Inclusion Criteria:
* Histologically confirmed diagnosis of atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), low grade malignant peripheral nerve sheath tumor (MPNST) or high grade MPNST in accordance with the Miettinen et al diagnostic criteria via biopsy
* Plexiform neurofibroma or other tumors such as optic pathway glioma, other low-grade glioma or other neoplasm in addition to the ANNUBP, low grade MPNST or high grade MPNST that is stable (has not required treatment in the last 12 months and is not anticipated to need treatment in the next 12 months)
* Measureable disease by RECIST criteria in at least one site.
* Karnofsky Performance Scale ≥ 60%
* No contraindications for Nivolumab or Ipilimumab
* Normal organ and marrow function on routine laboratory tests
* Evidence of post-menopausal status or negative urinary/serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause
* Ability to understand and willingness of sign consent form
* Willingness to comply with the protocol for the duration of the study
Exclusion Criteria:
* Chemotherapy or other investigational agent for the current episode of newly diagnosed atypical neurofibroma or MPNST
* Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL-2 antibody
* Known allergy to compounds of similar chemical or biologic composition to Nivolumab or Ipilimumab
* Pregnant or breastfeeding women
* Known history of Human Immunodeficiency Virus
* Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
* Active autoimmune disease, history of autoimmune disease or history of syndrome that required systemic steroids or immunosuppressive medications, e.g. organ, tissue, or allogenic hematopoietic stem cell transplant (HSCT) recipients. Exceptions include those with resolved childhood asthma/atopy. Subjects with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study. Subjects are also permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
* A condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up to 4 weeks (28 days) before receiving nivolumab and ipilimumab.
* Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
* Prior radiation doses equivalent to, or greater than, 8000 centigray (cGy) to the target lesions at 200 cGy fractions at any time point
* Any radiation to the the target lesions within 6 months of enrollment
* Other concurrent severe and/or uncontrolled medical disease, which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration, congestive heart failure, etc.)
