Objective   To investigate the clinicopathological characteristics, immunophenotypes, and molecular genetic changes in atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP).

  Methods   Fourteen cases of atypical or hypercellularity neurofibroma were collected from surgical specimens at the Pathology Department of Peking University International Hospital from December 2014 to August 2020. Seven cases had characteristics of ANNUBP. Microscopy, immunophenotype analysis, and summary were performed.

  Results   There were five males and two females, with ages ranging 14-44 years (average and median ages were 27 and 27 years, respectively); six had ANNUBP located in the retroperitoneum, whereas one was located in the head and neck. The maximum diameter ranged from 4.5 to 21.5 cm, the mean diameter was 11 cm, and the boundary was clear. Seven cases showed nuclear atypia, hypercellularity, loss of neurofibroma architecture, and increased mitotic image (>1/50 and<3/10 HPF). Four cases recurred multiple times, two patients developed malignant peripheral nerve sheath tumor (MPNST), and one patient survived without tumor. The recurrence rate was 85.71% (6/7) and the malignant transformation rate was 28.57% (2/7). S-100, Sox-10, and H3K27Me3 were all diffused and strongly expressed in seven cases. CD34 showed the disappearance of reticular structure in one case, and the Ki-67 proliferation index was less than 2%-5%.

  Conclusions   ANNUBP is a tumor with high recurrence and malignant transformation rates. Postoperative adjuvant therapy and close follow-up combined with immunohistochemistry should be provided, and overtreatment should be avoided, thus aiding its diagnosis.