Whorling-sclerosing meningioma. A review on the histological features of a rare tumor including an illustrative case.

Whorling-Sclerosing variant of meningioma (WSM) is a very rare variant of meningioma and only 28 cases were previously reported in the English medical literature. The term "whorling" describes different morphological features including psammoma bodies formed by precipitated calcium or by layered whorling sheets of tumor cells in meningothelial meningiomas. In WSM, the sclerosing structures are formed by typical paucicellular or acellular collagen whorls which form the majority of tumor volume. Hence, diagnosis of these tumors is based more often on morphological and histochemical features rather than on immunohistochemical findings. WSMs often contain cells with both fibroblast-like spindle cell morphology predominantly immunopositive for vimentin and meningoepithelial cells immnunopositive for EMA. The range of their Ki-67 indices differs between 0 and 4 percent. These tumors show no focal pleomorphism, necrosis and high mitotic activity. In some WSMs, entrapped GFAP immunopositive astrocytes may be seen during invasion of the adjacent neural parenchyma. Brain invasion by WSMs may give rise to erroneous diagnoses, i.e. malignant (Grade-3) meningioma, meningiosarcoma, ganglioglioma and even astrocytoma, leading detrimental overtreatment. However; hitherto, no WSM was reported exerting any aggressive behavior. Besides reviewing the literature, we also report a new WSM with abundant uncalcified paucicellular collagen whorls forming aggregates of nodules. Unlike to previous reports, this tumor was costained with p53 and progesterone receptor. The tumor showed no morphological malignancy characteristics, e.g. cellular atypia, prominent nucleoli, hypercellularity, micronecrosis/geographical necrosis, sheeting and small cells. This rare meningioma variant should be kept in mind among differential diagnoses to avoid overtreatment that might endanger patients' outcome.

Hemoglobins, Hemorphins, and 11p15.5 Chromosomal Region in Cancer Biology and Immunity with Special Emphasis for Brain Tumors.

In systemic cancers, increased hemolysis leads to extracellular hemoglobin (HB), and experimental studies have shown its provoking role on tumor growth and metastasis. However, investigations have shown that HB chains presented by tumor vascular pericytes or serum protein complexes of HB could also induce antitumor immunity, which may be harnessed to treat refractory cancers and brain tumors. Mounting recent evidence shows that expression of HBs is not restricted to erythrocytes and that HBs exist in the cells of lung and kidney, in macrophages, and in neurons and glia of the central nervous system (CNS). HBs mediate coping with hypoxia and free radical stress in normal and tumor cells, and they are increased in certain tumors including breast, lung, colon, and squamous cell cancers. Recent studies showed HBs in meningioma, in the cyst fluid of craniopharyngioma, in the cerebrospinal fluid (CSF) of pediatric patients with posterior fossa tumors, and in glioblastoma cell lines. Hemorphins, abundant brain peptides formed via HB-chain cleavage, exert opioid activity and antiproliferative and immunomodifier effects. Hence mutations in HBs may modify brain tumorigenesis via influencing hemorphins and perturbing regulations of immune surveillance and cell growth in the neuroectodermal tissues. The ß-globin gene cluster resides in the chromosome region 11p15.5, harboring important immunity genes and IGF2, H19, PHLDA2/TSSC3, TRIM3, and SLC22A18 genes associated with cancers and gliomas. 11p15.5 is a prominent region subject to epigenetic regulation. Thus the ß-globin loci may exert haplotypal interactions with these. Some clues support this theory. It is well established that iron load induces liver cancer in thalassemia major; however iron load-independent associations also exist. Enhanced rates of hematologic malignancies are associated with HB Lepore, association of hemoglobin E with cholangiocarcinoma, and enhanced gastric cancer rates in the thalassemia trait. In the African Herero population, a mutant form of δ-globin is very prevalent, and this population has higher rates of pediatric brain tumors. Globins are also expressed in healthy endothelia and in tumoral vessels, indicating potential involvement in angiogenesis. Studies on HBs and their cleavage peptides in cancers and brain tumors may lead to innovative treatment strategies.

Association between smoking and cognitive impairment in multiple sclerosis.

PURPOSE: Although smoking is known to cause various symptoms in multiple sclerosis (MS) patients, there have been no reports regarding the relationship between smoking and cognitive impairment in MS. Studying the effects of cigarette smoking in MS patients is imperative as there is a high prevalence of cognitive impairment in MS patients. In this study we examined the potentially deleterious effects of heavy smoking on mentation of patients with MS. PATIENTS AND METHODS: MS patients receiving care at the Neurology Clinic at Bezmialem Vakif University, between the ages of 18-65 years who have at least graduated elementary school were included in the study. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) is a commonly used method to assess cognitive function in MS patients and was utilized in our study. Patients that smoked for at least 10 pack-years were considered heavy smokers. RESULTS: ALL THE PATIENTS WERE STRATIFIED INTO TWO GROUPS: heavy smokers (n=20) and nonsmokers (n=24). For heavy smokers, their cognitive functioning was more impaired than that of nonsmokers (P=0.04, χ (2)=4.227). For patients with cognitive impairment, 78.9% of the Paced Auditory Serial Addition Test and 63.2% of the Symbol Digit Modalities Test scores were found to be lower. CONCLUSION: Previous reports have suggested that smoking increases the frequency of relapse among individuals with relapsing-remitting MS and accelerates disease progression in patients with progressive MS. According to the results of our study, heavy smokers had increased cognitive impairment when compared to nonsmokers. Extensive studies are necessary to further elucidate the relationship between smoking and cognitive impairment in MS patients.

A 17-year-old female with systemic lupus presents with complex movement disorder: possible relationship with antiribosomal p antibodies.

Complex movement disorder is a relatively rare presentation of neurolupus. Antiphospholipid antibodies are associated with movement disorders likely via aberrant neuronal stimulation. Antiribosomal P antibodies have been previously associated with neuropsychiatric disorders but their correlation with movement disorder was not previously established. Our case report involves a 17-year-old Caucasian female patient positive for only antiribosomal P antibody and lupus anticoagulant who presented with a sudden onset of complex movement disorder. After complete cessation of physical signs with olanzapine, anticardiolipin and anti- ß 2 glycoprotein I antibodies became positive which indicates a likely discordance between movement disorder and antiphospholipid antibodies. This also indicates a potential causal role of antiribosomal P antibodies in inducing movement disorder.