Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome

Inclusion Criteria: * Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol * Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 * Genetically confirmed diagnosis of VHL or measurable disease consistent with the clinical diagnosis of VHL * At least one measurable VHL related lesion, which is undergoing surveillance, and patient is not at immediate risk of needing intervention for this or other lesions; biopsy is not required given the known likely etiology and natural history in the setting of a positive genetic test * Brain: asymptomatic hemangioblastoma, \>= 0.5 cm * Spine: asymptomatic hemangioblastoma, \>= 0.5 cm * Renal: solid mass suspicious for renal cell carcinoma (RCC) \>= 1 cm or cystic mass (Bosniak 3-4) \>= 1 cm * Pancreas: solid mass \>= 1 cm and =\< 3 cm suspicious for neuroendocrine tumor, or neuroendocrine tumor \> 3 cm but not considered operable * Eye: asymptomatic peripapillary and/or macular hemangioblastoma, any size * Adrenal: asymptomatic or controlled pheochromocytoma greater than 1 cm in size * Patients may have received prior VHL-related systemic therapy, provided not within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib * Absolute neutrophil count (ANC) \>= 1.5 X 10\^9/L * Hemoglobin \>= 9 g/dL (5.6 mmol/L) * Subjects may not have had a transfusion within 7 days of screening assessment * Platelets \>= 100 X 10\^9/L * Prothrombin time (PT) or international normalized ratio (INR) =\< 1.2 X upper limit of normal (ULN) * Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation or if they are on low molecular weight heparin * Activated partial thromboplastin time (aPTT) =\< 1.2 X ULN * Total bilirubin =\< 1.5 X ULN * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.0 X ULN * Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted * Serum creatinine =\< 2.0 mg/dL (133 umol/L) OR, if \> 2.0 mg/dL: calculated creatinine clearance (ClCR) \>= 50 mL/min * Urine protein to creatinine ratio (UPC) \< 1 * If UPC \>= 1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value \< 1 g to be eligible * A female is eligible to enter and participate in this study if she is of: non-childbearing potential including * Any female who has had a surgical procedure rendering her incapable of becoming pregnant * Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for \>= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value \> 40 mIU/mL and an estradiol value \< 40 pg/mL (\< 140 pmol/L) * Subjects using HRT must have experienced total cessation of menses for \>= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT; childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception GlaxoSmithKline (GSK) acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: * Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product * Oral contraceptive * Injectable progestogen * Implants of levonorgestrel * Estrogenic vaginal ring * Percutaneous contraceptive patches * Intrauterine device (IUD) * Male partner sterilization * Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository); female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug Exclusion Criteria: * Prior malignancy. Subjects who have had another non VHL related malignancy and have been disease-free for 2 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible * Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: * Active peptic ulcer disease * Known intraluminal metastatic lesion/s with risk of bleeding * Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation * History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment * Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: * Malabsorption syndrome * Major resection of the stomach or small bowel * Presence of uncontrolled infection * Corrected QT interval (QTc) \> 480 msecs using Bazett's formula * History of any one or more of the following cardiovascular conditions within the past 6 months: * Cardiac angioplasty or stenting * Myocardial infarction * Unstable angina * Coronary artery bypass graft surgery * Symptomatic peripheral vascular disease * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) * Poorly controlled hypertension (defined as systolic blood pressure \[SBP\] of \>= 140 mmHg or diastolic blood pressure \[DBP\] of \>= 90 mmHg); Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP/DBP values from each BP assessment must be \< 140/90 mmHg in order for a subject to be eligible for the study * History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months; Note: subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible * Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major) * Evidence of active bleeding or bleeding diathesis * Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures * Unable or unwilling to discontinue use of prohibited medications list for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study * Treatment with any of the following anti-cancer therapies: * Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR * Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib * Any ongoing toxicity from prior investigational therapy that is \> grade 1 and/or that is progressing in severity, except alopecia