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PubMed1979

Eastern Cooperative Oncology Group experience with the rappaport classification of non-Hodgkin's lymphomas.

Eastern Cooperative Oncology Group experience in the clinical application of the Rappaport Classification on Non-Hodgkin's lymphomas (NHL) is reviewed in 670 cases studied since 1972. The diagnoses of institutional pathologists were reviewed by the Pathology Panel and Repository Center for Lymphoma Clinical Studies. Diagnostic agreement in regard to histologic pattern (nodular versus diffuse) was excellent (90%) but was less favorable when concurrence as to both pattern and cell type was assessed (82% in NLDP and 60% or less in other subtypes). Disagreement in regard to NHL diagnosis is related to the complexity of present nomenclature and to the lack of support of pathology activities within cooperative groups. It is suggested that patients entered into group NHL studies be randomized into favorable and unfavorable groups, primarily on the basis of histological pattern.

Humans↗

PubMed1992

Hilar cholangiocarcinoma. An evaluation of subtypes with CT and angiography.

Sixty-seven patients had hilar cholangiocarcinomas which were divided into 3 types based on tumor morphology as observed on cholangiography and CT. The pathology, vascularity, and pattern of tumor spread of these types were compared. Most of the infiltrative tumors (n = 44) were scirrhous adenocarcinomas, which on CT showed poor or no contrast enhancement with frequent lymph node metastases and liver atrophy. At angiography, there was vascular encasement in 52%, in rare cases neovascularity, and tumor stain. The exophytic type (n = 19) was divided into 2 subgroups depending on the main location of the tumor. The nodular subtype (n = 16) was mainly inside the liver and somewhat hypervascular similar to peripheral cholangiocarcinoma, often with intrahepatic metastases. The periductal subtype (n = 3) was hypovascular, similar to the infiltrative cholangiocarcinoma, and had a tendency to spread along the portal vein. The intraductal type (n = 4) was observed as a filling defect on cholangiography. CT revealed an intraluminal low density mass. Histologically, they were papillary adenocarcinomas. The radiologic types of hilar cholangiocarcinoma showed different characteristics with regard to pathologic findings, vascularity, and pattern of spread.

Adenoma, Bile Duct↗

PubMed2026

Salivary duct carcinoma- contemporary nuts and bolts from pathologist perspective.

INTRODUCTION: Salivary gland carcinomas are highly heterogeneous malignancies that present a complex variety of histological features and distinct clinical behaviors, with salivary duct carcinoma (SDCa) as the most clinically severe and aggressive subtype. The standard of care for these patients is a combined approach of surgery followed by radiotherapy. The aggressive clinical course of SDCa is primarily driven by frequent disease recurrences and systemic spread. AREAS COVERED: The publication of WHO 5th Classification of Head and Neck tumors has sparked a surge in research targeting SDCa. Owing to the highly aggressive behavior of the tumor, most literature heavily emphasizes the molecular pathology of SDCa.A systematic literature search was conducted using the PubMed with the following search terms: salivary duct carcinoma AND pathology OR updates OR molecular OR signaling pathway OR gene expression OR mutation OR oncogene OR tumor suppressor OR DNA methylation OR tumor microenvironment. Results were limited to primary research articles in English language. EXPERT OPINION: This article outlines key advancements in SDCa morphology, molecular pathology, and targeted therapies. Patient management in precision oncology will be fundamentally transformed by the classification of new morphologic subtypes, the discovery of molecular biomarkers, and an enhanced comprehension of tumor microenvironment.

HER 2↗

PubMed1996

A comparison between the efficacy of somatostatin receptor scintigraphy and that of in situ hybridization for somatostatin receptor subtype 2 messenger RNA to predict therapeutic outcome in carcinoid patients.

Predictive tests for treatment with somatostatin analogues have been asked for by clinicians. We have shown previously that somatostatin receptor (sstr) scintigraphy may be used to predict therapeutic outcomes for carcinoid patients receiving somatostatin analogues. However, almost 20% of patients with pathological tracer uptake fail to respond to such treatment. To increase further the reliability and prognostic value of sstr identification, we investigated the presence of mRNA for the subtypes sstr1 and sstr2 by in situ hybridization on tumor specimen from 25 carcinoid patients (22 midgut, 2 foregut, and 1 hindgut), all receiving somatostatin analogue treatment (12 lanreotide, 8 octreotide, and 5 octastatin) and compared this to the therapeutic response evaluated as inhibition of hormone secretion. Expression of sstr2 mRNA could be detected in 15 patients, all responding to somatostatin analogue treatment and showing pathological tracer uptake in tumor lesions at sstr scintigraphy. In the remaining 10 patients, no sstr2 mRNA could be detected, and none of the patients responded to somatostatin analogue treatment. Three of these 10 patients failed to accumulate tracer activity at sstr scintigraphy, whereas 7 had a pathological uptake of [(111)In-DTPA-D-Phe(1)]-octreotide. We conclude that in this group of carcinoid patients, there was complete agreement between the presence of mRNA for sstr2 detected by in situ hybridization and therapeutic outcome. In patients with pathological tracer accumulation without expression of somatostatin sstr2 mRNA, other sstr may be present that can bind the somatostatin analogue but not inhibit hormone secretion.

Aged↗

PubMed2004

The nicotinic acetylcholine receptor subtypes and their function in the hippocampus and cerebral cortex.

Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central nervous system and have been implicated in multiple behavioral paradigms and pathological conditions. Nicotinic therapeutic interventions require an extensive characterization of native nAChRs including mapping of their distribution and function in different brain regions. Here, we describe the roles played by different nAChRs in affecting neuronal activity in the hippocampus and cerebral cortex. At least three distinct functional nAChR subtypes (alpha 7, alpha 4 beta 2, alpha 3 beta 4) can be detected in the hippocampal region, and in many instances a single neuron type is found to be influenced by all three nAChRs. Further, it became clear that GABAergic and glutamatergic inputs to the hippocampal interneurons are modulated via different subtypes of nAChRs. In the cerebral cortex, GABAergic inhibition to the layer V pyramidal neurons is enhanced predominantly via activation of alpha 4 beta 2 nAChR and to a minor extent via activation of alpha 7 nAChR. Such diversity offers pathways by which nicotinic drugs affect brain function.

Animals↗

PubMed1999

Causal interactions, fuzzy sets and cerebrovascular 'accident': the limits of evidence-based medicine and the advent of complexity-based medicine.

In evidence-based medicine, stroke subtype is diagnosed after a sequential search for etiology; the first positive test result of significant severity rounds off to one overwhelming cause. Degree of severity, interaction among variables, and concomitant variable conditions are not considered in defining the cause of stroke. Yet, thrombus formation, and possibly vascular rupture, is an interactive process involving the vascular wall, flow properties of the blood and blood constituents; this process occurs in homeostasis and pathology. Evidence-based medicine ignores this process and instead studies stroke using crisp 'all or none' classification where subtypes are distinct and interactively relate only to outcome. As a result, scientific inquiry is focused on prediction for the collective of patients. The statistical approach of evidence-based medicine is founded on probability theory, itself rooted in classical set theory where elementhood is all (1) or none (0), and opposites interact only to form the null set. Fuzzy set theory, where set membership is to degree [0, 1], encompasses classical set theory, allows for an interactive process between variables, and therefore becomes the measure of complexity. Fuzzy set theory can change the scientific method of evidence-based medicine.

Cerebrovascular Disorders↗

PubMed2001

Angiotensin II subtype 1 receptor blockers and renal function.

Blood pressure reduction is the most significant factor in delaying onset and progression of renal disease. Blockade of the renin-angiotensin system (RAS) using angiotensin-converting enzyme inhibitors (ACEIs) delays renal disease progression. More recently, agents that block the RAS by preventing angiotensin II from binding to its subtype 1 receptor (ARBs) have been developed in an effort to prevent deleterious consequences of pathologic levels of angiotensin II and to reduce the adverse effects of RAS blockade associated with ACEIs. Human studies with a variety of ARBs have clearly demonstrated the antihypertensive and antiproteinuric efficacy of these agents in patients with progressive renal diseases. Moreover, the effects of ARBs are similar or identical to those of ACEIs. Ongoing long-term clinical trials are designed to determine whether ARBs also preserve renal function similar to ACEIs. Specifically, the role of ARBs in patients with hypertension and type 2 diabetes is being evaluated in 3 large trials, including Appropriate Blood Pressure Control in Diabetes-Part 2 With Valsartan, the Losartan Renal Protection Study, and the Irbesartan Diabetic Nephropathy Trial. Definitive evidence of the long-term protective effects of ARBs in chronic progressive renal disease is expected from these important studies.

Acute Kidney Injury↗

PubMed1996

Aggressive variants of chromophobe renal cell carcinoma.

BACKGROUND: Chromophobe renal cell carcinoma (RCC) is a distinctive subtype of RCC with a more favorable prognosis than clear cell RCC. We describe the pathologic features of 23 solitary cases and 2 cases with coexistent papillary RCCs, 7 of which developed metastases. METHODS: Cases were retrieved from the pathology files of our institutions. Clinical follow-up was obtained from the medical records. DNA analysis was performed on Feulgen-stained slides using image analysis. RESULTS: Twenty-five cases were identified. All cases had characteristic pathologic features, including diffuse cytoplasmic reactivity for Hale's colloidal iron. DNA ploidy analysis of ten cases revealed a diploid pattern in five, a hyperdiploid pattern in four, and a hypodiploid pattern in one. Follow-up was available for 20 cases, and metastases developed in 7 (from 4 to 120 months after surgery). In 5 of these cases, the tumors were solitary and more than 8 cm in greatest dimension and metastases developed in the liver. In both cases with papillary RCCs in the same kidney, metastases developed in the lung, although which tumor metastasized is unknown. CONCLUSIONS: Despite the overall favorable prognosis for chromophobe RCC, large tumors and those with coexistent papillary RCCs may produce in metastases.

Adenocarcinoma↗

PubMedDate not supplied

Immunophenotype of blast cells in acute myeloid leukemia may be a useful predictive factor for outcome.

The immunophenotype of peripheral blood blast cells was tested in 92 patients with acute myeloid leukemia (AML), who were diagnosed and treated at single centre, St Bartholomew's Hospital, from 1978-1987 with a standard adriamycin, cytosine arabinoside and 6-thioguanine regimen. Immunological analysis involved standard fluorescence flow cytometry and utilized 31 monoclonal antibodies to known myeloid antigens (of CD groups 11b, 11c, 13, 14, 15, 16, w17, 31, w32, 33, 34, 35 and 36), a number of relatively less well studied antibodies with potential specificity for AML, and a series of control antibodies to T and B lymphocytes, platelets, erythrocytes and of widespread distribution (CD45, leucocyte common; HLA-DR). The results highlighted a number of antibodies with wide myeloid reactivity, in addition to CD13 and 33 (present in 66 per cent and 76 per cent of cases, respectively), which may be of immunodiagnostic use. A number of correlations between AML cell immunophenotype and FAB morphology subtype were found; in particular five antibodies (CD11c, 10.1, Tu3, CD15 and CD16), of both predominant granulocytic and monocytic reactivity, reacted with cells of AML-M5 subtype (p less than 0.05). There was no significant correlation between immunophenotype and clinical and pathological features at presentation. Correlation with clinical outcome was not a prominent feature, in contrast to some reports based on multicentre data. However, of particular note was the strong association between early death (at less than 2 months) and the coexpression of Leucocyte Function Associated (LFA) antigens, CD11b and 11c, on patient's blast cells (p = 0.003). The relationship was independent of clinical features and persisted even if AML-M5 cases were excluded. The significance of this latter finding is unclear, but may be related to the known role of CD11b and 11c LFA antigens in the cellular response to infection.

Adult↗

PubMed1989

Pathology of Hodgkin's disease: anything new?

This presentation deals with the gross and microscopic pathology of HD. Recent advances in immunohistochemistry, gene rearrangement studies and cell culture are not discussed, except where they shed light on the pathology. Clinical and pathological experience, over the past 2 decades, suggests that HD should be divided into six subtypes, as originally proposed by Lukes et al. (1966b), rather than the four subtypes included in the Rye classification. Nodular lymphocyte/histiocyte predominant HD forms a clinicopathological entity separate from the other subtypes. It most frequently presents at a single nodal site and, even without therapy, progresses only slowly over a period of many years. A proportion of the patients (in the region of 10%) develop large cell NHL and a smaller number develop other types of Hodgkin's disease. This progression is not due to therapy since it most frequently occurs in untreated patients. Characteristic polylobated RS cell variants are seen in NLPHD. These differ from classic RS cells in that they have a B-cell phenotype, they do not show light chain restriction and, therefore, they do not appear to be a clonal proliferation. Although current dogma states that classic RS cells must be identified before a diagnosis of HD, including NLPHD, is made, it is the author's contention, supported by immunohistochemistry, that this type of RS cell does not occur in NLPHD. Polylobated RS cell variants in the appropriate cellular setting are, in themselves, diagnostic of NLPHD. They also serve to differentiate NLPHD from progressive transformation of germinal centres, an unusual proliferative expansion that may occur in association with HD but which, in itself, appears to be an entirely benign, reactive process. Diffuse lymphocyte/histiocyte predominant HD (DLPHD) differs from NLPHD in its diffuse growth pattern and the frequent presence of larger numbers of histiocytes. Polylobated RS cells are characteristic of both diseases. In some biopsies nodular and diffuse areas are seen in the same lymph node. Despite these similarities, the two diseases differ clinically (NLPHD is usually stage 1, DLPHD is frequently of a higher stage) and in their immunohistochemistry (fewer RS cell variants in DLPHD contain J-chain than in NLPHD). The reasons for these differences are not apparent and require further investigation. It may be due, at least in part, to the inclusion of cases of MCHD and NHL in the DLPHD category. Nodular sclerosis is the commonest category of HD in most reported series.(ABSTRACT TRUNCATED AT 400 WORDS)

Hodgkin Disease↗

PubMed1998

Presence and location of endothelin and endothelin-binding sites in human nasal mucosa under normal and metaplastic conditions.

The presence and site of production of endothelin-1 (ET-1) was investigated in biopsies obtained from the nasal mucosa of 10 healthy human subjects and 10 patients affected by chronic rhinitis. The presence and localization of receptors for ET-1 was also investigated. Bioptic fragments were examined by scanning electron microscopy. ET-1 was present in the vessels and in the respiratory epithelium of normal subjects, whereas in patients affected by epithelial metaplasia induced by chronic rhinitis, it was absent in the metaplastic epithelium and present in the endothelium and vascular wall. Receptors for ET (A- and B-receptor subtypes) were localized in the vessels of the nasal mucosa, both in normal and in pathological subjects. In particular, A-receptors were identified in the vascular wall, whereas B-receptors were mainly distributed in the endothelium. We suggest that ET-1 is involved in the homeostasis of nasal blood flow (shunting the blood toward the deep cavernous plexus and inducing mucosal swelling) by an autocrine and/or paracrine mechanism. Normal epithelium seems to be important in this mechanism, since it is able to produce ET. However, when pathologic conditions induce squamous or cuboidal metaplasia, the epithelium is no longer able to play this role.

Adult↗

PubMed2005

'Pure' invasive apocrine carcinoma of the breast: a new clinicopathological entity?

Invasive apocrine carcinoma (IAC) of the breast has a similar prognosis to infiltrating ductal carcinoma not otherwise specified (IDC-NOS). The existence of a pure IAC subtype (PIAC) and its possible prognostic implications have not been fully investigated. To this end, pathological inclusion criteria for the diagnosis of PIAC were defined and three pathologists reviewed their slides blind to identify it. To assess its clinical behavior, a case-control evaluation was performed, for which 122 cases were selected. There was 100% agreement among the pathologists on the diagnosis: PIAC was identified in 37 cases and IDC-NOS, in 68, while 17 cases were categorized as complex IAC. The probability of 6-year survival was 0.72 for PIAC and 0.52 for IDC-NOS (P=0.02), and was still better after adjustment for tumor grade and axillary status. PIAC may be a distinct clinicopathological entity with a less aggressive behavior than high-grade IDC-NOS and might be regarded as an independent prognostic factor in early breast cancer.

Adult↗

PubMed2005

Localized expression of specific P2X receptors in dystrophin-deficient DMD and mdx muscle.

Using a combination of molecular and immunohistochemical methods, we have obtained evidence for a distinctive change in the expression patterns of ATP-gated (P2X) receptor subunits in dystrophic muscle from both Duchenne muscular dystrophy (DMD) patients and the mdx mouse model. In control myofibres there was no staining for any P2X subtype studied here, although P2X1 stained the smooth muscle of the blood vessels and P2X6 nerves and the tunica intima in small arteries. In contrast, P2X1 and P2X6 were co-expressed strongly in small regenerating muscle fibres in the dystrophic muscles, whereas this expression decreased in fully regenerated fibres. Moreover, immunoreactivity for the P2X2 receptor re-appeared in dystrophic muscle, where it co-localised with the Type 1 fibres. There is, thus, a burst of production of several P2X receptor subtypes in regenerating dystrophic muscle, which may have implications for drug targets for this muscle pathology.

Animals↗

PubMed2003

Nephron-sparing surgery for renal cell carcinoma: clinicopathologic features predictive of patient outcome.

OBJECTIVES: To determine the clinicopathologic features associated with outcome in patients with sporadic renal cell carcinoma (RCC) treated with nephron-sparing surgery. METHODS: We studied 344 patients treated with nephron-sparing surgery between 1970 and 2000. The pathologic features of the tumors were reviewed by two urologic pathologists who recorded the histologic subtype, 2003 TNM stage, tumor size, and grade. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method, and log-rank tests were used to compare the outcome by histologic subtype. Univariate Cox proportional hazards models were fit to assess the associations between the clinicopathologic features and death from RCC, distant metastases, and local recurrence. RESULTS: The CSS rate at 5 and 10 years for patients with clear cell RCC was 94.4% and 91.5%, respectively. In contrast, the CSS rate at 5 and 10 years for patients with papillary or chromophobe RCC was 99.0%, because only 1 patient died of papillary RCC and no patient died of chromophobe RCC (P = 0.029). Among the patients with localized clear cell RCC, tumor stage and grade were significantly associated with death from RCC and metastases. Grade was significantly associated with local recurrence for clear cell RCC, but not for papillary RCC. CONCLUSIONS: In our series of patients with RCC treated with nephron-sparing surgery, patients with clear cell RCC had a significantly worse CSS than did patients with papillary and chromophobe RCC. Tumor stage and grade were associated with outcome among patients with localized clear cell RCC. These findings are similar to the results for patients with localized clear cell RCC treated with radical nephrectomy.

Adult↗

PubMed1998

The role of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission in the pathophysiology and therapeutics of psychiatric syndromes.

The study of excitatory amino acids (EAAs) has recently resulted in new and fundamental concepts in neuroscience. This progress has led to a growing awareness of the crucial role that brain EAAs systems play in a variety of physiological and pathological processes. The N-methyl-D-aspartate (NMDA) receptor, presently the most well understood subtype of EAAs receptors, has been implicated in crucial physiological processes such as synaptogenesis, learning and memory. Dysfunctions of NMDA receptors seem to play a crucial role in the neurobiology of disorders such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemic stroke. This paper is a review of emerging data indicating that alterations of NMDA receptor function may be pivotal to the pathophysiology of four common psychiatric syndromes: schizophrenia, major depression, posttraumatic stress disorder, and alcoholism. Special emphasis is placed on the current state of development of pharmacological strategies aiming at the modulation of NMDA receptor-mediated neurotransmission in these disorders.

Alcoholism↗

PubMed1999

Nasopharyngeal carcinoma.

Nasopharyngeal carcinoma represents a morphologic spectrum of neoplasms localized to the nasopharynx and arising from nasopharyngeal epithelium. Nasopharyngeal carcinomas have rather unique clinical, epidemiologic, pathologic, and biologic features. The morphologic spectrum of nasopharyngeal carcinoma includes keratinizing, nonkeratinizing, and undifferentiated subtypes. The separation of these morphologic types is not an academic exercise, but has practical importance relative to differential diagnosis, management, and prognosis. A similar morphologic classification applies to carcinomas arising in the palatine tonsils and the base of tongue. The nasopharynx, palatine tonsils, and base of tongue are collectively designated as Waldeyer's tonsillar tissues. Awareness of the morphologic spectrum of Waldeyer's ring carcinomas may assist in suggesting the primary tumor site in the face of an occult metastatic carcinoma to cervical neck lymph nodes.

Carcinoma↗

PubMed2000

Enhancement of persistent Na+ current by sea anemone toxin (ATX II) exerts dual action on hippocampal excitability.

We used anemone toxin II (ATX II) to study how a selective enhancement of persistent Na+ current (INaP) would affect the excitability of CA1 pyramidal neurons in the hippocampal slice. In whole-cell recordings from CA1 cell somata, local application of ATX II (10 microM) into the stratum pyramidale invariably depolarized the neurons and produced sustained burst discharges with depolarizing plateau potentials of variable amplitude and length. However, the strong excitatory action of ATX II, observed on the single cell level, was not mirrored in field potential recordings from the same hippocampal subfield. The amplitude of the electrically evoked population spike declined, reflecting the decreased availability of fast Na+ channels, and the intracellulary recorded burst discharges were not detected by the field electrode. The lacking synchronization of cellular bursting activity was seen during both local and bath application of ATX II, suggesting that the toxin, in addition to promoting burst discharges of individual neurons, simultaneously dampens network excitability. In fact, ATX II reduced afferent fibre volleys (reflecting axonal excitability) and field excitatory postsynaptic potentials (EPSPs) in a similar fashion. As the expression of different Na+ channel subtypes appears to be compartmentalized within hippocampal neurons, we propose that point mutations leading to pathologically enhanced INaP might exert quite opposite effects, depending on the type and location of the Na+ channel affected. Whereas alterations of somatodendritic Na+ channels would give rise to bursting activity, alterations of axonal Na+ channels would primarily decrease network excitability.

Action Potentials↗

PubMed2006

Therapeutic potential of melatonin ligands.

Melatonin is a neurohormone that is believed to be involved in a wide range of physiological functions. In humans, appropriate clinical trials confirm the efficacy of melatonin or melatoninergic agonists for the MT1 and MT2 receptor subtypes in circadian rhythm sleep disorders only. Nevertheless, preclinical animal model studies relevant to human pathologies involving validated reference compounds lead to other therapeutic possibilities. Among these is a recently developed treatment concept for depression, which has been validated by the clinical efficacy of agomelatine, an agent having both MT1 and MT2 agonist and 5-HT2C antagonist activity. A third melatonin binding site has been purified and characterized as the enzyme quinone reductase 2 (QR2). The physiological role of this enzyme is not yet known. Recent results obtained by different groups suggest: (1) that inhibition of QR2 may lead to "protective" effects and (2) that over-expression of this enzyme may have deleterious effects. The inhibitory effect of melatonin on QR2 observed in vitro may explain the protective effects reported for melatonin in different animal models, such as cardiac or renal ischemia-effects that have been attributed to the controversial antioxidant properties of the hormone. The development of specific ligands for each of these melatonin binding sites is necessary to link physiological and/or therapeutic effects.

Animals↗