Publications (48)92.65 Total impact
-
Article: Concurrent occurrence of primary intracranial Epstein-Barr virus-associated leiomyosarcoma and Hodgkin lymphoma in a young adult.
[show abstract] [hide abstract]
ABSTRACT: Although Epstein-Barr virus (EBV) infection has been known to be associated with a heterogeneous group of malignancies including Hodgkin lymphoma (HL), its association with smooth-muscle tumors (SMTs) has recently been described. Of these SMTs, a primary intracranial EBV-associated leiomyosarcoma (EBV-LMS) is extremely rare, and most of the reported cases were of immunocompromised and/or pediatric patients. A neurologically asymptomatic, previously healthy 27-year-old man was found to have a PET-positive brain lesion during a staging workup for his recently diagnosed HL. Subsequent MRI revealed a 2.6 × 4.0 × 3.3-cm inhomogeneously enhancing tumor with marked surrounding edema in the right anterior frontal lobe. He was serologically HIV negative. He underwent a right frontal lobectomy with gross-total resection of the tumor. Intraoperatively, the tumor had fairly discrete margins and appeared to arise from the anterior falx (that is, it was dural based). Microscopically, the tumor was composed of interlacing fascicles of spindle cells with brisk mitotic activity and multiple foci of necrosis. Immunohistochemically, the tumor cells were positive for caldesmon and smooth-muscle actin and negative for desmin, CD34, CD99, bcl-2, S100 protein, and GFAP. A Ki-67 labeling index was up to 30%. Epstein-Barr virus-encoded RNA in situ hybridization demonstrated strong diffuse positivity with more than 90% of tumor cells staining. Most of the Reed-Sternberg cells in HL were also labeled with Epstein-Barr virus-encoded RNA. This is the first case of a concurrent occurrence of rare intracranial EBV-LMS and HL in a seemingly "immunocompetent" adult patient (immunocompetence determined by routine laboratory data and clinical history). We should be aware of EBV-SMT as a differential diagnosis of dural-based spindle cell neoplasm in this setting given that patients with HL, even at presentation, exhibit a persistent defect in cellular immunity.Journal of Neurosurgery 04/2013; · 2.96 Impact Factor -
Article: Leptomeningeal carcinomatosis as initial presentation in adenocarcinoma of lung with signet ring cell features: an autopsy case report.
[show abstract] [hide abstract]
ABSTRACT: Signet ring cell (SRC) features are rare but well-recognized cytological changes of pulmonary adenocarcinoma (PA). PA with SRC features (PA-SRC) is frequently associated with anaplastic lymphoma kinase (ALK) gene rearrangement, and recognition of PA-SRC may be important for the administration of targeted treatment. To the authors' knowledge, leptomeningeal carcinomatosis (LMC) as an initial presentation of PA-SRC has not yet been reported. We report an autopsy case from a 59-year-old female who presented with intractable headache for 6 weeks and died of LMC as a result of metastatic PA-SRC. Premortem brain MRI showed nonspecific leptomeningeal enhancement. At autopsy, a tan rubbery mass was found in the hilar area of the right lung, which also surrounded the lower trachea and carotid arteries. A right posteromedial middle lobe mass was also found. Leptomeninges were slightly thickened, without discrete masses. Microscopic examination of the lung mass and leptomeninges showed solid sheets and nests of malignant cells with pleomorphic nuclei and frequent SRC features which comprised 50% of the mass. Immunohistochemically, the tumor cells demonstrated strong diffuse expression of cytokeratin (CK)-7, TTF-1, and napsin-A. Immunostains for CK-20 and ALK were negative. These features were consistent with PA-SRC. It has been reported that approximately 70% of PAs demonstrate ALK gene rearrangement when SRCs comprised >10% of the tumor cells. The presence of SRCs can be indicative of a lung primary and, because of frequent ALK gene rearrangement in PA-SRC, proper recognition of PA-SRC may be important in determining whether further testing is advisable (e.g., ALK immunostaining and/or ALK gene rearrangement).International journal of clinical and experimental pathology 01/2012; 5(9):972-6. · 1.89 Impact Factor -
Article: Minimal or no residual prostatic adenocarcinoma on radical prostatectomy: a 5-year experience with "vanishing carcinoma phenomenon".
[show abstract] [hide abstract]
ABSTRACT: "Vanishing carcinoma phenomenon" (VC) has been defined as the finding of minute or no cancer on radical prostatectomy specimens after a positive biopsy. To discuss our experience with VC and to recommend guidelines for its detection. One thousand seven hundred forty-one radical prostatectomy specimens (2004-2009) processed by whole-mount section procedure yielded 21 (1.2%) cases with VC and 6 (0.34%) cases with minimal carcinoma (≤ 2 mm) in the radical prostatectomy specimen. To find the eluding carcinoma in VC cases or more carcinoma in minimal carcinoma cases, the following was done: 3 levels of all the paraffin blocks were obtained; if negative, the paraffin blocks were melted, the tissue was flipped, and 3 levels were prepared. The tumor bank frozen tissue was also processed for routine examination. Three deeper levels in the radical prostatectomy specimen of 21 VC cases failed to show malignancy; however, the flipping and recutting of the tissue yielded a focus of carcinoma (1-5 mm) in 16 of 21 cases and in 3 of 16 cases in the saved frozen tissue. In 1 of the 6 cases with minimal carcinoma, subsequent recuts of the flipped tissue displayed carcinoma (2 foci of tumor, <1 mm each). In VC we recommend: embed and process any remaining prostatic tissue including any saved fresh-frozen tissue; obtain 3 levels of each paraffin block; if results are negative, melt and flip the tissue and obtain 3 more levels. Following the above guidelines, a hidden carcinoma may be detected in the majority of the cases of VC.Archives of pathology & laboratory medicine 11/2011; 135(11):1466-70. · 2.58 Impact Factor -
Article: Primary intracranial sarcomatoid carcinoma arising from a recurrent/residual epidermoid cyst of the cerebellopontine angle: a case report.
[show abstract] [hide abstract]
ABSTRACT: Primary intracranial squamous cell carcinomas (SCCs) are rare and mostly associated with an intracranial epidermoid or dermoid cyst. Sarcomatoid carcinoma is a rare biphasic tumor composed of both carcinomatous and sarcomatous components and has not previously been reported as a primary intracranial tumor. Here, we present a case of a 60-year-old man with a primary intracranial sarcomatoid carcinoma, arising from the remnants of the previously resected epidermoid cyst in the cerebellopontine angle. The resected material had portions of an epidermoid cyst lined by normal and dysplastic squamous epithelia and invasive keratinizing SCC. This area was in continuity with areas of highly pleomorphic, anaplastic sarcomatoid cells. Brisk mitotic activity and extensive areas of necrosis were found. On immunohistochemical staining, the cells of the conventional SCC were positive for cytokeratin 5/6, pancytokeratin, epithelial membrane antigen, p63, and p53. The sarcomatoid cells were diffusely and strongly positive for vimentin, p53, smooth muscle actin, and, focally, muscle-specific actin. Occasional sarcomatoid cells coexpressed cytokeratin 5/6, pancytokeratin, p63, and S100 protein. The patient subsequently developed leptomeningeal spread and died 4 months after the second surgery. This rare entity expands the morphologic spectrum encountered in primary intracranial carcinoma.The American journal of surgical pathology 08/2011; 35(8):1238-43. · 4.06 Impact Factor -
Article: S100P and XIAP expression in pancreatic ductal adenocarcinoma: potential novel biomarkers as a diagnostic adjunct to fine needle aspiration cytology.
[show abstract] [hide abstract]
ABSTRACT: The usefulness of 2 novel biomarkers in pancreatic surgical and cytological specimens that could reliably differentiate non-neoplastic pancreatic duct and benign gut epithelium from pancreatic ductal adenocarcinoma (PDA) was evaluated. A total of 14 pancreatic resection specimens (RSs), 23 endoscopic ultrasound-guided fine needle aspirations (EUS-FNAs) of PDA and 8 benign pancreatic EUS-FNAs were selected. Twelve of 14 RSs had corresponding EUS-FNAs with cell blocks (CBs). Non-neoplastic pancreatic tissue, including chronic pancreatitis, was evaluated in all RSs. Immunohistochemical stains for S100P and X-linked inhibitor of apoptosis protein (XIAP) were performed on tissue and CB sections. Staining intensity (0 no staining; 1+ weak; 2+ moderate; 3+ strong) and proportion of positive cells (less than 10% negative; 1+ 10-25%; 2+ 26-75%; 3+ greater than 75%) were assessed. Positive staining was defined as ≥10% cells with at least 1+ intensity. The sensitivity and specificity of S100P and XIAP immunoreactivity for a diagnosis of PDA in RSs were both 100%. In contrast, the sensitivity and specificity in EUS-FNA CBs of S100P were 78.2 and 87.5% and of XIAP 82.6 and 50.0%, respectively. The combined sensitivity of S100P and XIAP was 100% in 12 RSs and 83.3% in the corresponding EUS-FNA CBs. Two novel biomarkers have very high sensitivity and specificity in the diagnosis of PDA in RSs. S100P has slightly lower sensitivity and higher specificity of PDA than XIAP in EUS-FNA specimens. We recommend using both biomarkers as cytological diagnostic adjuncts, especially in difficult cases of well-differentiated PDA versus reactive ductal epithelium.Acta cytologica 01/2011; 55(2):142-8. · 0.49 Impact Factor -
Article: Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature.
[show abstract] [hide abstract]
ABSTRACT: Dual pathology has previously been reported in less than 10% of cases of Rasmussen's encephalitis (RE). Given the rarity of RE, it appears unlikely that dual pathology in RE is merely a coincidence. We therefore reviewed all cases of RE experienced in our institution to assess for an additional/associated pathology. A total of seven patients with RE were identified in our archives. Seven children (4 boys and 3 girls, age range: 3-16 years, mean: 9.5 years) with medically refractory epilepsy underwent surgical resection for intractable seizures. The surgical specimens were examined with routine neurohistological techniques, and immunohistochemistry was performed with an extensive panel of antibodies for viruses, lymphocytes, microglia/macrophages, human leukocyte antigen (HLA)-DR, astrocytes, and neurons. Relevant literature was reviewed. Microscopically, all seven cases demonstrated the inflammatory pathology of RE in the cortex and white matter with leptomeningeal and perivascular lymphocytic infiltration, microglial nodules with/without neuronophagia, neuronal loss and gliosis. The HLA-DR antibody was extremely helpful in highlighting the extent of microglial cell proliferation/activation that was not appreciable with standard histology. An unexpected finding in all seven cases was the presence of cortical dysplasia. In our series of seven cases, there was co-occurrence of the inflammatory/destructive pathology of RE with malformative/dysplastic features in cortical architecture in 100% of cases, raising questions about the possible relationships between the two entities. Awareness of the possibility of dual pathology in RE is important for clinical and pathological diagnosis, and may affect the management and outcome of these patients. Immunohistochemistry is very helpful to make a definitive diagnosis of both pathologies.Neuropathology 08/2010; 30(4):381-91. · 2.02 Impact Factor -
Article: Novel immunohistochemical markers in the diagnosis of nonglial tumors of nervous system.
[show abstract] [hide abstract]
ABSTRACT: Immunohistochemistry (IHC) has become an important adjunct tool in diagnostic neuro-oncology practice enabling immunophenotypic characterization of tumor cells. There have been several recent publications regarding new IHC markers that are useful for diagnosis of brain tumors. To introduce the latest advances in IHC in this field, we review the features of novel IHC marker antibodies applicable to selected nonglial tumors in the nervous system, based on recently published reports and our own experiences. We discuss (1) aquaporin-1 and alpha-inhibin for hemangioblastoma, (2) beta-catenin for craniopharyngioma, (3) brachyury for chordoma, and (4) INI-1 for hereditary schwannomas. All the markers presented here are used primarily for supporting or confirming the histologic diagnosis, with the exception of (4), which may be of help in identification of inherited forms in schwannomas. As with other surgical pathology practices, the judicious use of a panel of IHC antibodies selected on the basis of the histologic findings is important for an accurate diagnosis of brain tumors. Of note is that IHC results should be always interpreted in the histopathologic context.Advances in anatomic pathology 03/2010; 17(2):150-3. · 3.22 Impact Factor -
Article: Useful immunohistochemical markers in differentiating hemangioblastoma versus metastatic renal cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: Hemangioblastomas (HBs) account for nearly a tenth of all posterior fossa neoplasms and can be the presenting finding in patients with von Hippel-Lindau (VHL) syndrome. HB must be differentiated from renal cell carcinoma (RCC), also seen in VHL, as the distinction between these lesions dictates the management of these patients. Currently inhibin A and RCC marker have been used in the diagnosis of HB and metastatic RCC, both with inconsistent results. Additional immunohistochemical markers including CD10, PAX-2, D2-40, and FLi-1 have been shown to have potential for the distinction of these two entities. Fifteen cerebellar HBs and 17 metastatic clear cell RCCs to the brain were selected for the study. All cases were immunostained with RCC marker, inhibin, CD10, PAX-2, D2-40, and Fli-1. The staining patterns were scored based on intensity and extent of tumor staining. In the differentiation of HB and metastatic RCC, D2-40 and RCC marker proved to be poor markers with less than 50% of HBs and RCCs, respectively, showing positive staining. PAX-2 and CD10 were superior to RCC marker in the diagnosis of metastatic RCC, with PAX-2 having better specificity. Fli-1 failed to stain tumor cells in both HBs and RCC. Inhibin A, in combination with PAX-2, showed to be the most useful markers to differentiate HB from metastatic RCC.Neuropathology 03/2010; 30(6):580-5. · 2.02 Impact Factor -
Article: Long-term deep brain stimulation for essential tremor: 12-year clinicopathologic follow-up.
[show abstract] [hide abstract]
ABSTRACT: We describe the clinical course and postmortem pathological findings in a patient with essential tremor (ET) treated with deep brain stimulation (DBS) for 12 years. This 75 year old woman had a 13-year history of progressive ET prior to implantation of bilateral quadripolar DBS electrodes in the region of her ventral intermediate thalamic nuclei in 1996, producing immediate relief of arm tremor. Histopathological examination of the brain, performed 12 years after the initial implantation, demonstrated electrode catheter tracts rimmed by 20-25 micron fibrous sheaths, with multinucleated giant cells and reactive gliosis. Lymphocytic infiltration was seen by L26 immunoreactivity with CD3 (T cells) staining predominating over CD20 (B cells). Cerebellar axonal spheroids and Purkinje cell loss were found. The minimal foreign body reaction and gliosis around the electrodes 12 years after implantation supports the long-term safety of DBS. The case represents the longest reported follow-up with autopsy examination after DBS and confirmed histological changes associated with ET.Movement Disorders 01/2010; 25(2):232-8. · 4.51 Impact Factor -
Article: Atypical teratoid/rhabdoid tumor of the pineal region in an adult.
[show abstract] [hide abstract]
ABSTRACT: An atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal tumor most often occurring in the posterior fossa in children younger than 3 years of age. Adult cases of AT/RT are very rare, and 27 cases with a diagnosis of either AT/RT or (malignant) rhabdoid tumor have been reported to date. The authors report an adult case of an AT/RT occurring in the pineal region with molecular cytogenetic and immunohistochemical confirmation. A 33-year-old woman presented with a 2-month history of headache and blurred vision progressing to diplopia, and was admitted emergently due to deteriorating mental status. An MR image showed a heterogeneously enhancing mass involving the posterior third ventricle and pineal region with mild hydrocephalus. She underwent a subtotal resection of the tumor and was then treated with chemoradiation. Thirteen months after surgery, she was still alive with radiological evidence of recurrence/residual lesions. Histological sections showed epithelioid cellular sheets of rhabdoid tumor cells with scattered mitotic figures. Immunohistochemically, the tumor cells were diffusely and strongly positive for epithelial membrane antigen and vimentin, and showed focal expression of glial fibrillary acidic protein, pancytokeratin, and neurofilament protein. Loss of nuclear immunoreactivity for INI1 protein was observed. Fluorescence in situ hybridization analysis showed monosomy 22. Histologically, this tumor consisted exclusively of epithelioid tumor cells with rhabdoid features. The differential diagnoses include rhabdoid glioblastoma, metastatic carcinoma, and rhabdoid meningioma. Molecular testing to identify monosomy 22 or deletions of the chromosome 22q11 containing the INI1/hSNF5 gene and/or immunohistochemical staining with INI1 antibody is of great importance for the diagnosis of this tumor.Journal of Neurosurgery 11/2009; 113(2):374-9. · 2.96 Impact Factor -
Article: Cerebral mycosis: 7-year retrospective series in a tertiary center.
[show abstract] [hide abstract]
ABSTRACT: This study focuses on the epidemiology, clinical manifestations, risk factors, diagnosis and outcome of all cases of central nervous system (CNS) fungal infections in a tertiary center. Medical records of 18 patients of culture-proven CNS fungal infections were retrospectively reviewed from 2000 to 2007, including 12 isolated from the cerebrospinal fluid (CSF) and seven from tissue biopsy. Patient demographic data included 10 males and eight females. The mean age was 55 years (range: 24-89 years). All but one patient were immunocompromised. Fungal organisms isolated from CSF included: Cryptococcous neoformans (8 patients), Coccidioides immitis (3 patients), and Aspergillus versicolor (1 patient). Histopathology of seven biopsy cases revealed groups of pigmented golden-brown fungal forms in three cases; three cases showed septate fungi, two of which had melanin in their walls; and one case showed multiple round spherules. These cases on microbiological cultures grew Coccidioides immitis (1 patient), Aspergillus fumigatus (1 patient), Cladophialophora bantiana (2 patients), Fonsecaea monophora (1 patient) and Scedosporium apiospermum (2 patients). Five of the seven fungal organisms isolated from tissue biopsies were dematiaceous fungi. Twelve patients died after a period of a few weeks to months, two were lost to follow-up, and four are alive with severe neurological sequelae. CNS fungal infections in our cohort were more common in patients post-transplant and with hematologic malignancies. In our series, rare dematiaceous fungi are emerging agents for cerebral mycosis. The outcome of CNS fungal infections is poor despite vigorous antifungal therapy.Neuropathology 10/2009; 30(3):218-23. · 2.02 Impact Factor -
Article: Tumor-to-tumor metastasis to the central nervous system.
[show abstract] [hide abstract]
ABSTRACT: Tumor-to-tumor metastasis is a well-recognized phenomenon. Meningioma is the most common intracranial host tumor, with the breast and lung being the most common primary sites. We report herein two such cases of metastasis from pulmonary adenocarcinoma and malignant melanoma (MM) of vulva, respectively. Case 1: a 69-year-old female smoker who had a history of right upper lobectomy of lung for adenocarcinoma presented with a headache and altered mental status, and was found to have a left temporal contrast-enhancing mass with massive surrounding edema on MRI. The resection specimen revealed foci of metastatic adenocarcinoma within a microcystic meningioma. Case 2: a 75-year-old woman with a history of radical vulvectomy for MM died of widespread systemic metastasis of MM. At autopsy, a 2.5 x 2 x 2 cm firm nodule attached to the falx was incidentally found, with focal black discoloration at the periphery of the mass. Histologic examination showed a fibroblastic meningioma with a focus of metastatic MM. Case 1 is the first case report describing a microcystic variant of meningioma harboring metastatic carcinoma. Although MM is one of the most common metastatic brain tumors, MM-to-meningioma metastasis is reportedly extremely rare, but can occur.Neuropathology 06/2009; 29(3):303-8. · 2.02 Impact Factor -
Article: Cytomorphologic manifestations of Alzheimer's disease using brain squash smears: an autopsy study with histology-cytology correlation.
[show abstract] [hide abstract]
ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia. The cardinal histopathologic features include senile plaques (SPs) and neurofibrillary tangles (NFTs), and in addition, granulovacuolar degeneration (GVD) and Hirano bodies (HBs) are frequently observed in the hippocampus. We studied hippocampal cytological features of AD, compared with controls. Hippocampal squash smears were prepared from 26 autopsy brains and stained with three different solutions, including Papanicolaou stain (Pap-s). The smears were evaluated for the aforementioned four structures and gliosis, and their frequency was compared between AD (n = 15) and control (n = 11) groups. Hippocampal smears of all AD cases revealed NFTs and gliosis. NFTs were light gray with thick flame-like structures on Pap-s. GVD was identified in the majority of AD cases and was most easily observed on Pap-s. SPs were difficult to identify and were seen only in AD cases. HBs were rarely identified as long light eosinophilic hyaline structures on Pap-s. Cytological findings of hippocampi reflect the characteristic histological features of AD with the exception of HBs, which are difficult to identify on smears. NFTs and gliosis, and SPs seem to be sensitive and specific cytologic markers in hippocampal smears for AD, respectively.Diagnostic Cytopathology 04/2009; 37(9):654-60. · 1.16 Impact Factor -
Article: Immunohistochemical comparison of chordoma with chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma.
[show abstract] [hide abstract]
ABSTRACT: Chordoma originates from embryonic notochordal remnants in the midline along the spinal axis and is characterized by cords and lobules of neoplastic cells arranged within myxoid matrix. Because of histologic similarities with myxoid matrix and overlapping immunohistochemical profile, chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma enter in the histologic differential diagnosis at this site. Therefore, the judicious use of a panel of selected immunostains is unquestionably helpful in diagnostically challenging cases. To find useful immunohistochemical markers for assisting in differential diagnosis between chordoma and other tumors with chordoid morphology, an immunohistochemical study using D2-40, epithelial membrane antigen (EMA), pan-cytokeratin (panCK), glial fibrillary acidic protein (GFAP), S-100 protein, galectin-3, neural cell adhesion molecule (NCAM), beta-catenin, E-cadherin, and carcinoembryonic antigen was performed on 14 chordomas, 7 chondrosarcomas, 9 myxopapillary ependymomas, and 4 chordoid meningiomas. Chordoma typically showed positive for EMA and panCK and negative for D2-40 and GFAP; whereas chondrosarcoma revealed positive for D2-40, and negative for EMA, panCK, and GFAP; myxopapillary ependymoma positive for GFAP and negative for EMA; and chordoid meningioma positive for EMA, and negative for panCK and GFAP. On the basis of our immunohistochemical study, a panel of D2-40, EMA, panCK, and GFAP allowed the correct recognition of all tumors examined. Other immunohistochemical markers including S-100 protein, galectin-3, NCAM, beta-catenin, E-cadherin, and carcinoembryonic antigen were of little value in differential diagnosis. In summary, the best immunohistochemical markers useful for the evaluation of tumors with chordoid morphology were D2-40, EMA, cytokeratin, and GFAP. D2-40 was a true chondroid marker to be useful for the differential diagnosis with chordoma.Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 04/2009; 17(2):131-8. · 1.63 Impact Factor -
Article: Low-level copy gain versus amplification of myc oncogenes in medulloblastoma: utility in predicting prognosis and survival. Laboratory investigation.
[show abstract] [hide abstract]
ABSTRACT: Medulloblastoma (MB) is a malignant embryonal tumor of the cerebellum. Amplification of c-myc or N-myc is infrequently identified and, when present, is often associated with the large cell/anaplastic (LC/A) phenotype. The frequency of low-level copy gain of myc oncogenes and its relationship to prognosis of MB has not been explored. Archival cases of MB were histologically reviewed and classified into 3 major subtypes: classic, nodular, and LC/A. Using quantitative real-time polymerase chain reaction (PCR), the authors analyzed 58 cases with a pure histological subtype for the copy number (CN) of myc (c-myc and N-myc) oncogenes. Cases with > 5-fold CN were further analyzed using the fluorescent in situ hybridization (FISH) assay. Kaplan-Meier survival analysis was performed. A > 5-fold myc CN was noted in 5 (20.8%) of 24 LC/A, 1 (5.3%) of 19 classic, and 2 (13.3%) of 15 nodular subtypes. In a significant number of tumors (14 [56%] of 24 LC/A, 13 [68%] of 19 classic, and 10 [67%] of 15 nodular MBs) the CN was > 2-fold but < 5-fold. High-level amplification, defined as > 10-fold CN, was only seen in the LC/A subtype (5 cases), although moderate amplification (> 5-fold but < 10-fold) could be detected in other histological subtypes. Fluorescence in situ hybridization readily detected most cases corresponding to tumors with > 5-fold amplicon CN by quantitative real-time PCR, and could detect all 5 cases with > 10-fold CN by quantitative real-time PCR. The group of patients with > 5-fold myc amplicon CN showed significantly shorter survival than those with < 5-fold CN (p = 0.045), independent of histological subtype. Since FISH could easily detect most cases in the moderate-to-high myc gene amplification (> 5-fold CN) group, the FISH assay has utility in detecting subsets of MB with poorer prognosis.Journal of Neurosurgery Pediatrics 02/2009; 3(1):61-5. · 1.53 Impact Factor -
Article: Solitary subependymal giant cell astrocytoma incidentally found at autopsy in an elderly woman without tuberous sclerosis complex.
[show abstract] [hide abstract]
ABSTRACT: Subependymal giant cell astrocytoma (SEGA) is a benign, slowly growing tumor typically occurring in the setting of tuberous sclerosis complex (TSC). However there are several reported cases in which patients with a solitary SEGA had no other stigmata of TSC. We describe a case of SEGA in a 75-year-old woman representing the oldest patient reported to-date. The patient had a history of radical vulvectomy for malignant melanoma (MM), and died of autopsy-confirmed widespread systemic metastasis. Postmortem examination of the brain revealed a single 2.1 x 1.0 x 0.8 cm intraventricular nodule in the lateral ventricle. Histologically, it was composed of interlacing bundles of spindle-shaped tumor cells with thin delicate processes admixed with relatively large pleomorphic cells with abundant glassy eosinophilic cytoplasm, as seen in a SEGA. Immunohistochemically, GFAP, S-100 protein, and neuron specific enolase were positive, and synaptophysin labeled a few tumor cells. Also noted were rare isolated MM cells within the tumor (i.e., tumor-to-tumor metastasis). Autopsy showed no manifestations of TSC systemically or intracranially. The histopathological differential diagnosis was limited and included giant cell ependymoma and, much less likely, giant cell glioblastoma and pleomorphic xanthoastrocytoma. This case illustrates that SEGA can be found incidentally in an elderly individual with no associated symptoms and also indicates that SEGA can occur outside the setting of TSC. Tumor metastasis to an occult SEGA is extremely rare.Neuropathology 08/2008; 29(2):181-6. · 2.02 Impact Factor -
Article: Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas.
[show abstract] [hide abstract]
ABSTRACT: Meningiomas are well known to be responsive to estrogen/progesterone stimulation, and their expression of estrogen/progesterone receptor (ER/PR) has been documented. On the other hand, there are several reports studying expression of apoptosis-regulating proteins (ARPs) and its significance in meningiomas. However, very limited published information exists on the exact relation among sex hormone receptor status, apoptosis, proliferation index (PI), and histological grade in meningiomas. A total of 57 cases of non-malignant meningiomas were selected, and histologically reviewed and graded (WHO grades 1, 2). All these cases were immunostained for ER, PR, Ki-67, and ARPs including bax, bcl-2, and bcl-xL. Sections were graded semiquantitatively for intensity and extent of immunostaining. PI was expressed as a percentage of Ki-67 positive tumor cells. Expression of bax, bcl-2, bcl-xL, ER, and PR was seen in 100, 35.1, 24.6, 10.4, and 87.2% of cases, respectively. Bax was expressed diffusely and strongly, while Bcl-2 tended to be expressed weakly and focally. Bcl-xL appeared to be expressed relatively strongly and diffusely in a small subset. There was significantly higher PI as well as expression of PR in grade 1 group than in grade 2 group. A weak negative correlation was observed between Bcl-2 and PR (r =-0.472, P < 0.0014). Given high-level expression of pro-apoptotic bax, which seems to be constitutionally expressed, in contrast to low-level expression of antiapoptotic bcl-2 and bcl-xL, other antiapoptotic proteins may involve the proliferation of meningiomas. A significant negative relation exists between PR and Bcl-2 in meningiomas, which might have some biological and clinical significance.Neuropathology 02/2008; 28(1):62-8. · 2.02 Impact Factor -
Article: Brain tissue microarrays in neurodegenerative diseases: validation of methodology and immunohistochemical study of growth-associated protein-43 and calretinin.
[show abstract] [hide abstract]
ABSTRACT: A tissue microarray (TMA) was constructed using 47 neurodegenerative diseases (NDD), including Alzheimer's disease (AD; n = 30) and non-AD NDD (n = 17), and from seven controls. For validation of the methodology, the following three immunostains were used. Tau and beta-amyloid-related pathologies were more significantly recognized in tauopathies/AD compared to non-tauopathies/controls, and these results were comparable to the assessment of the whole brain sections. But no alpha-synuclein pathologies were observed despite five cases of dementia with Lewy bodies. It was concluded that the TMA technique is useful for NDD with diffuse pathological processes but not for those with patchy and occasional lesions or in early stages. Growth-associated protein (GAP)-43 and calretinin were also immunostained. A significant reduction in GAP-43 expression was seen in the frontal lobe and hippocampus in AD compared to non-AD cases, but not in other areas. No significant difference in number of anticalretinin immunoreactive neurons or in density of immunoreactive neurites was observed between any of the NDD and controls, which may indicate that calretinin-positive neurons are spared in the degenerative process. These results are compatible with the previous studies. These analyses were performed rapidly in a large number of cases using a single slide under uniform staining conditions.Pathology International 01/2008; 57(12):775-83. · 1.62 Impact Factor -
Article: Expression of oligodendroglial differentiation markers in pilocytic astrocytomas identifies two clinical subsets and shows a significant correlation with proliferation index and progression free survival.
[show abstract] [hide abstract]
ABSTRACT: The growth pattern of pilocytic astrocytoma (PAs) is unpredictable. Gene expression profiling has recently demonstrated an inverse relationship between myelin basic protein (MBP) expression and progression free survival (PFS) in PAs. We present here the pattern of expression of oligodendroglial differentiation markers (ODMs) in PAs by immunohistochemistry and their correlation with PI and PFS. Sixty-four cases of PA were reviewed and representative sections were stained for Ki-67 and ODMs, including MBP, platelet-derived growth factor receptor-alpha (PDGFR-alpha), Olig-1, and Olig-2. Sections were graded semi-quantitatively for intensity (I: 0-3+) and extent (E: 0-4+) of staining. PI was expressed as a percentage of Ki-67 positive cells. Immunoreactivity of MBP, PDGFR-alpha, Olig-1, and Olig-2 was observed in 84, 56, 97, and 75% of cases, respectively. There was a statistically significant inverse correlation between MBP expression and PI (r (2) = .696, p = .014). A positive correlation was observed between PDGFR-alpha and PI (r (2) = .727, p = .011). Further analysis showed a significant difference in PFS between low expressors [I + E score < or = 3] and high expressors (I + E score > or = 4) for PDGFR-alpha with p < .001. Notably, there was a significant difference in PFS between high expressors of MBP and high expressors of PDGFR-alpha with p < .001. These results suggest that expression of ODMs, especially MBP and PDGFR-alpha, may identify two clinical subsets of PA. In addition, we have shown the expression of 4 different ODMs in PAs, which may support the possibility that PAs arise from oligodendrocyte progenitor/precursor cells probably similar to the O2A progenitor cells in the mouse.Journal of Neuro-Oncology 01/2008; 86(2):183-90. · 3.21 Impact Factor -
Article: FOXG1 dysregulation is a frequent event in medulloblastoma.
[show abstract] [hide abstract]
ABSTRACT: Medulloblastomas represent 20% of malignant brain tumors of childhood. Although, they show multiple, non-random genomic alterations, no common, early genetic event involving all histologic types of medulloblastomas have been described. Nineteen medulloblastomas were analyzed using chromosomal comparative genomic hybridization (cCGH). Nine tumors with the most frequent number of genetic changes were further analyzed using bacterial artificial chromosome array CGH (aCGH). With aCGH, the frequency of gains and losses were higher than with cCGH. Chromosome 2p gains spanning 2p11-2p25 including N-myc locus, 2p24.1 were detected in 5/9 (55%) tumors while 14q12 gains were detected in 6/9 (67%) tumors. The 14q12 locus overlapped with the FOXGI gene locus. Quantitative real time PCR showed a 2-7-fold copy gain for FOXG1 in all the nine tumors. Protein expression was demonstrated by immunohistochemistry in all histologic types. The expression of FOXG1 and p21cip1 showed an inverse relationship. FOXG1 copy gain (>2 to 21 folds) was seen in 93% (55/59) of a validating set of tumors and showed a positive correlation with protein expression (Spearman's rank order correlation coefficient = 0.276; P = 0.038) representing the first report of FOXG1 dysregulation in medulloblastoma. Modulation of FOXG1 expression in DAOY cell line using siRNA showed a modest decrease in proliferation with a 2-fold upregulation of p21cip1. Current reports indicate that FOXG1 represses TGF-beta induced expression of p21cip1 and cytostasis, and forms a transcriptional repressor complex with Notch signaling induced hes1. Our findings are consistent with a role for FOXG1 in the inhibition of TGF-beta induced cytostasis in medulloblastoma.Journal of Neuro-Oncology 12/2007; 85(2):111-22. · 3.21 Impact Factor
Top co-authors
Top Journals
Institutions
-
2010
-
The Ohio State University
- Department of Pathology
Columbus, OH, USA
-
-
2007–2010
-
The Methodist Hospital System
Houston, TX, USA -
Sendai City Hospital
Sendai, Kagoshima-ken, Japan
-
-
2005–2009
-
Baylor College of Medicine
Houston, TX, USA
-
