Table 2

GEM nerve sheath tumor classification: diagnostic criteria and definitions

GEM nerve sheath tumor diagnostic criteria
 A spindled cell tumor arising in a mouse model can be designated as a nerve sheath tumor when at least one of the following criteria is met:
  The lesion is clearly originating from a nerve.
  In case of a high-grade lesion (see below), the lesion is clearly originating in a definite low-grade nerve sheath tumor.
  The tumor contains S-100 immunopositive cells and/or there is evidence on EMa of Schwannian and/or perineurial differentiation.
Tumors are described using 3 different parameters: cellular composition, grade, and pattern of growth and spread.
1. Cellular composition: as defined by histology and immunohistochemistry (S-100-positive cells are present) and/or EM.
  GEM schwannoma: a tumor composed of mature Schwann cells, as shown by immunohistochemistry or EM.
   GEM neurofibroma: a tumor composed of a mixed cell composition: mature Schwann cells, fibroblasts, and perineurial cells, as shown by immunohistochemistry or EM.
   GEM perineurioma: a tumor composed of mature perineurial cells as shown by EM.
   GEM PNST (not otherwise specified): a tumor arising from a peripheral nerve, with some evidence of Schwannian differentiation, by immunohistochemistry or EM, that does not fit any of the above categories.
  Divergent differentiation: differentiation along mesenchymal, epithelial, or neuroendocrine lines in a PNST.
2. Grade
  Grade evaluation depends on morphological features only. These include cellularity, pleomorphism, mitotic activity, and necrosis.
   Grade I: GEM tumor with low cellularity. Tumor cells have bland/uniform nuclear cytology. Mitoses are absent, and there is no necrosis.
   Grade II: GEM tumor with increased cellularity, nuclear atypia, and some mitotic activity. These lesions have histological similarities to low-grade MPNSTs in humans but may also include GEM cellular schwannomas (GEM schwannoma, grade II).
   Grade III: GEM tumor with marked cellularity, nuclear atypia, and high rate of mitotic activity. May contain areas of necrosis or hemorrhage. These lesions histologically correspond to MPNSTs in the WHO classification.
3. Stage (pattern of growth and spread)
  In addition to the histological features of the tumors, the panel recommends describing the following features:
   A) Interface of the tumor with adjacent normal tissues (circumscribed vs. infiltrative).
   When infiltrative, the pattern of infiltration should be noted (destructive vs. infiltration with preservation of tissue).
   B) Tumor size, measured as per greatest diameter.
   C) Metastasis, evidence of metastasis in liver or lung. However, the panel recognizes that in some of the GEM models, the distinction between multiple primary tumors arising in targeted cells and metastasis may be impossible.
  • a EM, electron microscopy; PNST, peripheral nerve sheath tumor; MPNST, malignant PNST.