Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases.

Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign or malignant lesion is difficult. This study evaluated the contribution of fluorescence in situ hybridization (FISH) first in 43 non-equivocal melanomas and nevi, and then in 113 ambiguous melanocytic tumors selected by expert pathologists from six different European institutions. We included two groups of ambiguous tumors: patients without recurrence (5-year minimal follow-up) and with metastases. An independent triple-blind histopathological review was performed to classify tumors as 'favor benign' (A-) or 'favor malignant' (A+). A four-color probe set targeting 6p25, 6q23, 11q13 and CEP6 was used for FISH. In the 43 non-equivocal melanomas and nevi, sensitivity was 85% and specificity 90%. Ninety out of 95 ambiguous melanocytic tumors included were FISH interpretable (67 FISH negative and 23 FISH positive). Of the 90 patients, 69 presented no recurrence and 21/90 exhibited metastases. These ambiguous tumors were mostly spitzoid tumors (45/90). Histopathological reviewers classified these tumors as favor malignant (49/90) and favor benign (32/90), whereas nine cases had a discordant diagnosis. By comparison with outcome, the sensitivity and specificity of histopathological review were 95 and 52%, and the sensitivity and specificity of FISH were 43 and 80%. Compared with histopathological review, the sensitivity and specificity of FISH were 34.5 and 91%. Interestingly, by combining the histopathological diagnosis with FISH results, the diagnosis was optimized, especially by increasing specificity (76% instead of 52% for expert diagnosis alone) and by improving sensitivity compared with FISH alone (90 vs 43% for FISH result alone). The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors. A positive FISH test reinforces the diagnosis of melanoma, allowing such tumors (particularly thick tumors) to be managed as melanomas.

[Clinical practice guideline: 2005 update of recommendations for the management of patients with cutaneous melanoma without distant metastases (summary report)]. / Recommandations pour la pratique clinique: mise à jour 2005 des recommandations pour la prise en charge des patients adultes atteints d'un mélanome cutané sans métastase à distance (rapport abrégé).

CONTEXT: The National French federation of comprehensive cancer centres (FNCLCC) and the French society of dermatology (SFD) initiated together the update of clinical practice guideline for the management of patients with cutaneous melanoma in collaboration with the French national cancer institute and with specialists from French public universities, general hospitals and private clinics. This work is based on the methodology developed in the "Standards, Options and Recommendations" (SOR) project. OBJECTIVES: To update SOR guidelines for the management of patients with cutaneous melanoma previously validated in 1998 and French melanoma consensus conference published by SFD and ANAES in 1995. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. RESULTS: This article is a summary version of the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concerned (1) The new AJCC-UICC classification (2) Excision margins (3) Sentinel node biopsy (4) Adjuvant treatments (5) Initial staging and follow up of operated patients.

[Bladder melanoma in a 7-year-old girl]. / Mélanome vésical chez une fillette de 7 ans.

Melanomas are very rare in children. The authors report an original case of bladder melanoma in a 7-year-old girl. The initial staging assessment and complete remission 7 years after partial cystectomy with healthy resection margins confirmed the primary nature of this tumour Bladder melanomas are exceptional in adults, as only about 20 cases have been published. To the best of our knowledge, this is the first published case in a child.

Role of the multidrug efflux system MexXY in the emergence of moderate resistance to aminoglycosides among Pseudomonas aeruginosa isolates from patients with cystic fibrosis.

This study investigates the role of active efflux system MexXY in the emergence of aminoglycoside (AG) resistance among cystic fibrosis (CF) isolates of Pseudomonas aeruginosa. Three genotypically related susceptible and resistant (S/R) bacterial pairs and three other AG-resistant CF strains were compared to four non-CF strains moderately resistant to AGs. As demonstrated by immunoblot experiments, pump MexY was strongly overproduced in all of the resistant bacteria. This MexXY upregulation was associated with a 2- to 16-fold increase in the MICs of AGs in the S/R pairs and lower intracellular accumulation of dihydrostreptomycin. Alterations in mexZ, the repressor gene of operon mexXY, were found in all of the AG-resistant CF isolates and in one non-CF strain. Complementation of these bacteria with a plasmid-borne mexZ gene dramatically reduced the MICs of AGs, thus highlighting the role played by MexXY in the development of moderate resistance in CF patients. In contrast, complementation of the three non-CF strains showing wild-type mexZ genes left residual levels of resistance to AGs. These data indicate that a locus different from mexZ may be involved in overproduction of MexXY and that other nonenzymatic mechanisms contribute to AG resistance in P. aeruginosa.

Clinical and histopathological characterization of cutaneous melanomas in the melanoblastoma-bearing Libechov minipig model.

Spontaneous animal tumors appear to be highly suitable models to study human oncology and cancer therapy. The aim of this study was to characterize the clinical and histological features of hereditary melanocytic lesions found in the French herd of melanoblastoma-bearing Libechov minipigs (MeLiM) and their Duroc crossbreeds. Clinically, we discriminated between three types of melanocytic skin lesions, which offer a lesion continuum from lentigo to metastatic melanomas. More than 70% of these lesions appear on piglets before they are 3 months old and preferentially on homogeneous black coat piglets. The incidence of melanoma reaches 50% in MeLiM. Most of the highly invasive melanomas regressed spontaneously in the first year of the piglet's life and the regression was followed by hair, skin and iris depigmentation. A histopathological study was conducted according to the human melanoma classification. Except for lentigo maligna, we observed the three main types of human melanoma in swine [superficial spreading melanoma (SSM), nodular or unclassified melanoma] with an excess of SSM (59-67%). The histological events leading to total spontaneous regression are chronologically described. The genetic predisposition, the high incidence of melanoma, the clinical and histopathological features similar to the human disease and the high rate of spontaneous regression offer an opportunity to use this model for studying genetic events controlling melanoma development and regression and the biological mechanisms involved in oncogenesis and anti-cancerous self-defense.

Reliability of the histopathologic diagnosis of malignant melanoma in childhood.

OBJECTIVE: To assess interrater reliability in the diagnosis of malignant melanoma in children. DESIGN, SETTING, AND PARTICIPANTS: We collected 85 slides of melanomas diagnosed in patients younger than 17 years through a network of dermatopathologists and dermatologists. The slides were classified into 3 categories: (1) slides from children with metastatic melanoma; (2) slides from disease-free children with a follow-up of less than 5 years; (3) slides from disease-free children with a follow-up of 5 years or longer. Category 1 was considered the gold standard. Four pairs of expert dermatopathologists reviewed the slides and classified them into melanoma, nevus (including Spitz nevus), or ambiguous tumors. INTERVENTION: None. MAIN OUTCOME MEASURE: Concordance between pairs of experts. RESULTS: For category 1 slides (n = 20), the concordance was weak to moderate. For category 2 slides (n = 47), the concordance was weak. For category 3 slides (n = 18), the concordance was poor to moderate. CONCLUSION: This study demonstrates that the reliability of diagnosis of melanoma in childhood is poor, even when submitted to experts.

Pancreatic Neuroendocrine Carcinoma Metastatic to the Breast as Part of the Multiple Endocrine Neoplasia Type 1 Syndrome.

Breast metastases from nonmammary tumors are rare. We report here the first case of pancreatic neuroendocrine carcinoma metastatic to the breast in a patient with possible multiple endocrine neoplasia type 1. The diagnosis was supported by histological examination, immunohistochemistry, and ultrastructural analysis. This observation emphasizes the importance of clinical data for an accurate diagnosis, especially during intraoperative examination. When pathologists are faced with an unusual breast tumor larger than 2 cm, we would recommend freezing and/or saving pieces of tissue for ultrastructural analysis, which might help in the diagnosis.