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P Dervan

Publications and source records attributed to P Dervan.

At least 19 recordsLinked to original sources
PubMed2007

Mycosis fungoides--a review of the management of 28 patients and of the recent literature.

BACKGROUND: Mycosis fungoides is an uncommon cutaneous T-cell lymphoma characterized by malignant monoclonal proliferation of T-helper lymphocytes. Its course is variable with a potential for lymphatic and hematogenous involvement. We report the investigations, staging, treatment, follow-up, and outcome of 28 patients. This is the first such study reported from Ireland. METHODS: Twenty-eight patients with mycosis fungoides (14 women, 14 men; average age, 52.5 years) were reviewed over 12 years in the dermatology clinic which assesses an average of 4500 patients per year. All mycosis fungoides patients were referred from their family physicians. The diagnosis was made in all cases from a combination of clinical findings, histology, and immunohistochemistry. TNM staging revealed 11 patients at diagnosis stage IA (T1), 12 at stage IB (T2), four at stage IIB (T3), and one at stage III (T4). RESULTS: The usual male preponderance was not found. Eight patients needed multiple biopsies to establish the diagnosis. Detailed investigations were not useful in the early stages. Patients were followed up over a 12-year period. Thirteen patients died as a result of cutaneous lymphoma. Two patients with stage IA disease progressed rapidly and died, a feature reported in only 10% of patients at this stage. Five patients showed unusual features, including a long history prior to presentation, the development of the rarely reported bullous mycosis fungoides, and aggressive disease beginning at a young age. CONCLUSIONS: Mycosis fungoides is rare; we reviewed 28 patients over 12 years. The prognosis is poor at the later stages; 13 patients died. Two patients who died were unusual in that they rapidly progressed from stage IA disease; however, in the majority of patients with this stage, the prognosis is excellent. Detailed investigations were unhelpful in early stage disease. Close clinical follow-up is essential to identify disease progression.

Adult↗
PubMed2004

Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

Breast Neoplasms↗
PubMed2004

Estrogen receptor alpha and beta profiling in human breast cancer.

BACKGROUND: The identification of a second estrogen receptor (ER-beta) has significant implications for therapeutic strategy in breast cancer management arising from the potential agonist effect of Tamoxifen at estrogen receptor sites and as such, antiestrogen therapy may be inappropriate in patients with a dominance of ER-beta. METHODS: To determine the proportion of breast cancer patients who may be so at risk, we developed a novel multiplexed RT-PCR technique to establish the relative ER-alpha and ER-beta levels in 53 primary breast cancers, 11 normal breast tissues and six cell lines. We further assessed the prognostic significance of receptor status relative to the Nottingham prognostic index (NPI). The ER-alpha and ER-beta status was also determined by immunohistochemistry using previously published and 'in-house' scoring systems. RESULTS: Using RT-PCR analysis, 46 tumours were hormone receptor positive (ER+) with 42 displaying ER-alpha predominance. Comparison with immunohistochemistry demonstrated 44/53 (ER-alpha) and 27/50 (ER-beta) concordance rates. There was no significant difference in the NPI between ER-alpha and ER-beta predominant cohorts or between ER+ and ER- cohorts. CONCLUSION: This study identifies the existence of a subgroup of ER+ patients in whom Tamoxifen therapy may be inappropriate and has significant implications for adjuvant therapy of primary breast cancer.

Adult↗
PubMed2004

Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology.

AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

Biomarkers, Tumor↗
PubMed2003

Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.

Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

Breast Neoplasms↗
PubMed2001

Aggressive multiple myeloma presenting as mesenteric panniculitis.

Mesenteric panniculitis is a rare disease of the bowel mesentery, characterized by tumor-like infiltration by chronic inflammatory cells, fat necrosis, and fibrosis. Reported cases cited clinical presentation ranging from abdominal pain to fever of unknown origin, the majority of which were idiopathic and associated with a benign prognosis. We report the case of a 43-yr-old male who presented with malaise, weight loss, microcytic anemia, and a high erythrocyte sedimentation rate. Radiographic and histological investigations revealed typical features of mesenteric panniculitis. Initial treatment with high-dose oral prednisolone led to rapid and complete resolution of symptomatology, radiographic, and laboratory anomalies. Within 6 months, the patient presented again with anemia, renal failure, and hypercalcemia. A diagnosis of IgA kappa chain myeloma was made. Despite chemotherapy and restoration of normocalcemia, he died from refractory pulmonary edema. This is the first report of a hematological malignancy initially presenting with features of mesenteric panniculitis culminating in an aggressive course and a fatal outcome.

Adult↗
PubMed2000

Selective inhibition of DNA gyrase in vitro by a GC specific eight-ring hairpin polyamide at nanomolar concentration.

The influence of an eight-ring hairpin DNA minor groove binder on the gyrase mediated DNA supercoiling and cleavage reaction step of the enzyme was investigated. The results demonstrate that supercoiling is affected by the hairpin polyamide in the millimolar concentration range while the enzyme catalyzed cleavage of a 162 bp fragment of pBR322 containing a single strong gyrase site is effectively inhibited at nanomolar concentration. As demonstrated by footprint analysis the latter effect is caused by a specific binding of the hairpin forming polyamide to the enzyme recognition site (GGCC), which indicates that the gyrase activity to produce a double strand break is blocked at this site. The pyrrole-imidazole hairpin polyamide is the most potent inhibitor of the gyrase mediated cleavage reaction compared to other known anti-gyrase active DNA binding agents.

Base Sequence↗
PubMed2000

Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.

It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.

Breast↗
PubMed1999

Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.

A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.

Breast Diseases↗
PubMed1998

Persistent infection of the chin with an unusual skin pathogen (Streptococcus milleri): a sign of intraoral carcinoma.

Streptococcus milleri is a commensal of the oropharynx and gastrointestinal tract which is not generally associated with skin disease. We now report a patient who presented with a pustular mass of the chin with lower lip anaesthesia. He was initially thought to have sycosis barbae, but response to treatment was poor and lesional swabs repeatedly cultured S. milleri. After some delay, squamous cell carcinoma of the mouth, involving the mandible and overlying skin, was detected. We consider that the S. milleri either invaded through the tumour from the mouth or root canal or colonized the skin from saliva dribbled over the numb lower lip. Isolation of an unusual organism and numbness of the chin are features that should suggest the need for early radiography.

Aged↗
PubMed1998

Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening, the greater use of breast-conserving surgery, and the recognition that certain histological subtypes are associated with a greater risk of local recurrence has led to the formulation of several new classifications of DCIS in recent years. There are, however, no data concerning the degree of consistency with which these schemes can be applied by reasonable numbers of pathologists. Thirty-three cases of DCIS were thus examined by a working group of 23 European pathologists who categorized them using five recently published classifications: (1) that of the European Pathologists' Working Group based on differentiation (a combination of nuclear grade and cell polarization) with categories of poorly, intermediately, and well differentiated; (2) one based entirely on nuclear grade with categories of high, intermediate, and low, currently in use in the UK national and EC-funded breast screening programs; (3) the same classification in which only two categories, high nuclear grade and other, were used; (4) the Van Nuys system in which lesions are divided into high grade, non-high grade with necrosis and non-high grade without necrosis; and (5) a two-category classification based entirely on the presence or absence of comedo necrosis. Of the three systems with three categories, Van Nuys gave the highest overall kappa statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that assessing cell polarization in addition to nuclear grade neither improves nor worsens consistency. In all three systems, the middle category was associated with the lowest value for kappa. Of the two systems with two categories, that based on nuclear grade gave the highest overall kappa of 0.46 and that based on comedo necrosis the lowest of 0.34. The most robust histological features were thus high- and low-grade nuclei and necrosis as long as the latter did not involve the recognition of a comedo growth pattern. These values probably represent the maximum achievable, at least by reasonable numbers of pathologists in everyday practice. They are better than those previously reported for classification based entirely on architecture, but further improvement is needed.

Breast Neoplasms↗
PubMed1995

Evaluation of Ki-67 reactivity in neuroblastoma using paraffin embedded tissue.

AIMS: To examine the pattern of reactivity of Ki-67 in neuroblastoma and correlate this with a) clinical prognostic criteria and b) cell cycle statistics (using flow cytometry). METHODS: Four micron sections of paraffin embedded (PE) tissue from 55 patients (25 pre chemotherapy and 30 post) were placed on to aminosialinised slides, dewaxed and rehydrated. Slides were pretreated in a microwave oven, endogenous peroxidase activity blocked using 3% hydrogen peroxide and Ki-67 reactivity investigated using a streptavidin/biotin/peroxidase technique. DNA ploidy was also performed from an immediately adjacent section on the same block using a FACScan and Cellfit software. RESULTS: Ki-67 reactivity was well defined and highly reproducible. Eighteen out of 30 post chemotherapy samples were totally negative, despite evidence of proliferation on flow cytometry and all subsequently died of disease. As interpretation post chemotherapy was therefore deemed unreliable, this group was excluded from analysis. Reactivity in pretreatment samples ranged from 0% to 67%; staining was restricted to the nucleus with a distinct pattern noted in the nucleolus. Ki-67 positivity was lower in aneuploid compared with diploid tumours (mean 26% vs 36%, NS). Among diploid tumours, a lower percentage positivity was noted in those patients with better clinical prognostic parameters. Correlation however between Ki-67 and SG2M phases of cell cycle was poor (RS = 0.39, NS). CONCLUSION: Assessment of proliferation in neuroblastoma by Ki-67 reactivity in paraffin embedded tissue is reliable in pretreatment samples and can be incorporated into routine immunohistochemical evaluation. Larger multicentre studies are required to further evaluate Ki-67 reactivity as a prognostic indicator.

Biomarkers, Tumor↗
PubMed1995

Prospective evaluation of a composite scoring system for mammographically detected cytologically assessed impalpable breast abnormalities.

The aim of all breast screening programmes is a reduction in deaths from the disease. It is hoped that this can be achieved with minimal intervention in the patient cohort who do not have cancer. In this study we have assessed the efficacy of a combination of mammographic and cytological scoring systems in the evaluation of 208 women with screen-detected non-palpable breast lesions. All mammograms were scored 1-5 and those with a score of 3 or more required needle localization. A cytology score of 1 to 5 was generated for each patient according to a similar system and an aggregate score for each patient was achieved by the addition of the mammographic and cytology score. Ninety-three of the 208 patients had malignancy--the positive predictive value for mammography alone in this series was 45%. All 58 patients who had an aggregate score of 8 or greater had cancer. The 60 patients who had an aggregate score of 4 had benign disease on excision biopsy. We suggest that a 'wait and repeat mammogram' approach is appropriate in patients with grade 3 mammography and benign (grade 1) cytology. Patients with an intermediate aggregate score of 5-7 should have an excision biopsy and those with an aggregate score of 8 could have definitive surgery rather than excision biopsy. Application of this aggregate scoring technique would enhance the delivery of more appropriate surgery to a majority of patients with screen-detected breast abnormalities.

Biopsy↗
PubMed1994

Stereotactic cytology in a regional breast-screening programme.

Stereotactic localization and fine-needle aspiration are new procedures for the management of non-palpable mammographic abnormalities. In this prospective study, stereotactically guided cytology with immediate reporting was performed before biopsy in a consecutive series of 166 patients with screen-detected non-palpable abnormalities. All specimens were obtained by multiple stereotactically guided passes with a 22-G Franzén needle and graded as: 1, acellular or inadequate; 2, benign; 3, atypical, probably benign; 4, probably malignant; or 5, malignant. After definitive surgery all tumours were staged according to the Union Internacional Contra la Cancrum classification. Of 71 patients with malignancy, 56 were correctly diagnosed by cytology before operation. Twelve patients with malignancy had grade 1 cytology and 50 of the 52 with grade 2 cytology had benign disease. This study confirms that stereotactic cytology is a valuable diagnostic test in a breast-screening programme.

Aged↗
PubMed1993

Fine needle aspiration cytology of thyroid nodules: review of 36 months experience.

Studies suggest that fine needle aspiration of thyroid nodules is a sensitive and specific tool for the detection of thyroid cancers thus preventing unnecessary operations. This technique was introduced in our institution in 1987 and performed where indicated under strictly defined criteria. We reviewed the aspirates performed over a 36 month period to critically evaluate the role of this procedure. Review was limited to F.N.A.s of nodules considered to be potentially malignant by conventional criteria and hence all the following criteria needed to be fulfilled: (1) solitary or dominant nodules in a multinodular goitre, (2) cold on isotope scanning, (3) solid or complex cystic nodule on ultrasonography. During the period May 1987 to May 1990 88 aspiration procedures were performed on 77 patients. 93% of the 77 patients had adequate aspirates and of these approximately 30% were considered suspicious or malignant. The overall resection rate was 23.4% which is approximately one third of the rate expected should suspicion have been based solely on conventional imaging criteria. The yield of neoplasia (adenoma and carcinoma) at resection was 89%. We found FNA to be a very useful adjunct in the management of nodular thyroid disease when used in conjunction with clinical laboratory and radiological evaluation. It is safe, inexpensive and provides useful additional information towards making appropriate decisions in an area beset with uncertainty.

Biopsy, Needle↗