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PubMed1993

Classification of Hodgkin's disease biopsies by a panel of four histopathologists. Report of 1,140 patients from the German National Trial.

First results from reviewing the diagnostic biopsies of Hodgkin's lymphomas (HL) are reported. Biopsies from 1,140 patients were evaluated by consensus diagnoses according to an extended classification of the British National Lymphoma Investigation. 95 of the recruited cases (8.3%) were omitted and not approved as Hodgkin's lymphoma. The remaining 1,045 biopsies were classified as follows: Lymphocytic predominance 31 (2.7%); Nodular sclerosis (NS) 660 (57.9%), Mixed cellularity (MC) 159 (13.9%); Lymphocytic depletion 8 (0.7%); unclassifiable Hodgkin's 148 (13.0%). The unproved Hodgkin's cases [95 (8.3%)] were divided into non-Hodgkin's lymphomas 32 (1.9%), uncertain due to inadequate techniques 32 (2.8%), borderline between Hodgkin's- and Non-Hodgkin's lymphoma 23 (2.0%). Major dissent on this question involved 17 cases (1.5%) and 1 case which was non-malignant. All unclassifiable, borderline or dissent cases were reassessed after the histologic techniques were improved, and immunophenotyping and clinical data reevaluated. The rate of agreement among the observers was about 81.6%, varying between 23.8% in grade 2 NS to 85.0% in both NS groups. Only 62.8% of all primary diagnoses were approved by the final diagnoses of the panel. Important differences in the classification of the British National Lymphoma Investigation concerns the NS-group and mainly its grade 2 subtype. MC was identical in both classifications. Clinico-pathologic correlation of actuarial survival times revealed a significantly worse outcome of MC vs NS, < 20% after 80 months observation. Only slightly significant better survivals were found in grade 1 vs grade 2 NS. Significant differences in unclear compared to all Hodgkin's, were found and the worst survival was in the NHL group.

Biopsy↗

PubMed2000

[Clinical staging classification of non-Hodgkin's lymphoma].

Ann Arbor staging classification (with Cotswolds modifications) is widely used to evaluate the cases of non-Hodgkin's lymphoma(NHL). Contrary to Hodgkin's disease, most patients with NHL have advanced and extranodal disease, and therefore Ann Arbor staging system is not satisfactory in all the cases of NHL. However, Ann Arbor clinical stage is a powerful prognostic factor when it is used with other prognostic factors, such as serum lactate dehydrogenase and performance status(International Prognostic Index). Clinical features of NHL are closely related to histologic subtypes, so newer staging system will be based on pathological diagnosis and clinical parameters.

Humans↗

PubMedDate not supplied

[Multifocal gastric carcinoid associated with chronic type A atrophic gastritis. Analysis of 2 clinical cases].

Gastric carcinoid is a rare disease, representing less than 1% of gastric tumours and 11-41% of all gastrointestinal carcinoids. The recent Solcia's classification distinguishes three subtypes of these neoplasms, which show specific clinical and pathological features. Type one arises in patients with chronic atrophic gastritis (CGA), achlorhydria, hypergastrinemia and consequent enterochromaffin-like cell hyperplasia and dysplasia. Type two is related to Zollinger Ellison syndrome and type three represents the sporadic kind. We report two cases of multifocal gastric carcinoid associated to CGA, one of them with pernicious anemia. Both patients had aspecific abdominal symptoms; the diagnosis was suspected by upper endoscopy and confirmed by histological examination. Patients were submitted to total gastrectomy. They are still alive six years after surgery, without signs or symptoms of recurrences. Treatment of these tumours is controversial, because of their uncertain biological and clinical behaviour. Some Authors propose a conservative strategy (only endoscopic surveillance or removal); others stress importance of surgery (antrectomy or gastric resection). We discuss and underline the role of surgical therapy and the relevance of radical approach.

Adult↗

PubMed1992

The epidemiology and differential diagnosis of obsessive compulsive disorder.

Obsessive compulsive disorder is now recognized as a common psychiatric disorder. The lifetime prevalence of 2% to 3% found in the United States has also been found in epidemiologic studies in several other countries with diverse cultures. This disorder has previously been underestimated due to a number of factors that include patients' reluctance to spontaneously admit to obsessions and compulsions and the omission of screening questions about obsessive compulsive disorder on routine mental status examinations. Depression and other anxiety disorders frequently co-occur with obsessive compulsive disorder, which may contribute to misdiagnosis. Patients with eating disorders, Gilles de la Tourette's syndrome, and schizophrenia have a greater comorbid risk compared with the general population. Differential diagnosis of obsessive compulsive disorder includes generalized anxiety disorder, panic disorder, phobias, compulsive personality disorder, and hypochondriasis. While many of these syndromes are characterized by intrusive thoughts, few have associated rituals. The complex tics seen in some patients with Tourette's syndrome may be difficult to distinguish from the compulsions seen in obsessive compulsive disorder, and, in fact, there is significant overlap in symptoms between the two disorders. Currently, the impulse control disorders, such as compulsive gambling and the paraphilias, are not considered to be part of obsessive compulsive disorder. Although the phenomenology of obsessive compulsive disorder appears to be quite diverse, with many distinct kinds of obsessions and compulsions, there are three important core features: abnormal risk assessment, pathologic doubt, and incompleteness. These features cut across phenomenological subtypes and may be useful in defining homogeneous subgroups with distinct treatment outcomes.

Anxiety Disorders↗

PubMedDate not supplied

[Cavernous hemangioma of the colon. Case report and review of the literature].

Colon and rectum hemangioma is a rare disease, and even more so when it presents as cavernous subtype; few of these hemangioma have been confirmed by pathology reports. The main presentation of this disease is observed by transrectal painless bleeding; other manifestations are less frequent. Diagnosis implies high index of suspicion and proper diagnostic workup; this entity has been frequently misdiagnosed as other more common entities. We present the case of a 15-year-old female patient with a cavernous hemangioma of the sigmoid colon; her principal complaint was abdominal pain. Diagnosis was suspected due to the finding of phleboliths in plain abdominal film and diagnostic findings in colonoscopy. The patient was treated by means of segmental resection of the colon and experienced a satisfactory postoperatory recovery. According to the literature, these hemangiomas originate from embryologic sequestrations of mesodermal tissue, while clinically they usually present between the ages of 5 and 25 years, most commonly with painless transrectal bleeding and less frequently with intestinal obstruction, tenesmus, urgency, abdominal pain or mass, and anemia. The majority of these hemangiomas are localized in rectosigmoid region of the colon and may infiltrate surrounding tissues; 26-50% show phleboliths in plain abdominal film. Colonoscopy is considered by many authors the best diagnostic tool; angiography, computed tomography (CT) scan and scintigraphy may be also useful. The only effective treatment of this disease is complete surgical resection, for which there have been many proposals regarding best method and approach.

Adolescent↗

PubMed2006

[Clinical characteristics and molecular biology of hereditary spinocerebellar ataxia type 7: study of 3 Chinese families].

OBJECTIVE: To study the clinical characteristics and molecular biology of hereditary spinocerebellar ataxia type 7 (SCA7). METHODS: Peripheral blood samples were collected from 245 with autosomal dominant SCA from 184 families and 71 sporadic SCA patients. Polymerase chain reaction, polyacrylamide gel electrophoresis, and capillary electrophoresis technique were used to detect the SCA7 (CAG) n trinucleotide repeat mutations. 163 healthy persons were used as controls. The abnormal allele fragments were sequenced by ABI 377 DNA sequencing machine. RESULTS: Three SCA families with 15 patients were identified with a positive rate of 1.6%. DNA sequencing showed that the abnormal SCA7 alleles with CAG repeat were expanded to 38 to 71 repeats, and the normal SCA7 alleles were carried from 6 to 15 CAG repeats. Analysis of parent-child couples demonstrated the existence of marked anticipation in 2 families, especially in paternal transmission. Linkage analysis found a maximum two-point LOD score of 2.82 in the microsatellite D3S1300 at recombination fraction (theta = 0.00). CONCLUSION: CAG expansion is the pathogenic cause of SCA7, a rare subtype of SCA. The 38 CAG is the minimum pathological expansion in mainland China.

Adult↗

PubMed2006

[Renal cell carcinoma metastatic to the ovary].

A 45-year-old woman underwent left radical nephrectomy in April 2002. Pathological diagnosis was a renal cell carcinoma, clear cell subtype, pT3a, v(-), NO. One year later, abdominal ultrasound revealed a left ovarian tumor which had an enlargement tendency. A laparoscopic bilateral salpingooophorectomy was performed. Immunohistochemical analysis confirmed the diagnosis of metastatic ovarian renal cell carcinoma. This is the 20th case in the literature.

Carcinoma, Renal Cell↗

PubMed1995

A multivariate analysis of prognostic factors in thymoma.

BACKGROUND: Considering the prognostic factors of thymoma, the clinical stage is the most important, while controversies exist about other clinicopathologic factors. A multifactorial study was carried out to clarify the relationship between prognosis and sex, age, tumor size, presence of myasthenia gravis, staging, epithelial subtyping, lymphocyte/epithelial cell ratio (L/E ratio) and other adjuvant pathological features. METHODS: One hundred and thirty-seven cases were collected in Veterans General Hospital-Taipei from 1961 to 1993. The aforementioned features were studied. Kaplan-Meier's actuarial survival analysis was adopted, with Logrank test, to determine the significance of overall heterogeneity and trend. Cox proportional hazard model was also used for multivariate analysis. RESULTS: Among all tested prognostic factors, staging had the highest significance (relative risk = 3.00, p < 0.001) and age had only a moderate one (relative risk = 1.04, p = 0.011). No other clinicopathological factor showed any statistical significance for prognosis. CONCLUSIONS: Staging remains of greatest usefulness in predicting the biological behavior of thymoma. The effect of age requires more investigation. Other clinicopathological features have no definite influence in survival expectancy.

Adolescent↗

PubMed1997

[Metastasis of renal cell carcinoma to ipsilateral adrenal residuum and contralateral adrenal gland after radical nephrectomy: a case report].

A 68-year-old woman had undergone radical nephrectomy via a transabdominal approach 4 years earlier for a 8 cm tumor located from the midportion to the upper pole of the right kidney. Pathological diagnosis was renal cell carcinoma (RCC), clear cell subtype, G2, pT2pN0M0. Four years postoperatively, followup computed tomography scan revealed masses in bilateral adrenal region (6 cm in diameter on the left side and 5 cm on the light). Bilateral adrenalectomy confirmed the diagnosis of adrenal metastases from clear cell carcinoma. It was concluded that the tumor had metastasized to the ipsilateral adrenal tissue as the residuum of the previous surgery. She has been treated by oral steroid supplementation without evidence of recurrence for 18 months.

Adrenal Gland Neoplasms↗

PubMed1998

[Somatostatin: a ubiquitous peptide].

Somatostatin (SRIF) was discovered in 1973, in Roger Guillemin's laboratory as a Growth Hormone (GH) inhibiting neurohormone. It is widely distributed in mammals where it acts also as a peripheral hormone, an autocrine or paracrine factor and a neuropeptide. SRIF receptors are located on several human tumours and SRIF agonists are in clinical use to monitor GH secretion in acromegalic patients. This short review summarizes the properties of the central and peripheral somatostatinergic systems, the three peptides belonging to the somatostatin family: (SRIF14, SRIF28 and cortistatin), the pharmacology of the five SRIF receptor subtypes, some ontogenetic and phylogenetic aspects, as well as pathological findings.

Amino Acid Sequence↗

PubMed2003

Plasticity of glutamate and GABAA receptors in the hippocampus of patients with Alzheimer's disease.

AIM: In Alzheimer's disease (AD) it is well known that specific regions of the brain are particularly vulnerable to the pathologic insults of the disease. In particular, the hippocampus is affected very early in the disease and by end stage AD is ravaged by neurofibrillary tangles and senile plaques (i.e., the pathologic hallmarks of AD). Throughout the past several years our laboratory has sought to determine the molecular mechanisms underlying the selective vulnerability of neurons in AD. METHODS: To this end, we employed immunohistochemical, biochemical, and in situ hybrization methods to examine glutamate and gamma-aminobutyric acid (GABAA) receptor subtypes in the hippocampus of patients displaying the full spectrum of AD pathology. RESULTS: Despite the fact that the hippocampus is characterized by a marked loss of neurons in the late stages of the disease, our data demonstrate a rather remarkable preservation among some glutamate and GABAA receptor subtypes. CONCLUSIONS: Collectively, our data support the view that the relatively constant levels of selected receptor subtypes represent a compensatory up-regulation of these receptors subunits in surviving neurons. The demonstration that glutamate and GABA receptor subunits are comparably unaffected implies that even in the terminal stages of the discase the brain is "attempting" to maintain a balance in excitatory and inhibitory tone. Our data also support the concept that receptor subunits are differentially affected in AD with some subunits displaying no change while others display alterations in protein and mRNA levels within selected regions of the hippocampus. Although many of these changes are modest, they do suggest that the subunit composition of these receptors may be altered and hence affect the pharmacokinetic and physiological properties of the receptor. The latter findings stress the importance of understanding the subunit composition of individual glutamate/GABA receptors in the diseased brain prior to the development of drugs targeted towards those receptors.

Adaptation, Physiological↗

PubMed2026

Stage-Independent Real-Time Subtype Classification and Comprehensive Biopsy Profiling of Urothelial Carcinomas by the Lund Taxonomy System.

Bladder cancer is a heterogeneous malignancy with diverse clinical outcomes, and conventional pathological assessment alone is insufficient to capture its underlying biology. Gene expression profiling can stratify tumors into molecular subtypes with prognostic and predictive potential, but the reliability of transcriptomic classification and its clinical utility remains to be established. The translational/observational UROSCANSEQ study (ISRCTN15459149) prospectively evaluates RNA-based Lund Taxonomy (LundTax) molecular subtype classification in a clinical setting. Among 784 consecutive biopsies collected between 2018 and 2022, RNA sequencing was successful for 90% of all biopsies, encompassing 662 bladder cancer patients with a stage distribution of 48% Ta, 27% T1, 24% ≥T2, and 1% CIS. We demonstrate that the LundTax subtype classification algorithm, applied to individual samples, accurately identifies cancer cell phenotypes with characteristic gene and protein expression patterns in a manner robust to RNA quality, data preprocessing strategies, and batch effects, supporting its clinical feasibility across both non-muscle-invasive and muscle-invasive disease. We further extend the LundTax framework by incorporating single-sample molecular risk scores reflecting tumor grade, proliferation, and progression risk, as well as tumor microenvironment signatures. Both risk scores and overall immune and stromal content in biopsies were significantly associated with an increased risk of clinical progression in noninvasive disease. In a separate analysis of the relative cellular composition of the tumor microenvironment, however, only the fraction of natural killer cells remained significant. Together, the expanded LundTax system provides a comprehensive molecular portrait of individual tumor biopsies. By explicitly separating cancer cell-intrinsic phenotypes, prognostic indexes, and microenvironmental signals, the framework minimizes biological confounding and establishes a strong foundation for future studies evaluating clinical outcomes and treatment responses.

Humans↗

PubMed1975

Distinct subtypes of type I fibers of human skeletal muscle.

We have identified two distinct and consistent type I fiber subtypes in histochemically normal biopsies (vastus lateralis or biceps brachialis) from 12 healthy persons, both sexes, ages 15 to 42. The type I fibers were uniformly light with the regular ATPase (9.4) and uniformly dark with the acid-preincubated reverse ATPase reactions. However, the subtype IA fibers were stained darker than subtype IB fibers with the nicotinamide adenine nucleotide dehydrogenase-tetrazolium reductase, Oil red O, reduced nicotinamide adenine dinucleotide phosphate-tetrazolium reductase, nonspecific esterase, succinic-tetrazolium reductase, nicotinamide adenine dinucleotide-linked malic-tetrazolium reductase, and "nicotinamide adenine dinucleotide-linked lactic-tetrazolium reductase," and stained lighter with the phosphorylase, periodic acid-Schiff for glycogen, and menadione-mediated alpha-glycerophosphate-tetrazolium reductase reactions. The IB fibers were not as light (or as dark, depending on the stain) as any of the type II fibers. In one pathologic case, all the "hypotrophic type I muscle fibers with central nuclei" were subtype IB. In case of chronic infantile spinal atrophy the muscle showed some type-grouping and marked type I fiber predominance--the great majority of type I fibers were subtype IB, among which were islands (subtype-groups) of IA fibers. Subtyping of type I fibers may be informative in evaluating the pathologic process of certain human neuromuscular diseases.

Adolescent↗

PubMed2006

Evidence for a single latent class of Diagnostic and Statistical Manual of Mental Disorders borderline personality pathology.

Borderline personality disorder (BPD) has been described as clinically heterogeneous, with numerous subtypes of the disorder posited. The present study investigated this potential heterogeneity by conducting both confirmatory factor analysis and latent class analysis of consensus ratings of Diagnostic and Statistical Manual of Mental Disorders (DSM) Revised Third Edition BPD criteria in a mixed clinical and nonclinical sample (n = 411). Confirmatory factor analysis results suggested that a single factor fit the data most parsimoniously. Latent class analysis results supported 2 latent classes: those with a high likelihood of BPD symptoms (n = 171) and those with a low likelihood (n = 240). The borderline latent class was more inclusive than diagnoses made based on DSM-III-R thresholds and improved prediction of symptom severity and interpersonal dysfunction, suggesting the clinical importance of 3 or more BPD criteria. Future research on subtypes of BPD may benefit by focusing on variables that supplement the DSM criteria.

Adult↗

PubMed2002

Two distinct signaling pathways upregulate NMDA receptor responses via two distinct metabotropic glutamate receptor subtypes.

Molecular processes regulating the gain of NMDA receptors modulate diverse physiological and pathological responses in the CNS. Group I metabotropic glutamate receptors (mGluRs), which neighbor NMDA receptors and which can be coactivated by synaptically released glutamate, couple to several different second messenger pathways, each of which could target NMDA receptors. In CA3 pyramidal cells we show that the activation of mGluR1 potentiates NMDA current via a G-protein-independent mechanism involving Src kinase activation. In contrast, mGluR5-mediated enhancement of NMDA current requires G-protein activation, triggering a signaling cascade including protein kinase C and Src. These results indicate that one neurotransmitter, glutamate, can activate two distinct and independent signaling systems to target the same effector. These two pathways are likely to contribute significantly to the highly differentiated control of NMDA receptor function.

Animals↗

PubMed1983

Characteristics of a benign subtype of dense deposit disease: comparison with the progressive form of this disease.

Pathologic, clinical and serum complement studies were performed on 18 patients with dense deposit disease (DDD). The patients were divided into 3 groups: group A (10 patients who developed end-stage renal failure within 2.9 +/- 1.0 years of onset) group B (3 patients who developed elevated serum creatinines within 6.8 +/- 4.8 years of onset) and group C (5 patients with no evidence of renal insufficiency after 11.0 +/- 1.4 years of follow-up). Renal biopsies from all patients showed intramembranous, electron-dense deposits in glomerular capillary basement membranes. Most group A and B patients presented with a nephritic and/or nephrotic syndrome and followed an active clinical course. In contrast, group C patients presented with either a nephrotic syndrome or asymptomatic proteinuria +/- hematuria and followed a benign course. Sera from group A and B patients contained reduced concentrations of C3 and factor B and large amounts of C3 nephritic factor (NeF) activity. In contrast, serum of group C patients contained normal amounts of C3 and factor B and low levels of C3 NeF activity. These studies show that some patients with DDD (group C) have a benign illness and that they can be identified by serum levels of C3, factor B and C3 NeF activity.

Child↗

PubMed1995

Does early-onset Alzheimer disease constitute a distinct subtype? The contribution of molecular genetics.

Alzheimer disease (AD) is a clinical and pathologic diagnosis and refers to the findings of neurofibrillary tangles and amyloid plaques in the brain of a patient with dementia. Clinically it is recognized that there are familial and sporadic forms, with further division into those with presenile and senile onset. Clinical, neuroimaging, neuropathological, and neurochemical studies have attempted to identify differences between cases with an earlier and later onset, but have not identified a categorical biologic difference between the two groups. Recent advances in the molecular genetics of familial Alzheimer disease (FAD) and the discovery of defined genetic abnormalities have provided a robust approach to distinguishing between early- and late-onset cases within the group of autosomal dominant FAD. The precise biologic classification made possible by molecular genetic analysis of FAD provides a benchmark against which phenotypic differences can be assessed. This article argues that future studies will be able to contrast early-onset familial versus late-onset familial disease, and early-onset familial versus early-onset sporadic disease. Previous reports of phenotypic differences within AD may have been the result of including FAD within early-onset groups, though this remains to be established.

Age of Onset↗

PubMed1997

Expression of nm23 protein in pulmonary adenocarcinomas: inverse 1orrelation to tumor progression.

Immunohistochemical assessment was made of nm23 protein expression in pulmonary adenocarcinoma. Of the 147 adenocarcinomas 67% (99/147) were weakly and 33% (48/147) strongly positive for nm23 protein. nm23 protein expression in primary tumors was shown to correlate inversely with advancing pathologic stage and the degree of metastasis in regional lymph nodes (P < 0.05). The staining of tumors without nodal metastasis was more intense than with nodal metastasis (P < 0.02). Nodal metastasis was seen in 37% (55/147) cases examined. The immunoreactivity to nm23 protein in tumor cells of nodal metastasis was essentially the same as in those of primary tumors (P < 0.01). Significant correlation between patient prognosis and immunoreactivity for nm23 in primary tumors (P < 0.05) was demonstrated. But none could be found between immunoreactivity and other parameters such as histologic grading, distant metastasis, tumor size or disease-free survival. Neither was there any significant correlation between pathologic parameters examined and the expression of nm23 in any histologic subtype. Multivariate analysis using Cox's proportional hazards regression model with five variables indicated nm23 and lymph node metastasis to contribute to overall patient survival. Based on risk ratio disadvantageous state/advantageous states, the gravity of prognostic factors was assessed for lymph node metastasis as 9.25, nm23 expression as 2.06, distant metastasis as 1.23, pathologic stage as 0.78 and tumor size as 0.77. The results suggested that in pulmonary adenocarcinoma a reduced expression of nm23 protein was associated with lymph node metastasis and poor patient survival.

Adenocarcinoma↗