Biomedical subjects

N Gale

Publications and source records attributed to N Gale.

At least 19 recordsLinked to original sources

PubMed2003

Inflammatory myofibroblastic tumour of paranasal sinuses with fatal outcome: reactive lesion or tumour?

Inflammatory myofibroblastic tumours (IMTs) are clinicopathologically distinctive but biologically controversial entities, which have been described in the lungs, abdomen, retroperitoneum, and extremities, but rarely affect the head and neck region. IMT usually follows a benign clinical course after radical excision, but invasive, locally recurrent, and metastatic forms of abdominal and mediastinal IMT have also been described. This report describes a case of IMT of the paranasal sinuses with a fatal outcome. A 22 year old woman was admitted to hospital as a result of epistaxis. Computed tomography scan and magnetic resonance imaging showed an expansive process in the paranasal sinuses, extending into the nasal cavity, orbita, and endocranium. The tumour progressed despite several surgical procedures. Radiotherapy, corticosteroids, and chemotherapy were unsuccessful, and the patient died four years after diagnosis, as a result of extensive intracranial spread of the tumour. This is the first known case of an IMT of the head and neck region with a fatal outcome. It shows that the aggressive behaviour of IMTs is not limited to abdominal and mediastinal locations, and supports recent observations that at least a subset of IMTs represents true neoplasia rather than reactive myofibroblastic proliferation.

Adult↗

PubMed2003

Human papillomavirus DNA in oral squamous cell carcinomas and normal oral mucosa.

To elucidate the putative etiologic role of human papillomaviruses (HPV) in oral carcinogenesis, a comparative study was carried out on 62 tissue specimens of oral squamous cell carcinoma (OSCC) and on 62 specimens of histologically normal oral mucosa obtained from the individuals who matched the subjects with OSCC in age, gender, localization of obtained tissue specimens, drinking and smoking habits. Internal control amplification showed that amplifiable DNA was recovered from 59/62 and 61/62 tissue samples of OSCC and normal oral mucosa, respectively. The amplification with two different HPV L1 and one HPV E6 consensus primer sets showed the presence of the HPV DNA genotypes 16, 33, 58 in 5/59 (8.4%) OSCC specimens and HPV genotypes 11, 16, 31, 68 in 4/61 (6.6%) tissue samples of normal oral mucosa tested. In the study in which a comparative examination of the presence of HPV DNA was for the first time performed on the tissue samples of the patients with OSCC and the age- and gender-matched control subjects there was no significant difference in the prevalence of HPV DNA among both study groups. Our results suggest that occasional findings of HPV DNA in OSCC tissue specimens may be the result of an incidental HPV colonization of oral mucosa, rather than of viral infection, and that HPVs play a limited role in the etiopathogenesis of the majority of OSCC.

Adult↗

PubMed2002

[The Ljubljana classification of epithelial hyperplastic laryngeal lesions: a morphometric evaluation of nuclear pleomorphism].

Epithelial hyperplastic laryngeal lesions (EHLL) are associated, with a varying degree of "epithelial risk"- to develop invasive carcinoma. Several classifications have been proposed but none has received a total agreement. The 1999 Ljubljana classification distinguished four grades: simple, abnormal and atypical hyperplasia and in situ carcinoma (ISC). The first two grades are considered benign lesions; the ISC is the malignant lesion, while the atypical hyperplasia is considered a "risky lesion". This is characterized by alterations of epithelial cells towards malignancy, but not to the extent to be found in carcinoma cells. Such characteristics refer to cytomorphological (e.g., nuclear hyperchromatism, nucleoli, increased nuclear/cytoplasmic ratio) and architectural (e.g. stratification, orientation, maturation) features. In the Ljubljana scheme, nuclear pleomorphism is one of the most important features. We wanted to improve the importance of nuclear pleomorphism in the basal cells layer in different classes of EHLL using morphometrical analysis. We studied 8 cases of simple hyperplasia, 10 of abnormal hyperplasia, 10 of atypical hyperplasia and 8 of ISC using the software SAM (Shape Analytical Morphometry). The results were submitted to univariate statistical analysis. Nuclear dimensions (maximum diameter, perimeter and area) showed a progressive increase from simple to atypical hyperplasias to ISC, while abnormal hyperplasia showed the lowest values. On the contrary, analytical parameters related to nuclear contour irregularities and asymmetries showed their highest values in abnormal hyperplasia nuclei. There were no significant differences between atypical hyperplasia and ISC, while it was possible to differentiate abnormal hyperplasia from the others. In conclusion basal nuclei of atypical hyperplasia and ISC are similar so that other cytological and morphological architectural parameters are necessary to distinguish the two lesions. Abnormal hyperplasia seems to be the biological category of 'proliferative " benign laryngeal epithelium; simple hyperplasia refers to "stable" - irritative epithelium.

Biopsy↗

PubMed2000

Wegener's granulomatosis in the upper respiratory tract.

Wegener's granulomatosis is a distinct clinico-pathological entity characterised by necrotising vasculitis of small arteries and veins in conjunction with the formation of granuloma in the upper and lower respiratory tracts, and glomerulonephritis. The vast majority of patients have antineutrophil cytoplasmic antibodies in the serum with a characteristic cytoplasmic pattern. However, in early phases of the disease only the upper respiratory tract may be affected, clinical and histological features may be nonspecific, and antineutrophil cytoplasmic antibodies not present. In this paper we present four patients with involvement of the upper respiratory tract suspicious for early Wegener's granulomatosis. We emphasise the significance of clinical, histological and serological parameters in the early detection of Wegener's granulomatosis.

Aged↗

PubMed2000

Eph receptors and ephrin expression in cranial motor neurons and the branchial arches of the chick embryo.

Cranial motor axons navigate along a variety of pathways to their targets in the periphery of the head. Whereas somatic motor axons innervate tongue and eye muscles, visceral motor axons innervate parasympathetic ganglia, and branchiomotor axons innervate the branchial arches. The formation of these diverse pathways must depend upon molecules present in the environment traversed by growing axons. We have analyzed the potential roles of the ephrin ligands and their Eph tyrosine kinase receptors during cranial motor neuron development and axon pathfinding, by investigating expression patterns of these molecules at relevant stages in the chick. We detected expression of EphA3 and EphA4 among trigeminal and facial motor neurons, at times when these neurons are projecting to their muscle targets in the branchial arches. Corresponding ephrin-A ligands for these receptors were found to be expressed in specific regions of the arches during the same period, implicating ephrin-mediated interactions in cranial motor axon pathfinding.

Animals↗

PubMed2000

Clinical applicability of the Ljubljana classification of epithelial hyperplastic laryngeal lesions.

The diagnosis, prognosis, and choice of treatment of various laryngeal lesions depends almost entirely on the interpretation of changes in the covering epithelium. These abnormalities, referred to as epithelial hyperplastic laryngeal lesions, have been graded according to the Ljubljana classification into simple, abnormal and atypical (risky epithelium) hyperplasia and carcinoma in situ. The aim of this study was to evaluate the clinical applicability and prognostic value of this classification and to determine the incidence of malignant transformation. A retrospective clinical-pathological analysis was performed in a series of 4167 patients with 4574 biopsies, treated from 1979 to 1994. Simple (benign prickle cell) hyperplasia was the predominant grade in nodules, polyps, Reinke's oedema, granulomas, and papillomas, accounting for 37.6-68.6% of cases. In chronic laryngitis, abnormal (benign basal cell) hyperplasia was predominant with 43.9% of cases. Atypical ('risky') hyperplasia was observed almost exclusively in patients with chronic laryngitis (16.1%) and papillomas (10.1%), and only exceptionally in patients with vocal cord nodules (0.9%) and Reinke's oedema (0.3%). The percentage of malignant transformation in atypical hyperplasia was 11.6% (13/112 patients in 2-12 years), while in simple and abnormal hyperplasia, it was 0.3% (8/2920 patients in 1.5-11 years). The data support the concept of the Ljubljana classification dividing epithelial hyperplastic laryngeal lesions into benign (simple and abnormal hyperplasia), potentially malignant (atypical hyperplasia) lesions and carcinoma in situ.

Adolescent↗

PubMed2000

The Ljubljana classification: a practical strategy for the diagnosis of laryngeal precancerous lesions.

There is no internationally accepted classification of epithelial hyperplastic laryngeal lesions (EHLL). The majority of current classifications follow criteria similar to those commonly used for cervical epithelial lesions. However, the different etiology of laryngeal cancer and its particular clinical and histologic features necessitate a grading system more appropriate to this region. The Ljubljana classification of EHLL was devised in 1971 to cater to this requirement. Detailed criteria for histologic grading in this classification were formulated by a working group on EHLL of the European Society of Pathology in 1999. The system recognizes four grades: simple and abnormal hyperplasia are benign categories; atypical hyperplasia ("risky" epithelium) is potentially malignant, and carcinoma in situ actually malignant. The main features by which the proposed grading system differs from other classifications are: 1. the distinction between benign and potentially malignant lesions; 2. the positive separation of carcinoma in situ from atypical hyperplasia; 3. the lack of prognostic significance for any surface keratin layer. The eventual outcome of EHLL patients so graded justifies the proposal for separating the lesions into a benign group, showing malignant transformation in only 0.9% of cases, from a potentially malignant group showing malignant transformation in 11% of cases. For diagnostically difficult cases, supplementary techniques such as those using morphometry, immunohistochemical and molecular biology are advised to improve the accuracy of diagnosis and predictions of their biological behavior.

Carcinoma in Situ↗

PubMed2000

Chromosomes 7,17 polysomies and overexpression of epidermal growth factor receptor and p53 protein in epithelial hyperplastic laryngeal lesions.

PURPOSE: To visualize directly a sequence of genetic changes underlying the entire spectrum of epithelial hyperplastic laryngeal lesions (EHLL) and laryngeal cancer by the use of non-isotopic in situ hybridization (ISH) for chromosomes 7 and 17 in correlation with overexpression of p53 protein and epidermal growth factor receptor (EGFR). The specific aim was to compare the results and prognostic significance between the two types of EHLL: isolated, mainly atypical hyperplasia or risky epithelium, and EHLL associated with squamous cell carcinoma (SCC). PATIENTS AND METHODS: 59 tissue specimens of EHLL obtained from 34 patients, graded according to the Ljubljana classification into simple (SH), abnormal (AbH) and atypical hyperplasia (AtH), and carcinoma in situ (CIS) were included in the study. Non-fluorescent ISH for chromosomes 7 and 17 was performed by biotinylated alpha-satellite DNA probes. Immunohistochemical staining for EGFR and p53 protein was analyzed on the same tissue samples. RESULTS: Polysomy for both chromosomes increased in correlation with progressive grades of EHLL. The most important finding was the statistically significant difference in chromosome copy numbers between the isolated AtH and AtH associated with SCC. Overexpression of EGFR and p53 protein was found in 61 (36/59) and 52% (31/59) of cases, respectively. The immunoreactivity for both markers increased with the grade of lesions, but the staining pattern was not so uniform in isolated EHLL. On the other hand, the immunoreactivity was expressed more constantly in EHLL adjacent to SCC. CONCLUSIONS: Numerical changes in chromosomes 7 and 17 might be associated with an upregulation of EGFR and p53 genes, and could contribute to critical events in laryngeal carcinogenesis. For daily practice, the cytogenetic and immunohistochemical analyses could be of assistance in distinguishing between low- and high-risk groups of AtH. However, the isolated forms of atypical hyperplasia need considerable further study by evaluating genetic changes with the described methods regarding their ultimate transformation to carcinoma.

Adult↗

PubMed2000

Laryngeal granuloma: characteristics of the covering epithelium.

The purpose of the present study was to evaluate the biological behaviour of the marginal epithelium, that proliferates and eventually covers laryngeal granulomas, and to reveal the applicability of the recently re-introduced Ljubljana classification when reporting reactive epithelial hyperplastic lesions. A retrospective clinical and histomorphological analysis was performed on 149 laryngeal granuloma biopsies. Epithelial changes were classified according to the Ljubljana classification into normal epithelium; simple, abnormal, or atypical hyperplasia; and carcinoma in situ. Atrophic epithelium, not evaluated separately in the Ljubljana classification, was additionally assessed. Simple hyperplasia was found in 98 cases (65.8 per cent), abnormal hyperplasia in seven (4.7 per cent), atrophic epithelium in 24 (16.1 per cent), and normal squamous epithelium in 20 (13.4 per cent). Atypical hyperplasia and carcinoma in situ were not observed. The results of our study clearly showed that the proliferation of the covering epithelium mostly in the form of simple hyperplasia, is entirely reactive and therefore reversible. No epithelial hyperplastic lesions were found that were previously described to be associated with an increased risk of malignant alteration, namely atypical hyperplasia and carcinoma in situ. However, since an initial growth of an invasive malignant neoplasm might macroscopically imitate the appearance of laryngeal granuloma, a histological examination in all aetiological forms of laryngeal granulomas is required. By clearly discerning the benign nature of epithelial changes in laryngeal granulomas, the recently re-evaluated and further formulated Ljubljana classification may also influence the clinical handling of patients.

Adolescent↗

PubMed2000

Rapid extraction of DNA from archival clinical specimens: our experiences.

The analysis of DNA extracted from archival clinical specimens using polymerase chain reaction represents the basis of a variety of research and diagnostic protocols in medicine. However, the selection of optimal DNA extraction method is critical if such an analysis is to be successful. Recently, we have evaluated a number of rapid DNA extraction protocols in order to find the most suitable method for routine processing of the most common archival materials in pathological and cytological laboratories: paraffin-embedded tissues and Papanicolaou- or Giemsa-stained smears. Our results demonstrate that rapid DNA extraction methods have comparable DNA extraction efficiencies with standard DNA isolation protocols on archival clinical specimens with the exception of Giemsa-stained smears.

Archives↗

PubMed2000

A mouse model of chronic bacterial lesions (a cotton trap) for studying oral bacteria-lymphocyte interactions.

We established a mouse model of chronic bacterial infection (cotton trap) to get a deeper insight into interactions between immune cells and bacterial strains, that are most commonly isolated from periapical processes. We have used flow cytometry to identify the presence of intracellular cytokines of activated T cells collected from cotton traps, previously infected with different strains of bacteria and implanted subcutaneously into the back of the mice. We provide an evidence that anaerobic bacteria (Bacteroides sp.) and nocardiae are more effective in inducing cytotoxic immunity and Th1 response compared to oral streptococci. Differences in immune response against anaerobic bacteria when compared to streptococci are probably dependent on some non-specific immune cell stimulation (e.g. by bacterial cell wall components), nevertheless the role of specific antigen-dependent immune mechanism can not be excluded.

Animals↗

PubMed1999

Criteria for grading in the Ljubljana classification of epithelial hyperplastic laryngeal lesions. A study by members of the Working Group on Epithelial Hyperplastic Laryngeal Lesions of the European Society of Pathology.

AIMS: To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly-used model of intraepithelial neoplasia in the cervix. METHODS AND RESULTS: Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion). CONCLUSIONS: Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semiobjective methods of quantitative morphometry and immunohistochemistry.

Epithelium↗

PubMed1999

Authors' reply

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Journal Article↗

PubMed1999

Cervical metastases of head and neck squamous cell carcinoma correlate with loss of heterozygosity on chromosome 16q.

To assess the potential involvement of putative tumor suppressors or metastasis suppressors on chromosome 16q in head and neck squamous cell carcinoma (HNSCC), we have examined 42 primary HNSCCs for loss of heterozygosity (LOH) at 16q and correlated these findings with the occurrence of cervical nodal metastases and other clinical parameters. Seven of the 42 (17%) HNSCCs examined displayed LOH at chromosome 16q24. Three of the seven HNSCCs showed LOH at all of the informative loci analyzed along the chromosome arm, whereas the other four showed only loss of a subset of markers. When LOH at 16q was correlated with clinical parameters, there was no significant correlation with age, sex, clinical stage, T stage, N stage or survival. However, there was a correlation between LOH at chromosome 16q24 and involvement of cervical lymph nodes. Of the seven HNSCCs that had lost heterozygosity at 16q24, six had local metastases to lymph nodes indicating that LOH at 16q24 may have predictive value for the metastatic potential of HNSCCs.

Adult↗

PubMed1998

Detection of human papillomaviruses in tissue specimens.

During the past decade, molecular methods based on the detection of viral DNA have become a key tool for the detection of human papillomaviruses (HPVs) in tissue. The methods can be divided into two groups: those in which tissue destruction is unavoidable for the detection of HPV DNA, and those in which the detection of viral DNA is performed in a way that allows tissue morphology preservation. Polymerase chain reaction is currently the most sensitive method for HPV detection and an excellent research tool. However, because of frequent contamination problems and lack of standardization, it is not readily applicable to diagnostic laboratories. The recent improvements in in situ hybridization have made it possible for this method to become the most appropriate method for routine detection of HPVs in tissue. At present, however, the use of at least two independent HPV DNA detection methods is indispensable for accurate determination of HPVs.

DNA, Viral↗

PubMed1997

Quantitative pathology of laryngeal epithelial hyperplastic lesions.

We studied 40 laryngeal biopsies samples in order to ascertain the reliability of light microscopical criteria for subdividing laryngeal epithelial hyperplastic lesions (EHL) and carcinoma in situ as well as to determine the relationship between proliferative activity of their epithelial cells and the histological grade. The biopsies were divided into four groups in accordance with the Kambic-Lenart classification: simple, abnormal and atypical hyperplasia and carcinoma in situ. 10 cases in each group were included. The morphometrical analysis was carried out by a semiautomatic image analysis system. The proliferative activity was determined by the high percentage of cell nuclear antigen (PCNA) and Ki-67 positive epithelial cells and with counting nucleolar organizer regions (Ag-NORs) per nucleus. Our results suggest that measuring the nuclear area of the basal cells. augmented with basaloid cells and carcinomatous cells, is the most useful morphometrical method of differentiating three types of laryngeal EHL and carcinoma in situ, while the proliferative activity progressively increased with the degree of epithelial hyperplasia. Morphometrical methods and proliferative activity should be regarded as useful in conjunction with the traditional histopathological methods allowing more of objective grading of EHL.

Biopsy↗

PubMed1997

Human papillomaviruses: a study of their prevalence in the epithelial hyperplastic lesions of the larynx.

This study investigated the prevalence of human papillomavirus (HPV) infection in various laryngeal epithelial hyperplastic lesions using the Kambic classification from simple hyperplasia to invasive squamous cell carcinoma. For detection of HPV infection polymerase chain reaction (PCR) with 3 different HPV consensus primer sets and in situ hybridization were used. The presence of the HPV DNA was detected in only 2 of the 88 specimens tested: HPV type 6 was detected in 1 case of simple hyperplasia and HPV type 16 in 1 case of invasive squamous cell carcinoma. In conclusion, our study suggests that most laryngeal epithelial hyperplastic lesions are not associated with HPV infection and that other pathogenic mechanisms are more important in the etiology of these lesions.

Carcinoma, Squamous Cell↗

PubMed1997

Langerhans and other immunocompetent cells in vocal cord epithelial hyperplastic lesions of patients with chronic laryngitis.

The aim of the study was to evaluate the intraepithelial and stromal density of Langerhans cells and lymphoid infiltrate in different stages of carcinogenesis in vocal cord biopsies of 24 randomly selected patients with chronic laryngitis. The Langerhans and lymphoid cells were counted using immunolabelling with antibodies against CD1a, S100, CD3, CD20, and CD68 on paraffin-embedded sections of 24 archival laryngeal vocal cord mucosa biopsy specimens, 6 classified as simple, 7 as abnormal, and 11 as atypical epithelial hyperplasia. Results were statistically evaluated using the Kruskal-Wallis and Wilcoxon sign rank tests. The mean number of Langerhans cells and T lymphocytes per mm2 of cross-sectioned epithelium was found to increase from simple to atypical hyperplasia. There were statistically significant differences in Langerhans cell density between atypical hyperplasia and each of the other 2 grades, simple and abnormal hyperplasia, with p < 0.05. Our study suggests the involvement of immune mechanisms, particularly cell mediated, during laryngeal carcinogenesis and the possibility that the assessment of Langerhans cell density might be of prognostic significance.

Adult↗