Francesco Feoli

Trisomy 6 in Merkel cell carcinoma: A recurrent chromosomal aberration

We retrospectively investigated 17 cases of primary and metastasizing Merkel cell carcinomas (MCC) from 14 patients using chromosomal in‐situ hybridization (CISH) to study the occurrence of trisomy 6 in these lesions.

Epidermal growth factor receptor expression in pre-invasive and early invasive bronchial lesions.

The 1999 World Health Organization/International Association for the Study of Lung Cancer histological classification of preneoplastic bronchial lesions has been shown to be reproducible but little is known about its biological significance. The current study evaluated the correspondence between the morphological changes of the bronchial epithelium and epidermal growth factor receptor (EGF-R) expression. Thirteen normal bronchial epithelia, 19 hyperplasia, 16 metaplasia, 10 mild dysplasia, one moderate dysplasia, 10 severe dysplasia (SD), 14 carcinoma in situ (CIS) and 11 microinvasive tumours were assessed. A global EGF-R score obtained by the sum of the positivity score plus the EGF-R staining intensity score was calculated for each lesion. A global EGF-R score of >5 was reached only in one metaplasia, in six SD, in six CIS and in six microinvasive tumours. There was no difference in EGF-R expression between normal, hyperplastic and metaplastic epithelia versus mild dysplasia or between severe dysplasia versus CIS and microinvasive tumours but there was a statistically significant difference between mild versus severe dysplasia. This study demonstrates that epidermal growth factor receptor expression rate changes with the stage of the bronchial lesion, increasing from normal epithelium to carcinoma in situ and microinvasive tumours with a statistically significant difference between mild versus severe dysplasia.

Fine needle aspiration cytology of the breast: impact of experience on accuracy, using standardized cytologic criteria.

OBJECTIVE To evaluate the impact of experience on the accuracy of breast fine needle aspiration cytology (FNAC) using standardized microscopic criteria and review the possible complementarities between FNAC and core biopsy (CB). STUDY DESIGN We studied 292 breast FNAC samples and their subsequent biopsies. The cytologic samples were blindly reevaluated 4-7 years later, when we had gained more experience and refined our diagnostic criteria. The accuracy of the first reading was compared to that obtained at the second reading. Inadequate smears were included in the accuracy calculations. RESULTS In the second reading, the identification of carcinomas and of benign lesions became more accurate. The improvement was statistically significant. Absolute sensitivity passed from 59.9% to 67.7%. Specificity increased from 52.0% to 56.0%. The inadequacy rate varied from 12.7% to 14.0% and complete sensitivity from 92.2% to 91.7%. The majority of inadequate smears were associated with benign lesions. CONCLUSION Significant improvements are associated with increased experience. A more detailed evaluation of nuclear atypia and the use of Papanicolaou-stained material were also important. Accurate selection of patients may improve specificity. FNAC could be used in a complementary way with CB.

Ki67 expression in bronchial preneoplastic lesions and carcinoma in situ defined according to the new 1999 WHO/IASLC criteria: a preliminary study

Aims : The World Health Organization classification of bronchial intraepithelial neoplastic lesions has been shown to be reproducible. However little is known about its biological value. The aim of this study was to assess the proliferative activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in situ (CIS) by the expression of Ki67 on biopsy specimens obtained during fluorescence bronchoscopy.

De novo CD5-positive diffuse large B-cell lymphoma of the skin arising in chronic limb lymphedema

We report the case of a 79-year-old woman with a longstanding lymphedema of the right arm who developed a skin lymphoma involving the right wrist area. Microscopically, the lesion was composed of numerous centroblasts infiltrating both the dermis and the subcutaneous tissue. Phenotypic investigations showed expression of CD20, CD79a, and bcl-2 protein by neoplastic cells. In addition, these cells were CD5 positive. No expression of anaplastic large cell lymphoma kinase (ALK), CD10, CD23, CD30, CD43, bcl-6, cyclin D1, p53 or p16INK4a could be seen. Polymerase chain reaction (PCR) analysis demonstrated a clonal rearrangement of the genes coding for the kappa light chain of the immunoglobulin (Ig). No rearrangement of the genes coding for the Ig heavy chain, t(14;18) or t(11;14) chromosome translocations, or Epstein-Barr virus (EBV) genomic sequences could be found. The tumor was classified as stage IE and was first cured by complete surgical excision. Nineteen months later, a recurrence was noted in the right elbow area. This study further illustrates that lymphoma of the skin may complicate chronic limb lymphedema. Like most of the previously reported cases, this neoplasm belonged to the category of diffuse large B-cell lymphoma. However, it showed CD5 expression as a singular feature.

Angiogenesis in preinvasive, early invasive bronchial lesions and micropapillomatosis and correlation with EGFR expression

Aims:  To study the association between morphological changes of the bronchial epithelium and its angiogenic status evaluated by microvessel count (MVC), in order to gain a better understanding of bronchial carcinogenesis. Also, to correlate MVC with epidermal growth factor receptor (EGFR) expression.

058 Carcinogenèse bronchique précoce : expression de p14 et sa relation avec celle de p53 et de MDM2 dans les lésions prénéoplasiques bronchiques

Introduction Un des oncogenes cles dans la carcinogenese bronchique est p53. En se liant a p53, MDM2 le regule negativement et voit sa transactivation, a son tour, stimulee par p53 sauvage. Une autre proteine, pi4, inhibe la formation du complexe entre MDM2 et p53 en retenant MDM2 dans le nucleole et en phosphorylant ces proteines. Nous avons deja montre precedemment que l’expression de MDM2 etait correlee a celle de p53 dans les lesions preneoplasiques bronchiques ( Lung Cancer 2005 ; 49 supplement 2 : S5, O-002). Le but de cette nouvelle etude est d’evaluer l’expression de pl4 dans les lesions preneoplasiques bronchiques et d’analyser ses relations avec celles de p53 et de MDM2. Methodes 43 biopsies recoltees en bronchoscopie en fluorescence chez des patients a haut risque de cancer du poumon ont evalue par immunohistochimie pour ces trois marqueurs. Resultats Parmi les 43 biopsies, 35 etaient de bas grade (BG) et 8 de haut grade (HG), dysplasie severe et plus. 9 lesions (21 %) n’exprimaient pas pl4; 34 (79 %) exprimaient pl4 dont 8 exprimaient pl4 au niveau nucleolaire et 26 de maniere homogene au niveau nucleaire. Le taux de negativite pour pl4 etait de 14 % et de 50 % respectivement parmi les lesions de BG et de HG. Une majorite (87,5 %) des lesions de HG etait soit negative, soit positive au niveau nucleolaire. Par contre, une majorite de lesions de BG (71 %) montraient une positivite nucleaire homogene. Les lesions qui n’etaient positives ni pour p53, ni pour MDM2 presentaient toutes un marquage pour pl4 au niveau nucleaire de maniere homogene et etaient toutes de BG. 90 % des lesions positives pour pl4 au niveau du nucleole exprimaient simultanement p53 et MDM2 et 67 % des lesions negatives pour pl4 etaient positives pour p53 et MDM2. Conclusions Nos resultats suggerent un role actif de pl4 des les stades preneoplasiques. Tantot situee au niveau nucleoaire, elle bloquerait MDM2 a ce niveau et p53 s’accumulerait. Tantot situee au niveau nucleaire et ce principalement sans expression de p53 ni de MDM2 dans les BG, cette voie serait inactive. Tantot perdue et ce le plus souvent en la presence des 2 autres proteines, MDM2 garderait sa capacite de bloquer p53.