Michele R. Aizenberg

Multifocal Histologically Malignant Epstein–Barr Virus–Associated Smooth Muscle Tumor in a Pediatric Transplant Patient With an Indolent Course

Epstein–Barr virus–associated smooth muscle tumors (EBV-SMTs) are rare lesions that occur in immunocompromised patients. Dural involvement appears to be less common in organ transplant recipients than in HIV patients. Due to the paucity of reported cases following organ transplantation, the natural history of these lesions is unclear. We describe an 8-year-old female who presented with adrenal, small bowel, and intracranial tumors 6 years following renal transplantation. Histopathological analysis revealed a highly cellular, mitotically active, smooth muscle neoplasm without necrosis. The tumor stained diffusely for smooth muscle actin and myosin. In situ hybridization for EBV-encoded RNA was diffusely positive. Following gross total resection, antiviral therapy, and a reduction in immunosuppression, the patient is tumor-free at 3 years follow-up. In patients with compromised immune systems, it is important to recognize this unique form of SMT because, even when there are multiple lesions, the prognosis may be excellent.

Intrathecal interleukin-2 for melanomatous meningitis.

Introduction One person dies as a result of melanoma every 64 minutes in the United States; it is the most common cancer killer in women age 30 to 35 years. Melanoma is among the three cancers most likely to spread to the leptomeninges, with a 23% rate of meningeal spread. In a retrospective review of 110 patients with melanomatous meningitis (MM), median overall survival from time of diagnosis of MM was 10 weeks. The majority of patients with MM and leptomeningeal disease from other solid tumors are frequently treated with intrathecal methotrexate, cytarabine, thiotepa, or topotecan, but published reports of treatment with intrathecal interleukin (IT IL-2) are rare. This report describes a patient with MM who was treated with IT IL-2 and experienced subsequent extended survival. Case Report A 23-year-old white woman was diagnosed with stage IIB melanoma of the upper extremity after wide resection and sentinel lymph node biopsy. Ten months later, metastatic disease developed, requiring palliative resection of a large chest wall mass and axillary lymph node dissection. A positron emission tomography scan demonstrated bilateral pulmonary nodules and bilateral hilar adenopathy. Magnetic resonance imaging (MRI) of the brain showed multiple enhancing lesions. Palliative whole-brain radiation was given, followed by two courses of high-dose IL-2 systemic therapy. A restaging positron emission tomography scan demonstrated an excellent partial response of the lung disease. Five months later, lower extremity neurologic deficits developed. MRI of the thoracic and lumbar spine showed multiple intramedullary masses and significant spinal cord edema from the fourth through eleventh thoracic vertebral levels (T4 through T11). Radiation therapy (RT; 30 Gy) was administered to T3 to T12 over 2 weeks. Immediately after finishing RT, temozolomide (200 mg/m per day for 5 days) was begun; however, during the last day of RT and the first few days of

Atypical presentation of primary central nervous system non-Hodgkin lymphoma in immunocompetent young adults.

OBJECTIVE Primary central nervous system non-Hodgkin lymphoma (PCNSL) is a malignant lymphoma limited to the cranial-spinal axis in the absence of systemic lymphoma. Historically, PCNSL accounts for fewer than 5% of all cases of primary intracranial neoplasms. PCNSL is rare in immunocompetent young adults. Although the prognosis for PCNSL is poor, approximately 20%-30% percent of cases achieve a cure. METHODS We report two cases of PCNSL originating in the ventricle in otherwise healthy immunocompetent young adults. RESULTS A 27-year-old man presented with 10 days of nausea, vomiting, and headache and was found to have a large intraventricular mass emanating from the choroid plexus with resultant hydrocephalus. He underwent placement of external ventricular drain and systemic and intrathecal chemotherapy for cytologically proven PCNSL. A 31-year-old pregnant woman presented with headaches, vision difficulties, and ataxia and was found to have a septum pellucidum mass. She underwent craniotomy and subtotal resection of the mass with subsequent systemic therapy and whole brain radiation for treatment of PCNSL. CONCLUSIONS To our knowledge, this is the first report of primary CNS lymphoma of the choroid plexus and septum pellucidum in otherwise healthy, immunocompetent young adults.

Assessment of vascularity in glioblastoma and its implications on patient outcomes

Abstract There is little data on why glioblastomas (GBM) hemorrhage and how it may affect patient outcomes. The aim of this study was to investigate the mechanisms of hemorrhage in glioblastoma by examining molecular and genetic features by immunohistochemistry (IHC) and mRNA expression profiles in association with imaging and clinical outcomes. An observational retrospective cohort analysis was performed on 43 FFPE GBM tissue samples. MR images were assessed for the presence of hemorrhage and extent of resection. Specimens were examined for CD34 and CD105 expression using IHC. Tumor mRNA expression profiles were analyzed for 92 genes related to angiogenesis and vascularity. Forty-three specimens were analyzed, and 20 showed signs of hemorrhage, 23 did not. The average OS for patients with GBM with hemorrhage was 19.12 months (95% CI 10.39–27.84), versus 13.85 months (95% CI 8.85–18.85) in those without hemorrhage (p > 0.05). Tumors that hemorrhaged had higher IHC staining for CD34 and CD105. mRNA expression analysis revealed tumor hemorrhage was associated with increased expression of HIF1α and MDK, and decreased expression of F3. Hemorrhage in GBM was not associated with worsened OS. Increased expression of angiogenic factors and increased CD34 and CD105 IHC staining in tumors with hemorrhage suggests that increased hypoxia-induced angiogenesis and vessel density may play a role in glioblastoma hemorrhage. Characterizing tumors that are prone to hemorrhage and mechanisms behind the development of these hemorrhages may provide insights that can lead to the development of targeted, individualized therapies for glioblastoma.

Primary Intracranial Leiomyoma in Immunocompetent Patients: Case Report, Review of Literature and Treatment Recommendations

Objective: Primary intracranial leiomyomas are rare tumors. These tumors are mostly described in immunocompromised patients and associated with Epstein-Barr virus (EBV). The following report is an intracranial leiomyoma that was resected twice from a young, immunocompetent male. Methods: This is a report of a patient who initially presented with tremor and headaches. He was ultimately found to have a large 6 cm×8 cm tumor that was removed. Nine years later, he was found to have a small recurrence that was removed. No adjuvant therapies have been given. Results: His follow-up totals well over 11 years and he remains on observation. Extensive review of this rare entity is provided. Conclusion: It is suggested that observation without any adjuvant therapy be the treatment of choice after resection of primary intracranial leiomyomas. These uncommon, benign tumors should be followed long-term given their slow-growing nature.

Extent of resection in glioblastoma

The article by Nam and de Groot provides a good overview of treatment options and considerations forglioblastoma. Surgery is a critical mainstay providing diagnostic and therapeutic benefits. The importance of extent of resection for glioblastoma has been debated for decades. Not only important at diagnosis, the relevanceof extent of resection at recurrence is increasing as patients with glioblastoma are surviving longer. After surgery, the neuro-oncologist or medical oncologist may be the sole provider obtaining follow-up imaging. At the time of recurrence or progression, it is crucial to identify patientswhomaybenefit from another resection and obtain neurosurgical evaluation. It is established that maximal safe resection should be performed if benefits outweigh risks and patient wishes are congruent with this approach. Gross total resection is the desired goal for benefit in survivaltimes.Thedogmaticall-or-nothing philosophy for resection is something to reconsider, however. Growing data support varying degrees of subtotal resection for graduatedbenefits insurvival times.Another benefit of resection, either gross total resectionor subtotal resection, is theacquisition of tissue for molecular testing. This is of utmost importance as we continue to elucidate factors affecting prognosis and responsiveness to therapies and develop personalized treatment plans. The definition ofmaximal safe resection becomes individual for each patient as variables are considered in determining the safest operative approach (biopsy, varied degrees of subtotal resection, or gross total resection) for each patient. Whether repeat resection benefits patients is not entirely clear as a result of conflicting studies, most often performed retrospectively, based on differing surgical indications in relatively heterogeneous populations who then receive varied adjuvant therapies. In addition, the extent of resection is often not quantified, the definitions of gross total resection and subtotal resection vary, and all resections may be grouped in comparison with biopsy, further adding to our uncertainty as to the significance of resection in this setting. The majority of both retrospective and prospective data since the turn of the century have favored repeat resection. Focusing on studies done within the era of temozolomide, Bloch et al performed a retrospective review of 107 patients undergoing reresection for glioblastoma and found that gross total resection (. 95%) increased overall survival at salvage surgery for patients who initially had subtotal resection. Karnofsky performance status and extent of resection at progression independently predicted survival. The SN1 study group reported on 503 patients from 20 institutions and found that the extent of resection at recurrence, Karnofsky performance status, and adjuvant therapy after resection increased overall survival. Investigators matched a cohort of 71 patients receiving reresection with patients who did not undergo resection from the prospective Dose-Intensified Rechallenge With Temozolomide (DIRECTOR) trial, wherein patients were randomly assigned to one of two dose-intensified schedules of temozolomide. Overall, surgery did not improve survival, but within the resection cohort, patients with 100% resection of all enhancing tumor had a 6.4-month improvement in postrecurrence survival (P, .001).