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.

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.

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.

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.

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.

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.

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.

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.

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.

Platelet-derived growth factor expression correlates with tumor grade and proliferative activity in human oligodendrogliomas.

BACKGROUND: For the last one and a half decade, it has been found that platelet-derived growth factor (PDGF) promotes glial tumor growth through autocrine and paracrine loops, by expression of PDGFalpha receptor (PDGFRalpha) on glioma cells and PDGFbeta receptor (PDGFRbeta) on proliferating endothelial cells. However, studies on oligodendrogliomas, correlating expression of PDGF and its receptor with tumor grade and proliferative activity, through MIB-1 labeling index (LI) are relatively few as compared to astroglial counterpart. METHODS: Formalin-fixed paraffin-embedded tissues from 55 cases of oligodendrogliomas (34 World Health Organization [WHO] grade II and 21 WHO grade III tumors) were subjected to immunohistochemistry. MIB-1 LI was calculated, and a semiquantitative scoring system for expression of PDGF and PDGFRalpha was used. RESULTS: MIB-1 LI and PDGF expression increased with histologic grades of malignancy ("t" test, P < .001 and Mann Whitney test, U = 109, P < .001 respectively). The PDGF expression scores had a positive correlation with MIB-1 LI, irrespective of tumor grade (Pearson's correlation coefficient, r = 0.566; P < .001). However, there was no significant difference of PDGFRalpha expression between 2 grades of tumors. CONCLUSIONS: The results of this study showed that MIB-1 LI is a rapid and cost-effective modality for predicting tumor grade in oligodendrogliomas. Immunohistochemistry for PDGF was found to be useful in differentiating various grades of oligodendroglioma, and therefore, it may be involved in tumor cell proliferation and malignant transformation. Platelet-derived growth factor receptor alpha, although expressed in oligodendroglial neoplasms, was not found to be useful in predicting tumor grade.

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.

The role of immunohistochemistry in medullomyoblastoma--a case series highlighting divergent differentiation.

AIMS: To analyse the histo-morphology of cases of medullomyoblastoma and identifying its divergent differentiation. METHODS: A retrospective review of all cases reported as medulloblastoma between the period of Jan 2000 to Dec 2006 was carried out on Hematoxylin and eosin (H & E) stained slides. The cases were screened on light microscopy for primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. All these cases were subjected to a panel of immunohistochemical stains, including Desmin, GFAP, NFP, HMB45, SMA, S100, CK and EMA. Ultrastructural analysis was done on tissue obtained from paraffin blocks in 2 cases. RESULTS: Male predominance (M:F = 5:1) was noted with an incidence of five percent of all cases of medulloblastoma (6 out of 120 cases) over a period of 6 years. Primitive neuroectodermal areas were accompanied with areas of "myoid" differentiation, 5 cases showing strap cells. Two cases with epithelial and cartilaginous differentiation were seen. Three cases showed focal melanocytic differentiation, identified only on HMB45 immunostaining. Four cases showed glial differentiation. Neuronal differentiation again was very focally seen in two cases, of which one was identified only by NFP immunostain. Seventh case is included in the study, however it is not considered to calculate incidence as it occurred beyond the period of 6 years of records search. CONCLUSION: Medullomyoblastoma is a rare childhood tumor of cerebellum. Majority of cases reveal divergent differentiation, which are identified with the help of panel of immunostains indicating multi-potential nature of primitive neuroectodermal cells.

Adamantinoma: a clinicopathological review and update.

Adamantinoma is a primary low-grade, malignant bone tumor that is predominantly located in the mid-portion of the tibia. The etiology of the tumor is still a matter of debate. The initial symptoms of adamantinoma are often indolent and nonspecific and depend on location and extent of the disease. Histologically, classic adamantinoma is a biphasic tumor characterized by epithelial and osteofibrous components that may be intermingled with each other in various proportions and differentiating patterns. To assure the histological diagnosis, pathologists should employ immunohistochemistry for demonstrating the sometimes sparse epithelial cell nests when the radiological features are suggestive of adamantinoma. There is paucity of compiled data over adamantinoma in the literature, hence authors tried to make a comprehensive review which must be of use to beginners and trained pathologists. Our objective is to further define the clinicoradiologic features and pathologic spectra of adamantinoma.

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.