Glucose and methionine uptake and proliferative activity in meningiomas

Abstract

Despite similar benign histological appearances, proliferative activity of meningiomas varies tumor to tumor, and even region to region in a tumor. To predict proliferative potential before surgery, we compared regional uptake of2-[18F]fluoro-2-deoxyglucose ([18F]FDC) and L-fmethyl-11 CJmethionine ([71C]MET) with histological indices of tumor proliferative activity in 17 specimens from six patients with meningioma obtained by PET guided stereotactic biopsies. Uptake of I11C]MET', an index of protein synthesis rate, significantly correlated not only with the count of nucleolar organizer regions (NORs), a histological index of protein synthesis, but also with Ki-67 index, a histological index of proliferative activity. On the other hand, [18F]FDC uptake showed no significant correlation with Ki-67 index or clinical malignancy. These results suggest that [11 C]MET-PET is a useful tool for predicting tumor proliferative potential in meningiomas. [Neurol Res 1999; 21: 640-644]     

Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.     

Investigation of blood flow in meningothelial and fibrous meningiomas by xenon-enhanced CT scanning

Abstract

We investigated whether xenon-enhanced computed tomography was able to separate meningothelial meningioma from fibrous meningioma. Cerebral blood flow was studied by xenon-enhanced computed tomography in six patients with incidentally detected intracranial meningiomas. All of the tumors were small (<32mm) and there was little or no péritumoral edema. Three patients had meningothelial meningioma and three patients had fibrous meningioma. The tumor blood flow and the contralateral tissue blood flow were determined. The ratio of these parameters was 7.753 ± 0.467 for meningothelial meningiomas and 0.809±0.105 for fibrous meningiomas, with a significant difference between the two tumor subtypes (p = 0.0185). There was no correlation between the signal intensity on magnetic resonance imaging and tumor subtype, and the findings on cerebral angiography also did not indicate the subtype. In conclusion, xenon-enhanced computed tomography showed a difference between smaller meningothelial and fibrous meningiomas in patients with normal surrounding brain tissue. We could not confirm that xenon-enhanced computed tomography was able to distinguish the subtype of meningioma because of the small number of subjects in this study, but our findings might expand interest in the clinical use of this method. [Neurol Res 2000; 22: 615-619]     

ALK-negative lung inflammatory myofibroblastic tumor in a young adult: A case report and literature review of molecular alterations

Rationale:Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that is prevalent among children and adolescents. Surgery is the most important therapeutic approach for IMT and complete resection is recommended. Although 50% of IMTs show anaplastic lymphoma kinase (ALK) rearrangements, crizotinib has proven an effective therapeutic approach. However, the genetic landscape of this tumor is still not fully understood and treatment options are limited, especially in the majority of ALK-negative tumors.Patient concerns:We describe the clinical case of a healthy 18-year-old female in whom a pulmonary nodule was incidentally detectedDiagnoses:Following a small increase in the size of the nodule, the patient underwent both ¹⁸FDG-PET/CT and ⁶⁸Ga-PET/CT, resulting in a suspicion of bronchial hamartoma.Interventions:The patient underwent surgery and a salivary gland-like lung tumor was diagnosed.Outcomes:After surgery, the patient was referred to our cancer center, where a review of the histology slides gave a final diagnosis of ALK-negative lung IMT. Given the histology, it was decided not to administer adjuvant therapy and the patient was placed in a 3-monthly follow-up program. The patient is still disease-free 2 years post-surgery.Lessons:Although there is no standard of care for the treatment of IMT, identifying genomic alterations could help to redefine the management of patients with negative-ALK disease. Our review of the literature on IMT and other kinase fusions revealed, in addition to ALK rearrangements, the potential association of ROS1, NTRK, RET, or PDGFR beta alterations with the tumor.     

Mitotic Index is an Independent Predictor of Recurrence‐Free Survival in Meningioma

While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within‐grade heterogeneity with respect to recurrence‐free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on hematoxylin and eosin sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment, we evaluated 363 meningiomas with phospho‐histone H3 (Ser10) and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grade I (n = 268), grade II (n = 84) and grade III (n = 11) tumors were 1, 4 and 12. Classification and regression tree analysis to categorize cut‐offs identified three subgroups defined by mitotic indices of 0–2, 3–4 and ≥5, which on univariate analysis were associated with RFS (P < 0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (P < 0.01) after adjustment for Simpson grade, WHO grade and MIB‐1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and grade II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification.     

Childhood anaplastic large cell lymphoma has a high incidence of ALK gene rearrangement as determined by immunohistochemical staining and fluorescent in situ hybridisation: a genetic and pathological correlation

Anaplastic large cell lymphoma (ALCL) comprises 10-15% of childhood non-Hodgkin lymphomas (NHL). Systemic ALCL is highly associated with anaplastic lymphoma kinase (ALK) gene translocations with over-expression of ALK protein. We studied ALK rearrangements using fluorescence in situ hybridisation (FISH) and ALK immunohistochemical staining in 43 paediatric systemic ALCLs. FISH (performed on 35 cases) identified a translocation in 29 cases (83%). Immunohistochemistry identified ALK over-expression in 42/43 cases (97%) with the single ALK-negative case demonstrating an ALK rearrangement by FISH, indicating 100% incidence of ALK translocations.     

Anaplastic large-cell lymphomas of B-cell phenotype are anaplastic lymphoma kinase (ALK) negative and belong to the spectrum of diffuse large B-cell lymphomas

There is controversy in the literature as to whether anaplastic large-cell lymphoma of B-cell phenotype is related to the t(2;5)-positive T- or 'null' cell lymphoma of the same morphology. We report a study of 24 lymphomas with morphological features of anaplastic large-cell lymphoma which expressed one or more B-cell markers and lacked T-lineage markers. Clinical features were more in keeping with large B-cell lymphoma than with classical t(2;5)-positive anaplastic large-cell lymphoma, and immunostaining for anaplastic lymphoma kinase (ALK) protein provided no evidence for the (2;5) translocation (or one of its variants). The staining patterns for CD20 and CD79 were typical of diffuse large B-cell lymphoma, CD30 expression was variable, and most cases (15/22) lacked epithelial membrane antigen (EMA). These findings support the view that 'B-cell anaplastic large-cell lymphoma' is unrelated to t(2;5)-positive (ALK-positive) lymphoma, and that it represents a morphological pattern occasionally encountered among diffuse large B-cell lymphomas. By the same reasoning, most tumours diagnosed as 'ALK-negative anaplastic large-cell lymphoma of T-cell or null phenotype' probably belong to the spectrum of peripheral T-cell lymphomas.