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Isolated Castleman's disease in the neck.

It can be difficult for the clinician to diagnose Castleman's disease when cervical lymphadenopathy is its only manifestation. The diagnostic challenge may be compounded by the presence of a profound fibrotic reaction secondary to multiple biopsy attempts that are frequently required to establish a diagnosis. Castleman's disease is a benign lymphoproliferative disorder and it most frequently involves the mediastinal lymph nodes. The recognition of an occasional variant of this disorder with a potential malignant course and its association with AIDS calls for a greater awareness of this disease among all clinicians.

Adult↗

The relationship between immunodiffusion and agglutination serotypes of Mycobacterium avium and Mycobacterium intracellulare.

Twenty Mycobacterium avium/intracellulare strains of diverse origins and two reference strains of each of Schaefer's serotypes 1-21 were examined by immunodiffusion analysis. The results produced three distinct groups, which we have called A, B and C. Two of these, A and B, appear to be variants, perhaps subspecies of M. avium, and Group C is M. intracellulare. Within each group, rough variants, untypable by Schaefer's agglutination method, were found to be antigenically identical to the smooth parent strain by immunodiffusion analysis. The results obtained were essentially in agreement with those of some previous workers based on animal pathogenicity studies, skin-test studies in sensitized guinea-pigs and DNA homology.

Agglutination Tests↗

[The theoretical analysis of Fick's equation. On the centennial of the use of Fick's principle in physiology].

In the first section Adolf Fick's outstanding scientific performances are pointed out in their historical sequence, particularly the derivation of the laws of diffusion (1855) and the basic equation for determining the heart-minute-volume (Fm) by O2-absorption per time (V02) and arteriovenous O2-difference (AVD), known as Fick's Principle. The latter was derived theoretically in 1870 by Fick, but it found it practical employment by other investigators, in dog not before 1886 and in man not earlier than 1930. In the following two sections the universality of Fick's Principle is shown by explaining its internal relation 1. to Fick's first law of diffusion and 2. to the general law of solution. This is done by mathematical transformation of the relations (formulas)of the physical resp. the physiological standards (parameters). By analyzing the diffusion of a substance into a streaming fluid according to the first diffusion law, perfectly isomorphic equations to Fick's Principle (No. 7 and No. 9) are obtained by what Fick's formula as a determinant of the heart-minute-volume is just proved to be derivable from Fick's first diffusion law. Furthermore by transforming the trivial formula for the determination of substance concentration in a fluid provement is given, that Fick's Principle may be considered a variant of the solution theory. By this the internal relation of the so-called dilution respectively indicating methods depending on the Stewart-Hamilton-Principle to the original Fick's Principle is made visible. In the last section an attempt is made to produce a relation to 1. the so-called physical methods determining the minute volume which primarily are known as a measurement for stroke volume and frequency, and, besides that, 2. to Vierordt's equation, by which the heart-minute-volume is determinable from circulating blood volume and circulation time. This trial is made by equating the value of the minute volume given by Fick's Principle (VO2/AVD) with the product from stroke volume and beating frequency, and on the other hand by equating it with the quotient from circulating blood volume Qc and complete circulation time Tc (Qc/Tc). Finally, physiological arguments are derived from these relations, allowing an evaluation of the relative proportions in circulation adaption during muscular work of the magnitudes of changes in stroke volume, beating frequencies, or the O2-pulse.

Biological Transport↗

Failure of the splicing variant p65 delta of the NF-kappa B subunit p65 to transform fibroblasts.

A naturally occurring splice variant of the p65 subunit of the inducible transcription factor NK-kappa B, called p65 delta, has recently been reported to transform rat-1 fibroblasts in transfection experiments. Criteria for transformation included focus formation, growth in soft agar and tumor formation in athymic mice. In the present study we provide evidence that p65 delta cannot transform either rat-1 or rat-2 cells although p65 delta was efficiently expressed and showed all transcriptional activities reported previously. Eleven rat-1 fibroblasts cells lines selected for stably overexpressing p65 delta also showed neither focus formation nor anchorage-independent growth in soft agar. No transformation of primary rat fibroblasts was evident when p65 delta was cotransfected with either ras or myc oncogenes, whereas a combination of the two oncogenes caused focus formation. We submit that the transforming potential of p65 delta is highly conditional and presumably restricted to a particular subclone of rat-1 cells.

Animals↗

AFLP analysis of nephthytis (Syngonium podophyllum Schott) selected from somaclonal variants.

This study analyzed genetic differences of 19 cultivars selected from somaclonal variants of Syngonium podophyllum Schott along with their parents as well as seven additional Syngonium species and six other aroids using amplified fragment length polymorphism (AFLP) markers generated by 12 primer sets. Among the 19 somaclonal cultivars, 'Pink Allusion' was selected from 'White Butterfly'. Tissue culture of 'Pink Allusion' through organogenesis resulted in the development of 13 additional cultivars. Self-pollination of 'Pink Allusion' obtained a cultivar, 'Regina Red Allusion', and tissue culture propagation of 'Regina Red Allusion' led to the release of five other cultivars. The 12 primer sets generated a total of 1,583 scorable fragments from all accessions, of which 1,284 were polymorphic (81.9%). The percentages of polymorphic fragments within 'White Butterfly' and 'Regina Red Allusion' groups, however, were only 1.2% and 0.4%, respectively. Jaccard's similarity coefficients among somaclonal cultivars derived from 'White Butterfly' and 'Regina Red Allusion', on average, were 0.98 and 0.99, respectively. Seven out of the 15 cultivars from the 'White Butterfly' group and three out of six from the 'Regina Red Allusion' group were clearly distinguished by AFLP analysis as unique fragments were associated with respective cultivars. The unsuccessful attempt to distinguish the remaining eight cultivars from the 'White Butterfly' group and three from the 'Regina Red Allusion' group was not attributed to experimental errors or the number of primer sets used; rather it is hypothesized to be caused by DNA methylation and/or some rare mutations. This study also calls for increased genetic diversity of cultivated Syngonium as they are largely derived from somaclonal variants.

Araceae↗

Identification of two alternate splice variants of a novel serine protease expressed in steroidogenic tissues.

During the search for the serine protease that cleaves pro-gamma-melatropin to stimulate adrenal growth, we identified another novel protease, which we called Adrenal mitochondrial protease (AmP). In situ hybridisation detected AmP transcripts in steroidogenic tissues such as the brain, testis, in ovarian follicles as well as in the adrenal cortex. Full length cloning identified two splice variants differing by a 222 nucleotide insertion in the 5' end of the short variant. The shorter variant codes for a 371 amino acid protein of 40.7 kDa and computer analysis predicts it to be targeted to the cytosol while the longer 445 amino acid protein of 48.4 kDa is mitochondrial. Cellular targeting was confirmed by tagging with GFP. The short variant was clearly cytosolic however, the cells expressing AmP-Long had large vacuoles, possibly as a result of distended (apoptotic?) mitochondria. Due to the mitochondrial localisation of the long variant of the protease and its expression in steroidogenic tissues, it may be expected to be involved in the steroidogenic pathway, possibly by cleaving steroidogenic acute regulatory protein (StAR). We investigated this by co-transfecting AmP-Long with StAR and F2 plasmid into COS-1 cells and measuring the effect on pregnenolone production. It was found that AmP-Long has no effect on steroidogenesis nor cleaves StAR as was shown by western blot analysis using StAR antibody.

Adrenal Glands↗

Genetics of essential hypertension: from families to genes.

Family studies demonstrated the contribution of genetic factors to the development of primary hypertension. However, the transition from this phenomenologic-biometric approach to the molecular-genetic one is more difficult. This last approach is mainly based on the Mendel paradigm; that is, the dissection of the poligenic complexity of hypertension is brought about on the assumption that the individual genetic variants underlying the development of hypertension must be more frequent in hypertensive patients than in controls and must cosegregate with hypertension in families. The validity of these assumptions was clearly demonstrated in the so-called monogenic form of hypertension. However, because of the network of the feedback mechanisms regulating BP, it is possible that that the same gene variant may have an opposite effect on BP according to the genetic and environmental backgrounds. Independent groups of observations (acute BP response to saline infusion, incidence of hypertension in a population follow-up of 9 yr, age-related changes on BP) discussed in this review suggest a positive answer to this question. Therefore the impact of a given genetic variant on BP level must be evaluated within the context of the appropriate genetic epistatic interactions. A negative finding or a minor genetic effect in a general population may become a major gene effect in a subset of people with the appropriate genetic and environmental backgrounds.

Blood Pressure↗

Expression profiling of MMA-1a and splice variant MMA-1b: new cancer/testis antigens identified in human melanoma.

Using high-density oligonucleotide array analysis, we have recently compared the gene expression profiles of 2 human melanoma cell lines with marked difference in metastatic behavior after subcutaneous inoculation into nude mice (de Wit et al., Melanoma Res, in press). We identified an expressed sequence tag (EST), which we called malignant melanoma-associated 1 (MMA-1a), showing evident differential expression between the 2 cell lines. The MMA-1a gene is localized on chromosome 21q22.2 and its mRNA exists of 4 exons. Homology search displayed a splice variant of MMA-1a that lacks exon 3 and that was called MMA-1b. Expression profiles of MMA-1a and MMA-1b are determined by reverse transciptase polymerase chain reaction (RT-PCR) analysis. Among 30 different normal tissue samples, expression of MMA-1a and MMA-1b was exclusively found in the testis after a first PCR of 30 cycles. Even more sensitive screening achieved by performing multiple semi-nested RT-PCR showed no or very low expression in the other normal tissues tested. During melanocytic tumor progression, MMA-1a and/or MMA-1b exhibited an emergence of expression in primary melanoma (20%) and melanoma metastasis samples (30%) after only 1 round of PCR. Expression of MMA-1a and/or MMA-1b was also identified in other tumor cell lines and fresh tumor samples of variable origin, e.g., lung, liver, bladder and soft tissues (sarcomas). We conclude that MMA-1a and MMA-1b are new members of the family of cancer/testis antigens.

Alternative Splicing↗

A novel allelic variant of serum amyloid A, SAA1 gamma: genomic evidence, evolution, frequency, and implication as a risk factor for reactive systemic AA-amyloidosis.

Reactive systemic amyloidosis, also called AA-amyloidosis is a rare fatal complication of common chronic inflammatory diseases such as rheumatoid arthritis. It has been proposed that as yet undefined factors other than persistent elevation of serum level of the precursor protein, serum amyloid A (SAA), are also important for the development of AA-amyloidosis. In this work we show genomic evidence for a novel allelic variant of human SAA, SAA1 gamma, which we have recently identified at the protein level. The SAA1 gamma [Ala52(GCC), Ala57(GCG)] differed from SAA1 alpha [Val52(GTC), Ala57(GCG)] only at one base, indicating a single point mutation. On the other hand, SAA1 beta [Ala52(GCC), Val57(GTG)] had not only one, but additional differences in a nearby intron and this portion was identical to the SAA2 gene, suggesting a crossing-over between the SAA1 and SAA2 genes. Furthermore, we report that there was a significant difference in the observed numbers of SAA1 alleles between rheumatoid arthritis patients with AA-amyloidosis and the control population (chi 2(2) = 11.59, p = 0.003) with a higher frequency of gamma-allele in the AA-amyloid group (0.70 vs. 0.37). There was also a notable difference in the distribution of SAA1 genotypes (chi 5(2) = 14.63, p = 0.012) with an increased frequency of gamma/gamma-homozygotes in the AA-amyloid group (0.60 vs. 0.18). Thus our findings indicate that this novel allelic variant may be an important risk factor for the development of AA-amyloidosis.

Adult↗

Surgical correction in complete levotransposition of the great arteries with an unusual subaortic ventricular septal defect.

Six children with an uncommon variant of complete (that is, physiologically uncorrected) transposition of the great arteries are described. In this malformation, levoposition of the aorta is coincident with situs solitus and concordant atrioventricular relations. All patients underwent successful surgical correction. Four had a ventricular septal defect; in three, the defect was subaortic and because of its unusual anatomic features, a right ventriculotomy was required for repair. Interatrial transposition of venous return was carried out in all cases by insertion of a baffle, as in complete dextrotransposition of the great arteries. The surgical verification of the arterial positions in these cases illustrated the fallibility of the so-called loop rule. The significance of the cases in relation to terminology, classification and morphogenesis of this variant is discussed.

Angiocardiography↗

Hb F-Porto Torres [Agamma75(E19)Ile-->Thr, 136(H14)Ala-->Ser]: a novel variant of the Agamma chain having two substitutions, one being that of Hb F-Sardinia.

The abnormal Hb F-Porto Torres [Agamma75(E19)Ile-->Thr, 136(H14)Ala-->Ser] was observed during a cord blood survey for hemoglobinopathies in North Sardinia. This silent variant showed the same mobility as Hb F-Sardinia in isoelectric focusing (IEF) of the tetramers, whereas the abnormal globin chain was clearly separated by acid-urea-Triton polyacrylamide gel electrophoresis (AUT-PAGE) from the normal Ggamma- and Agamma-globin chains. Separation of the globin chains by reversed phase high performance liquid chromatography (HPLC) indicated the following percentages: Ggamma 68.4, Agamma 14.0, Xgamma 17.6, that strongly suggested the abnormal chain as being a variant of the Agamma-globin. Sequencing of the gamma-globin genes indicated that the mutated gene was in fact an Agamma with two nucleotide replacements, one being the ATA-->ACA (Ile-->Thr) at codon 75 (the so-called AgammaT of the rather common Hb F-Sardinia) and the second the GCA-->TCA (Ala-->Ser) at codon 136. This new variant is the seventh having the sequence of the AgammaT chain with an additional mutation so far described and the third characterized by gene sequencing.

Amino Acid Substitution↗

[Immune complex hyperuricemic nephritis: aspects of its morphology and pathogenesis].

The authors described the results of an immunohistochemical, electron microscopic and morphometric study of the kidney bioptates of 45 patients with latent glomerulonephritis with hyperuricemia, 8 patients with primary gout and 12 patients with latent glomerulonephritis without hyperuricemia. Two possible variants of the involvement of the renal glomerula were revealed against a background of purine metabolism: typical immunocomplex glomerulonephritis and the so called "reactive" mesangial changes. The expression of interstitial changes (by the results of histometric investigation) was maximum in gout, slightly less in latent nephritis with hyperuricemia and minimum in nephritis without hyperuricemia. The authors emphasized the possibility of immunocomplex nephritis as one of the variants of renal lesion in gout and hyperuricemia and the necessity of specifying therapeutic modalities to be used in this condition including general nephrological approaches to the treatment of latent nephropathies.

Biopsy, Needle↗

Exploring the evolution of Wolbachia compatibility types: a simulation approach.

Wolbachia-induced cytoplasmic incompatibility (CI) is observed when males bearing the bacterium mate with uninfected females or with females bearing a different Wolbachia variant; in such crosses, paternal chromosomes are lost at the first embryonic mitosis, most often resulting in developmental arrest. The molecular basis of CI is currently unknown, but it is useful to distinguish conceptually the male and female sides of this phenomenon: in males, Wolbachia must do something, before it is shed from maturing sperm, that will disrupt paternal chromosomes functionality [this is usually termed "the modification (mod) function"]; in females, Wolbachia must somehow restore embryonic viability, through what is usually called "the rescue (resc) function." The occurrence of CI in crosses between males and females bearing different Wolbachia variants demonstrates that the mod and resc functions interact in a specific manner: different mod resc pairs make different compatibility types. We are interested in the evolutionary process allowing the diversification of compatibility types. In an earlier model, based on the main assumption that the mod and resc functions can mutate independently, we have shown that compatibility types can evolve through a two-step process, the first involving drift on mod variations and the second involving selection on resc variations. This previous study has highlighted the need for simulation-based models that would include the effects of nondeterministic evolutionary forces. This study is based on a simulation program fulfilling this condition, allowing us to follow the evolution of compatibility types under mutation, drift, and selection. Most importantly, simulations suggest that in the frame of our model, the evolution of compatibility types is likely to be a gradual process, with new compatibility types remaining partially compatible with ancestral ones.

Animals↗

[Non-Hodgkin's lymphoma. Cytology and cytochemistry].

Imprints of lymph nodes and tumor specimens from 442 patients with non-Hodgkin's lymphoma (NHL) were evaluated cytologically and cytochemically. With the exception of hairy cell leukemia, special forms of peripheral pleomorphic T-cell lymphoma, and lymph node plasmacytoma, all types of NHL of the Kiel classification were included in this study. The investigations were performed on slides stained with Pappenheim (May-Grünwald-Giemsa) or conventional cytochemical techniques for substrate and enzyme demonstration, such as periodic acid Schiff (PAS), neutral and acid non-specific alphanaphthyl acetate esterase, and acid and alkaline phosphatase. In certain cases further techniques for substrate and enzyme demonstration, including myeloperoxidase and naphthol AS-D chloroacetate esterase, were used. We combined the cytologic and cytochemical evaluation with an attempt to diagnose the type of lymphoma on imprints without prior knowledge of the histologic findings or clinical data, in other words, blind. At the same time, we attempted to distinguish the NHL from reactive lymph node lesions, nonlymphoid malignant tumors, and systemic diseases. For this purpose, 75 cases of lymphadenitis and 33 cases of nonlymphoid neoplasia were mixed with the NHL for a blind test. In the following we will summarize the results pertaining to the NHL only. Chronic lymphocytic leukemia of B type (B-CLL; n = 75) was cytologically characterized by the presence of so-called prolymphocytes and paraimmunoblasts and a predominance of lymphocytes. In our opinion, there are four main variants of B-CLL: small-cell ("mature") CLL, a type in which prolymphocytes are plentiful ("immature" CLL), LP immunocytoma-like ("basophilic") CLL, and a type of CLL with centrocyte-like lymphocytes ("B2-CLL"). B-CLL had no cytochemical profile of its own. The reproducibility of the diagnosis on imprints was 80%. In prolymphocytic leukemia of B type (B-PLL; n = 1) prolymphocytes and blast cells were plentiful. In the case studied, acid phosphatase activity was moderately strong (evident as granules distributed in a semicircular fashion and focally accumulated). In the blind test we diagnosed it only descriptively as an "acid phosphatase-rich lymphoma of low-grade malignancy with a high prolymphocyte and blast cell content". Chronic lymphocytic leukemia of T type (T-CLL) and prolymphocytic leukemia of T type (T-PLL) could not be distinguished with certainty in sections or imprints. There was also no strict delineation between T-CLL and T-PLL in blood smears. The T-CLL and T-PLL cases we evaluated (n = 4) belonged to the so-called helper cell type.(ABSTRACT TRUNCATED AT 400 WORDS)

B-Lymphocytes↗

[Efficacy of PCR-microwell plate hybridization method (Amplicor Mycobacterium) for detection of M. tuberculosis, M. avium and/or M. intracellulare in clinical specimens].

Recently, a new kit to detect and identify mycobacteria in clinical specimens was developed by Japan Roche Co. Limited. The new method is based on amplification of DNA of mycobacteria in clinical specimens by PCR and hybridization of amplified DNA by microwell plate hybridization method, which is the "Amplicor Mycobacteria, Roche, (AMP-M)". Cooperative study was organized with 15 tuberculosis hospitals and institutions throughout Japan, and 349 clinical specimens from newly admitted tuberculosis patients and/or suspects were collected during July and August, 1993. All the specimens were examined by smear microscopy (Ziehl-Neelsen's staining), culture on Ogawa egg media, culture on variant 7H9 liquid media and by AMP-M. Excluding 25 specimens which had failed to identify the species of mycobacteria because of contamination, disability to multiply on the transplanted solid media and so on, the results of the examinations in 324 specimens consisting of 167 specimens from previously untreated cases and those of 157 specimens from previously treated cases were analysed. Main results obtained were as follows; 1. Of 70 smear positive specimens from previously untreated cases, culture positive on Ogawa media and 7H9 media, and by AMP-M positive were 59 (84.3%), 61 (87.1%) and 66 (94.3%), respectively. Of 97 smear negative specimens, culture positive were 20 (20.6%), 22 (22.7%) and 27 (27.8%), respectively. The AMP-M showed the highest positive rate in both groups. 2. The sensitivity and the specificity of AMP-M in previously untreated cases were calculated by assuming that positive on Ogawa and/or variant 7H9 media is "positive". The sensitivity was 95.8% (68/71) and the specificity was 94.8% (91/96) for M. tuberculosis in previously untreated cases. The sensitivity and the specificity for M. avium and M. intracellulare were all 100%, although the numbers observed were small. 3. So-called false positive of the AMP-M were observed in 5 cases out of 96 culture negatives on both Ogawa and variant 7H9 media. However, all 5 cases were positive by repeated AMP-M, 3 become culture positive later, and another 2 showed clinical findings consistent with tuberculosis. Hence, the authors considered that the false positive rate of the AMP-M method is to be very low in previously untreated cases. 4. Of 86 smear positive cases with history of previous chemotherapy, the positive culture on Ogawa media, variant 7H9 media and that by AMP-M method were 64 (74.4%), 77 (89.5%) and 85 (98.8%), respectively. In the smear negative cases, culture positive was 10 out of 71 (14.1%), 13 (18.3%) and 24 (33.8%), respectively.

DNA, Bacterial↗

DNA polymorphisms as modulators of genotoxicity and cancer.

Cancer arises as a result of several factors, including multiple genes and environmental exposures. It is generally accepted that genetic polymorphisms are associated with most common disorders like cancer. The majority of polymorphisms are single nucleotide polymorphisms (SNPs) which occur with a frequency of 10(-6). Susceptibility-conferring alleles are not sufficient to cause disease, but modulate the risk in combination with other alleles and environmental exposures, except in the extreme case of Mendelian cancer syndromes (e.g. FAP, HNPCC, Rb). The Environmental Genome Project identifies, among others, two lines of research along which we have been working and are the topic of the present paper, namely (i) allele-disease associations and (ii) functional studies of allelic variants. Case-control association studies conducted by us and others showed that polymorphism at a single site could increase risk-predictability by a factor < 2. It is known, however, that the individual risk predictability increases by associating multiple genetic polymorphisms as was demonstrated for breast, renal and thyroid cancer. Functional genomics of the putative susceptibility-alleles involved in cancers can improve substantially the strength of association studies. This calls for cell-systems capable of tracking different gene activities, which may clarify the possible role of allelic variants in certain cancers. This endeavour is likely to be met by the bacterial tester strain, MTC, described here.

Alleles↗

Histogenesis of clear cell chondrosarcoma. An immunohistochemical study with osteonectin, a non-collagenous structure protein.

The histogenesis of clear cell chondrosarcoma is still unclear: Apart from typical clear cell tumor areas, extensive production of woven bone formation suggests within the clear cell cartilagenous stroma is an intriguing phenomenon. Three cases of clear cell chondrosarcoma documented in the Bone Tumor Registry of Westphalia were examined for their patterns of osteonectin expression, and compared with other bone tumors of either osseous or cartilaginous origin, and with normal cartilage tissue. Found predominantly in osseous structures, the protein osteonectin takes part in the formation of new bone. The three clear cell chondrosarcomas showed a strong immunoexpression of osteonectin in clear cell, chondroid and in osseous tumor areas. Similarly, evidence of osteonectin was also found in osteoblastic and in chondroblastic osteosarcomas as well as in osteoblastomas. In contrast, osteonectin could not be demonstrated in the chondrosarcomas and mesenchymal chondrosarcomas from our registry that were analysed for comparison, and was found only minimally in the fibroblastic areas of dedifferentiated chondrosarcomas. The chondroblastic tumor components were always negative. There was no immunoexpression of osteonectin either in fetal or adult intervertebral disc tissue. The present immunohistochemical study of osteonectin has distinctly separated clear cell chondrosarcoma from the other variants of chondrosarcoma, and aptly verified the specificity of this entity. Moreover, the study would call for further histogenetic evaluation of clear cell chondrosarcoma, since the pattern of osteonectin expression in that tumor seems to indicate an osteogenic rather than a chondrogenic origin.

Adenocarcinoma↗

Dysembryoplastic neuroepithelial tumor.

Dysembryoplastic neuroepithelial tumors (DNTs) were first described in 1988. A DNT is a cortical tumor that produces enlargement of a gyrus, forming a megagyrus that exceeds the normal thickness of the cortex. This tumor is generally seen in young patients with a long-standing history of drug-resistant and disabling seizures mostly of the complex partial type. No neurological deficits are found between the interictal periods in the majority of the reported cases. A general agreement exists over the clinical and radiological manifestations of a DNT as well as the benign biological behavior. Two pathological variants of DNT have been recognized: the single form, composed only of the so-called specific glioneuronal element, and the complex form that additionally shows glial nodules and foci of cortical dysplasia. Nevertheless, and despite the benign biological course, nuclear atypias, cellular monstruosities, foci of necrosis and mitosis can also be found. Surgical eradication of the tumor will usuallly have a good prognosis, without recurrences and with a positive control to seizure-free clinical outcome. Controversy continues to exist over a hamartomatous or a neoplastic origin of this lesion. The DNT has been placed among the neuronal and mixed neuronal-glial neoplasms in the revised World Health Organization (WHO) brain tumor classification, a category that includes the gangliogliomas and the central neurocytomas. Ultrastructural studies and immunostaining techniques may suggest that these three lesions represent different spectrums of the same condition. This paper reviews the most recent publications to offer a better understanding of DNTs and their implications in diagnosis and management.

Journal Article↗