Atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP)

Atypical neurofibromas and atypical neurofibromatous neoplasms of uncertain biologic potential (collectively AN/ANNUBP) refer to neurofibromas with atypical histological features. They are considered premalignant with an increased risk of progressing to a malignant peripheral nerve sheath tumor.

Terminology

Atypical neurofibroma should be used to denote atypical histological features that do not meet the criteria for a malignant peripheral nerve sheath tumor in the setting of sporadic neurofibromas ¹.  

In contrast, the term ANNUBP should be used when atypical changes are encountered in the context of neurofibromatosis type 1 (NF1) ¹. 

Pathology

To make a diagnosis of AN/ANNUBP at least two of the following features need to be identified on histology and immunohistochemistry:

• hypercellularity
• cytological atypia
• loss of normal neurofibroma architecture
• increased mitotic count > 1 mitosis/50 HPF but less than < 3 mitoses/10 HPF of 0.51 mm in diameter and 0.2 mm2 in area)

Grading

Neurofibromas are considered WHO grade 1 tumors in the WHO classification of CNS tumors ¹ whereas malignant peripheral nerve sheath tumors (MPNST) are designated as low-grade or high-grade in the WHO classification of soft tissue and bone tumors ². 

Presumably, due to the uncertainty of the biological behavior of AN/ANNUBP and the inconsistency in the grading nomenclature of neurofibromas and MPNST, they are not given a grade ¹. 

Radiographic features

The imaging characteristics of AN/ANNUBP are intermediate sharing similarities with both localized intraneural neurofibromas and malignant peripheral nerve sheath tumors, and are therefore not repeated here.