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PubMed1994

[Multiplanar transesophageal echocardiography in a case of hypernephroma].

A 78-year-old man admitted to our hospital with signs and symptoms of right ventricular failure, consisting of severe edema of the scrotum and the penis, ankle edema, hepatomegaly, and a history of asthenia associated with a recent weight loss. Two-dimensional echocardiography showed an intracavitary mass in the right atrium and a moderate pericardial effusion; the remaining structures were normal. To better define the origin of this mass, transesophageal echocardiography was performed. The mass extended from the inferior vena cava with no sites of attachment to the atrial wall. The mass was elongated, mobile, with a triangular termination near the tricuspid valve, without signs of right ventricular obstruction. An abdominal-pelvic CT scan demonstrated the origin of the mass at the superior pole of the left kidney extending through the renal vein and the inferior vena cava into the right atrium. The mass was surgically removed and the pathological examination revealed a renal cell carcinoma (hypernephroma) of the clear cells subtype. After surgery, the patient did well with the resolution of the picture of right ventricular failure.

Aged↗

PubMed1994

Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas.

We analyzed 47 primary sporadic human renal cell carcinomas (39 clear cell and 8 non-clear cell) for mutations of the von Hippel-Lindau (VHL) tumor suppressor gene using the polymerase chain reaction and single strand conformational polymorphism analysis of DNA. All of the positive cases in single strand conformational polymorphism analyses were further characterized by direct sequencing. Somatic mutations were detected in 22 (56%) of 39 clear cell renal carcinomas including 15 deletions, 3 insertions, 3 missense mutations, and 1 nonsense mutation. Nineteen of these mutations predicted to produce truncation of the VHL protein. These mutations mainly occurred in the last one-third region of exons 1, 2, and 3. In addition, loss of heterozygosity of the VHL gene was observed in 16 (84%) of 19 informative clear cell renal carcinomas. No somatic mutations were detected in 8 non-clear cell carcinomas. These results show that the VHL tumor suppressor gene is one of the major tumor suppressor genes in human renal cell carcinomas, especially in the clear cell subtype renal cell carcinoma. Clear cell carcinoma might be distinguished from other pathological types of renal cell carcinomas by molecular genetic techniques.

Base Sequence↗

PubMed2007

Dendritic cells in transplantation and immune-based therapies.

Dendritic cells (DCs) are specialized, bone marrow-derived leukocytes critical to the onset of both innate and adaptive immunity. The divisions of labor among distinct human DC subtypes achieve the most effective balance between steady-state tolerance and the induction of innate and adaptive immunity against pathogens, tumors, and other insults. Maintenance of tolerance in the steady state is an active process involving resting or semimature DCs. Breakdowns in this homeostasis can result in autoimmunity. Perturbation of the steady state should first lead to the onset of innate immunity mediated by rapid responders in the form of plasmacytoid and monocyte-derived DC stimulators and natural killer (NK) and NK T-cell responders. These innate effectors then provide additional inflammatory cytokines, including interferon-gamma, which support the activation and maturation of resident and circulating populations of DCs. These are critical to the onset and expansion of adaptive immunity, including Th1, Th2, and cytotoxic T-lymphocyte responses. Rodent models are now revealing important data about distinct DC precursors, homeostasis of tissue-resident DCs, and DC turnover in response to inflammation and pathological conditions like graft-versus-host disease. The use of defined DC subtypes to stimulate both innate and adaptive immunity, either in combination or in a prime-boost vaccine sequence, may prove most useful clinically by harnessing both effector cell compartments.

Animals↗

PubMed2005

Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation.

We have investigated the pathological correlates of dementia in the brains from a consecutive series of 70 patients dying with a clinical diagnosis of frontotemporal lobar degeneration (FTLD). Clinical misdiagnosis rate was low with only 3 patients (4%) failing to show pathological changes consistent with this diagnosis; 1 patient had Alzheimer's disease and 2 had cerebrovascular disease (CVD). In the remaining 67 patients, the most common underlying histological cause was ubiquitin pathology with 24 (36%) cases so affected. In these, ubiquitin-positive inclusions were present in the cerebral cortex as small, rounded or crescent-shaped structures within the cytoplasm of neurones of layer II, together with coiled or curvilinear bodies within neurites, and in the hippocampus as small, solid and more spherical-shaped inclusion bodies within the cytoplasm of dentate gyrus granule cells. In one patient, "cat's eye" or "lentiform" intranuclear ubiquitin inclusions were also present. The second most common histological type was dementia lacking distinctive histology (DLDH), in which neither tau nor ubiquitin inclusions were present, with 16 cases (24%) being affected. Pick-type histology was seen in 14 cases (21%) and tau histological changes associated with frontotemporal dementia (FTD) linked to chromosome 17 (FTDP-17) were present in 11 cases (16%). One case (1%) showed an unusual tau pathology that could not be allocated to any of the other tau groups. Only 1 case (1%) had neuronal intermediate filament inclusion dementia. No cases with ubiquitinated, valosin-containing protein-immunoreactive intranuclear inclusion bodies of the type seen in inclusion body myopathy with Paget's disease of bone and frontotemporal dementia were seen. Clinicopathological correlation showed that any of these histological subtypes can be associated with FTD. However, for FTD with motor neurone disease (FTD+MND), semantic dementia or primary progressive aphasia (PA), the histological profile was either ubiquitin type or DLDH type; Pick-type histology was seen in only 1 case of PA. None of these latter three clinical subtypes was associated with a mutation in tau gene and FTDP-17 type of tau pathology. All cases of progressive apraxia were associated with Pick-type histology. Present data therefore indicate that, although ubiquitin pathology is the most common histological form associated with FTLD, this pathology is not tightly linked with, nor is pathologically diagnostic for, any particular clinical form of the disease, including FTD+MND.

Adenosine Triphosphatases↗

PubMed1996

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Dementia↗

PubMed1996

Muscarinic acetylcholine receptor expression in memory circuits: implications for treatment of Alzheimer disease.

Cholinergic transmission at muscarinic acetylcholine receptors (mAChR) has been implicated in higher brain functions such as learning and memory, and loss of synapses may contribute to the symptoms of Alzheimer disease. A heterogeneous family of five genetically distinct mAChR subtypes differentially modulate a variety of intracellular signaling systems as well as the processing of key molecules involved in the pathology of the disease. Although many muscarinic effects have been identified in memory circuits, including a diversity of pre- and post-synaptic actions in hippocampus, the identities of the molecular subtypes responsible for any given function remain elusive. All five mAChR genes are expressed in hippocampus, and subtype-specific antibodies have enabled identification, quantification, and localization of the encoded proteins. The m1, m2, and m4 mAChR proteins are most abundant in forebrain regions and they have distinct cellular and subcellular localizations suggestive of various pre- and postsynaptic functions in cholinergic circuits. The subtypes are also differentially altered in postmortem brain samples from Alzheimer disease cases. Further understanding of the molecular pharmacology of failing synapses in Alzheimer disease, together with the development of new subtype-selective drugs, may provide more specific and effective treatments for the disease.

Alzheimer Disease↗

PubMed2000

Risk of systemic metastases in clinical stage I nonseminoma germ cell testis tumor managed by retroperitoneal lymph node dissection.

PURPOSE: We assess the risk of systemic recurrence after retroperitoneal lymph node dissection for clinical stage I nonseminoma germ cell testis tumor based on predominance of embryonal carcinoma and/or vascular invasion in the orchiectomy specimen. MATERIALS AND METHODS: A total of 292 cases of clinical stage I nonseminoma germ cell testis tumor treated with retroperitoneal lymph node dissection from 1990 to 1995 were identified from the Indiana University database. A minimum of 2 years of followup was required for study entry. Review of the written pathological reports classified tumors as embryonal carcinoma predominant, when it was present at a level greater than any other histology, nonpredominant, when it was present but not as the main histological subtype, and absent. Vascular invasion was categorized as present or absent. RESULTS: Of the 292 cases 226 (77. 4%) were pathological stage I and relapse rate after retroperitoneal lymph node dissection was 10.2%. Vascular invasion and embryonal carcinoma predominance in the orchiectomy specimen were predictors of relapse in this group. None of the 35 pathological stage II cases treated with adjuvant chemotherapy had relapse, whereas relapse occurred in 7 of 31 pathological stage II cases (22.6%) not treated with adjuvant chemotherapy. CONCLUSIONS: Pathological stage I cases with predominant embryonal carcinoma and/or vascular invasion in the orchiectomy specimen have a higher probability of systemic recurrence after retroperitoneal lymph node dissection. Dissection alone still has a major therapeutic impact (77%) in patients with clinical stage I, pathological stage II nonseminoma germ cell testis tumor.

Adolescent↗

PubMed2001

Clinicopathological and molecular evidence indicating the independence of bronchioloalveolar components from other subtypes of human peripheral lung adenocarcinoma.

Although human lung adenocarcinoma has diverse histological subtypes, the correlation between histological subtypes and occurrence of the p53 gene mutation has been given less attention. We investigated 145 surgically resected lung adenocarcinomas to search for the incidence of p53 mutations and for record data on survival in each histological subtype, according to the new WHO criteria (1999). The frequency of p53 mutation in bronchioloalveolar carcinoma (BAC; 0% in 17 cases) and BAC with invasive growth component (BAC-invasive; 11% in 27 cases), which is conventionally categorized as the mixed subtype in WHO typing, were apparently significantly lower than in other types (non-BAC including acinar, papillary, solid, or mixed histology with these subtypes; 48% in 101 cases; P < 0.01). Multivariate analysis revealed that the histological subtype including BAC-invasive was a strong, independent, and significant prognostic factor (P < 0.03), as were tumor size and pathological stage (P < 0.001 and 0.002, respectively) for overall survival. However, the occurrence of p53 mutation itself was seen to be significant only in case of the univariate analysis. Therefore, histological subtyping may be a better prognostic indicator than is p53 mutation. These findings suggest that the WHO classification with the BAC and BAC-invasive from other histological subtypes may prove useful to predict the outcome for surgically treated patients with lung adenocarcinoma.

Adenocarcinoma↗

PubMed1997

Papillary (chromophil) renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 62 cases.

For more than two decades, papillary renal cell carcinoma has been recognized as a possible distinct clinicopathologic subtype of renal cell carcinoma (RCC). However, the histologic criteria for its diagnosis and the clinical outcome are still debated. In an attempt to clarify the diagnostic criteria and resolve issues pertaining to biologic potential, we have evaluated the histologic spectrum of 62 papillary RCCs and assessed significance of conventional pathologic prognostic parameters (Fuhrrman's nuclear grade [NG], pathologic stage [Robson and TNM], tumor size, multifocality, necrosis, and foam cells) and correlated these with outcome. The mean age of patients was 61.8 years (range 22-83), and males were more commonly affected (1.8:1). Grossly, most tumors were well circumscribed, averaged 6.7 cm in size (range 1.8-18), and were predominantly localized to the renal poles (polar vs. mid-renal, 3:1). Multifocality was a prominent feature (24 cases), and in three cases tumors were bilateral. Microscopically, papillary RCCs were predominantly papillary or tubulopapillary, often with a thick fibrous capsule, foam cells, necrosis, hemorrhage, and multifocality. Thirty-five percent of these tumors were low grade (NG I and II) and 65% high grade (NG III and IV). Sixteen of these tumors presented in a higher stage (stages III and IV), and the overall stage correlated with NG (chi 2, p = 0.009). Tumors were further distinguished by cytoplasmic features: eosinophilic (42%), basophilic (34%) and mixed (24%). Eosinophilic tumors were predominantly high grade, and basophilic tumors low grade (chi 2, p = 0.000). A mean follow-up of 57 months showed progression (metastasis, recurrence, or death due to disease) in 21%, whereas 63% were free of disease. Eleven percent died of unrelated causes, and 5% were lost to follow-up. Kaplan-Meier survival analysis showed that both high NG and stage were strongly associated with decreased survival (p = 0.0000 each), as were decreased foam cell (p = 0.0025) and vascular invasion (p = 0.0002). Comparison of 196 reported cases of papillary RCC, including the current series, with reported large series of conventional RCC indicates that papillary RCC usually presents at an early stage, and stage I (Robson) papillary RCC has better 5 year survival rates (87%-100%) than does RCC of the same stage (65-75%). The overall 5 years survival rate for papillary carcinoma (82-90%) was also higher than that of conventional RCC (44-54%). In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable (p = 0.0000, hazard ratio 10.1) in predicting outcome among papillary RCC. Based on this experience, we conclude that (a) papillary RCC is a malignant tumor, with a tendency to present at a lower stage, but with a distinct potential for progression and aggressive behavior; (b) stratification of these tumors according to cell type, amount of foam cells, presence or absence of vascular invasion, nuclear grade, and pathologic stage provides useful prognostic information; (c) the better 5-year survival rate of papillary RCC (overall and for stage I tumors) compared with that of conventional RCC suggests that it is a tumor with lower malignant potential. Thus, histologic subcategorization of a renal carcinoma as papillary RCC appears to have prognostic implications.

Adenocarcinoma, Clear Cell↗

PubMed2004

Expert review of non-Hodgkin's lymphomas in a population-based cancer registry: reliability of diagnosis and subtype classifications.

Incidence rates of non-Hodgkin's lymphomas (NHLs) have nearly doubled in recent decades. Understanding the reasons behind these trends will require detailed surveillance and epidemiological study of NHL subtypes in large populations, using cancer registry or other multicenter data. However, little is known regarding the reliability of NHL diagnosis and subtype classification in such data, despite implications for the accuracy of incidence statistics and studies. Expert pathological re-review was completed for 1526 NHL patients who were reported to the Greater Bay Area Cancer Registry and who participated in a large population-based case-control study. Agreement of registry diagnosis with expert diagnosis and with International Classification of Diseases for Oncology-2 (Working Formulation) subtype classifications was measured with positive predictive values and kappa statistics. Agreement of registry and expert diagnoses was high (98%). Thirty patients were found on review not to have NHL; most of these had leukemia. For subtypes, agreement of registry and expert classification was more moderate (59%). Agreement varied substantially by subtype from 5% to 100% and was 77% for the most common subtype, diffuse large cell lymphoma. Seventy-seven percent of 128 registry-unclassified lymphomas were assigned a subtype on re-review. Our analyses suggest excellent diagnostic reliability but poorer subtype reliability of NHL in cancer registry data information that is critical to the interpretation of lymphoma time trends. Thus, overall NHL incidence and survival statistics from the early 1990s are probably accurate, but subtype-specific statistics could be substantially biased, especially because of high (15-20%) proportions of unclassified lymphomas.

Adult↗

PubMed2004

Relationship among Dexamethasone Suppression Test, personality disorders and stressful life events in clinical subtypes of major depression: An exploratory study.

: BACKGROUND: The present study aimed to investigate the relationship between dexamethasone suppression test, personality disorder, stressful life events and depression. MATERIAL: Fifty patients (15 males and 35 females) aged 41.0 +/- 11.4 years, suffering from Major Depression according to DSM-IV criteria entered the study. METHOD: Diagnosis was obtained with the aid of the SCAN v 2.0 and the IPDE. Psychometric assessment included the HDRS, HAS, the Newcastle Scale (version 1965 and 1971), the Diagnostic Melancholia Scale, the Personality Deviance Scale and the GAF scale. The 1 mg DST was used. STATISTICAL ANALYSIS: Included MANOVA, ANOVA with LSD post hoc test and chi-square test. RESULTS: Sixteen (32%) patients were non-suppressors. Eight patients without Personality Disorder (PD) (23.5%), and 5 of those with PD of cluster B (50%) were non-suppressors. Atypical patients were the subtype with the highest rate of non-suppression (42.85%). No difference between suppressors and non-suppressors was detected in any of the scales. DISCUSSION: The results of the current study suggest that pathological DST is not a core feature of major depression. They also suggest that there are more than one subtypes of depression, concerning the response to stress. It seems that the majority of depressed patients (50%) does not experience high levels of stress either in terms of self reported experience or neuroendocrine function. The rest of patients however, either experience high levels of stress, or manifest its somatic analogue (DST non-suppression) or have a very low threshold of stress tolerance, which makes them to behave in a hostile way.

Journal Article↗

PubMed1999

Current aspects of the pathology of soft tissue sarcomas.

In soft tissue sarcomas, advances in pathological techniques, including immunohistochemistry, cytogenetics, and molecular genetics, have improved diagnostic accuracy, confirmed or clarified interrelationships between tumor subtypes, and revealed mechanisms of tumorigenesis. Many sarcomas are associated with abnormalities of tumor-suppressor genes, and several types have been found to have specific chromosomal translocations. These data and correlative clinicopathologic studies, although confirming many traditional pathological views, enable refinement or reassessment of terminology and classification of some small round cell, spindle cell, pleomorphic, and lipogenic tumors. New factors are emerging for prediction of tumor behavior, which might ultimately relate to therapy once a wider range of treatment options becomes available. This article reviews these current aspects of sarcoma pathology.

Cell Transformation, Neoplastic↗

PubMed2002

Concordance of histopathologic and cytologic grading in musculoskeletal sarcomas: can grades obtained from analysis of the fine-needle aspirates serve as the basis for therapeutic decisions?

BACKGROUND: Utilization of fine-needle aspiration (FNA) for the diagnosis of musculoskeletal lesions has been de-emphasized by many clinicians because of concerns regarding the technique's ability to supply all information necessary for prognostication and appropriate selection of therapy. Paramount among the concerns is the belief that FNA is incapable of supplying precise subtyping and grading in many cases. Secondary concerns regarding the use of FNA involve its perceived inability to supply adequate tissue for ancillary studies including immunohistochemistry and molecular diagnostic analysis. The authors investigated the ability of FNA to accurately subtype and grade a series of 107 primary sarcomas of the musculoskeletal system. METHODS: The files of the Departments of Pathology at Duke University Medical Center and the University of California at Los Angeles and the private consultation files of one of the authors were searched for all fine-needle aspirates of sarcomas arising within the musculoskeletal system. A total of 107 cases were obtained and reviewed by three board-certified cytopathologists. Each cytopathologist independently assigned subtype when possible and generated a grade for each of the sarcomas. Corresponding surgical material was available for 77 cases. The surgical material was re-reviewed for accuracy of diagnosis and assignment of grade independently of the cytologic examination. Correlation of cytologic grade with histopathologic grade was made and analyzed by the kappa test. In addition, agreement on grade between cytopathologists was analyzed, and accuracy of histologic subtype prediction by cytologic analysis was studied. RESULTS: Most of the sarcomas were cytologically graded as Grade 1 or 2 but were assigned a histologic grade of 2 or 3. Cytopathologist A graded 93% of the sarcomas as either Grade 1 or 2, cytopathologist B graded 89% of cases as Grade 1 or 2, and cytopathologist C graded 94% of cases as Grade 1 or 2. Histologic evaluation demonstrated 82% of cases to be Grade 2 or 3. Correlation of cytologic and surgical grade varied among the observers. Cytopathologist A showed the highest degree of correlation between cytologic and surgical grade with an r value of 0.5. The corresponding r values for cytopathologists B and C were 0.46 and 0.41, respectively. Correlation between cytologic and surgical grade was significant for all three observers (P < 0.001). Only nuclear grade showed a consistent correlation in predicting final surgical pathology grade. Cellularity, mitotic rate, and the presence of necrosis were not statistically significant for predicting histopathologic grade. Accurate exact subtyping by cytologic examination was achieved in approximately 55% of cases. Prediction of histopathologic subtype by cytologic analysis was most successful when a distinctive stroma was present or high-grade features indicative of malignant fibrous histiocytoma were observed. There was little agreement as to histopathologic type as predicated by cytology for low-grade spindle cell sarcomas. CONCLUSIONS: Although there was a statistically significant correlation between cytologically assigned grade and final histopathologic grade, statistical analysis revealed only a moderate correlation between the two with an overall r value of approximately 0.57. Cytologic analysis tended to undergrade in comparison to final histopathologic grading. Only analysis of nuclear atypia showed good correlation with final surgical grade. Fine-needle aspiration was only moderately successful at predicting histopathologic subtype for musculoskeletal sarcomas in this series.

Adult↗

PubMed2004

Somatostatin receptors in pituitary function, diagnosis and therapy.

Recent studies have demonstrated that human pituitary adenomas express multiple somatostatin receptor (sst) subtypes. The expression of sst subtypes in human pituitary adenomas is highly variable. This variability in sst subtype expression may explain the variable responsiveness of patients with pituitary adenomas to medical treatment with the sst2-preferring SS-analogs octreotide and lanreotide. In human GH-secreting pituitary adenomas, both sst2 and sst5 are involved in the regulation of GH secretion. In prolactinomas, sst5 receptors are the key receptors in regulating responsiveness to SS. The low abundance of sst2 in prolactinomas explains the lack of efficacy of octreotide in lowering the elevated PRL levels in prolactinoma patients. Octreotide and lanreotide successfully suppress TSH levels, including normalization of thyroid hormone levels in the large majority of patients with TSH-secreting pituitary adenomas, probably due to the high level of sst2, expression in the adenomas. Although sst2 receptors are expressed by a significant proportion of gonadotroph and clinically non-functioning pituitary adenomas, the overall efficacy of sst2-preferring SS-analogs seems low in this type of patients. Finally, corticotroph adenomas may express multiple sst subtypes as well. Octapeptide SS-analogs do not lower circulating ACTH levels in patients with untreated pituitary-dependent Cushing's disease, whereas SS and the SS-analog octreotide suppress pathological ACTH release in some patients with Nelson's syndrome. This review discusses the expression and potential role of sst subtypes in the different types of human pituitary adenomas.

Adenoma↗

PubMedDate not supplied

Assessment of pathological tau proteins in frontotemporal dementias: qualitative and quantitative approaches.

A large group of clinically and neuropathologically heterogeneous frontotemporal dementias (FTDs) is distinguished by the accumulation of filamentous tau proteins in neuronal and non-neuronal cells, and these disorders are collectively designated as tauopathies. Recent advances in the development of new reagents and the utilization of new multidisciplinary approaches have made substantial progress in the extensive characterization of tau proteins in different tauopathies. Until recently, semi-quantitative assessment of specific pathological lesions in FTDs was limited to immunohistochemical methods. However, it has become increasingly evident that biochemical analyses of pathological tau proteins in diseased brains also play a significant role in establishing the diagnosis of specific FTD subtypes. In this review, the authors summarize recent findings of the unique biochemical tau signatures for a number of specific tauopathies. Moreover, the quantitative assessment of abnormal tau proteins described here reveals heterogeneity in the biochemical features of tau pathologies in FTDs. The identification of highly insoluble tau species that may be more prone to physiological clearance, other than those that form paired helical filaments, could provide additional insights into the role of tau in mechanisms of neurodegeneration in FTDs.

Aged↗

PubMed1996

Bronchioloalveolar lung carcinomas: K-ras mutations are constant events in the mucinous subtype.

Bronchioloalveolar carcinoma (BAC) is a form of peripheral lung adenocarcinoma growing as a single layer of malignant cells along the walls of terminal airways. The existence of BAC as a separate clinico-pathological entity has been a matter of controversy, mainly because its histogenesis is uncertain and it is not easily distinguishable from conventional lung adenocarcinoma (CLA). Three subtypes of BAC have been described using histological and cytological criteria: mucinous, non-mucinous, and sclerosing. The clinical behaviour of BAC appears to be dependent on the histological subtype. The different morphological patterns and clinical outcome of the subtypes of BAC suggest that their biological behaviour may be different from one another and from CLA. This study has investigated 58 BACs (10 mucinous, 40 non-mucinous, and 8 sclerosing) and 50 control CLAs for mutations at codon 12 of the K-ras oncogene. Twenty-one (36 per cent) BACs and 13 (26 per cent) CLAs showed K-ras mutations. A clear association (P < 0.0001) between K-ras mutations and the mucinous type of BAC was observed: all 10 mucinous tumours examined were scored positive for mutations in the K-ras gene, while only 9 (23 per cent) of the 40 non-mucinous and 2 (25 per cent) of the 8 sclerosing BACs were found to be positive. The frequency of ras mutations in non-mucinous BAC, sclerosing BAC, and CLA was not statistically different. Our data indicate that BACs are a heterogeneous group of lung tumours and that the mucinous form might represent a biological entity separate from both the other two BAC types and CLA.

Adenocarcinoma↗

PubMed2026

Sarcomas: Research on Ultrarare Subtypes Gains Ground.

Rare cancers account for almost one fourth of all cancers. Sarcomas belong to the group of cancerous diseases with an incidence of less than 6 cases per 100,000 inhabitants. Over the past decade, activities were launched worldwide to elucidate the peculiarities of many of the more than 100 sarcoma subtypes described in the World Health Organization handbook. The major contributor to exact diagnosis is molecular pathology. The subgroup of ultrarare sarcomas (URS) poses a significant problem as each URS type has its own morphology, biology, natural history, and prognosis. In 2020, 35 international sarcoma centers agreed to standards of evaluating URS. The threshold was set to an incidence of less than 1 case per 1,000,000 inhabitants, and 77 URS subtypes were defined. Also quality criteria for centers to be selected for retrieving data to registries were consented. This issue of Cancer Epidemiology, Biomarkers & Prevention contains the first article to validate these principles of URS using the data from a nationwide cancer database. The authors from Taiwan also pointed out limitations of the approach. Combination with the national death database allowed to calculate overall survival (OS) and identified age as a significant factor for OS per URS type. These new data might foster future research on diagnosis and treatment of URS. See related article by Lee et al., p. 1654.

Humans↗

PubMed2001

Atypical glandular cells of undetermined significance. Subtyping as a predictor of outcome.

OBJECTIVE: To determine whether subtyping of atypical glandular cells of undetermined significance (AGUS) cervical smears into reactive process favored (AGUS-RPF) and not otherwise specified (AGUS-NOS) correlates with rates of underlying pathology. STUDY DESIGN: We performed a retrospective chart review of 129,676 routine Pap smears at Kaiser Permanente, San Diego, from June 1998 to November 1999. One hundred fifty of the 129,676 were evaluated as AGUS (0.12%). Subjects with concomitant AGUS/SIL Pap smears, a prior history surgery for dysplasia, prior AGUS, a history of cancer or prior hysterectomy were excluded from the study. The remaining AGUS smears were then subtyped into AGUS-NOS and AGUS-RPF based on the criteria of the 2nd Workshop of the Bethesda System. Sixty-eight subjects with an initial AGUS smear underwent evaluation with colposcopy, endocervical curettage, endometrial biopsy and directed cervical biopsies. Significant pathology was determined to be any tissue diagnosis that required further treatment more than a follow-up Pap smear. AGUS subclassifications and underlying pathology were then compared using the chi 2 test with Fisher's Exact Test. RESULTS: Twenty-seven patients (40%) had AGUS-NOS, and 41 (60%) had AGUS-RPF. There were no significant differences between the groups in regard to age, race, parity, menopause status, HRT use or tobacco use. CONCLUSION: Subtyping AGUS cervical smears correlates with underlying rates of pathology. However, AGUS-RPF smears were still associated with an approximately 10% incidence of significant underlying pathology. Patients with AGUS on cervical smears need thorough evaluation, regardless of subtyping.

Adult↗