Pathological Basis for Classification (Cytomolecular Aspects)

Abstract

Peripheral nerve sheath tumors are neoplasms with clear morphological diagnostic features and, sometimes, nosological challenges. Their subtypes were described since the very beginning of the history of surgical pathology. Recently, they have been the subject of exciting diagnostic developments regarding their morphological and molecular characterization. Their molecular analysis has been fruitful in their classification and the understanding of the molecular pathway to malignant transformation due to their well-known relationship to genetic disorders. This approach has the added benefit of suggesting novel targeted therapeutic approaches. In this chapter, diagnostic criteria and differential diagnoses for the significant categories of nerve sheath tumors are reviewed, including neurofibroma, schwannoma, perineurioma, and malignant peripheral nerve sheath tumors (MPNSTs).

The growing current literature with hard to classify heterogeneously mixed “hybrid tumors” is discussed and illustrated.

MPNST represents a diagnostically controversial group; difficulties in grading and guidelines to separate “atypical neurofibroma” from MPNST are provided. Finally, we include differential diagnostic features between significant entities in the current WHO classification. The contemporary “omics” methodology may be useful in providing better, more biological, categorization systems. To sum up, although, for the skilled pathologists, the diagnosis and classification of the most common peripheral nerve sheath tumors are relatively reproducible, some uncertain and complex neoplasms continue to be tricky. In the current review, we intend to provide some conceptual approaches for surgeons and clinicians to safely navigate these issues.