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Simple Summary: Although primary central nervous system lymphoma (PCNSL) is sometimes indistinguishable from glioblastoma, isocitrate dehydrogenase (IDH)-wildtype, the role of operation on them is very different; therefore, accurate preoperative diagnosis is crucial. In this study, we evaluated whether amide proton transfer-weighted (APTw) imaging was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. The mean APTw signal value did not significantly differ between them; however, the percentile values from the 1st percentile to the 20th percentile APTw signals and the width1–100 APTw signals between the two diseases were significantly different. The area under the curve, sensitivity, and specificity were 0.796, 64.3%, and 88.9%, respectively, using the width1–100 APTw signal values. APTw imaging was useful to differentiate between PCNSL and glioblastoma, IDH-wildtype. Performing APTw imaging is recommended in cases in which PCNSL is one of the differential diagnoses. Distinguishing primary central nervous system lymphoma (PCNSL) from glioblastoma, isocitrate dehydrogenase (IDH)-wildtype is sometimes hard. Because the role of operation on them varies, accurate preoperative diagnosis is crucial. In this study, we evaluated whether a specific kind of chemical exchange saturation transfer imaging, i.e., amide proton transfer-weighted (APTw) imaging, was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. A total of 14 PCNSL and 27 glioblastoma, IDH-wildtype cases were evaluated. There was no significant difference in the mean APTw signal values between the two groups. However, the percentile values from the 1st percentile to the 20th percentile APTw signals and the width1–100 APTw signals significantly differed. The highest area under the curve was 0.796, which was obtained from the width1–100 APTw signal values. The sensitivity and specificity values were 64.3% and 88.9%, respectively. APTw imaging was useful to distinguish PCNSL from glioblastoma, IDH-wildtype. To avoid unnecessary aggressive surgical resection, APTw imaging is recommended for cases in which PCNSL is one of the differential diagnoses. [ABSTRACT FROM AUTHOR]

Cardiac angiosarcoma is a rare malignant tumor with a poor prognosis, characterized by the high uptake of 18F-fluorodeoxyglucose (FDG). This case report presents two cases of cardiac angiosarcoma with a marked difference in FDG uptake and prognosis. Case Summary : Case 1 : A 40-year-old male presented with syncope. Ultrasound echocardiography demonstrated a cardiac tumor with a high uptake of 18F-FDG (maximum standardized uptake value=9.2). The patient underwent heart catheterization and tumor biopsy. The pathological result was high-grade angiosarcoma, and the MIB-1(Ki-67) proliferation index was approximately 20%. Systemic chemotherapy was administered ; however, the patient died 2 years and 5 months after disease onset. Case 2 : A 65-year-old female had a right atrial tumor incidentally diagnosed during routine ultrasound echocardiography. The tumor exhibited a low uptake of 18F-FDG (maximum standardized uptake value=1.8). Open heart surgery was performed, and the tumor was completely resected. Histological analysis revealed low-grade angiosarcoma, and the MIB-1(Ki-67) proliferation index was less than 5%. The patient was followed-up and had not relapsed 2 years after surgery. Conclusion : 18F-FDG uptake may reflect pathological tumor grade and prognosis in cardiac angiosarcoma. [ABSTRACT FROM AUTHOR]

We reviewed the medical records of 392 patients who underwent initial surgery for skull base meningiomas between 1983 and 2008. Among them, 32 (8.2%) showed tumor recurrence. Risk factors for recurrence were analyzed clinically and biologically. Recurrent cases were treated with radiotherapy, surgery, or both. In reoperation cases, pathological and biological changes were analyzed and compared between groups with or without radiotherapy. The recurrence rate was statistically high in cases of partial tumor removal and in patients with tumor in the cavernous sinus, tumors with histological WHO (World Health Organization) grade ≥ II or MIB-1 index > 3. The local control rate of postoperative radiotherapy for recurrent cases was 66.7%. Malignant transformation and MIB-1 index elevation was observed more frequently in patients who underwent reoperation after radiotherapy than in the reoperation-only group. Risk factors for recurrence of skull base meningiomas are as follows: (1) partial tumor removal, (2) tumor in the cavernous sinus, (3) histological WHO grade ≥ II, or (4) MIB-1 index > 3. Postoperative radiotherapy might be effective for tumor recurrence. However, the indications for radiotherapy should be carefully considered because postsurgical radiotherapy may increase biological activity, inducing malignant transformation. [ABSTRACT FROM AUTHOR]

c-Met has been shown to be associated with tumor growth in several human cancers. This study aims to evaluate the correlation between the c-Met expression and histopathologic/clinical characteristics. A total of 153 patients with histologically defined World Health Organization grade II–IV diffuse astrocytic and oligodendroglial tumors were analyzed. For each histopathologic diagnosis, the number of cases and positive rate of c-Met expression are as follows: oligodendroglioma, IDH -mutant, and 1p19q codeletion (OD): 16 cases, 6.3%; anaplastic oligodendroglioma, IDH -mutant, and 1p19q codeletion (AO): 11 cases, 36.4%; diffuse astrocytoma (DA), IDH -mutant: 21 cases, 28.6%; anaplastic astrocytoma (AA), IDH - mutant: 15 cases, 20%; glioblastoma, IDH -mutant: 2, 100%, DA, IDH -wildtype: 9 cases, 33.3%; AA, IDH -wildtype: 20 cases, 30.0%; and glioblastoma, IDH -wildtype: 59 cases, 52.5%. c-Met expression was correlated with progression-free survival in oligodendroglial tumors and glioblastoma, IDH -wildtype. Furthermore, it was correlated with overall survival in AO, oligodendroglial tumors, DA, IDH -mutant, DA, IDH -wildtype, and glioblastoma, IDH -wildtype, and tend to be correlated with overall survival in IDH -mutant lower-grade astrocytic tumors. c-Met expression was revealed to be a useful marker for prognosis prediction in IDH- mutant lower-grade gliomas and glioblastoma, IDH -wildtype, representing a new independent prognostic marker that can be easily measured. [ABSTRACT FROM AUTHOR]

Background The prognosis for World Health Organization (WHO) grade II/III meningiomas is worse than for WHO grade I meningiomas. Histopathologic grade should ideally be identified during tumor resection, but current methods are time-consuming and have doubtful reliance. The aim of this study was to evaluate intraoperative flow cytometry (iFC) as a method for providing ultrarapid evaluation of meningioma malignancy. Methods A total of 117 meningiomas were analyzed with iFC during surgery. For each, the malignancy index (MI) was calculated as the number of cells with a greater than normal DNA content as a proportion of the total number of cells. Each specimen was investigated histopathologically and was diagnostically graded according to the 2016 WHO grading system. MI results were compared with WHO grades of the meningiomas. Results The automatic measurement of iFC took approximately 9 minutes on average. The difference in MI between grade I and grade II/III meningiomas was statistically significant (P < 0.001). Receiver operating characteristic analysis provided an optimal cutoff MI value of 8.0% for discrimination between grade I and grade II/III groups, with 64.7% sensitivity and 85.0% specificity for grade II/III meningiomas. Conclusions Our method of calculating MI with iFC appears to be technically feasible and reliable for ultrarapid evaluation of meningioma malignancy. MI with iFC could potentially enable determination of an optimal treatment strategy during surgery, such as extent of resection of the tumor and management of invaded normal brain or nerves. Highlights • WHO grade II/III meningiomas are more malignant than grade I meningiomas. • More radical tumor resection is required for malignant grade II/III meningiomas compared with that required for grade I. • Malignancy evaluation of meningiomas by iFC using our methods is rapid, effective, and reliable. • The findings obtained by iFC correlate with WHO grade. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective analysis.Objective: The goal of this study was to examine the relationship of the proliferation potency based on the MIB-1 index and motor status with features of T2-weighted images (T2WI) and contrast T1-weighted images (T1WI) of spinal schwannoma.Summary Of Background Data: Spinal schwannomas account for 55% of spinal tumors, but the relationship of cellular proliferation with MRI findings for spinal schwannoma is unknown.Methods: The subjects were 48 patients (22 males and 26 females) with spinal schwannoma who were classified into three subgroups: iso/homo, high/rim, and hetero/hetero, based on T2WI/contrast T1WI. A retrospective analysis of tumor size and MIB-1 index was performed in the context of these MRI findings. Intraoperative findings and pre- and postoperative motor performance were also examined.Results: The average tumor size was 32.4 mm (range 10-130 mm) and the average MIB-1 index was 3.8% (range 1-12). In the three subgroups, there were no significant differences in sex, age, duration of disease, tumor lesion, and dumbbell type. In the hetero/hetero group, the tumor size was significantly greater and the MIB-1 index was significantly higher (both P < 0.05), than the other two groups. The tumor adherence rate was significantly higher for hetero tumors (P < 0.05) and preoperative paralysis was more common in cases with tumor adhesion. The rate of paralysis improvement at 1 month was significantly lower for hetero tumors, but all cases had improved at 6 months.Conclusion: Contrast T1WI MRI was useful for prediction of the proliferative activity and growth of spinal schwannomas, which are associated with increased tumor size and adhesion. A heterogeneous pattern on contrast T1WI indicated an increase in size and adhesion of the tumor. This pattern reflected the preoperative motor status and postoperative motor recovery.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Three methods for the analysis of cell proliferation, mitotic index/10 high-power fields (10 HPF), mitotic index/four sets of 10 HPF (40 HPF), and MIB-1 index were evaluated in a series of canine mammary gland tumors, as well as the possible correlation between them. Fifty-six canine mammary gland tumors, including 23 benign and 33 malignant, were studied. In addition, the prognostic impact of mitotic index/10 HPF, and histological malignancy grade were evaluated in 17 malignant tumors, being seven ductal and 10 metaplastic carcinomas. The three methods used to evaluate cell proliferation were correlated with the prognostic impact of mitotic index/10 HPF and histological malignancy grade. The results showed a strong association between mitotic figure counts and MIB-1 index (PAvaliaram-se três métodos de proliferação celular, índice mitótico/10 campos de grande aumento (10 CGA), quatro vezes 10 CGA (40 CGA) e índice de marcação por MIB-1, em uma série de tumores mamários caninos, e as possíveis correlações entre estes métodos. Foram estudados 56 tumores mamários caninos, 23 benignos e 33 malignos. Foi também avaliado o impacto prognóstico do índice mitótico (10 CGA) e o grau histológico maligno em 17 tumores malignos, sete carcinomas ductais e 10 carcinomas metaplásicos. A correlação entre os três métodos para avaliar a proliferação celular e o impacto prognóstico do índice mitótico por 10 CGA e o grau histológico maligno foi realizada. Os resultados mostraram que existe uma forte associação entre contagem de mitose e o índice de marcação por MIB-1(P

Background: Spheno-orbital meningioma (SOM) typically presents with a classic triad of symptoms (i.e., proptosis, visual impairment, and ocular paresis), resulting from intraorbital tumor invasion. The authors present a very rare case of SOM in which the chief complaint was swelling of the left temporal region, which, to the best of their knowledge, has not been reported previously., Observations: The patient presented with marked extracranial extension to the left temporal region but unremarkable intraorbital extension, even on radiological examination. Physical examination of the patient showed almost no exophthalmos or restriction of left eye movement, consistent with the radiological findings. Four separate meningioma specimens were removed by extraction (i.e., one each from the intracranial, extracranial, and intraorbital segments of the tumor and one from the skull). The World Health Organization grade was 1 and the MIB-1 index was less than 1%, indicating a diagnosis of a benign tumor., Lessons: SOM may be present even in patients with only temporal swelling and few ocular-related symptoms, and detailed imaging evaluations may be required to identify the tumor.

Purpose: The aim of this study was to examine the clinical outcomes of treating atypical meningioma at the skull base region following surgical resection and adjuvant radiotherapy, and to analyze the association between clinical characteristics and progression free survival. Materials and methods: Twenty-eight patients with skull base atypical meningiomas underwent microsurgical resection between June 2001 and November 2009. The clinical characteristics of the patients and meningiomas, the extent of surgical resection, and complications after treatment were retrospectively analyzed. Results: Thirteen patients (46.4%) had disease recurrence or progression during follow up time. The median time to disease progression was 64 months. The extent of the surgical resection significantly impacted prognosis. Gross total resection (GTR) of the tumor improved progression free survival (PFS) compared to subtotal resection (STR, p = 0.011). An older patient age at diagnosis also resulted in a worse outcome (p = 0.024). An MIB-1 index <8% also contributed to improved PFS (p = 0.031). None of the patients that underwent GTR and received adjuvant radiotherapy had tumors recur during follow up. STR with adjuvant radiotherapy tended to result in better local tumor control than STR alone (p = 0.074). Three of 28 patients (10.7%) developed complications after microsurgery. The GTR group had a higher rate of complications than those with STR. There were no late adverse effects after adjuvant radiotherapy during follow up. Conclusion: For patients with skull base atypical meningiomas, GTR is desirable for longer PFS, unless radical excision is expected to lead to severe complications. Adjuvant radiation therapy is advisable to reduce tumor recurrence regardless of the extent of surgical resection. Age of disease onset and the MIB-1 index of the tumor were both independent prognostic factors of clinical outcome. [ABSTRACT FROM AUTHOR]

Background: Despite the wide spectrum of adenoma behavior in patients with acromegaly, the ability of most pathological markers to predict clinical and radiological behavior remains controversial. The authors sought to comprehensively examine clinical and radiological correlates of growth hormone (GH)-secreting pituitary adenomas with regard to several commonly used immunocytochemical techniques in patients undergoing transsphenoidal surgery for acromegaly. Method: We performed a retrospective review of histopathological findings in 101 surgically resected GH adenomas. Tumors were assessed radiologically for different patterns of extension. Each tumor specimen was subject to immunocytochemical analysis, including assessments of granulation patterns, MIB-1 labeling indices, prolactin cosecretion, p53 expression and mitotic activity. Endocrinological outcome was assessed in 93 patients, with remission defined by the 2010 consensus criteria. Results: Most tumors were macroadenomas and almost half were invasive. When compared to densely granulated tumors, sparsely granulated adenomas were associated with a younger age at presentation, higher preoperative IGF-1 levels, elevated MIB-1 index and pure GH immunostaining, but did not differ significantly in terms of extrasellar invasion or outcome. Increased mitotic activity and p53 expression were also associated with higher proliferation indices and a younger age at presentation. Mixed GH/prolactin tumors demonstrated significantly higher remission rates, independent of variations in extrasellar growth. MIB-1 indices did not correlate with the preoperative GH/IGF-1 levels, adenoma size or Knosp grade. Conclusion: The pathobiology of acromegaly is complex, and the clinicoradiological significance of subtyping on the basis of the markers employed in this study is debatable. Further investigation of newer molecular markers is warranted. [ABSTRACT FROM AUTHOR]

Objective: Presence of steroid hormone receptors in meningiomas is well-known, but their correlation with tumour behaviour is unclear. The purpose of this study was to assess the relation between steroid hormone receptor expression and tumour behaviour. Methods: We retrospectively reviewed 48 patients undergoing surgery for intracranial meningioma between January 2002 and December 2004. We included World Health Organization (WHO) Grade I meningiomas in Group 1 and WHO Grades II and III in Group 2. Tumour grade, progesterone receptor (PR), oestrogen receptor (ER) expressions, MIB-1 Index and Mitotic Index were assessed. W e sought the correlation between tumour grade and MIB-1, Mitotic Indices, and also PR expression. Furthermore, the correlation between PR expression and MIB-1 and Mitotic Indices was assessed in Group 1 and Group 2, separately. Results: 26 patients were in Group 1 and 22 patients in Group 2. PR expression was determined in 56% of the tumours while there was no ER expression. PR expression was found to be higher in Group 1 compared to Group 2. The Mean MIB-1 Index and the Mean Mitotic Index were significantly higher in Group 2 compared to Group 1. However, when Groups 1 and 2 were assessed separately, PR expression does not appear to be correlated with MIB-1 and Mitotic Indices in benign and also in non-benign meningioma groups. Conclusion: Our findings suggest that tumour grade, but not PR expression, is correlated with meningioma behaviour. [ABSTRACT FROM AUTHOR]

Glioblastomas, which are the most common primary intracranial tumor, are associated with the poorest survival time, which is typically 1-2 years. Age at initial diagnosis, Karnofsky performance score, and O-methylguanine DNA-methyltransferase ( MGMT) promoter methylation status are the most well-documented predictors of survival in patients with newly diagnosed glioblastoma. Few studies have examined prognostic factors in patients with recurrent glioblastomas. At relapse, the pathological features of glioblastomas are affected by tumor regrowth and the influence of chemoradiotherapy during the initial treatment. Morphological transformations at recurrence include quantitative changes in tumor cells, such as the presence of giant cells and gemistocytic cell formation, radiation necrosis, and vascular structural changes. Therefore, we should carefully examine pathological findings at recurrence. In this report, we analyzed MGMT promoter status, the MIB-1 index, and the pathology of tumor samples at the first (primary tumor) and second (recurrent tumor) surgeries and clarified prognostic factors in patients with recurrent cases. In the multivariate analysis, we showed that MIB-1 indexes at the time of the second surgery ( p = 0.004) persisted as a significant independent prognostic factor in survival of patients with recurrent glioblastoma. [ABSTRACT FROM AUTHOR]

Clinically nonfunctioning pituitary adenomas (CNFPAs) consist of several histological subtypes, including null cell adenoma (NCA), silent gonadotroph cell adenoma (SGA), silent corticotroph adenoma (SCA), and other silent adenomas (OSA) (i.e., GH, TSH, and prolactin adenomas). To detect possible correlations between MRI findings and the subtypes, we retrospectively studied 390 consecutive patients with CNFPA who underwent surgery between 2008 and 2010. They were classified into three groups: NCA/SGA (313 cases), SCA (39 cases), and OSA (36 cases); in addition there were two unusual cases of plurihormonal adenoma. Three MRI findings were less common in NCA/SGA than in the other groups ( P < 0.0001): giant adenoma (>40 mm), marked cavernous sinus invasion (Knosp grade 4), and lobulated configuration of the suprasellar tumor. When these MRI findings were negative in patients older than 40 years old, 91.0 % (212/233) were NCA/SGA. These MRI findings were frequently noted despite a low MIB-1 index in SCA. OSA showed a high MIB-1 index and a preponderance in younger patients. In conclusion, although SCA and OSA consisted of only 20 % of CNFPAs, their frequency significantly increased when the tumor was large, invasive, and lobulated, and the patient was younger than 40 years old. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The main goal of the present study was evaluation of proton magnetic resonance spectroscopy (1H-MRS) in diagnosis of histopathologically aggressive intracranial meningiomas. Methods: Single-voxel 1H-MRS of 100 intracranial meningiomas was performed before their surgical resection. Investigated metabolites included mobile lipids, lactate, alanine, N-acetylaspartate (NAA), and choline-containing compounds (Cho). According to criteria of World Health Organization (WHO) 82 meningiomas were assigned histopathological grade I, 11 grade II, and 7 grade III. The MIB-1 index varied from 0% to 27.3% (median, 1.6%). In 43 cases tight adhesion of the tumor to the pia mater or brain tissue was macroscopically identified at surgery. The consistency of 49 meningiomas was characterized as soft, 26 as hard, and 25 as mixed. Results: No one metabolic parameter had statistically significant association with histopathological grade and subtype, invasive growth, and consistency of meningioma. Univariate statistical analysis revealed greater 1H-MRS-detected Cho content (P =0.0444) and lower normalized NAA/Cho ratio (P =0.0203) in tumors with MIB-1 index 5% and more. However, both parameters lost their statistical significance during evaluation in the multivariate model along with other clinical and radiological variables. It was revealed that non-benign histopathology of meningioma (WHO grade II/III) is mainly predicted by irregular shape (P =0.0076) and large size (P =0.0316), increased proliferative activity by irregular shape (P =0.0056), and macroscopically invasive growth by prominent peritumoral edema (P =0.0021). Conclusion: While 1H-MRS may be potentially used for the identification of meningiomas with high proliferative activity, it, seemingly, could not add substantial diagnostic information to other radiological predictors of malignancy in these tumors. [Copyright &y& Elsevier]

Aim: Expressions of the myc target genes Mina53 and mimitin are high in esophageal squamous cell carcinoma and colon cancer, and their relationship to cell proliferation and patient prognosis has been reported. Because c-myc gene expression is closely related to hepatocellular carcinoma (HCC) growth or formation and/or maintenance, we examined the Mina53 and mimitin expressions in HCC. Methods: Surgically resected 53 HCC tissues were immunohistochemically examined for Mina53 and mimitin expressions and their relationship to clinicopathological factors. Results: Diffuse Mina53 expression was observed in the nuclei of cancer cells in the tumor nodule, but was often strong at the periphery of tumor nodules. Diffuse or scattered expression of mimitin was observed in the cytoplasm of HCC cells in tumor nodules. Mina53 expression was higher in poorly differentiated HCC than in well-differentiated HCC, and significant relationship to histological grade was observed. The cases with a high Mina53 expression also had a high expression of a proliferation marker MIB-1. This suggested the involvement of Mina53 in cell proliferation. Mina53 expression was high in the tumors of >2 cm of diameter than in ≤2 cm ( P < 0.01). Mimitin expression tended to be high in tumors of >2 cm, but no significant relationship was observed either to histological grade, MIB-1 expression, or the other clinicopathologic factors. Conclusions: Our findings suggested that Mina53 expression is accelerated in HCC with a lower histological grade, with cell proliferation capability, or with a larger diameter, and Mina53 is related to biological malignancy of HCC. [ABSTRACT FROM AUTHOR]

Meningioma is a common neoplasm that constitutes almost 30% of all primary central nervous system tumors and is associated with inconsistent clinical outcomes. The extracellular matrix proteins play a crucial role in meningioma cell biology and are important in tumor cell invasion and in progression to malignancy. SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular matrix proteins. The aim of this study was to evaluate the expression of SPARC with proliferation index, p53 reactivity in WHO grade 1 (benign), grade 2 (atypical) and grade 3 (anaplastic) meningiomas and correlate with clinical features of the patients, including location of the tumor, recurrence of the tumor and survival of patients. We studied 111 meningiomas, 69 being benign, 34 being atypical and eight being anaplastic meningiomas of various histological types. Using immunohistochemical analysis, we evaluated the expression of SPARC, Ki-67 (MIB-1) and p53 in meningiomas. Immunohistochemical scores of SPARC were determined as the sum of frequency (0–3) and intensity (0–3) of immunolabeling of the tumor cells. A high immunohistochemical score (4–6) for SPARC was more frequent in atypical and in anaplastic meningiomas than in benign meningiomas (p < 0.01). MIB-1 proliferation index showed significant association between tumor grades in meningiomas (p < 0.01). At the end of a follow-up period of 47.53 ± 25.04 months, 30 tumors recurred. A high SPARC expression was significantly associated with tumor recurrence (p = 0.02). The immunoreactivity of p53 protein and MIB-1 score were significantly higher in recurrent meningiomas than in non-recurrent meningiomas. The cumulative survival of patients with high SPARC expression was significantly lower than patients with low SPARC expression. The high SPARC expression scores were predominantly identified in meningothelial, fibrous and chordoid meningiomas; low SPARC expression scores were mostly spotted in secretory and psammomatous meningiomas. Evaluating SPARC expression might help assessing recurrence risk and survival estimation in meningiomas. [ABSTRACT FROM AUTHOR]

Akt/Protein kinase B (PKB) is a common downstream molecule of Ras signaling essential for cell survival. In an attempt to find a novel prognostic marker of diffuse astrocytoma, we performed an immunohistochemical analysis of Akt/PKB with regard to patient survival and regrowth patterns. Twenty-four adult patients with diffuse astrocytoma were similarly managed without early post-operative radiotherapy and followed up for a median period of 7.5 years. They were analysed by immunohistochemistry for Akt/PKB expression as well as p53 protein accumulation, epidermal growth factor receptor (EGFR) expression, and MIB-1 labeling index. The prognostic significance of each molecular covariate was tested by multivariate analysis using Cox’s proportional hazard model including age, performance status, and extent of surgical resection. Akt/PKB overexpression significantly correlated with both shorter overall survival (OS) and progression-free survival (PFS) ( p = 0.0110). All the Akt/PKB-positive patients with post-operative residual tumours experienced tumour recurrences, whereas only a small fraction of the Akt/PKB-negative individuals had recurrences ( p = 0.0070). Invasive recurrence into surrounding brain occurred only in the Akt/PKB-overexpressed tumours. In contrast, MIB-1 labeling index correlated only with OS, while p53 protein accumulation correlated only with PFS. The Cox’s proportional hazard model identified Akt/PKB overexpression as a significant prognostic factor for shorter PFS ( p = 0.0117). These results show that Akt/PKB overexpression would be suggestive of malignant progression and invasive regrowth of diffuse astrocytoma, and it can serve as a novel prognostic marker for this tumour. [ABSTRACT FROM AUTHOR]

Simple Summary: The World Health Organization (WHO) classification grades meningiomas exclusively due to their histopathological features. Meningiomas are predominantly benign intracranial entities, and surgical resection represents the therapy of choice. However, risk of progression and tailored scheduling of follow-up appointments are significantly influenced by various items, such as immunohistochemistry (e.g., MIB-1 index). Emerging evidence focuses attention on the anatomic location of meningiomas, especially regarding the differentiation between skull base and non-skull base meningiomas. In the present study, we therefore investigated demographic, histopathological, and laboratory variables regarding their association with the anatomic location. We found that spinal meningiomas have a significantly lower proliferative activity, less density of macrophage infiltrates, and a longer time to tumor progression. Moreover, increased MIB-1 indices are significantly associated with location-specific baseline symptoms (e.g., convexity: seizure burden, medial skull base: decreased vision, spinal: ambulatory ability). Therefore, anatomic location might be considered as a future subclassification in the grading of the prognosis of meningiomas. Emerging evidence emphasizes the prognostic importance of meningioma location. The present investigation evaluates whether progression-free survival (PFS), proliferative potential, World Health Organization (WHO) grades, and inflammatory burden differ between anatomical locations (skull base, non-skull base, and spinal) meningiomas. Five-hundred-forty-one patients underwent Simpson grade I or II resection for WHO grade 1 or 2 meningiomas. Univariable analysis revealed that spinal meningioma patients are significantly older, had a worse baseline Karnofsky Performance Status (KPS), higher acute-phase protein levels, lower incidence of WHO grade 2, lower mitotic counts, lower MIB-1 index, and less CD68+ macrophage infiltrates. Multivariable analysis identified WHO grade 2 (OR: 2.1, 95% CI: 1.1–3.7, p = 0.02) and cranial location (OR: 3.0, 95% CI: 1.8–4.9, p = 0.001) as independent predictors of diffuse CD68+ macrophage infiltrates. The mean PFS in cranial meningiomas was 115.9 months (95% CI: 107.5–124.3), compared to 162.2 months (95% CI: 150.5–174.0; log-rank test: p = 0.02) in spinal meningiomas. Multivariable Cox regression analysis revealed cranial location as an independent predictor (HR: 4.7, 95% CI: 1.0–21.3, p = 0.04) of shortened PFS. Increased MIB-1 indices ≥5% were significantly associated with location-specific deficits at presentation, such as decreased vision and seizure burden. Spinal meningiomas have a significantly longer PFS time and differ from the cranial meningiomas regarding MIB-1 index and density of tumor-associated macrophages. [ABSTRACT FROM AUTHOR]

This article discusses a study which assessed cell proliferation and prognostic factors in canine mammary gland tumors. The study emphasized the importance of mitotic count and histological grade and type for assessing the prognosis of canine mammary tumors. It also indicates that the criteria used for this assessment should be well standardized and controlled. It showed that mitotic count per 10 HPF and histological grading as proposed by C. W. Elston and I. O. Ellis can be used as prognostic factors of canine mammary gland tumors, as well as of human breast cancer.

Abstract: Background: The primary malignant dural lymphoma of B-cell type is rare. Our review of the literature (24 cases) indicated that patients with this tumor had female predominance, immunocompetency, and longer survival compared with those with primary malignant intracerebral lymphomas. Based on its clinicopathological features, this dural lymphoma may be classified differently from other types of malignant lymphomas in the central nervous system. Case Description: The authors report an example of a patient who had a favorable course of malignant dural lymphoma. A 59-year-old woman presented with primary malignant dural lymphoma in the frontal area. Histological diagnosis was a diffuse large B-cell–type lymphoma of intermediate malignancy, but MIB-1 index was extremely high. Subtotal tumor removal was followed by 4 courses of chemotherapy. Thirty months after surgery, the patient is asymptomatic with no MRI evidence of recurrence. A combination of subtotal resection and chemotherapy for a primary malignant dural lymphoma is an effective means to attempt cure of this tumor. Conclusion: These rare tumors may be managed successfully by subtotal resection and postoperative treatment. We believe that chemotherapy is the treatment of choice after subtotal resection of malignant dural lymphomas, as experienced in our case. [Copyright &y& Elsevier]

Abstract: The E-cadherin/catenin complex (α-catenin, β-catenin, and E-cadherin) plays a crucial role in cell–cell adhesion and tissue remodeling, and abnormalities in these molecules have been suggested to participate in the proliferation and invasive and metastatic potentials of several human carcinomas. However, in human lung adenocarcinomas, its importance has not yet been sufficiently investigated. We immunohistochemically examined the expressions of E-cadherin/catenin complex in 35 primary lung adenocarinomas, and evaluated their expressions in a semiquantitative manner. Correlations between these expression levels, MIB-1 and nuclear p53 indices, and clinicopathological factors were analyzed by subdividing the cases into high- and low-expression groups for each protein. The reduction in membranous E-cadherin/catenin complex expression correlated significantly with low-grade histological differentiation and with high MIB-1 index. Survival analyses were also performed to clarify which factors potentially affected the prognosis of lung adenocarcinoma patients. The low expression of β-catenin and the high MIB-1 index had a significantly unfavorable influence on the patients’ survival. Moreover, the immunohistochemical expression of β-catenin by cancer cells and MIB-1 index are considered useful prognostic factors for lung adenocarcinoma. [Copyright &y& Elsevier]

Purpose: To investigate the differences of pathological, radiological, and prognostic features between cellular schwannoma (CS) and non-cellular schwannoma (NCS).Methods: CT and MRI images of 24 patients with CSs and 30 patients with NCSs were reviewed retrospectively. Clinico-pathological characteristics of CSs and NCSs and tumor radiological features including location, shape, size, border, cystic-solid components, hemorrhage, calcification, bone remodeling, pattern of CT/MRI precontrast scan, degree of enhancement, target sign, and tumor vessels were recorded. Statistical analyses were performed with Chi square or Fisher's exact test, independent sample t test, and logistic regression analysis to compare the differences between CSs and NCSs.Results: Four CSs showed mitotic activity, which was not found in the NCS group (P = 0.034). The CS group showed higher MIB-1 index than that in the NCS group (P = 0.002). Two patients with CS presented with tumor recurrence. Compared to NCSs, CSs were often located in spinal area (P = 0.028) and irregular (P = 0.013) with larger size (P = 0.005). Target sign, a common finding in NCSs (7/22, 31.8 %), was not seen in CSs (P = 0.014). The tumor vessels were only seen in CS group (4/22, 18.2 %; P = 0.027). Regression analysis revealed that location (P = 0.048) and size (P = 0.012) were independent indicators in differentiating CSs from NCSs.Conclusions: CS is a rare subtype of schwannoma with some significant radiological features including a predilection for the spinal area, irregular shape, large tumor size, absent target sign, tumor vessels, and potential risk of recurrence. Location and size of the schwannomas were the most useful indicators in differentiating CSs from NCSs. [ABSTRACT FROM AUTHOR]

Aims Three gastrointestinal autonomic nerve tumours (GANT) were characterized by immunohistochemistry and flow cytometry. Two of the three cases occurred in the small intestine, while the third was found in the stomach. Besides the immunohistochemical and ultrastructural description, the aim of this study was to examine the relation between the known and accepted predictive factors (ploidy data, the S-phase fraction, the mitotic and MIB-1 index and the size of the tumour) and the survival of the patients. Methods and results The immune profile showed that 3/3 cases were vimentin and NSE, 2/3 were synap-tophysin and PGP 9.5 positive, while 1/3 also showed S100 positivity. Ultrastructurally, all the cases had dense core granules, one of them contained skenoid fibres. The flow cytometry revealed diploid DNA in all cases, however, significant differences could be seen in the proliferative activity of the individual neoplasms. Conclusions In spite of the published data of gastrointestinal stromal tumours (GIST) generally, neither the MIB-1 index and the ploidy data nor the size of the primary tumour helped to predict the clinical progression of the examined GANTs. However, the high proliferative activity (57 mitoses/10 HPF) and the elevated S-phase fraction (24%) was associated with advanced, metastatic and recurring disease in case 3. On the basis of these three cases, high mitotic activity is the most reliable factor in predicting aggressive clinical behaviour. [ABSTRACT FROM AUTHOR]

A case of multiple intracranial germ cell tumor in which a pineal tumor regressed spontaneously after resection of the cerebellar mass is reported. Immunohistochemical staining of the cerebellar mass showed that most of the infiltrating lymphocytes were positive for CD3 and CD8. The anti-Ki-67 monoclonal antibody MIB-1 staining of the resected tumor revealed a high MIB-1 positivity ratio (36.1%) among the large tumor cells, and TUNEL staining demonstrated that positivity in up to 6% of the tumor cells. Possible mechanisms responsible for this spontaneous regression including immunological responses and apoptosis induced by T lymphocytes are discussed. [ABSTRACT FROM AUTHOR]

Aims To evaluate the prognostic value of tumour proliferative activity, p53 accumulation and bcl-2 expression in a retrospective series of 216 patients with soft tissue sarcomas (STS). Methods and results The immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity was assessed by use of the monoclonal antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. The percentage of proliferating cells (the MIB-1 index) ranged between 1% and 85% (median 12%). A significant increase in mean MIB-1 index was seen with increasing histological malignancy grade. Variation in the incidence of p53 accumulation and bcl-2 positivity among different histological subtypes was observed. p53 accumulation was frequent in synovial sarcomas and leiomyo- and rhabdomyosarcomas, whereas bcl-2 preferentially was expressed in synovial sarcomas. Univariate analysis identified patient age, tumour size, histological grade of malignancy, MIB-1 index and p53 accumulation as significant prognostic parameters. Multivariate Cox analysis, including tests for interaction terms between histological subtypes and MIB-1 index, showed independent prognostic effect of MIB-1 index and tumour size in patients with high-grade tumours of other subtypes than malignant fibrous histiocytoma (MFH). Conclusions Histopathological malignancy grading is the most important single prognostic factor for overall survival in STS, but estimation of MIB-1 index is useful for identifying the least favourable subgroup of high grade STS of other subtypes than MFH, for whom adjuvant therapy may be indicated. [ABSTRACT FROM AUTHOR]

Abstract: The imaging findings of a solitary fibrous tumor of the prostate are presented. A 35-year-old male presented with urinary retention and was found on transrectal ultrasonography to have a hypoechoic tumor of the prostate, measuring 5.5 cm in size. Magnetic resonance imaging on, the tumor showed low signal intensity on T1-weighted images and heterogeneous mixed signal intensity on T2-weighted images. Gadolinium-enhanced dynamic study showed gradual enhancement from the periphery to the center, and the enhancement is sustained. On immunohistochemistry, the spindle cells of the tumor showed positive staining for CD34 and bcl-2. Although the tumor was labeled as a low-grade malignancy on account of a low mitotic index (MIB-1 index) of about 5%, the patient developed local recurrence of the tumor with bladder wall invasion 12 months later. [Copyright &y& Elsevier]

Objective: Clear cell meningioma (CCM) is a rare disease, and controversy about treatment and prognosis of CCMs still exists. We aimed to clarify the natural history, radiological features, histological characteristics, management and prognosis of intracranial CCMs., Patients and Methods: We performed a retrospective study of 24 patients with intracranial CCM who were treated at West China Hospital from January 2006 to January 2018. The clinical features, radiologic findings, diagnosis, treatment, and outcome of these patients were analyzed retrospectively. Additionally, a literature review of intracranial CCMs was performed., Results: Among 3554 surgeries for intracranial meningiomas, we identified 24 (0.7%) cases of CCMs. The most common localization was the frontal lobe (n = 9, 37.5%). The mean age at diagnosis of CCMs was significantly younger than that of total meningiomas patients (46.7 ± 15.8 versus 55.4 ± 14.8 years). They had a high rate (54.2%) of atypical radiological manifestations, such as cystic component, heterogeneous enhancement, and irregular shape. During the average follow-up of 61.1 months, four patients (19.0%) suffered from tumor recurrence. Kaplan-Meier analysis showed that patients with subtotal resection (STR) or a MIB-1 index ≥3% had significantly shorter progression-free survival (PFS) compared to gross total resection (GTR) and MIB-1 index <3%., Conclusions: CCMs are rare diseases which have a predilection to affect younger patients and a high rate of recurrence and metastasis. Surgery resection is the first treatment choice. For patients underwent STR or with MIB-1 index ≥3%, we hold further radiotherapy is necessary. Close follow-up of the brain and spine for years is crucial to monitor recurrence or metastasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Late malignant transformation of vestibular schwannoma (VS) following irradiation has previously been reported 29 times in the literature. Here, the authors report the first late malignant transformation of VS unrelated to neurofibromatosis or radiation exposure. After undergoing a near-total excision of a histologically benign VS, the patient developed malignant regrowth of the tumor remnant 42 months after the primary excision. This case challenges the dogmatic belief of absolute causality between radiation exposure and late malignant transformation of VS, and has important implications regarding future counseling and consent for the treatment of patients with VS.

Purpose: The aim of this study was to examine the clinical outcomes of treating atypical meningioma at the skull base region following surgical resection and adjuvant radiotherapy, and to analyze the association between clinical characteristics and progression free survival., Materials and Methods: Twenty-eight patients with skull base atypical meningiomas underwent microsurgical resection between June 2001 and November 2009. The clinical characteristics of the patients and meningiomas, the extent of surgical resection, and complications after treatment were retrospectively analyzed., Results: Thirteen patients (46.4%) had disease recurrence or progression during follow up time. The median time to disease progression was 64 months. The extent of the surgical resection significantly impacted prognosis. Gross total resection (GTR) of the tumor improved progression free survival (PFS) compared to subtotal resection (STR, p = 0.011). An older patient age at diagnosis also resulted in a worse outcome (p = 0.024). An MIB-1 index <8% also contributed to improved PFS (p = 0.031). None of the patients that underwent GTR and received adjuvant radiotherapy had tumors recur during follow up. STR with adjuvant radiotherapy tended to result in better local tumor control than STR alone (p = 0.074). Three of 28 patients (10.7%) developed complications after microsurgery. The GTR group had a higher rate of complications than those with STR. There were no late adverse effects after adjuvant radiotherapy during follow up., Conclusion: For patients with skull base atypical meningiomas, GTR is desirable for longer PFS, unless radical excision is expected to lead to severe complications. Adjuvant radiation therapy is advisable to reduce tumor recurrence regardless of the extent of surgical resection. Age of disease onset and the MIB-1 index of the tumor were both independent prognostic factors of clinical outcome., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Ependymomas are uncommon tumors that arise in the brain, spinal cord or cauda equina. Myxopapillary ependymomas is located exclusively in the conus medullaris or cauda equina, or film terminale region. In most myxopapillary ependymomas, the histological examination reveals low mitotic activity that is associated with a low MIB-1 labeling index (LI). The prognosis is generally favorable, when the appropriate treatment, including a total resection, is performed. The authors encountered a 39-year-old man with multifocal type of myxopapillary ependymomas compressing the cauda equina from the L2 to L3 level and L5-S1 level. A subtotal resection of the tumor was carried out. The histological examination revealed extremely high mitotic activity with a MIB-1 LI of 9.1%. Therefore, cranio-spinal radiation was added after surgery. The postoperative course was uneventful over the 3.5 year follow-up period.