Immunopathology of Tumefactive Demyelinating Lesions-From Idiopathic to Drug-Related Cases

Tumefactive demyelinating lesions (TDL) represent a diagnostic dilemma for clinicians, and in rare atypical cases a collaboration of a neuroradiologist, a neurologist, and a neuropathologist is warranted for accurate diagnosis. Recent advances in neuropathology have shown that TDL represent an umbrella under which many different diagnostic entities can be responsible. TDL can emerge not only as part of the spectrum of classic multiple sclerosis (MS) but also can represent an idiopathic monophasic disease, a relapsing disease with recurrent TDL, or could be part of the myelin oligodendrocyte glycoprotein (MOG)- and aquaporin-4 (AQP4)-associated disease. TDL can appear during the MS disease course, and increasingly cases arise showing an association with specific drug interventions. Although TDL share common features with classic MS lesions, they display some unique features, such as extensive and widespread demyelination, massive and intense parenchymal infiltration by macrophages along with lymphocytes (mainly T but also B cells), dystrophic changes in astrocytes, and the presence of Creutzfeldt cells. This article reviews the existent literature regarding the neuropathological findings of tumefactive demyelination in various disease processes to better facilitate the identification of disease signatures. Recent developments in immunopathology of central nervous system disease suggest that specific pathological immune features (type of demyelination, infiltrating cell type distribution, specific astrocyte pathology and complement deposition) can differentiate tumefactive lesions arising as part of MS, MOG-associated disease, and AQP4 antibody-positive neuromyelitis optica spectrum disorder. Lessons from immunopathology will help us not only stratify these lesions in disease entities but also to better organize treatment strategies. Improved advances in tissue biomarkers should pave the way for prompt and accurate diagnosis of TDL leading to better outcomes for patients. Copyright © 2022 Vakrakou, Brinia, Svolaki, Argyrakos, Stefanis and Kilidireas

Extranodal cytotoxic T-cell lymphoma in a patient with X-linked agammaglobulinaemia

This report documents the occurrence of an extranodal cytotoxic peripheral T-cell lymphoma (PTCL) in a patient with X-linked agammaglobulinaemia (XLA). The diagnosis was based on the immunohistochemical detection of T-cell antigens and of the cytotoxic proteins TIA1 and Granzyme B in the tumour cells. This report provides further evidence that cytotoxic lymphomas are part of the differential diagnosis of neoplasia in patients with immunodeficiencies

Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: Correlations with clinical outcome

Aims To study anaplastic lymphoma kinase (ALK) protein expression and possible underlying gene alterations in glioblastoma (GBM), correlating them with clinical outcome. Methods We studied ALK immunohistochemical expression and fluorescent in situ hybridisation (FISH)-detected ALK gene alterations in 51 GBMs (46 isocitrate dehydrogenase-1 (IDH1) R132H-negative and 5 IDH-mutant (IDH1 R132H-positive)). We compared two anti-ALK antibodies and immunohistochemical detection systems (5Î '4/Nichirei Biosciences, D5F3/Ventana). The results were correlated with tumour cell proliferation and clinical outcome. Results Intense granular cytoplasmic ALK immunostaining was observed in 10/51 (19.61%) GBM and correlated with high Ki67 proliferation index; only 1 in 10 ALK-positive cases displayed multiple alk gene signals by FISH. Moderate ALK immunostaining was observed in 21 (41.17%), weak immunostaining in 5 (9.80%) while 15 (29.42%) cases were negative. p53 was expressed in 26/51 GBM (50.9%) (10% cut-off). IDH1 R132H-negative GBM showed higher ALK expression compared with IDH-mutant GBM (65.2% vs 20%). ALK overexpression was more common in older patients but did not correlate with other clinicopathological variables or patient overall survival. Conclusions ALK overexpression can be identified in up to 70% of GBMs and does not correlate with underlying alk gene amplification. Despite being more common in rapidly growing, clinically aggressive GBM, ALK overexpression did not show correlation with prognosis in this study. © 2017 Published by the BMJ Publishing Group Limited

Malignancies of the anal canal

Background The carcinomas of the anal canal consist of truly rare clinical entities compared to the most common colorectal malignancies. Consequently, little have been reported on their natural history and course. Purpose The present study is aiming to describe the experience of our clinic with anal cancer and to clarify the incidence of the disease in the Hellenic population. Material and methods A 5-year retrospective study was conducted. We searched all cases of patients, diagnosed with anal carcinoma in our medical center. Medical records and histological examination results were all thoroughly registered and evaluated. Results On the whole, 60 patients were diagnosed with a malignant tumor of anal canal. Among them, 25 cases involved anal adenocarcinoma, 26 cases referred to a squamous cell carcinoma and in 5 cases, Bowen disease was identified. Two melanomas, one GIST stromal tumor and one case of Paget disease, were recognized as well. Conclusions It seems that in our center the frequency and prevalence of anal adenocarcinoma is increased compared to the results from international data. More studies involving larger series of patients are required in order to shed further light in the true incidence of anal cancer and it subtypes in Hellenic population

Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity

Background: Nonalcoholic steatohepatitis (NASH) is common in morbid obesity. Our goal was to evaluate the alterations in liver histology and biochemistry before and after weight loss in 51 morbidly obese patients following Mason's vertical banded gastroplasty. Methods: Two biopsies were performed (on entry and after an average of 18 months), while 16 of these subjects had a third biopsy 17 months after the second. Results: On entry, steatosis and steatohepatitis (mostly grade 3) were present in 98.0% and fibrosis (mostly stage 2) in 94.1% of the subjects. After an excess weight loss of 66%, steatosis and steatohepatitis improved significantly (P<0.001). Although a significant overall decrease in fibrosis occurred (P=0.002), 21 patients (41.1%) did not change and only 6 patients (11.7%) increased in fibrosis. None developed cirrhosis. The decrease in steatohepatitis was significantly correlated (P=0.011 ) with the reduction of BMI. Fasting serum glucose, lipids, lipoproteins, transaminases, gamma-glutamyl transpeptidase, alkaline phosphatase and fibrinogen were also significantly improved at the time of the second biopsy. The third biopsy performed in 16 of the subjects showed further significant improvement in liver histology. Conclusion: NASH improved significantly with massive weight loss in non-diabetic, non-alcoholic, morbidly obese subjects, while fibrosis improved in nearly half of the patients. © FD-Communications Inc

The Evangelismos hospital central nervous system tumor registry: Analysis of 1414 cases (1998-2009)

Background: The Evangelismos Hospital central nervous system (CNS) Tumor Registry represents the current effort of the Departments of Neurosurgery and Pathology to collect data for primary and metastatic CNS tumor patients. In the present study, 12-year hospital data (1998-2009) were reviewed and analyzed. Methods: Patients that underwent surgery for CNS tumors for the first time were identified. Histologically confirmed tumor rates by age and gender were compared. Time trends in annual rates for specific tumor types were investigated. In-hospital mortality rates and length of hospital stay were analyzed by age and gender and their putative variations across the study period investigated. Results: A total of 1414 patients (age 15-89 years) were identified. The most frequently encountered histologies were gliomas and meningiomas, accounting for, respectively, 32.8% and 29.1% of the total sample. A greater proportion of meningiomas was found in women; the proportion of glioblastomas and metastatic tumors, as well as of mixed gliomas, were greater in men. Increased rates of glioblastoma and meningioma with advancing age at diagnosis were also apparent. There were no significant variations in time trends for specific tumor types. In-hospital mortality was significantly higher for older patients (≥70 years). An increase in the length of hospital stay was apparent between the first and middle third of the study period. Conclusions: Analysis of tumor rates in relation to age at diagnosis and gender showed significant bias in accordance with salient literature. Available data indicated no significant variations in time trends for specific tumor types across the study period, while an adverse effect of advanced age on in-hospital mortality was shown. The present findings can guide the formulation of future treatment programs and preventive strategies and provide the basis for further intra-And/or interdepartmental research. Copyright © 2013 Stranjalis G