Primitive Neuroectodermal Tumor in a Child with Human Immunodeficiency Virus Infection: A Rare Association.

Children with human immunodeficiency virus (HIV) infection are reported to have various malignancies, most common being Non-Hodgkin lymphoma. Despite higher risk of malignancies, brain tumors are infrequently described in these children. We report Primitive Neuroectodermal tumor (PNET) in a young boy with HIV infection. PNET has never been described in association with HIV infection. Though a causative association cannot be established, it does emphasize that with longer survivals on effective antiretroviral therapy, we may see a wide range of malignancies more frequently.

In vitro study of iron deposition in normal human brains: An Indian Scenario.

An increase in brain iron is a normal physiological process during brain development but excess accumulation is a risk factor for various neurodegenerative diseases. Thus, knowledge of the normal range of brain iron content is mandatory. The present study was planned to collect normative data on iron deposition in human brains by in vitro analysis. Iron deposition in basal ganglia was determined by Perl's staining in 31 (18 males, 13 females) nonpathological postmortem brains aged from 18 to 80 years and by inductively coupled plasma mass spectrometry (ICP-MS) in 13 of them (seven males, six females). After conventional paraffin embedding, 5 µm thick sections were prepared, fixed and stained with freshly prepared Perl's stain along with a control section. For ICP-MS analysis, approximately 12-13 mg samples of tissue from each region of interest were dried, weighed, and digested with 2 mL of concentrated nitric acid. After digestion, the samples were dissolved in ICP grade water for trace analysis and the iron concentration was determined against standards using an ICP-MS analyzer and recorded in parts per billion (ppb). Nonheme iron deposits were observed in the globus pallidus in 16.13% of cases with no significant sex difference. Iron was deposited in the perivascular area, predominantly in the tunica media and tunica adventitia. ICP-MS analysis revealed the highest iron concentration of 595 ppb (0.595 µg/g tissue) in the globus pallidus with no significant gender or age related differences. In conclusion, the present study revealed a low (16%) incidence of brain iron deposition in normal adult postmortem brains. Clin. Anat. 31:275-281, 2018. © 2017 Wiley Periodicals, Inc.

Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure.

In vitro and in vivo studies have suggested that reduced astrocytic uptake of neuronally released glutamate, alterations in expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP-4) contribute to brain edema in acute liver failure (ALF). However, there is no evidence to date to suggest that these alterations occur in patients with ALF. We analyzed the mRNA expression of excitatory amino acid transporters (EAAT-1, EAAT-2), GFAP, and AQP-4 in the cerebral cortex obtained at autopsy from eight patients with ALF and from seven patients with no evidence of hepatic or neurological disorders by real-time PCR, and protein expression was assessed using immunoblotting and immunohistochemistry. We demonstrated a significant decrease in GFAP mRNA and protein levels in ALF patients compared to controls. While the loss of EAAT-2 protein in ALF samples was post-translational in nature, EAAT-1 protein remained within normal limits. Immunohistochemistry confirmed that, in all cases, the losses of EAAT-2 and GFAP were uniquely astrocytic in their localization. AQP-4 mRNA expression was significantly increased and its immunohistochemistry demonstrated increased AQP-4 immunoreactivity in the glial end-feet process surrounding the microvessels. These findings provide evidence of selective alterations in the expression of genes coding for key astrocytic proteins implicated in central nervous system (CNS) excitability and brain edema in human ALF. We investigated the gene expression of astrocytic proteins involved in astrocyte swelling causing brain edema in autopsied brain tissues of patients with acute liver failure. This study demonstrated loss of GFAP expression and up-regulation of AQP-4 protein expression leading to cerebral edema, and loss of EAAT-2 expression implicated in excitatory neurotransmission. These findings may provide new drug targets against CNS complications of acute liver failure.

Nuclear expression of ß-catenin and stem cell markers as potential prognostic indicators in medulloblastoma.

AIMS: To study the prognostic role of ß-catenin and stem cell markers in medulloblastoma (MB). MATERIALS AND METHODS: Sixty cases of MB were retrospectively analyzed to study the expression of ß-catenin, CD15, and CD133 by immunohistochemistry. Their expression was correlated with histological subtypes and event-free survival (EFS). Patients were divided into Group 1 and 2 based on non-occurrence and occurrence of events during the follow-up period. RESULTS: Fifty of the 60 cases were of classic type of MB while nine were of desmoplastic subtype and one case showed chondroid and rhabdomyoblastic differentiation. Immunoreactivity for ß-catenin was observed as nuclear and/or cytoplasmic positivity within the tumor cells. Forty-one (68.3%) cases showed cytoplasmic positivity, while nuclear positivity was seen in 21 (35%) cases. There was a significant correlation between nuclear expression of ß-catenin and different histological subtypes by Chi-square test (P value<0.05). A statistically significant positive correlation of ß-catenin nuclear positivity with EFS was observed. Among 60 cases, 37 cases (67.3%) showed presence of CD15+ tumor cells with percentage of positivity varying between 0.1 to 17.1%. Overall, 42 of 60 (70%) cases showed presence of CD133+ cells. The percentage of positivity varied between 0.1 to 16.5%. A statistically significant negative correlation of CD15 and CD133 positivity with EFS was observed. CONCLUSIONS: Nucleopositive ß-catenin cases were associated with a favorable outcome on univariate analysis. Both CD15 and CD133 positivity were associated with a worse outcome on univariate analysis.

Efficacy of Leishmania donovani ribosomal P1 gene as DNA vaccine in experimental visceral leishmaniasis.

The acidic ribosomal proteins of the protozoan parasites have been described as prominent antigens during human disease. We present here data showing the molecular cloning and protective efficacy of P1 gene of Leishmania donovani as DNA vaccine. The PCR amplified complete ORF cloned in either pQE or pVAX vector was used either as peptide or DNA vaccine against experimentally induced visceral leishmaniasis in hamsters. The recombinant protein rLdP1 was given along with Freund's adjuvant and the plasmid DNA vaccine, pVAX-P1 was used alone either as single dose or double dose (prime and boost) in different groups of hamsters which were subsequently challenged with a virulent dose of 1×10(7) L. donovani (MHOM/IN/DD8/1968 strain) promastigotes by intra-cardiac route. While the recombinant protein rLdP1 or DNA vaccine pVAX-P1 in single dose format were not found to be protective, DNA vaccine in a prime-boost mode was able to induce protection with reduced mortality, a significant (75.68%) decrease in splenic parasite burden and increased expression of Th1 type cytokines in immunized hamsters. Histopathology of livers and spleens from these animals showed formation of mature granulomas with compact arrangement of lymphocytes and histiocytes, indicating its protective potential as vaccine candidate.

Lipidized glioblastoma: a rare differentiation pattern.

We report a rare case of lipidized glioblastoma arising in the tempo-parietal lobe of a 65 year-old woman. The tumor was composed of diffuse sheets of lipidized cells with abundant xanthomatous cytoplasm comprising 60% of the tumor mass. These cells revealed immunopositivity with glial fibrillary acidic protein (GFAP) and the accumulation of lipid was confirmed ultrastructurally. This report highlights the extremely rare lipidized differentiation pattern occurring in glioblastoma and adds observational data to the existing literature on lipid accumulation occurring in glioblastomas.

Congenital immature teratoma mimicking Cushing's disease.

Cushing's disease in a neonate is rare and has been reported secondary to pituitary macroadenoma. A case of Cushing's syndrome due to congenital immature teratoma in the region of the pituitary has never been reported. We discuss a case of a neonate who presented with Cushing's syndrome secondary to a congenital immature teratoma in sellar, suprasellar and parasellar regions with ectopic ACTH secretion, thereby mimicking Cushing's disease. The management issues and prognosis of congenital teratomas and neonatal Cushing's syndrome have been discussed. We describe the first case of intracranial ectopic ACTH secreting teratoma in a young infant. The prognosis is usually bad unless total excision is achieved. In the preoperative period and in case of subtotal excision, chemotherapy to take care of hypercortisolemia may be given.

Prolactin-adjusted ACTH Ratio in Predicting Lateralization of ACTH Source During Simultaneous Bilateral Inferior Petrosal Sinus Sampling in Patients with Cushing's Disease.

INTRODUCTION: Prolactin-adjusted adrenocorticotropic hormone (ACTH) ratio is used to improve the diagnostic accuracy of bilateral inferior petrosal sinus sampling (BIPSS) for lateralization of pituitary adenoma. OBJECTIVE: To study the use of prolactin for successful catheterization during BIPSS, the role of prolactin-normalized ACTH ratio for confirmation of Cushing's disease (CD) and prolactin-adjusted ACTH ratio in predicting the lateralization. PATIENTS AND METHODS: BIPSS was done in patients with CD; prolactin-adjusted ACTH ratio was compared with intersinus ACTH ratio, magnetic resonance imaging, and intraoperative findings for localization of pituitary adenoma. Histopathology was taken as "gold standard" for the diagnosis of CD. RESULTS: Eight patients underwent BIPSS. All the patients underwent transsphenoidal surgery. All these patients had proper venous sampling during BIPSS as determined by inferior petrosal sinus (IPS):Peripheral prolactin ratio of ≥1.8. Prolactin-normalized ACTH ratio of ≥1.3 was achieved in all the eight patients, which was consistent with the diagnosis of CD. Concordance of intersinus ACTH ratio ≥1.4 with the intraoperative findings was found in five of eight (62.5%) patients depicting correct lateralization. Concordance of prolactin-adjusted ACTH ratio with intraoperative findings was found in four of eight (50%) patients. Seven of eight patients had concordance of intersinus ACTH ratio with prolactin-adjusted ACTH ratio. CONCLUSION: Prolactin is a useful marker for successful catheterization, confirming the diagnosis of CD during BIPSS, and prolactin-adjusted ACTH ratio does not add to the accuracy of lateralization of pituitary adenoma compared with intersinus ACTH ratio.

Refolding of HLA-B27 heavy chains in the absence of beta2m yields stable high molecular weight (HMW) protein forms displaying native-like as well as non-native-like conformational features: implications for autoimmune disease.

Refolding of the heavy chain of the Class I HLA molecule, HLA-B27, in the absence of beta(2)m, yields soluble high molecular weight (HMW) oligomers reminiscent of the oligomeric forms of beta(2)m-free heavy chains (FHCs) of class I HLA antigens observed on cell surfaces. Here we examine the structural characteristics of HMW B27 in respect of features potentially relevant to autoimmunity, such as: (a) retention of native-like structure, since this could facilitate non-canonical interactions with T-cell receptors even in the absence of bound beta(2)m and peptide, or (b) presence of non-native structure, since this could yield novel (non-self) antigenic conformational epitopes that could elicit immune attack. We report that HMW B27 is characterized by high secondary structural content, structural stability, stability to proteolysis by trypsin, and structural features that are both partly native-like, and partly non-native-like, as assessed through the binding of conformationally-distinguishing and cross-reacting scFv antibodies specifically selected against HMW B27. We also present cell ELISA data with conformation-specific scFv antibodies that distinguish between lymphocytes from individuals who are healthy and B27 positive, and those who are B27 positive but suffering from ankylosing spondylitis.

Pulmonary embolism in medical patients: an autopsy-based study.

Pulmonary embolism, though treatable, is a devastating disease and an important cause of morbidity and mortality among hospitalized patients. In all, 1000 autopsies were reviewed in adult medical patients. The overall incidence of pulmonary embolism in adult medical autopsies was 15.9% (159/1000). The incidence of pulmonary embolism contributing significantly to the death of the patients (groups 1 and 2) is 126/1000 (12.6%). Thus, pulmonary embolism very significantly contributed to death in 126/159 (79.24%) of group 1 and 2 patients. Pulmonary embolism affected a younger population as 79.87% of the overall patients, 66.67% of the fatal cases (group 1) and 73% of combined group 1 and 2 cases were below the age of 50 years. Sepsis was the primary diagnosis in 32% of total and in 42% of fatal cases. Hence, pulmonary embolism is considered as an important cause of death in patients admitted to the medical wards. It affects a younger population in India and needs to be tackled appropriately.

Diaphyseal sclerotic osteosarcoma presenting as a pathological fracture.

A diaphyseal, intramedullary, highly sclerotic lesion presenting as a pathological fracture, without a periosteal reaction or an appreciable soft tissue component on radiographs was investigated. A discrepancy between the MRI and histopathological findings led to marginal excision of the lesion only to reveal later that it was a sclerotic variety of osteosarcoma. Such a presentation has not been reported in literature as per our knowledge. We forfeited the opportunity of limb salvage by doing initial marginal excision and fixation. In such circumstances, a representative biopsy is critical and repeat biopsy is warranted before going for definitive management.

Blocking osteopontin-fibronectin interactions reduce extracellular fibronectin deployment and arthritic immunopathology.

Elevated levels of a thrombin-cleaved fragment of osteopontin (OPNT) are seen in synovial fluid (SF) and tissues of rheumatoid arthritis (RA) patients. OPNT binds to integrins on cell surfaces, inducing adhesion, migration and survival of inflammatory cells in the synovial joints, where OPNT binds to fibronectin to link fibroblast-like synoviocytes (FLS) with B cells, stimulating the latter to produce inflammatory cytokines. Our aim was to block OPNT-fibronectin interactions and examine whether this reduces inflammation. A human antibody (phage displayed) library was used to select scFv antibodies cognate to OPNT, and a particular scFv antibody (scFv 31) was evaluated. Adhesion, migration and fibronectin polymerization of FLS cells derived from RA patients were monitored, in cultures incorporating scFv 31. Also, scFv 31 was used in mice with CAIA (collagen antibody-induced arthritis), subjected to clinical and histological assessment, analysis of fibronectin and cartilage damage and induction of pro-inflammatory cytokines. The scFv antibody, scFv 31, appeared to cause significantly reduced migration of synovial fibroblasts, altered cell morphology, changes in actin stress fiber arrangement, and marked reduction in fibronectin. In CAIA mice, scFv 31 appeared to prevent arthritic changes through inhibition of synovial hypertrophy and loss of articular cartilage, decrease in fibronectin polymerization and expression of pro-inflammatory cytokines implicated in arthritis. Osteopontin-fibronectin interaction(s) appear to play a role in the expression of key inflammatory molecules by B cells infiltrating the synovial joint. The scFv antibody, scFv 31, provides a potential therapeutic lead for inhibition of some processes implicated in rheumatoid arthritis.

Amelioration of collagen antibody induced arthritis in mice by an antibody directed against the fibronectin type III repeats of tenascin-C: Targeting fibronectin type III repeats of tenascin-C in rheumatoid arthritis.

Tenascin-C (TN-C) levels are elevated in the synovial tissue and fluid, as well as cartilage of rheumatoid arthritis (RA) patients. In addition, the presence of TN-C fragments has also been documented in arthritic cartilage. We have previously shown that a single chain variable fragment antibody (TN64), directed against the fibronectin type III repeats 1-5 (TNfnIII 1-5) of TN-C, effectively inhibits fibrotic pathology. Given that fibrosis results from chronic inflammation, and the fact that increased levels of TN-C in the synovial fluid of patients with RA contributes to synovial inflammation and joint destruction, we aimed to investigate the role of TNfnIII 1-5 region of TN-C in RA pathogenesis. Using either the wild type or variants of the two integrin-binding motifs (RGD and AEIDGIEL) present within the TNfnIII 1-5 polypeptide, we demonstrate that the adhesion and migration of synovial fibroblasts is RGD-dependent. The antibody TN64 is effective in inhibiting migration of cells in response to TnfnIII 1-5, and prevents fibroblast-mediated destruction of cartilage. The TN64 antibody was further tested in collagen antibody induced arthritic (CAIA) mice. Our data shows the efficacy of TN64 in preventing induction of arthritis, with significant downregulation of RA-associated cytokines. This suggests that components of the extracellular matrix such as the TNfnIII 1-5 region of TN-C could be exploited to develop therapies to suppress inflammation seen in RA. The TN64 antibody is one such promising candidate in the development of novel treatments for RA.

Disseminated metastasis following periampullary cancer resection masquerading as uveitis.

The Uveitis Masquerade Syndromes (UMS) are a group of ocular diseases that mimic intraocular inflammation, but are in fact neoplastic in nature. We report a patient with disseminated malignancy who presented with uveitis 5 years after an apparently successful resection of periampullary adenocarcinoma. The Masquerade Syndrome was detected by cytological examination of the vitreous.

Dural metastasis masquerading as an en plaque meningioma.

Metastatic adenocarcinoma mimicking meningioma is rare; and any metastatic lesion masquerading as an en plaque meningioma is extremely rare. We report the case of a 50-year-old female, who presented with headache and left hemiparesis for 1 month and on imaging showed a dural-based enhancing mass along the right hemisphere. The patient was operated with a working diagnosis of en plaque meningioma. Histopathology revealed metastatic adenocarcinoma. This report highlights an unusual radiological presentation of a metastatic lesion as dural based en plaque variety. Metastasis should be borne in mind for any en plaque lesion with rapid clinical progression.

Optic nerve glioma: A great mimicker.

BACKGROUND: Arachnoid proliferation, although rare, is known to occur in association with optic gliomas. However, chondroid and chordoid metaplasia has not been reported previously. CASE DESCRIPTION: A 27-year-old male presented with progressive, painless loss of vision in right eye, associated with vomiting and headache for one and a half months. Computed tomography (CT) scan revealed a contrast enhancing mass arising from planum sphenoidale. Perioperative findings showed the tumor adherent to the right optic nerve and attached to basal dura and falx. A clinical impression of an intradural, optic nerve sheath meningioma was made. Histopathological examination revealed a glial tumor with adjacent areas displaying marked fibroblastic and arachnoid cell proliferation with chondroid as well as chordoid differentiation along with myxoid change and dense collagenisation. Reticulin stain, immunochemistry with glial fibrillary acid protein (GFAP), epithelial membrane antigen (EMA), and S-100 helped to arrive at the final diagnosis of optic glioma displaying exuberant arachnoid proliferation with cartilaginous metaplasia. CONCLUSION: We report a case of optic nerve glioma displaying extensive arachnoid proliferation, chordoid, and cartilaginous metaplasia, which mimicked chondrosarcoma or chordoid meningioma, posing a diagnostic dilemma. A clinical feedback, simple reticulin stain, and GFAP staining is of immense value in such cases to arrive at the correct diagnosis.

Neuropathology of acute liver failure.

Cerebral edema has been identified in all forms of liver disease and is closely related to the development of hepatic encephalopathy. Cerebral edema is most readily recognized in acute liver failure (ALF), while the main cause of death in patients with ALF is multi-organ failure; brain herniation as a result of intracranial hypertension does remain a major cause of mortality. The mechanisms responsible for cerebral edema in ALF suggest both cytotoxic and vasogenic injury. This article reviews the gross and ultrastructural changes associated with cerebral edema in ALF. The primary cause of cerebral edema is associated with astrocyte swelling, mainly perivascular edema and ammonia still remains the primary neurotoxin involved in its pathogenesis. The astrocytic changes were confined to the gray matter. The other organelles involved in the pathogenesis of ALF include mitochondria, basement membrane, pericytes, microglial cells, blood-brain barrier (BBB) etc. Discrete neuronal changes have recently been reported. Recent studies in animal and humans have demonstrated the microglial changes which have the potential to cause neuronal dysfunction in ALF. The alterations in BBB still remain unclear though few studies have showed disruption of tight junction proteins indicating the involvement of BBB in cellular swelling.

Noncirrhotic portal hypertension.

Portal hypertension is characterized by an increase in portal pressure (> 10 mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic diseases. When portal hypertension occurs in the absence of liver cirrhosis, noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this disease is much better than that of cirrhosis. Noncirrhotic diseases are the common cause of portal hypertension in developing countries, especially in Asia. NCPH is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. In most cases, these disorders can be explained by endothelial cell lesions, intimal thickening, thrombotic obliterations, or scarring of the intrahepatic portal or hepatic venous circulation. Many different conditions can determine NCPH through the association of these various lesions in various degrees. Many clinical manifestations of NCPH result from the secondary effects of portal hypertension. Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae include hyperdynamic circulation, pulmonary complications, and other effects of portosystemic collateral circulation like portosystemic encephalopathy. At present, pharmacologic and endoscopic treatments are the treatments of choice for portal hypertension. The therapy of all disorders causing NCPH involves the reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart from prevention and treatment of complications of portal hypertension.

Embolization of cyanoacrylate glue in systemic circulation in a case of hepatocellular carcinoma: an autopsy report.

We report a case of embolism of the sclerosant dye with subsequent formation of foreign-body giant cell reaction within the veins of pulmonary and portal circulation in an autopsy case of hepatocellular carcinoma developing over an underlying primary biliary cirrhosis.