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A 65-year-old male patient with a history of Myelodysplastic Syndrome (MDS) and Systemic Mastocytosis (SM) presented with an invasive disease of the external auditory canal (EAC) and a parotid gland abscess. Abscess drainage and treatment for a malignant otitis externa (MOE) was started, which did not lead to clinical improvement. Computed Tomography (CT) of the petrous bone as well as a Positron Emission Tomography/Computed Tomography with 2-[fluorine-18]-fluoro-2-deoxy- d -glucose (FDG-PET-CT) showed bony erosion of the EAC with a symmetrical FDG distribution at the level of both EACs. Histopathological biopsies of the EAC revealed a rarely encountered localization of systemic mastocytosis (SM). Especially patients with a hematological disorder such as a MDS are at risk to develop SM. In case of a fulminant infectious disease of the EAC in these patients, a localization of SM should be considered as well. This is the first report on SM with a localization in the EAC.

Summary The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7. Additionally immuno-stainings for p53, Cyclin D1 and (p)FADD expression were evaluated. Malignant progression was recorded. Eighteen patients with carcinoma in situ (CIS) were treated after diagnosis and excluded from follow-up. Chromosome instability was strongly associated with a high risk of malignant transformation, especially in lower grade lesions (hyperplasia, mild and moderate dysplasia; odds ratio = 8.4, p = 0.004). Patients with lesions containing chromosome instability showed a significantly worse 5-year progression-free survival than those with premalignancies without chromosome instability ( p = 0.002). Neither histopathology nor the protein markers predicted progression in univariate analysis, although histo-pathological diagnosis, p53 and FADD contributed positively to chromosome instability in multivariate analysis. Chromosome instability is associated with malignant progression of laryngeal premalignancies, especially in lower grade lesions. These results may contribute to better risk counselling, provided that they can be validated in a larger patient set.

Contains fulltext : 125535.pdf (Publisher’s version ) (Open Access) OBJECTIVES: One of the main problems in reducing the incidence of oral squamous cell carcinoma (OSCC) is the inability to appropriately deal with leukoplakia. Accurately identifying lesions which will progress to malignancy is currently not possible. The present study aims to establish the value of chromosome instability (CI) detection by DNA image cytometry and FISH analysis for prognosis and monitoring of oral leukoplakia. MATERIALS AND METHODS: For this purpose, we included from our archives 102 oral leukoplakia cases, which had been diagnosed between 1991 and 2008. Patient follow-up data were collected and the histopathological diagnosis was revised. CI assessment was carried out on paraffin-embedded tissue sections using both DNA image cytometry (ICM) and dual target FISH for chromosomes 1 and 7. RESULTS: 16 of 102 Patients developed carcinoma in situ or OSCC. Both detection methods were found to yield prognostic information independent of the histopathological diagnosis. CI was a strong individual marker of progression, with hazard ratios (HRs) of 7.2 and 6.8 for ICM and FISH respectively. Moreover, this approach seems suitable for monitoring lesions over time (especially ICM). Combining histopathology and CI enables subdivision of patients into three risk groups, with different probabilities of malignant progression. CONCLUSION: CI detection seems a reliable method for risk assessment of oral premalignancies and its application may contribute to a better risk-counselling and appropriate treatment regimen or watchfull-waiting approach of patients.

The objective of this study is to measure interobserver variability in the classification of laryngeal mucosal premalignant lesions by reassessing the histopathology of previously diagnosed cases and to determine the possible therapeutic consequences of disagreement among observers. Histopathological assessment of 110 laryngeal mucosal premalignant lesions was done by three pathologists. Each slide had to be classified according to the World Health Organization, Squamous Intraepithelial Neoplasia, and the Ljubljana Squamous Intraepithelial Lesions systems. After the independent assessment, a joint meeting took place. To assess the relation between histopathological grading and subsequent clinical management, we created a two-and a three-grade system besides one comprising all options. For all analyses, the SAS/STAT statistical software was used. The highest unweighted kappa-values concerning the all-options system are observed for the Squamous Intraepithelial Neoplasia classification (0.28, 95% confidence interval 0.23-0.33), followed by the World Health Organization and Ljubljana classifications. For the two-grade system the Ljubljana classification shows the highest unweighted kappa-values (0.50, 95%, 0.39-0.61), followed by the World Health Organization and Squamous Intraepithelial Neoplasia classifications. For the three-grade system, the unweighted kappa-values are similar. The implementation of weighted kappa-values led to higher scores within all three classification systems, although these did not exceed 0.55 (moderate agreement). Given the high level of consensus, simultaneous pathological assessment may be said to provide added value in comparison with independent assessment. In the current study, no clear tendency is observed in favor of any one classification system. The proposed three-grade system could be an improved histopathological tool because it is easier to correlate with clinical decision making and because it yields better unweighted kappa-values and proportions of concordance than the all-options system. Furthermore, clinical management could benefit from assessment by more than one pathologist in suspected cases of dysplasia or carcinoma. Modern Pathology (2011) 24, 892-898; doi: 10.1038/modpathol.2011.50; published online 15 April 2011

Purpose It is known that despite efforts of improving adequate ablation in head and neck cancer, the local recurrence rate has not decreased sufficiently over the last two decades. This is partly due to the presence of potentially malignant groups of cells in the resection margins (minimal residual disease). Chromosomal instability (CI) detection in these histologically diagnosed tumour-free margins might help predict patients at risk for recurrence. Material and methods We have included 25 patients with oral squamous cell carcinoma (OSCC) treated with surgery alone between 1994 and 2003. All resections were histopathologically radical. Follow-up was documented for at least 5 years. Fluorescence in situ hybridization (FISH) was used to examine all resection margins of all tumours for the presence of CI, which is indicated by the nuclear detection of chromosome imbalances and/or polyploidization for chromosomes 1 and 7. In addition, tissue sections were analysed for p53 expression by immunohistochemistry. Results Of the 25 patients, 11 developed a recurrence. FISH analysis showed that of the 11 recurrences, 8 exhibited CI in at least one resection margin. This relation was significant with a p -value of 0.011. There was a trend for p53 overexpression in the resection margins of tumours with recurrence, however, this trend was not statistically significant ( p = 0.082). Conclusion CI in the resection margins of OSCCs, even though histologically tumour-free, can reliably identify patients at risk for developing a local or locoregional recurrence. A future goal will be to investigate how radiotherapy following surgery influences the prognosis of these patients.