Biomedical subjects

A M Rojiani

Publications and source records attributed to A M Rojiani.

At least 19 recordsLinked to original sources

PubMed2001

Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APP(SW) mice.

Mounting evidence suggests that cholesterol may contribute to the pathogenesis of Alzheimer disease (AD). We examined whether cholesterol might be present in senile plaques, a hallmark neuropathological feature of AD. We employed 2 different fluorometric-staining techniques (filipin staining and an enzymatic technique) for the determination of cholesterol in brains of postmortem confirmed AD patients and in nondemented, age-matched histopathologically normal controls. AD patient brains showed abnormal accumulation of cholesterol in congophilic/birefringent dense cores of senile plaques that was essentially absent in histopathologically normal controls. To determine whether increased senile plaque-associated cholesterol occurred generally in all plaques or was restricted to a specific subset, quantitative analysis was performed. Data indicate abnormal accumulation of cholesterol in cores of mature plaques but not in diffuse or immature plaques. Additionally, transgenic mice that overexpress the "Swedish" amyloid precursor protein (Tg APP(SW), line 2576) exhibited a similar pattern of abnormal cholesterol accumulation in mature, congophilic amyloid plaques at 24 months of age that was absent in their control littermates or in 8-month-old Tg APP(SW) mice (an age prior to amyloid deposition). Taken together, our results imply a link between cholesterol and AD pathogenesis and suggest that cholesterol plays an important role in the formation and/or progression of senile plaques.

Aged↗

PubMed2001

Pathognomonic MR imaging findings in Balo concentric sclerosis.

Irregular, concentric zones of increased signal on T2-weighted cranial MR imaging studies may strongly suggest Balo concentric sclerosis (BCS), a rare but recognized variant of multiple sclerosis. Differentiating BCS from multiple sclerosis or neoplasm can be difficult clinically, but MR imaging findings noted in this case may be pathognomonic.

Adult↗

PubMed2001

Proximal myotonic myopathy: clinical, neuropathologic, and molecular genetic features.

The primary genetic abnormality in myotonic dystrophy (DM) is an expansion of the CTG trinucleotide repeat on chromosome 19q. Recently, patients with similar clinical features, but without this genetic alteration, have been designated as proximal myotonic myopathy (PROMM). We describe two additional cases of PROMM, both of whom presented with clinical features suggestive of myotonic dystrophy. The patients had electromyographic (EMG) evidence of myotonia, normal cardiac evaluation, and no cataracts. Genetic analysis of peripheral blood leukocytes revealed no expansion of the trinucleotide repeat by polymerase chain reaction (PCR) and Southern blot analysis. Muscle biopsies in both cases were significant with features suggestive of myotonic dystrophy, such as large numbers of fibers containing multiple internal nuclei, occasional nuclear chains, and fiber atrophy, although sarcoplasmic masses and ring fibers were absent. These cases illustrate the clinical and neuropathologic findings of PROMM and underline the importance of correlating these aspects with genetic studies in patients with myotonic muscle disorders.

Adult↗

PubMed2000

Necrotizing sarcoid granulomatosis mimicking an intracranial neoplasm: clinicopathologic features and review of the literature.

We present a unique case of biopsy-proven necrotizing sarcoidosis involving the central nervous system (CNS) in a 52-year-old woman. The patient presented with a 3-month history of left-sided headache and sharp, shooting pains on the left side of her face. She also has a previous history of sarcoidosis, histopathologically confirmed on parotid gland biopsy 24 years before. Imaging studies of the present lesion revealed a 1.8 x 1.4-cm mass in the left temporal lobe with signal intensity suggestive of meningioma or low-grade glial neoplasm. Surgical resection was initiated, and intraoperative consultation with frozen sections revealed granulomata. The lesion was biopsied, and surgical intervention was terminated. Permanent sections failed to reveal bacteria, mycobacteria, fungi, or foreign bodies. A diagnosis of necrotizing neurosarcoidosis was rendered. The patient was administered steroid therapy and clinically responded favorably. At the most recent follow-up almost 2 years later, there was no evidence of recurrence or progression. Necrotizing sarcoidosis has been reported most commonly in the lungs and rarely in other organ systems. We report the first histologically proven case involving the CNS as well as a rare example of sarcoidosis and necrotizing sarcoid granulomatosis in the same patient. Sarcoidosis and its necrotizing variant should be considered in the differential diagnosis of a granulomatous mass lesion involving the CNS, particularly in the context of a history of systemic disease.

Brain Diseases↗

PubMed2000

Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant condition characterized by benign tumor (neurofibroma) growth and increased risk of malignancy. Dermal neurofibromas, arising from superficial nerves, are primarily of cosmetic significance, whereas plexiform neurofibromas, typically larger and associated with deeply placed nerves, extend into contiguous tissues and may cause serious functional impairment. Malignant peripheral nerve sheath tumors (MPNSTs) seem to arise from plexiform neurofibromas. The NF1 gene, on chromosome segment 17q11.2, encodes a protein that has tumor suppressor function. Loss of heterozygosity (LOH) for NF1 has been reported in some neurofibromas and NF1 malignancies, but plexiform tumors have been poorly represented. Also, the studies did not always employ the same markers, preventing simple comparison of the frequency and extent of LOH among different tumor types. Our chromosome 17 LOH analysis in a cohort of three tumor types was positive for NF1 allele loss in 2/15 (13%) dermal neurofibromas, 4/10 (40%) plexiform neurofibromas, and 3/5 (60%) MPNSTs. Although the region of loss varied, the p arm (including TP53) was lost only in malignant tumors. The losses in the plexiform tumors all included sequences distal to NF1. No subtle TP53 mutations were found in any tumors. This study also reports the identification of both NF1 "hits" in plexiform tumors, further supporting the tumor suppressor role of the NF1 gene in this tumor type.

Adolescent↗

PubMed1999

Chemotherapy for pancreatic cancer: a neuroimaging clinicopathologic correlation.

This 52-year-old male without a significant medical history was receiving chemotherapy with diethylnorspermine (DENSPM), a polyamine analogue, for a partially resected pancreatic adenocarcinoma. Ten months after his initial diagnosis, he was admitted to an outside hospital for evaluation of altered mental status. Over the course of the next few days the patient developed progressive neurologic signs and symptoms including lethargy, tonic deviation of his eyes to the left, asymmetic pupils, and right-sided decerebrate posturing elicited by painful stimuli. Neuroimaging studies revealed multiple lesions scattered in the periventricular white matter, thalamus, midbrain pons, and cerebellar peduncles. The clinical and neuroimaging differential diagnoses are discussed, and postmortem neuropathologic correlation is presented.

Adenocarcinoma↗

PubMed1998

Calcified cystic lesions in a patient with epilepsy and progressive dementia.

A 67-year-old woman had intractable epilepsy and developed a progressive dementia with upper motor neuron signs over the last 6 years. Magnetic resonance imaging (MRI) revealed multiple areas of large calcified cysts, which increased in number and size over the last 3 years. Discussion includes the appearance of these lesions radiologically and pathologically, as well as their differential diagnosis and clinical significance, focusing on the increasing detection of these lesions with current imaging techniques.

Aged↗

PubMed1998

Erythropoietin immunolocalization in renal cell carcinoma.

Erythropoietin (EPO) is a well-recognized hormone that induces erythrocytosis in a wide range of physiologic and pathologic situations in mammals. One of these situations is a paraneoplastic erythrocytosis, which might be seen in association with various neoplasms, including renal cell carcinoma (RCC), hepatoma, and cerebellar hemangioblastoma. Although there have been multiple studies confirming the association between this erythrocytosis and the production of EPO by tumor cells, immunohistochemical detection of EPO in formalin-fixed, paraffin-embedded tissue was not described. We report on the use of microwave antigen retrieval to detect EPO in RCCs in such routinely processed tissues. We selected 19 RCCs received as nephrectomy specimens, fixed in formalin, and routinely processed. These cases were previously diagnosed on the basis of morphologic, immunohistochemical, and clinical features. We examined the immunoreactivity of these specimens with a monoclonal anti-EPO antibody. Fetal (20 wk gestational age) liver served as a positive control. Intense positive immunoreactivity was observed as cytoplasmic, granular staining in fetal hepatocytes. Fourteen RCCs (10 clear cell and 4 tubulopapillary types) demonstrated unequivocal cytoplasmic immunoreactivity. Additionally, two clear cell tumors were only focally positive, whereas three (16%) were negative. EPO immunoreactivity might thus prove to be of value in the diagnosis or confirmation of RCC, particularly in the context of routinely processed material.

Antibodies, Monoclonal↗

PubMed1998

Neuropathologic applications of immunohistochemical fiber typing in the non-neoplastic muscle biopsy.

The determination of fiber types is routinely accomplished in skeletal muscle biopsy specimens by enzymatic histochemical analysis, which detects adenosine triphosphatase (ATPase) activity on cryostat sections. This study assesses postmortem antigen degradation, the effects of fixation and processing, and the neuropathologic applications of MY-32, a monoclonal antibody to fast twitch skeletal myosin. Formalin-fixed, paraffin-embedded sections of skeletal muscle biopsy specimens obtained from the quadriceps femoris were immunoreacted with this antibody. Cryostat sections of the same muscle biopsy specimens were examined after brief fixation in either acetone or formalin. Parallel cryostat sections of frozen muscle were also assessed with ATPase preparations at pH 9.4 and 4.3. To evaluate the effect of postmortem interval and autolysis on antigen degradation, skeletal muscle samples obtained at 12 hours postmortem were immunoreacted after 12, 24, or 36 additional hours. These specimens were examined as immunoreacted cryostat sections and compared with parallel sections reacted for ATPase at pH 9.4 and 4.3. Representative sections from each time point were also fixed in formalin, routinely processed, paraffin embedded, and immunoreacted. Selected muscle biopsy specimens with a range of neuropathologic diagnoses, including fiber type grouping, Type II atrophy, and congenital fiber type disproportion, were also assessed for immunoreactivity. Our results indicate that the MY-32 monoclonal antibody specifically reacts with Type II (fast twitch) fibers. Immunoreactivity is most intense in cryostat sections immersion fixed in acetone, but moderately intense, specific immunoreactivity can be clearly identified in formalin-fixed (frozen or paraffin-embedded) tissue obtained even 48 hours after death. Application of this nonenzymatic method for fiber type determinations in the neuropathologic evaluation of skeletal muscle biopsies is presented.

Adenosine Triphosphatases↗

PubMed1997

Salivary gland-like tumors of the sellar region.

Herein we present a group of rare tumors of the sella region that have not been previously recognized. Although clinically and radiographically the tumors resemble nonfunctioning pituitary adenomas, their histologic, immunohistochemical, and ultrastructural features differ and indicate a salivary gland origin. The lesions cover a morphologic spectrum that includes cellular pleomorphic adenoma, monomorphic adenoma, oncocytoma, and low-grade adenocarcinoma of the salivary gland. All tumors except the oncocytoma were immunoreactive for cytokeratin and were negative for pituitary hormones and synaptophysin. Ultrastructural characteristics in the cases examined include hypodense stromal material, basal lamina, and tonofilament bundles. The single oncocytoma was packed with mitochondria and lacked membrane-bound secretory granules. DNA ploidy based on image analysis and MIB-1 labeling indices showed diversity within this group of tumors, with labeling indices ranging from 0.06% to 15%. The presumed origin of these rare neoplasms is from salivary gland rests related to the normal pituitary gland. Despite their varied morphology, such tumors are easily confused with pituitary adenoma. Although rare, tumors of salivary gland origin should be considered in the differential diagnosis of unusual adenohypophyseal tumors.

Adenocarcinoma↗

PubMed1997

Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases and review of the literature.

Composite pleomorphic xanthoastrocytoma (PXA)-ganglioglioma (GG) is a rare recently described entity. Only three examples have been documented, one of which showed evidence of malignant transformation. We report an additional four cases and update the literature. With the exception of an 82-year-old man, all patients have been under 30 years of age. The temporal lobe was involved in three cases and cerebellum in another three. Radiologic features were those common to PXA and GG. Histologically, all were "collision tumors" composed of abutting, although spatially distinct, PXA and GG components. In two cases, the second element was only recognized at reexcision or recurrence. Histologic anaplasia, always in the PXA component, was evident as brisk mitotic activity and/or necrosis in five cases. Of the seven patients, one died of disease 17 years after the onset of seizures and after multiple recurrences, the last of which largely resembled glioblastoma. We conclude that the composite PXA-GG is a rare neoplasm that shares many features of its individual components. In addition to its temporal lobe predilection, the cerebellum is frequently affected. As when it occurs in isolation, the PXA component of composite PXA-GG possesses the potential for malignant transformation.

Adolescent↗

PubMed1997

White matter neuronal heterotopia in temporal lobe epilepsy: a morphometric and immunohistochemical study.

A frequent abnormality in temporal lobes (TL) resected for pharmacoresistant epilepsy is the presence of heterotopic neurons within white matter (WM). We compared heterotopic neuron density in 22 TLs surgically resected from epilepsy patients with TLs from 22 non-neurologic cases obtained at autopsies. Neuronal density was assessed on LFB-PAS-stained and parallel sections immunoreacted for microtubule-associated-protein-2 (MAP-2). The white matter area was outlined by an image analysis system. Neurons, identified by morphologic features, were counted within the marked area. Results are expressed as mean +/- SD neurons/mm2. LFB/PAS sections: Epilepsy cases 4.11 +/- 1.86 Autopsy (normal) 2.35 +/- 0.96; MAP-2 sections: Epilepsy cases 4.08 +/- 1.22, autopsy (normal) 1.68 +/-0.92 (significant at 0.05 level by Wilcoxon's Rank Sums test). The lower number of MAP-2-immunopositive neurons in the control group as compared with the histologically identified group is most likely the result of antigen degradation resulting from an increased postmortem interval. These results indicate that normal TLWM contains a heterotopic population of neurons, and that this neuronal density is significantly higher in epilepsy patients. It is felt that this increased neuronal density is an epiphenomenon rather than the cause of seizures, and may be the result of decreased white matter either secondary to disruption of myelination, or loss of neurons as part of mesial temporal sclerosis.

Adolescent↗

PubMed1997

Primary intracerebral malignant fibrous histiocytoma: immunohistochemical findings and etiopathogenetic considerations.

We report a case of malignant fibrous histiocytoma (MFH) arising as a second malignancy in a 13-year-old girl with a previous primitive neuroectodermal tumor of the cerebellum (medulloblastoma). The earlier tumor had been resected and treated with chemotherapy. Because of the age of the patient, no radiation therapy was used. The second neoplasm (an MFH), which presented almost 12 years later, was located within the left frontal region and had discrete meningeal attachment. Histologically, it showed the characteristic storiform pattern and pleomorphism of an MFH and displayed characteristic immunohistochemical reactivity. Careful clinical and radiologic investigation failed to reveal any other neoplasm in the body. This case is unique in that the MFH occurred in a young child after an earlier primary primitive neuroectodermal tumor, although at a distant site, and, importantly, without prior radiation therapy. In this report, we briefly review the literature with an emphasis on immunohistochemistry and histogenesis, raising the possibility that the MFH was induced by chemotherapy.

Adolescent↗

PubMed1996

Disseminated microsporidiosis especially infecting the brain, heart, and kidneys. Report of a newly recognized pansporoblastic species in two symptomatic AIDS patients.

Microsporidia have emerged as important opportunistic AIDS pathogens of the alimentary, respiratory, and urinary tracts. Although nonhuman mammalian microsporidia infections typically include encephalitis, CNS microsporidiosis has not been reported in patients with AIDS. A 33-year-old white male and an 8-year-old black girl presented with seizures and declining mental status. Central nervous system (CNS) imaging studies revealed small peripherally and diffusely enhancing lesions present for at least 2 and 4 months before death, respectively. Both patients expired despite empirical anti-toxoplasma therapy. Their brains contained innumerable soft gray matter lesions that consisted of central areas of necrosis, filled with free spores and spore-laden macrophages, surrounded by microsporidia-infected astrocytes. The complete autopsy of the child also revealed necrotizing and sclerosing cardiac and renal microsporidiosis and infection of the pancreas, thyroid, parathyroids, liver, spleen, lymph nodes, and bone marrow. Infected cells included astrocytes, cardiac myocytes, epithelium, endothelium, vascular smooth muscle cells, hepatocytes, adipocytes, Schwann cells, and macrophages. Light and electron microscopic studies revealed pansporoblastic development within thick-walled sporophorous vacuoles of parasite origin. Although most similar to Pleistophora sp and Thelohania sp, this microsporidian is different from any known species. Microsporidiosis should be considered as the possible cause of a wide range of diseases in AIDS patients, including CNS, cardiac, and renal.

AIDS-Related Opportunistic Infections↗

PubMed1996

Divergent differentiation in pleomorphic xanthoastrocytoma. Evidence for a neuronal element and possible relationship to ganglion cell tumors.

We report the detection of cytoplasmic immunoreactivity for neuronal/neuroendocrine antigens in a subpopulation of tumor cells within seven pleomorphic xanthoastrocytomas (PXAs). The expression of glial and neuronal polypeptides was examined in routinely prepared surgical resections by immunohistochemistry using well-characterized antibodies that recognize glial fibrillary acidic protein (GFAP), synaptophysin (SYN), and neurofilament triplet polypeptides (NFPs) in microwave-enhanced single- and double-immunolabelling experiments. Each neoplasm contained cells that were immunoreactive for SYN and/or NFPs, GFAP, and occasionally for both GFAP and either NFP or SYN. We conclude that abortive neuronal/neuroendocrine differentiation may occur in PXAs, suggesting a relationship between PXA and other developmental neoplasms that reveal a more overt neuronal phenotype, such as ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic ganglioglioma, and with tumors expressing ambiguous glial/neuronal lineage, such as the subependymal giant cell tumor of tuberous sclerosis. These findings suggest that aberrant expression and accumulation of neuronal intermediate filaments may account for the large, pleomorphic cell morphology observed in many of these tumors.

Adolescent↗

PubMed1996

Distribution of heterotopic neurons in normal hemispheric white matter: a morphometric analysis.

One of the frequent abnormalities described in the context of surgically resected temporal lobe (TL) specimens is the presence of heterotopic neurons within white matter (WM). We have attempted to morphometrically define the distribution of the heterotopic neurons in normal subjects, comparing the incidence of heterotopic neurons in TL WM with that in occipital (OL) and frontal lobe (FL) sections. Using a a combination of routine and special stains combined with immunohistochemical confirmation 20 adult autopsy cases were examined. WM from TL, FL, and Ol sections was outlined and the area measured by image analysis. Using defined criteria, heterotopic neurons within these areas were counted. Results confirm our hypothesis that normal adult TL WM contains a significantly higher population of residual/heterotopic neurons than OL and FL WM groups. It is felt that these neurons represent interstitial remnants of the subplate which have failed to undergo programmed cell death. The significance of these findings with regard to assessment of similar findings in temporal lobectomy specimens is addressed. A second intriguing association of this TL WM heterotopia concerns its possible relationship to the more frequent occurrence of ¿malformative neoplasms¿ with neuronal elements (such as ganglioglioma and dysembryoplastic neuroepithelial tumor) in the temporal lobe.

Adult↗

PubMed1996

Glomeruloid vascular structures in glioblastoma multiforme: an immunohistochemical and ultrastructural study.

Microvascular proliferation and glomeruloid vascular structures are important histopathological features of glioblastoma multiforme (GBM). The nature of cells participating in the formation of these structures remains unclear and is the subject of this study. To define these cells better, immunohistochemical markers directed against Factor VIII-related antigen (FVIIIR:Ag), alpha smooth-muscle actin (alpha-SMA), and the lectin Ulex europaeus agglutinin type I (UEA-I) were used. Cells lining the vascular channels and a large number of proliferating abluminal cells participating in glomeruloid vascular structure formation showed positive cytoplasmic staining for FVIIIR:Ag and UEA-I. Abluminal and luminal cells were variably labeled for alpha-SMA. Ultrastructurally, complex aggregates of focally anastomosing capillaries with narrow lumina composed the glomeruloid vascular structure. Endothelial cells were hyperplastic, varied in size and shape, overlapped focally, and contained numerous cytoplasmic filaments. Tight junctions bound together adjacent and overlapping endothelial cells. Weibel-Palade bodies, usually absent from brain microvessels, were present in increased numbers in the newly formed capillaries. Each capillary loop was surrounded by basal lamina encompassing a discontinuous layer of pericytes. This study indicates that glomeruloid vascular structures in GBM are complex aggregates of newly formed microchannels lined with hyperplastic endothelial cells that have an altered morphological phenotype and that these microchannels are supported by basal lamina and pericytes and are devoid of astrocytic end-feet.

Actins↗

PubMed1995

Myelinoclastic diffuse sclerosis presenting as a mass lesion in a child with Turner's syndrome.

A rare case of myelinoclastic diffuse sclerosis (MDS), occasionally referred to as Schilder's disease, is reported in a child with Turner's syndrome. The child originally presented with a 3-week history of nausea, vomiting and frontal headaches. Magnetic resonance imaging showed a large, contrast-enhancing, right frontal lobe mass which was ultimately resected uneventfully. Complete laboratory investigations and pathological evaluation of the resected specimen verified the case to be MDS. The clinical presentation, laboratory evaluation, imaging characteristics and diagnosis are discussed in this review of the disease. The importance of including demyelinating diseases in the differential diagnosis for newly discovered mass lesions in the pediatric population is underscored by this case.

Brain Neoplasms↗