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Differentiation in the medulloblastoma. A histological and immunohistochemical study.

The histological and immunohistological features of medulloblastomas were investigated in patients participating in an ongoing cooperative study of the Societé International d'Oncologie Pédiatrique (SIOP). Of 51 neoplasms, four were the classic desmoplastic variant. In regard to the histological features used to grade neoplasms, considerable inter- and intratumoral variation was observed. The neoplasms with the most pleomorphic and coarsely structured nuclei tended to be neuroblastic, whereas the most delicate and uniform nuclei were found in the desmoplastic neoplasms. Twenty-one of the cases exhibited neuroblastic differentiation in the form of neuroblastic rosettes. Of these, three also contained neoplastic ganglion cells. Of the five medulloblastomas that were calcified, four contained neuroblastic rosettes in accord with the tendency for calcification in neuroblastic neoplasms. In many of the neuroblastic neoplasms, islands of markedly neuron-specific enolase (NSE)-positive cells were seen. Although the limited specificity of this marker enzyme is recognized, we believe that this focal intense staining could indicate neuronal differentiation somewhat more advanced than in small NSE-positive islands of reduced cellularity, many of which were strongly positive. The nuclei in these island were usually larger and more vesicular than those in the surrounding densely cellular areas. These features and the frequent association with Homer-Wright rosettes suggest that these foci represent a form of neuronal differentiation. Astrocytic differentiation was more difficult to define and required the use of staining for glial fibrillary acidic protein (GFAP). Six neoplasms contained GFAP-positive cells that were clearly neoplastic. Many others contained scattered reactive astrocytes and dispersed cells whose neoplastic versus reactive nature could not be defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Iodine-123-alpha-methyl tyrosine in gliomas: correlation with cellular density and proliferative activity.

UNLABELLED: Amino acid transport rate in gliomas can be assessed using SPECT and the amino acid L-123I-alpha-methyl tyrosine (IMT). This study attempted to correlate the uptake of IMT by gliomas with the proliferative activity and cellular density of these neoplasms. METHODS: The study used 27 patients with gliomas, including 18 patients with high-grade tumors and nine patients with low-grade neoplasms. Amino acid transport rate was determined using IMT and the triple-headed SPECT camera. Proliferative activity was immunohistochemically assessed as the relative number of cells expressing the Ki-67 nuclear antigen; cellular density was evaluated using light microscopy. RESULTS: Relative IMT uptake correlated significantly with the proliferative fraction of tumor cells (r = 0.6, p < 0.001). There was no significant correlation between IMT uptake and cellular density (r = 0.25, p > 0.05). CONCLUSION: The uptake of the SPECT radiopharmaceutical IMT is related to proliferative activity rather than to the cellular density of gliomas.

Astrocytoma↗

Salivary mucoepidermoid carcinoma: revisited.

Mucoepidermoid carcinoma (MEC) is a malignant epithelial neoplasm composed of varying proportions of mucous, epidermoid, intermediate, columnar, and clear cells and often demonstrates prominent cystic growth. MEC is usually subclassified as low, intermediate, or high grade on the basis of its histologic features, including the presence of cystic spaces, cellular differentiation, proportion of mucous cells, growth pattern, type of invasion, and cytologic atypia. Because even low-grade neoplasms may metastasize, the term mucoepidermoid tumor is inappropriate. The 3-level grading approach to tumor classification has found general acceptance among pathologists; differences in biologic behavior can be demonstrated even though clinical stage has become a better prognosticator. However, in the case of MEC, no universal agreement exists regarding which histologic grading criteria are most the useful, and grading has varied. These issues have led to the investigation of more subjective systems. We describe these new schemes, the histologic variants of MEC, and the ancillary methods that allow for further stratification of patients with MEC, especially for patients with grade 2 tumors, which have a variable and unpredictable clinical course.

Carcinoma, Mucoepidermoid↗

Dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum: a lesion often misdiagnosed as glioma: report of 10 cases.

The authors report a series of 10 low-grade neoplasms arising in the midline anteriorly in the region of the septum pellucidum with many of the histologic features of dysembryoplastic neuroepithelial tumor (DNT). The patients (five female, five male) ranged in age from 6 to 35 years (mean age, 21.5 years). The most common presenting symptoms were headache, nausea and vomiting, and visual disturbances. Radiographically, the tumors extended into the lateral ventricles from the septal region and obstructed the foramen of Monro. Varying degrees of hydrocephalus were present. The lesions were lobular, well-delineated, hypointense to brain on T1-weighted magnetic resonance imaging, and hyperintense on T2-weighted images. They were uniformly nonenhancing or showed only minimal peripheral enhancement. The tumors, in aggregate, had the histologic features of DNT. These included a mucin-rich background, oligodendrocyte-like cells, "floating neurons," and a "specific glioneuronal element." Seven patients underwent gross total resection and two underwent subtotal resection. No patients received adjuvant chemotherapy or radiotherapy. On follow-up (n = 6; median, 14 months), all tumors had either not recurred or were radiologically stable. On the basis of both neuroimaging and histopathology, DNT-like lesions should be considered in the differential diagnosis of midline intraventricular tumors in children and young adults. Distinction from more aggressive neoplasms is essential because these tumors appear to behave in a benign fashion.

Adolescent↗

Primary neuroendocrine carcinomas of the mediastinum: review of current criteria for histopathologic diagnosis and classification.

Primary neuroendocrine neoplasms occurring in the mediastinum are rare. The spectrum of such tumors can range from low- to high-grade neoplasms. The histogenesis of these tumors is varied, and some of them may originate from ectopic tissues in the mediastinum whereas others represent tumors native to the thymus. Primary thymic neuroendocrine carcinomas therefore need to be separated from other neuroendocrine neoplasms of the mediastinum, namely ectopic parathyroid tumors and paragangliomas. The histopathologic classification of primary neuroendocrine carcinomas of the mediastinum is still under debate and continues to be controversial, as is attested to by the different publications on the topic. Some authors continue to use old terms such as "carcinoid" and "atypical carcinoid" to designate these lesions, whereas others favor the use of a more unifying nomenclature that acknowledges the malignant nature of these lesions, namely that of neuroendocrine carcinoma. However, one aspect that all agree on is that, when they occur in the thymic region, these tumors should be considered as aggressive neoplasms capable of local recurrence and distant metastasis. This review will center on the morphologic spectrum of neuroendocrine carcinomas of the thymus, with special emphasis on diagnostic features and criteria for classification.

Carcinoma, Neuroendocrine↗

Fine needle aspiration biopsy of the parotid gland. Diagnostic problems and 2 uncommon cases.

OBJECTIVE: To describe the diagnostic problems and present our findings in 2 uncommon tumors, malignant myoepithelioma and small cell undifferentiated carcinoma, by examining fine needle aspiration (FNA) biopsies of parotid gland masses. STUDY DESIGN: The study group consisted of 34 females and 41 males 12-80 years old, with an average of 44. Excluding inflammatory results, all adequate aspirates were confirmed histologically to determine the correlation. RESULTS: Sensitivity of FNA cytology was 91%, with specificity of 98%. We encountered some difficulties, and therefore misdiagnoses, in evaluating specific neoplasms, such as adenoid cystic carcinoma and Warthin's tumor, which have well-established cytologic diagnostic criteria. Two cases of uncommon neoplasms of salivary glands, small cell undifferentiated carcinoma and malignant myoepithelioma, were cytologically found to be malignant but not further classified. In addition, tuberculous parotitis, with its well-defined features, should to be referred since unnecessary surgery can be avoided by using FNA cytology. CONCLUSION: FNA is a sensitive and specific diagnostic tool for parotid gland masses. However, specific classification of neoplasms may sometimes be difficult. Pathologists should be aware of specific entities, such as malignant myoepithelioma, when evaluating high grade neoplasms.

Adenolymphoma↗

Survivin expression in ganglioglioma.

Gangliogliomas are unusual central nervous system (CNS) neoplasms occurring mainly in children and young adults and inducing chronic pharmacoresistant epilepsy. These are usually well differentiated neuroepithelial tumors composed of neurons in association with neoplastic glial cells. Gangliogliomas present with favorable outcome. However, some may recur and/or progress to anaplasia and be associated with a dismal prognosis. Since histopathological features do not consistently correlate with clinical outcome, reliable prognostic factors have yet to be defined in gangliogliomas. Survivin is an anti-apoptotic protein whose expression has been found to be of prognostic significance in many human cancers, including gliomas. The objective of this study was to assess survivin expression using immunohistochemistry in 15 gangliogliomas. Ten lesions were low-grade neoplasms whereas 5 were high-grade tumors. Survivin expression appeared restricted to the neoplastic glial component and was detected in 6/15 gangliogliomas. Two additional tumors expressed survivin upon relapse. Half survivin expressing lesions displayed less than 1% immunoreactive cells. Survivin expression in more than 5% neoplastic glial cells was detected only in malignant and/or recurrent gangliogliomas. Extended lifespan in survivin expressing cells might enhance aggressive behavior in these tumors through accumulation of mutations, thereby allowing progression to malignant phenotypes. Survivin expression may carry a negative prognostic value in gangliogliomas.

Adolescent↗

Comparison of permeability in high-grade and low-grade brain tumors using dynamic susceptibility contrast MR imaging.

OBJECTIVE: The purpose of this study was to compare permeability measurements in high-grade and low-grade glial neoplasms using a T2(*)-weighted method. Our hypothesis was that permeability measurements using a T2(*)-weighted technique would show permeability in high-grade neoplasms to be higher than that in low-grade neoplasms. MATERIALS AND METHODS: Twelve patients with biopsy-proven high-grade neoplasms and 10 patients with biopsy-proven low-grade neoplasms underwent dynamic susceptibility contrast MR perfusion imaging (TR/TE, 1500/80) after bolus infusion of 0.2 mmol/kg of MR contrast material. Color-coded permeability-weighted maps were created using a model that weights relative contributions to signal intensity from intravascular T2(*) effects and extravascular T1 effects from blood-brain barrier permeability. Two measures of permeability were performed: mean value of highest permeability found on three images through the tumor (mean regional value) and highest value found at any region of interest in the tumor (single area of maximum permeability). Depending on the normality of the data sets, we used the Wilcoxon's rank sum test or the two-tailed Student's t test for statistical analysis. RESULTS: For low-grade tumors, the range was 0.006-0.041, and the median of the mean regional value for each image was 0.017. For high-grade tumors, the range was 0.005-0.092, and the median of the mean regional value was 0.035 (p = 0.025). For low-grade tumors, the range was 0.008-0.045, and the mean of the single area of maximum values was 0.02. For high-grade tumors, the range was 0.007-0.136, and the mean of the single area of maximum values was 0.054 (p = 0.018). CONCLUSION: Permeability values for high-grade tumors obtained using a T2(*)-weighted method were significantly greater than those for low-grade tumors and are consistent with previous studies reporting results using T1-weighted methods.

Adult↗

Characterization of lipids from human brain tissues by multinuclear magnetic resonance spectroscopy.

Multinuclear ((1)H, (13)C, and (31)P) magnetic resonance spectroscopy are applied to the biochemical characterization of the total lipid fraction of healthy and neoplastic human brain tissues. Lipid extracts from normal brains, glioblastomas, anaplastic oligodendrogliomas, oligodendrogliomas, and meningiomas are examined. Moreover, the unknown liquid content of a cyst adjacent to a meningioma is analyzed. Two biopsies from glioblastomas are directly studied by (1)H-NMR without any treatment (ex vivo NMR). The (1)H- and (13)C-NMR analysis allows full characterization of the lipid component of the cerebral tissues. In particular, the presence of cholesteryl esters and triglycerides in the extracts of high grade tumors is correlated to the vascular proliferation degree, which is different from normal brain tissue and low grade neoplasms. The (31)P spectra show that phosphatidylcholine is the prominent phospholipid and its relative amount, which is higher in gliomas, is correlated to the low grade of differentiation of tumor cells and an altered membrane turnover. The ex vivo (1)H-NMR data on the glioblastoma samples show the presence of mobile lipids that are correlated to cell necrotic phenomena. Our data allow a direct correlation between biochemical results obtained by NMR and the histopathological factors (vascular and cell proliferations, differentiation, and necrosis) that are prominent in determining brain tumor grading.

Brain Chemistry↗

Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers.

Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodies specific for the Bcl-2, Bax, Bcl-X, and Mcl-1 proteins in combination with immunohistochemical methods, we examined for the first time the expression of these bcl-2 family genes in 64 cases of adenocarcinoma of the prostate, including 10 Gleason grade 2 to 4 tumors, 21 grade 5 to 7 tumors, 17 grade 8 to 10 tumors, 8 lymph node metastases, and 8 bone metastases. In addition, 24 cases of prostatic intraepithelial neoplasia (PIN) or PIN coexisting with carcinoma were also evaluated. All immunostaining results were scored with regard to approximate percentage of positive tumor cells and relative immunostaining intensity. Expression of the anti-apoptotic protein Bcl-2 was present in 16 of 64 (25%) adenocarcinomas and tended to be more frequent in high grade tumors (Gleason grade 8 to 10; 41%) and nodal metastases (38%) than in lower grade (Gleason 2 to 7) primary tumors (16%; P < 0.05). Bcl-X was expressed in all 64 (100%) tumors evaluated. Bcl-X immunointensity was generally stronger in high grade primary tumors (grade 8 to 10) and metastases compared with PIN and low grade neoplasms (P < 0.0001). In addition, the proportion of specimens with > 50% Bcl-X-immunopositive tumor cells also was higher in advanced grade primary tumors (Gleason 8 to 10) and metastases than in PIN and low grade tumors (Gleason 2 to 7; P < 0.005). The anti-apoptotic protein Mcl-1 was expressed in 52 of 64 (81%) tumors, compared with only 9 of 24 (38%) cases of PIN (P < 0.001). In addition, the percentage of Mcl-1-positive cells was typically higher in Gleason grade 8 to 10 tumors and metastases than in PIN or lower grade tumors (P = 0.025). In contrast, the pro-apoptotic protein Bax was expressed in all prostate cancers evaluated, with high percentages of immunopositive cells and strong immunointensity typically occurring regardless of tumor grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate.

Adenocarcinoma↗

The expression of the epitope H recognized by the monoclonal antibody H is higher in astrocytomas compared to anaplastic astrocytomas and glioblastomas.

The epitope H contains an O-linked N-acetylglucosamine residue in a specific conformation and/or environment recognized by the monoclonal antibody H (mAbH). mAbH stains two bands with Mr x0.001 of 209 and 62 in lysates of cultured rat astrocytes. In normal human brains epitope H is absent from the overwhelming majority of normal astrocytes and only sparse reactivity is observed, confined mostly to fibrous astrocytes. Upregulation of the epitope H takes place in reactive astrocytes. In the present study we used the mAbH to investigate the immunohistochemical expression of the epitope H in 41 cases of astrocytic tumors including 19 cases of astrocytomas, 8 cases of anaplastic astrocytomas and 14 cases of glioblastomas. Seven out of 19 cases (37%) of astrocytomas showed weak staining, 10 cases (53%) moderate staining and 2 cases (10%) intense staining. Two out of 8 cases (25%) of anaplastic astrocytomas appeared negative, 3 cases (37.5%) showed weak staining and 3 cases (37.5%) moderate staining. Four out of 14 cases (28.5) of glioblastomas appeared negative, 7 cases (50%) showed weak staining, 2 cases (14%) showed moderate staining and only one case (7.5%) showed intense staining. There was a statistically significant elevation of the expression of the epitope H in astrocytomas compared to anaplastic astrocytomas and glioblastomas (p=0.047). These results indicate that the expression of the epitope H decreases in parallel with the increase of the grade of astrocytic tumors from low to higher grade neoplasms. This could be of interest for predicting the progression of an astrocytic tumor since it is documented that astrocytomas progress to tumors of higher grade of malignancy. Further investigation of the antigens bearing the epitope H might help to gain further insight into the mechanisms which regulate the progression of astrocytic tumors and to examine the relevance of the mAbH staining with respect to the prognosis of these neoplasms.

Animals↗

Clonal analysis of human astrocytomas.

Clonal analysis of many human cancers have generally confirmed that they are monoclonal. Although astrocytic neoplasms are the most frequently occurring primary tumors in the central nervous system, their clonal composition has not been systematically studied. In this report, the clonal composition of 22 human astrocytomas of all histological grades (2 well-differentiated astrocytomas, 3 anaplastic astrocytomas and 17 glioblastoma multiforme) was determined by analysis of the pattern of X-chromosome inactivation. Leukocyte and non-tumor brain DNA were used as controls. In addition, specimens from different parts of four glioblastoma multiforme were analyzed to determine whether remote areas of the same tumor had the same clonal composition. Eighteen of nineteen informative astrocytomas had a monoclonal pattern of X-chromosome inactivation; one glioblastoma multiforme had loss of heterozygosity on the X chromosome. Specimens from different areas of the same tumor all had identical patterns of X-chromosome inactivation. Leukocytes and non-tumor brain used as controls uniformly had a polyclonal pattern of X-chromosome inactivation. Furthermore, loss of heterozygosity for chromosomes 10 or 17 p loci was found in 64% (9/14) of informative specimens and identical allelic patterns were observed in specimens from different areas of the same tumor. Our results demonstrate that human astrocytomas from low to high-grade are characterized by monoclonal cell populations. The presence of monoclonality in even low-grade neoplasms suggests that in astrocytic tumors the establishment of monoclonality occurs quite early. Also, the finding of a monoclonal pattern in intermediate- and high-grade astrocytomas further supports the hypothesis that clonal expansion underlies astrocytic tumor progression.

Adult↗

The relationship between number of interphase nors and nor-bearing chromosomes in non-Hodgkin's lymphoma.

The ribosomal genes (located on the acrocentric chromosomes 13-15, 21-22) may be identified by their silver stained gene products, i.e. NOR related proteins. The NOR bearing chromosome activity can be observed at metaphase with the potential for all ten chromosomes to be positively stained. On the other hand, during interphase they fuse so that eventually only a single silver positive structure is seen in resting normal cells. Investigations of histopathological sections of non-Hodgkin's lymphoma (NHL) have demonstrated a correlation between the numbers of interphase NORs and the grade of tumour. There is generally a higher number of interphase in high-grade, and a lower number in low-grade tumours. This histopathological and cytogenetic study of 13 patients with NHL shows that the higher numbers of interphase NORs in the high-grade tumours is not necessarily a reflection of increased numbers of NOR-bearing chromosomes. Examples were found of high-grade neoplasms, showing the expected high numbers of interphase NORs, but not an increased number of NOR-bearing chromosomes. Conversely, some low-grade tumours, with the expected low number of interphase NORs, had increased numbers of NOR-bearing chromosomes. Our conclusion is that the interphase NOR number is related to factors other than chromosome numbers. We suggest that NOR numbers at interphase may be related to cell turnover. This is supported by previous investigations using DNA flow cytometry and the monoclonal antibody Ki67.

Chromosomes, Human↗

Diagnosis and prognosis of renal cell carcinoma: highlights from an international consensus workshop.

An International Consensus Conference reviewed the current state of histologic classification of renal cell carcinoma, grading, TNM staging, current and future prognostic factors, and clinical research priorities. International agreement was reached on the histologic classification of renal cortical epithelial neoplasms. Grading of renal cell carcinoma was recognized as subjective; nuclear grading was preferred, but the optimal system has not yet been described or tested. Current methods of staging for renal cell carcinoma have evolved and merit attention for future changes; new standards for 1997 have been reported by the American Joint Committee on Cancer and the Union International Contre le Cancer (UICC). Prognostic factors are stratified according to their utility prior to treatment, after nephrectomy, and in the presence of recurrent or metastatic cancer. New and pending prognostic factors merit serious consideration for further investigation, with emphasis on practical relevance. Future research priorities include a multitude of new targets for intervention recognized by molecular biology, as well as chemoprevention, immunotherapy, gene therapy, and vaccine therapy.

Carcinoma, Renal Cell↗

The prognostic significance of histological grading and pathological staging in carcinoma of the prostate.

Histological grading and pathological staging are relevant factors in the prognosis of patients with prostatic cancer. Of 115 consecutive patients with carcinoma of the prostate that was staged fully before treatment 16 had stage A2 disease. Low grade neoplasms were present in 6 of these patients and evidence of nodal metastases was documented at lymphadenectomy in 2. Similarly, 4 of 35 patients with low grade stage B1 disease had nodal metastases. With the enzymatic and/or radioimmunoassay techniques for acid phosphatase determination we were unable to select those patients with nodal metastases. From these studies we believe that low grade, low stage carcinoma of the prostate retains a potential for metastatic disease and that acid phosphatase determinations are unreliable in detecting bulky regional nodal involvement.

Acid Phosphatase↗

The distribution of non-Burkitt, non-Hodgkin's lymphomas in Uganda in relation to malarial endemicity.

Biopsies of malignant lymphomas collected from all districts of Uganda, filed in the Kampala Cancer Registry for the 8-year period 1966-1973, were reviewed. This review confirmed a relatively low frequency of follicle-centre-cell lymphomas with a follicular growth pattern and the geographical co-distribution between malaria and Burkitt's lymphoma (BL). It also showed a similar, though less marked, association between non-Burkitt, non-Hodgkin's lymphoma (NBNHL) and malarial endemicity, and a correlation in the regional incidence between BL and NBNHL. In both comparisons, these associations were strong for high-grade lymphomas and weak for low-grade neoplasms. BL and other NHL may therefore share, to a varying degree, some common pathogenesis. The excess in frequency of NBNHL of high-grade malignancy in malarial endemic areas appears to be in contrast to Western countries where most non-Hodgkin's lymphomas are of low-grade malignancy.

Humans↗

Neuroendocrine Tumors of the Head and Neck: A Selected Review with Emphasis on Terminology.

Virtually every variant of neuroendocrine neoplasia can occur, at least rarely, in the head and neck region. This review focuses on the terminology surrounding neuroendocrine carcinomas of the larynx and their distinction from morphologically similar but biologically distinctive neoplasms. It is suggested that rare typical laryngeal carcinoids be labeled as such. There is little evidence that these lesions are part of a morphologic continuum. In contrast, more common "carcinoid-like" carcinomas, previously referred to as "atypical carcinoids" are more appropriately labeled as "moderately differentiated neuroendocrine carcinomas." These neoplasms should, in turn, be distinguished from "small cell neuroendocrine carcinomas," although these latter two neoplasms do represent a morphologic and behavioral spectrum. Light microscopic and immunohistochemical features distinguishing neuroendocrine carcinomas of the larynx from paraganglioma, metastatic medullary carcinoma, malignant melanoma, and basaloid squamous cell carcinoma are presented. The second portion of this review outlines the clinicopathologic features of two head and neck neoplasms exhibiting varying degrees of neuroendocrine differentiation. Olfactory neuroblastomas have well-developed neuroendocrine differentiation, almost invariably arise from the olfactory mucosa, typically exhibit low-grade cytologic features, and may have protracted clinical course with an approximately 50% overall 5-yr survival. In contrast, sinonasal undifferentiated carcinoma is a microscopically high-grade neoplasm with minimal, abortive neuroendocrine features, a highly aggressive clinical course, and virtually 100% mortality. They can arise throughout the sinonasal region.

Journal Article↗

[Primary pulmonary B-cell lymphoma of the MALT type].

The malignant B-cell lymphoma of the MALT-type shows significant differences from nodal lymphomas with respect to its biological, molecular genetic, and clinical properties. According to the proposal from the International Lymphoma Study Group for a Revised European-American Classification of Lymphoid Neoplasms, MALT-B-cell lymphomas have been defined as an extranodal subgroup of marginal zone B-cell lymphomas and may have lower and higher grade types. We have applied this classification to 24 cases of primary B-cell lymphomas of the lung. These tumors showed histopathologic features of low (n = 20) and/or high grade neoplasms (n = 4) recapitulating the structure of the acquired bronchus-associated lymphoid tissue (BALT). According to our experience, the diagnosis of BALT-type B-cell lymphoma, is both practically feasible and reproducible not only for surgical material but even for biopsy specimens.

Adult↗