was associated with a bone lesion, bone primaries were considered. In cytology, carcinomas are generally tightly cohesive, whereas sarcoma, lymphoma and melanoma are more dyscohesive.
Neuroblastomas (NT) are small round blue cell tumors, which usually arise within the first two years of life and are most common in the adrenal gland but also can be seen in extra-adrenal paraganglia of the retroperitoneal and mediastinal soft tissue. The tumor cells have open chromatin, oval nuclei, and inconspicuous nucleoli and a background of neuropil and ganglion cells. NTs stain positive for S100 immunohistochemically. Sporadic NTs are associated with MYCN amplification, whereas familial NTs more commonly have PHOX2B or ALK gene mutations.
Compared to EWS, rhabdomyosarcomas have more eccentric, plasmacytoid nuclei and eosinophilic to granular cytoplasm. Immunohistochemically, rhabdomyosarcomas stain for muscle markers including desmin and smooth muscle actin. Although uncommon in this age group, metastatic small cell carcinoma could be considered due to the cell molding and increased mitoses. Neuroendocrine immunohistochemical stains such as synaptophysin, chromogranin, INSM1, and CD56 would be positive in small cell carcinoma. Melanoma, the great mimicker, can present as a small round cell / spindle lesion. These tumors would stain for melanocytic markers (HMB-45, Melan-A, S100, SOX 10).
This case highlights a pediatric small round blue cell tumor that was first detected in a pleural effusion specimen. Determining CD99 immunohistochemical positivity and t(11;22)(24q;12q) ESWR1-FLI1 by FISH are important steps that can assure proper and prompt patient care.