Immunohistology of Pediatric Neoplasms

Overview

Solid neoplasms of childhood and adolescence comprise a diverse group of diagnostically challenging entities with the basic morphologic themes of round cell, spindle cell, and epithelioid tumors. Immunohistochemistry (IHC) and molecular diagnostic tests have greatly improved our ability to classify these lesions. Ancillary diagnostic techniques have become increasingly important in the diagnosis and evaluation of recurrent or metastatic disease and, in some cases, in genomic or prognostic classification. In addition, ancillary diagnostic tests must be interpreted in the context of the light microscopic findings, and specimen adequacy is a critical factor. IHC is a valuable tool, although it has significant pitfalls in specific instances. Tissue fixation; necrosis; focality of marker expression; artifactual changes on very small specimens, such as core needle biopsies; matrix quality, such as densely sclerotic matrix; and other technical factors may influence the IHC results. Techniques such as flow cytometry for leukemias and lymphomas, electron microscopy (EM), and molecular testing may be necessary to support the diagnosis or provide prognostic information. Therefore, tumor protocols for handling specimens and procuring tissues can provide important guidelines for pathologic evaluation.

This chapter reviews the diagnostic evaluation, IHC findings, and genomic and prognostic aspects of pediatric and adolescent solid neoplasms including neuroblastoma (NB) and related neuroblastic tumors, rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), desmoplastic small round cell tumor (DSRCT), malignant rhabdoid tumor (MRT), Wilms tumor (WT), and osteosarcoma (OS). In many cases the combination of the clinical and radiologic presentation and the light microscopic appearance are sufficient for diagnosis. In other cases the tumor may have a predominantly round or spindle cell pattern, which leads to a differential diagnosis that depends on the clinical, radiologic, and morphologic findings. For example, a tumor in an infant with an adrenal mass, elevated serum and urine catecholamine levels, and the microscopic finding of neuroblasts in a background of neuropil with calcification and thin fibrovascular septa can be confidently diagnosed as NB. On the other hand, a primitive RMS may require IHC and/or molecular analysis to reach a diagnosis. The decision about when to order special tests and which to select depends on the complexity of the tumor and the individual pathologist’s experience. IHC is often the first step toward refining or confirming the diagnosis. If this results in unexpected or contradictory findings, additional IHC tests may be obtained, and cytogenetic or molecular genetic testing can be considered. Use of a panel of IHC stains, rather than overreliance on a single antibody, is an important diagnostic principle. Furthermore, adopting a comprehensive panel approach can save time in arriving at a diagnosis that is important for patient management decisions, can reduce hospital length of stay, and may ultimately reduce medical costs.

Biology of Antigens and Antibodies: Principal Antibodies

Many different antibodies are used for the IHC evaluation of pediatric solid neoplasms. The more generally used antibodies are discussed in other chapters. This section summarizes antibodies with particular importance for the tumors covered in this chapter; these include myogenic transcriptional regulatory proteins, CD99, the FLI1 protein, the WT1 protein, the SMARCB1 (formerly hSNF5/INI1) protein, and PHOX2B.