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.

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.

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.