Patient description: The patient is a 60 year old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is worsening. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions are detected in the head and face. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. His serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). His family history is only significant for hypertension in his mother and DM type 2 in his father. The diagnosis of Paget's Disease of Bone was confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 0.0-999.0,  Neurofibromatosis Type 1 Malignant Peripheral Nerve Sheath Tumor Plexiform Neurofibroma Optic Glioma Neurofibroma Age Less than or equal to 35 years of age for new patients evaluated at NIH No upper age limit for patients previously enrolled on clinical trials at NIH or for patients diagnosed with MPNST, or with clinical concern for MPNST, or with infrequent or unusual NF1 related manifestations. 2. Diagnosis: Patients who are diagnosed with NF1 using the NIH Consensus Conference or have a confirmed NF1 mutation with analysis performed in a CLIA-certified laboratory. NF1 mutation testing to confirm will not be performed on this protocol, but as part of a separate screening study. Histologic confirmation of NF1 related benign tumors is not necessary in the presence of consistent clinical and radiographic findings, but is required for individuals with MPNST who enroll on this study. For the clinical diagnosis of NF1 all study subjects must have at least two or more diagnostic for NF1 listed below (NIH Consensus Conference): 1. Six or more cafe-au-lait spots (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects). 2. Greater than or equal to 2 neurofibromas or 1 plexiform neurofibroma. 3. Freckling in the axilla or groin. 4. Optic glioma. 5. Two or more Lisch nodules. 6. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex). 7. A first-degree relative with NF1. 3. Prior and current therapy: For NF1 related benign tumor manifestations there is no standard effective medical treatment, and surgery is the only standard treatment. Chemotherapy and radiation therapy are additional treatment options for malignant NF1 related tumors. For the purpose of this study, subjects who have not previously received medical or surgical treatment, patients, who have previously received medical or surgical treatment, and patients who are currently receiving medical treatment and/or radiation for a NF1 related manifestation will be eligible. Prior and current treatment for NF1 related manifestations will be recorded at trial entry and throughout the study. 4. Performance Status: ECOG less than or equal to 3. Subjects who are wheelchair bound because of paralysis will be considered ambulatory when they are up in their wheelchair. Subjects have to be able to travel to the NIH for evaluations. 5. Informed Consent: All patients or their legal guardians (if the patient is less than 18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related studies are performed. When appropriate, pediatric subjects will be included in all discussions. 6. Durable Power of Attorney (DPA): All subjects greater than or equal to 18 years of age will be offered the opportunity to assign DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired. 7. In addition, subjects participating in evaluation for variation in gene expression must Have at least 1 plexiform neurofibroma and be able to undergo MRI analysis of the plexiform neurofibroma(s) If possible, but not absolutely required, have one or both biologic parents (NF1 affected or not) willing to donate a blood or cheek swab, or mouthwash sample for DNA extraction. A separate informed consent will be obtained from biologic parents  In the opinion of the investigator the patient is not able to return for follow-up visits or obtain required follow-up studies. 2. In the opinion of the investigator the patient is not able to obtain an MRI scan. 3. Individuals who are pregnant or breast feeding or who become pregnant while enrolled on this trial will not be excluded from participation, but will not undergo radiographic evaluations or MRI scans requested for research purposes, or other studies which might negatively impact on the pregnancy. FOR TUMOR / FOR 1. Age greater than 12 years, and neurofibroma, cafe-au-lait macule, xanthogranuloma, or other skin area, which is easily accessible, and sufficiently distant from vital structures to allow for biopsy. 2. Platelet count has to be greater than or equal to 100,000/microL, and PT and PTT have to be within normal limits within 1 week of each biopsy. 3. The subject or parent/guardian must sign a separate biopsy consent, and the participant, if minor, must sign a separate assent describing the biopsy. 4. No medical treatment specifically directed at NF1 related tumor within six weeks prior to collection of specimen Biopsies will not be performed if the participant requires general anesthesia. 2. Requirement for medications, which interfere with platelet function, such as aspirin, which cannot be stopped within 1 week prior to the biopsy. (NEUROCOGNITIVE AND QOL 1. Availability of a sibling not affected with NF1 for longitudinal evaluation of neurocognitive function and quality of life evaluation. An assent form will be prepared for unaffected minor siblings, and written informed consent will be obtained from siblings 18 years of age or older A medical condition which would preclude the sibling from participation in the evaluation of neurocognitive function or quality of life. OF (GENETIC 1. Biologic parents (one or both) of patients with NF1 will be eligible if they are willing to provide a blood, cheek swab, saliva, or mouthwash sample for DNA extraction for analysis of gene modifiers. These individuals may be of any gender and ethnicity. Written informed consent will be obtained from each parent willing to participate in this part of the study A medical condition, which would preclude the parent from providing a biologic sample. OF (QUESTIONNAIRES) Parents (one or both) of patients with NF1 will be eligible if they are willing to t complete the questionnaires for NF1 assessment itemized in Section 1.2.8