Aggressive natural killer (NK)-cell leukaemia and extranodal NK/T-cell lymphoma are two distinct diseases that differ in their clinical presentation and cytogenetic findings.

AIMS: Aggressive natural killer (NK)-cell leukaemia (ANKCL) and extranodal NK/T-cell lymphoma (ENKTCL) with secondary bone marrow involvement are rare bone marrow NK/T-cell neoplasms and share similar features. This study aimed to distinguish these two entities. METHODS AND RESULTS: We studied bone marrow NK/T-cell neoplasms by classifying them into those with no extramedullary mass (group 1, eight cases) and those with extramedullary mass (group 2, 13 cases). The two groups showed similar clinical presentations and pathological features. Fever and cytopenia were the most common clinical presentations in both groups. The neoplastic cells varied from small and relatively monotonous cells to large pleomorphic cells. In six cases (two in group 1, and four in group 2), the neoplastic infiltrate was inconspicuous, consisting of ≤10% of marrow cells in the interstitium, which were hardly identified by haematoxylin and eosin staining alone. Nearly all patients rapidly died, regardless of the neoplastic infiltrate volume. All of the group 1 patients fulfilled the World Health Organisation 2017 diagnostic criteria of ANKCL, and their survival was significantly worse than that of the group 2 patients (P = 0.035). In addition, there was a significant association between being in group 1 and chromosome 7 abnormalities. Chromosome 6q deletion, which is commonly reported in ENKTCL, was seen in two of our group 2 patients, and was not observed in any of our group 1 patients. CONCLUSION: ANKCL with no extramedullary mass should be distinguished from ENKTCL with bone marrow involvement, as the former shows distinct outcomes and genetic features.

Cognitive and epilepsy outcomes after epilepsy surgery caused by focal cortical dysplasia in children: early intervention maybe better.

BACKGROUND: Focal cortical dysplasia (FCD) is a specific malformation of cortical development harboring intrinsic epileptogenicity, and most of the patients develop drug-resistant epilepsy in early childhood. The detrimental effects of early and frequent seizures on cognitive function in children are significant clinical issues. In this study, we evaluate the effects of early surgical intervention of FCD on epilepsy outcome and cognitive development. METHODS: From 2006 to 2013, 30 children younger than 18 years old underwent resective surgery for FCDs at Taipei Veterans General Hospital. The mean age at surgery was 10.0 years (range 1.7 to 17.6 years). There were 21 boys and 9 girls. In this retrospective clinical study, seizure outcome, cognitive function, and quality of life were evaluated. To evaluate the effects to outcomes on early interventions, the patients were categorized into four groups according to age of seizure onset, duration of seizure before surgery, and severity of cognitive deficits. RESULTS: Eleven of 22 (50 %) patients demonstrated developmental delay preoperatively. The Engel seizure outcome achievements were class I in 21 (70 %), class II in 2 (7 %), class III in 6 (20 %), and class IV in 1 (3 %) patients. The locations of FCDs resected were in the frontal lobe in 18 cases, temporal lobe in 7, parietal lobe in 2, and in bilobes including frontoparietal lobe in 2 and parieto-occipital lobes in 1. Eight cases that had FCDs involved in the rolandic cortex presented hemiparesis before surgical resection. Motor function in four of them improved after operation. The histopathological types of FCDs were type Ia in 1, type Ib in 7, type IIa in 7, type IIb in 12, and type III in 3 patients. FCDs were completely resected in 20 patients. Eighteen (90 %) of them were seizure free (p < 0.001) with three patients that received more than one surgery to accomplish complete resection. The patients who had early seizure onset, no significant cognitive function deficit, and early surgical intervention with complete resection in less than 2 years of seizure duration showed best outcomes on seizure control, cognitive function, and quality of life. CONCLUSION: Delay in cognitive development and poor quality of life is common in children treated for FCDs. Early surgical intervention and complete resection of the lesion help for a better seizure control, cognitive function development, and quality of life. FCDs involved eloquent cortex may not prohibit complete resection for better outcomes.

Frequent overexpression of HMGA2 in human atypical teratoid/rhabdoid tumor and its correlation with let-7a3/let-7b miRNA.

PURPOSE: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b microRNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT. EXPERIMENTAL DESIGN: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1(-/-)) were investigated by antisense inhibition and ectopic overexpression studies. RESULTS: The copy number of let-7a3/let-7b miRNA was substantially decreased in 4 of 11 AT/RT samples. A significantly inverse correlation between let-7a3/let-7b miRNA expression and HMGA2 mRNA expression was observed in AT/RT tissues (R = -0.34; P < 0.05). Immunohistochemistry analysis demonstrated that HMGA2 was highly overexpressed in 83.3% (15 of 18) of AT/RT tissues. Restoration of let-7 miRNA or knockdown of HMGA2 expression significantly suppressed proliferation and colony formation, and almost abolished the invasive potential of G401 cells. CONCLUSION: Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. HMGA2 oncoprotein plays critical roles in the pathogenesis of AT/RT development; and reconstitution of let-7 miRNA or knockdown of HMGA2 oncoprotein may provide a novel therapeutic strategy for the treatment of patients with AT/RT.

Clinical manifestation and neurosurgical intervention of encephalocraniocutaneous lipomatosis--a case report and review of the literature.

INTRODUCTION: Currently, there are only a few reported cases of symptomatic or asymptomatic subpial (intramedullary) spinal lipoma, and therefore no guidelines are available to indicate surgery. These lesions are infrequently associated with spina bifida. CASE REPORT: Herein, we provide our experience in the neurosurgical intervention of compressive myeloradiculopathy for encephalocraniocutaneous lipomatosis (ECCL). The patient initially presented with bilateral upper hand paralysis, then regained muscle power after surgery and during 1 year of follow-up. We discuss the neurosurgical indications and intervention, imaging studies, other associated symptoms, and the pathogenesis of ECCL in an infant.

Exclusion of histiocytes/endothelial cells and using endothelial cells as internal reference are crucial for interpretation of MGMT immunohistochemistry in glioblastoma.

We evaluated the predictive value of O6-methylguanine-DNA methyltransferase (MGMT) protein expression and MGMT promoter methylation status in glioblastomas (GBM) treated with temozolomide (TMZ) in a Taiwan medical center. Protein expression by immunohistochemical analysis (IHC) and MGMT promoter methylation detected by methylation-specific polymerase chain reaction (MSP) were performed in a series of 107 newly diagnosed GBMs. We used endothelial cells as an internal reference for IHC staining because the staining intensities of the MGMT-expressing cells in different specimens varied considerably; a positive result was defined as the staining intensity of the majority of tumor cells similar to that of the adjacent endothelial cells. Immunostainings for microglial/endothelial markers were included as part of the MGMT IHC evaluation, and in cases that were difficult to interpret, double-labeling helped to clarify the nature of reactive cells. The MGMT protein expression was reversely associated with MGMT promoter methylation status in 83.7% of cases (MSP/IHC and MSP/IHC; Pearson r=-0.644, P<0.001). Twenty-two of 24 (91.7%) IHC tumors did not respond to TMZ treatment. Combining MSP and IHC results, all the 15 MSP/IHC GBMs were TMZ resistant. The MGMT status detected by either IHC or MSP was significantly correlated with the TMZ treatment response (both P<0.001) and survival of GBM patients (both P<0.05).

Direct measurement of the signal intensity of diffusion-weighted magnetic resonance imaging for preoperative grading and treatment guidance for brain gliomas.

BACKGROUND: Magnetic resonance diffusion-weighted imaging (DWI) has been widely used clinically in imaging diagnosis of intracranial disorders. The purpose of current study was to present a quantitative method of direct measuring the DWI signal intensity of brain gliomas on the monitors of hospital picture archiving and communicating system (PACS) for grading gliomas. METHODS: This study recruited 135 patients with treatment-naïve brain gliomas. Direct measurement of the signal intensity of selected tumoral regions of interest (ROIs) by DWI on the monitors of the hospital PACS was performed for all patients. From the measurements, we obtained three values, defined as DWI(T) (tumor), DWI(N) (the homologous normal-appearing area of the tumor ROI in the contralateral hemisphere), and DWI(WM) (normal-appearing white matter) in the contralateral frontal lobe. Two ratios, DWI(T/WM) and DWI(T/N), were obtained for each tumoral ROI. The same method was used for apparent diffusion coefficient (ADC) ratios of the tumoral ROI. Fractional polynomial regression and the Mann-Whitney U test were applied to determine the correlation between tumor grading, MIB-1 labeling index, and DWI and ADC ratios. Logistic regression models and receiver operating characteristic curve analysis were used to establish diagnostic models. Measurements of intraobserver and interobserver agreement were also made at 1-month interval. RESULTS: The DWI ratios correlated positively with tumor grade and MIB-1 value (p < 0.01). Cut-off ratios of 1.62 for DWI(T/WM) and 1.47 for DWI(T/N) generated the optimal combination of sensitivity (0.82, 0.80), specificity (0.79, 0.86), and sound discriminating power, with an area under the curve of 0.87 and 0.84, respectively, to differentiate low-grade from high-grade gliomas. ADC ratios showed relatively worse sensitivity, specificity, and discriminating power than DWI ratios. Almost all intraobserver and interobserver measurements were within 95% agreement. CONCLUSION: The proposed method - direct measuring of tumor signal intensity of DWI on PACS monitors - is feasible for grading gliomas in clinical neuro-oncology imaging services and has a high level of reliability and reproducibility.

Constructing prognostic model incorporating the 2004 WHO/ISUP classification for patients with non-muscle-invasive urothelial tumours of the urinary bladder.

AIM: To construct a prognostic model for recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) for patients who have undergone transurethral resection of non-muscle-invasive (pTa/pT1) urinary bladder urothelial tumours. METHODS: 1366 patients who had undergone transurethral resection of primary non-muscle-invasive urothelial tumours (pTa, 891 patients; pT1, 475 patients) confined to the bladder were retrospectively studied. Tumours were classified according to the 2004 WHO/International Society of Urologic Pathology grading system. Kaplan-Meier and stepwise Cox regression models were applied, and 200 bootstrap resamples were used to generate survival estimates and 95% CIs. A nomogram was developed that incorporated significant variables predicting survival. RESULTS: RFS, PFS and CSS probabilities for non-muscle-invasive bladder urothelial tumours were calculated. Incorporating salient prognostic factors (tumour grade, pT stage, patient age, status of intravesical instillation), the model satisfactorily predicted PFS (concordance index=0.79) and CSS (concordance index=0.87). CONCLUSIONS: Robust nomograms were created to predict PFS and CSS. These data provide an overall perspective of disease outcomes which may aid in developing individualised follow-up programmes.

Prognostic significance of the 2004 WHO/ISUP classification for prediction of recurrence, progression, and cancer-specific mortality of non-muscle-invasive urothelial tumors of the urinary bladder: a clinicopathologic study of 1,515 cases.

To verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non-muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non-muscle-invasive bladder urothelial tumors.

Immunohistochemical and molecular genetic profiling of acquired cystic disease-associated renal cell carcinoma.

AIMS: Acquired cystic disease-associated renal cell carcinoma (ACD-associated RCC) is a unique neoplasm that specifically develops in the background of acquired cystic disease of the kidney. The aim was to analyse nine ACD-associated RCCs from three patients to determine their immunohistochemical and molecular characteristics using immunohistochemistry, comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). METHODS AND RESULTS: ACD-associated RCC preferentially expressed proximal nephron phenotype (CD10+ /RCC marker+/alpha-methylacyl-CoA racemase+ /glutathione S-transferase-alpha+ /BerEP4+ /cytokeratin 7- /E-cadherin- /high-molecular-weight cytokeratin- /MOC31-). CGH combined with FISH demonstrated non-random chromosomal gains clustering on chromosomes 3 (8/9), 7 (6/9), 16 (7/9), 17 (4/9) and Y (5/9). Chromosomal losses were uncommon. The chromosomal aberrations in all multifocal tumours were not identical for the same kidney or for the same patient, indicating a 'field effect' that induces multiple independent clones. CONCLUSIONS: Although the genetic profiles of ACD-associated RCC showed some similarity to those of papillary RCC, ACD-associated RCC distinctly revealed frequent gains on chromosomes 3 and Y. ACD-associated RCC is characterized not only by its particular clinical setting and histology, but also by its unique immunohistochemical and molecular genetic profiles.

Responsiveness of progressive optic pathway tumors to cisplatin-based chemotherapy in children.

BACKGROUND: Though the pathology of optic pathway tumor is mostly pilocytic astrocytoma, the benign tumor behaves like malignant tumor because total resection is not feasible. Adjuvant chemotherapy might be a reasonable strategy for management of these low grade tumors which keep growing. We evaluate the responsiveness of optic pathway tumor to cisplatin-based chemotherapy. METHODS: Patients with unresectable and progressive optic pathway tumors received conventional chemotherapy including cisplatin, etoposide, and vinblastine were enrolled in this study from 1992 to 2007. Patients treated with radiotherapy previously were excluded. Brain MRI was performed every 3 months to evaluate the objective response to chemotherapy. RESULTS: There are seven girls and nine boys enrolled in this study. The median age at diagnosis was 30 months old (range from 3 months to 11 years old). The median follow-up duration was 81.5 months (range from 24 months to 14.5 years). The pathology showed pilocytic astrocytomas in 11 patients, astrocytoma in one patient, and anaplastic astrocytomas in two patients. The 6-month progression-free survival (PFS) is 100%, 12-month PFS is 81.3%, 3-year PFS is 71.4% and 5-year PFS is 55.5% respectively. The toxicity of the cisplatin-based chemotherapy showed mild bone marrow suppression in 13 patients (81.3%), infection in nine patients (56.3%), gastrointestinal discomfort in seven patients (43.8%), renal insufficiency in two patient (12.5%), cerebral salt wasting syndrome with hyponatremia in one patient (6.25%) and high pitch hearing loss in two patients (12.5%). CONCLUSION: Cisplatin-based chemotherapy is an effective regimen for control of progressive optic pathway tumors.

Germinoma involving the basal ganglia in children.

BACKGROUND: Germinoma originating in the basal ganglia is rare, and the majority of reported papers have been from Japan. In a collection of the first 500 cases of primary brain tumors in children in Taipei Veterans General Hospital, six pure germinomas with tissue diagnosis situated in this location. MATERIALS AND METHODS: We reviewed the clinical features, neuroimaging studies, tumor markers, management, and outcome of these six patients. RESULTS: All of them were boys. The median age of onset of symptoms was 9.7 years. They uniformly presented with hemiparesis. The average duration of symptoms before surgical management was 1 year. One patient had bilateral basal ganglia tumors. Serum beta-human chorionic gonadotropin levels was elevated (128 mIU/ml) in one patient. Longitudinal neuroimaging studies in four patients clearly showed that the tumor arose as a tiny lesion at the lenticular nucleus. Five patients had cysts within tumors. Five patients received partial, subtotal, to total resection. One patient had stereotactic biopsy of the tumors. Postoperative primary adjuvant therapies included radiotherapy, chemotherapy alone, and combined chemotherapy and radiotherapy. Five patients survived, and one patient died of radiation-induced sarcoma with median follow-up period of 13.7 years. Local recurrence was observed in all of three patients after solitary postoperative chemotherapy. CONCLUSIONS: The lenticular nucleus is a significant locus for germinomas and can be bilateral. Although rarely reported in Western countries, it does exist in Taiwan as well. Treatment of germinomas in this specific location is similar to germinoma in other intracranial locations.

Malignant ganglioneuroma arising from mediastinal mixed germ cell tumor.

Mixed germ cell tumors with non-germ cell malignant components rarely occur in the anterior mediastinum. We report a case of a 34-year-old man who presented with an anterior mediastinum mass. Mixed germ cell tumor was initially diagnosed based on the pathologic findings of germinoma on thoracoscopic biopsy and clinical findings of elevated serum alpha-fetoprotein and beta-human chorionic gonadotropin. The patient received preoperative chemotherapy and subsequent complete resection of the residual tumor. Pathologic examination of the excised specimen showed predominantly malignant ganglioneuroma and small residual foci of teratoma. To our knowledge, this is the first reported case of a malignant ganglioneuroma arising from mediastinal mixed germ cell tumor.

Conjunctival biopsy in sarcoidosis.

BACKGROUND: Conjunctival biopsy is considered to be a simple, safe and specific diagnostic procedure for sarcoidosis. This study was designed to determine the value of this procedure in Taiwan. METHODS: This study was conducted from December 2003 to April 2005 at the uveitis clinic of Taipei Veterans General Hospital. Blind sampling was conducted, obtaining a biopsy sample measuring 1 cm long by 3 mm wide from both lower fornices. A positive result was defined as the presence of non-caseating granuloma when other granuloma-forming processes had been excluded. RESULTS: Twenty-nine patients (7 men, 22 women) were enrolled. Mean age at diagnosis was 47.8 +/- 12.4 years. The most common initial symptom was eye-related problems in 19 (65.5%) patients. Of 58 biopsies, 15 (25.9%) specimens in 11 (37.9%) patients proved to be positive. Four patients experienced bilateral involvement; 7 patients had unilateral involvement. No prominent conjunctival nodules or follicles were noted. Gender, age, presence of uveitis, initial symptoms, and chest condition comparisons revealed no association between positive and negative conjunctival biopsies. CONCLUSION: Blind and bilateral conjunctival biopsy, due to its ease, safety and specificity, could be the first biopsy inpatients with clinical or chest X-ray abnormalities suggesting sarcoidosis. None of our patients with positive biopsy had nodular lesions.

Primary neurocytoma in the spinal cord. A case report.

Central neurocytoma is defined as an intraventricular benign brain tumor. Extraventricular location of central neurocytoma is rare: only nine cases of spinal neurocytoma had been reported in the English literature. We hereby present a case of atypical neurocytoma involving unusual long segments (8-segment) of cervico-thoracic spinal cord in a 29-year-old woman with emphasis on pre- and post-surgical neuroimaging, pathological correlation, and review the pertinent literature.

Primary pediatric brain tumors: statistics of Taipei VGH, Taiwan (1975-2004).

BACKGROUND: The purpose of the current study was to investigate a hospital series of 986 cases of primary pediatric brain tumors in Taiwan. METHODS: The authors reviewed the database of primary pediatric brain tumors in patients < 18 years of age collected in Taipei Veterans General Hospital (Taipei VGH) from 1975 to May 2004. Age and gender distribution, location, and classification of brain tumors were analyzed. Intracranial tumors with diagnostic imaging were included. Nontumoral lesions, cysts, and vascular malformations were excluded. RESULTS: The mean age of these 986 patients was 7.8 years, and the male to female ratio was 1.4:1. Supratentorial (including pineal-quadrigeminal) located tumors (58.3%) was predominant to infratentorial tumors (41.1%). In these series, 886 patients had either histologic diagnosis (842 patients) or clinical diagnosis (44 patients). The most common 5 categories of tumors were astrocytic tumors (31.1%), germ cell tumors (14.0%), medulloblastomas (13.3%), craniopharyngiomas (8.3%), and ependymal tumors (5.8%). Atypical teratoid/rhabdoid tumors (AT/RTs), a rare but highly malignant tumor, were 2.1%. The high incidence of primary intracranial germ cell tumors correlated with reported series from Japan and Korea. For the remaining 100 patients without diagnostic classifications, the majority were most likely astrocytic tumors in brain stem. CONCLUSIONS: The authors analyzed a large hospital series of primary brain tumors in children. Both histologically verified and unverified tumors were recruited to avoid selective bias. Although it was not a study of a population-based brain tumor registry, it could still be representative of primary pediatric brain tumors in Taiwan.

Pineal germinoma with intratumoral hemorrhage after neuroendoscopic tumor biopsy.

CASE REPORT: We report an intratumoral hemorrhage immediately after a ventricular endoscopic procedure in an 18-year-old man who had a pineal germinoma with symptomatic hydrocephalus. The patient was successfully treated using long tract external ventricular drainage and urgent radiation therapy. DISCUSSION: The contributing factors for the acute reduction of intracranial pressure to zero during the endoscopic procedure are discussed.

Surgery of intractable temporal lobe epilepsy presented with structural lesions.

BACKGROUND: Structural lesions are found in about 30% of surgical specimens resected for intractable temporal lobe epilepsy (TLE). Detailed presurgical evaluations can identify the epileptogenic foci, the structural lesions and their correlation. Different surgical approaches have variable seizure control outcomes. METHODS: The preoperative investigations for the intractable TLE consisted of serial electroencephalogram (EEG) recordings, long-term EEG/video monitoring with sphenoidal electrodes, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), positron emission tomography with fluorodeoxyglucose (FDG-PET) and neuropsychological assessment. Among the 217 patients who underwent anterior temporal lobectomy (ATL) for TLE at Taipei Veterans General Hospital between 1987 and 1998, 47 (21.7%) had structural lesions in the resected specimen. The patients were divided into neoplastic (n = 35) and vascular (n = 12) groups, based on the pathological findings. RESULTS: In the neoplastic group, the interictal scalp-sphenoidal EEG recordings were abnormal in all 35 cases and lateralizing in 30 (85.7%). MRI revealed tumor growth within the temporal lobe in 26 patients (74.3%). FDG-PET was performed on 17 patients. Fifteen (88.2%) of them revealed unilateral mesial temporal lobe hypometabolism. In the vascular group, the interictal EEG tracings revealed unilateral mesial temporal lobe spikes in 11 patients (91.6%). MRI revealed abnormal enhanced lesions within the temporal lobes in all 12 patients. FDG-PET was available for 7 patients, 6 (86%) of whom had unilateral mesial temporal lobe hypometabolism. At the last follow-up (range 2-10 years, with a mean period of 4.2 years), 25 patients (73%) in the neoplastic group became and remained seizure-free postoperatively, 3 (9%) had fewer than 3 attacks per year. Among the vascular group, all 12 patients became and remained seizure-free after surgery. CONCLUSIONS: For intractable TLE with structural lesions, detailed presurgical evaluations are mandatory to identify the concordance of the lesions and the epileptogenic foci. Standard ATL with removal of the lesion may offer good seizure control postoperatively.