Direct measurement of monoclonal plasma cell mass in bone marrow biopsies may be a useful parameter to establish in plasma cell dyscrasia. In this study monoclonal plasma cells/mm2 in light chain immunoglobulin immunostained archival bone marrow sections from 22 patients in whom a diagnosis of multiple myeloma (MM) had been excluded but who had monoclonal proteins were counted by two observers at light microscopic level. There was good correlation between the counts of the two observers. The levels of monoclonal plasma cells/mm2 in biopsies were not related to the &#x25; counts in the aspirates taken at the same time as the biopsies. Three of seven patients with biopsy levels in excess of the polyclonal levels in patients without plasma cell dyscrasia developed progressive MM within the observation time. Monoclonal plasma cell levels/mm2 of bone marrow biopsies can be measured and they provide a useful parameter for the assessment of patients with low volume plasma cell dyscrasia. Colour figure can be viewed on <a target="_blank" href="http://www.esacp.org/acp/2003/25&#x2010;4/markey.htm">http://www.esacp.org/acp/2003/25&#x2010;4/markey.htm</a>.

G. M. Markey

P. Kettle

T. C. M. Morris

N. Connolly

H. Foster

Quantitation of Monoclonal Plasma Cells in Bone Marrow Biopsies in Plasma Cell Dyscrasia

Objective: We describe four patients presenting early oral cancers, detected cytologically on non&#x2010;invasive brush biopsies including DNA&#x2010;image cytometry as an adjunctive method before histology on scalpel biopsies confirmed the evidence of malignancy. Methods: Brush biopsies were performed and smears thereof investigated cytologically. After Feulgen restaining, DNA&#x2010;measurements were performed using a DNA&#x2010;Image&#x2010;Cytometer. Case reports: Oral squamous cell carcinomas were diagnosed cytologically in macroscopically suspicious lesions and malignancy confirmed by DNA&#x2010;cytometry. The initially performed scalpel biopsies did neither supply evidence of oral cancer nor of severe dysplasia. After at least one to 15 months the occurrence of cancer was finally proven histologically on a second scalpel biopsy each (three microinvasive and one in situ carcinoma). Conclusion: Non&#x2010;invasive brush biopsies are a suitable instrument for early cytologic detection of cancer of the mouth. DNA&#x2010;image&#x2010;cytometry, as an adjunctive method, can be used to confirm the cytologic diagnosis or suspicion of cancer in patients with doubtful lesions (dysplasias). DNA&#x2010;aneuploidy is a marker for (prospective) malignancy in smears of the oral cavity, which may detect malignancy months prior to histology. In future this method could be used as a mass screening tool in dentists practise. Colour figures can be viewed on <a target="_blank" href="http://www.esacp.org/acp/2003/25&#x2010;4/remmerbach.htm">http://www.esacp.org/acp/2003/25&#x2010;4/remmerbach.htm</a>.

Torsten W. Remmerbach

Horst Weidenbach

Alexander Hemprich

Alfred B&#xf6;cking

Earliest Detection of Oral Cancer Using Non-Invasive Brush Biopsy Including DNA-Image-Cytometry: Report on Four Cases

Jon Sudb&#xf8;

Non-Invasive Early Diagnosis of Oral Cavity Malignancies

Jan Delabie

Book Review

Objective: To analyse how DNA ploidy and S-phase fraction (SPF) by flow cytometry (FCM) and an optimised fully
automatic DNA image cytometer (ICM) correlate with grade in TaT1 urothelial cell carcinomas (UC) of the urinary bladder.
Materials and methods: Two-hundred-and twenty-eight consensus cases were analysed. Single cell suspensions were stained
(DAPI for FCM, Feulgen for ICM). There was enough material for both FCMand ICMin 202 of these cases. FCMand optimised
ICM measurements were performed on the 202 UCs. To discriminate between different grades, single- and multivariate analyses
was performed on DNA histogram features obtained with the MultiCycle program (using DNA index (DI) and SPF). Results:
Overall measurement time of the adapted ICM method was 10.7 minutes per case (range 5.9–29.8 min.) and required little
additional interactive object rejection (average 152 objects (84–298) on 3000 objects per case measured, which took 9.9 minutes
on average, range 8.3–15.5 minutes). The ICM histograms looked much “cleaner” with less noise than the FCM graphs. The
coefficient of variation (CV) of the diploid peak for ICM(5.4%) was significantly lower than for FCM(5.9%) (p &#x3C; 0.0001). ICM
features were more strongly correlated to grade than FCMfeatures. In multivariate analysis, the best discriminating set of features
was DNA ploidy and SPF (both by ICM). Conclusions: The adapted fully automated DNA ICM works very well for UCs. Low
CV DNA ICM histograms are obtained in a time comparable to FCM. The DNA ICM results have stronger discriminative power
than DNA FCM for grade in TaT1 UCs. Colour figures can be viewed on <a target="_blank" href="http://www.esacp.org/acp/2003/25-3/bol.htm">http://www.esacp.org/acp/2003/25-3/bol.htm</a>.

Marco G. W. Bol

Jan P. A. Baak

Bianca v. Diermen

E. A. M. Janssen

Susanne B. K. Buhr-Wildhagen

Kjell-Henning Kjellevold

Correlation of Grade of Urothelial Cell Carcinomas and DNA Histogram Features Assessed by Flow Cytometry and Automated Image Cytometry

Objective: The aim of this retrospective study was to report on the diagnostic accuracy of AgNOR&#x2010;analysis as an adjunctive diagnostic tool of conventional oral exfoliative cytology taken from suspicious lesions in our clinic. Study design: Cytological diagnoses obtained from brush biopsies of macroscopically suspicious lesions of the oral mucosa from 75 patients (final diagnoses: 53 histologically proven squamous cell carcinomas, 11 leukoplakias and other inflammatory oral lesions) and from 11 patients with normal mucosa as a negative control group were compared with histological and/or clinical follow&#x2010;ups. Five smears were doubtful and seven suspicious for tumor cells in the cytologic report. Number of AgNOR's were counted in 100 squamous epithelial cell&#x2010;nuclei per slide after silver&#x2010;restaining. Results: Sensitivity of our cytological diagnosis alone on oral smears for the detection of squamous carcinomas was 92.5&#x25;, specificity 100&#x25;, positive predictive value was 100&#x25; and negative 84.6&#x25;. The best cut&#x2010;off value of the mean number of AgNOR dots per nucleus distinguishing benign from malignant cells was 4.8. The percentage of nuclei with more than three AgNORs had a cut&#x2010;off level of 70&#x25;. Applying these methods to twelve doubtful or suspicious cytological diagnoses we were able to correctly establish the diagnosis of malignancy in ten cases of histologically proven cancers and to reveal benignity in two histologically proven cases. Thus we achieved a positive and negative predictive value of 100&#x25; each. Conclusions: Smears from brushings of visible oral lesions, if clinically considered as suspicious for cancer, are an easily practicable, non&#x2010;invasive, painless, safe and accurate screening method for detection of oral cancerous lesions. We conclude that AgNOR&#x2010;analysis may be a useful adjunct to other methods in routine cytological diagnosis of oral cancer that can help to solve cytologically suspicious or doubtful cases. Colour figures can be viewed on <a target="_blank" href="http://www.esacp.org/acp/2003/25&#x2010;3/remmerbach.htm">http://www.esacp.org/acp/2003/25&#x2010;3/remmerbach.htm</a>.

Conrad M&#xfc;ller

Natalja Pomjanski

Birgit Buckstegge

Diagnostic Value of Nucleolar Organizer Regions (AgNORs) in Brush Biopsies of Suspicious Lesions of the Oral Cavity

Nuclear morphometry is a method for quantitative measurement of histopathologic changes in the appearance of stained cell nuclei. Numerous studies have indicated that these assessments may provide clinically relevant information related to the degree of progression and malignant potential of breast neoplasia. Nuclear features are derived from computerized analysis of digitized microscope images, and a quantitative Feulgen stain for DNA was used. Features analyzed included: (1) DNA content; (2) nuclear size and shape; and (3) texture features, describing spatial features of chromatin distribution. In this study replicated measurements are described on a series of 54 breast carcinoma specimens of differing pathologic grades. Duplicate measurements were performed using two serial sections, which were processed and analyzed separately. The value of a single feature measurement, the nuclear area profile, was shown to be the strongest indicator of progression. A quantitative nuclear grade was derived and shown to be strongly correlated with not only the pathologic nuclear grade, but also with tubule formation, mitotic grade, and with the overall histopathologic grade. Analysis of replication precision showed that the standard methods of the histopathology laboratory, if practiced in a uniform manner, are sufficient to ensure reproducibility of these assessments. We argue that nuclear morphometry provides a standardized and reproducible framework for quantitative pathologic assessments.

N. Poulin

A. Frost

A. Carraro

E. Mommers

M. Guillaud

P.J. van Diest

W. Grizzle

S. Beenken

Risk Biomarker Assessment for Breast Cancer Progression: Replication Precision of Nuclear Morphometry

Wojciech Polkowski

J. Jan B. van Lanschot

Johanna W. van Sandick

Jan P.A. Baak

The Role of Quantitative Pathology in Clinical Decision Making for Barrett’s Oesophagus

In order to identify genomic changes associated with a resistant phenotype acquisition, we used comparative genomic hybridization (CGH) to compare a human ovarian cell line, Igrov1, and four derived subcell lines, resistant to vincristine and presenting a reversion of malignant properties. Multicolor FISH (Multiplex&#x2010;FISH and Spectral Karyotype) and conventional FISH are also used to elucidate the karyotype of parental cell line. The drug&#x2010;resistant subcell lines displayed many chromosomal abnormalities suggesting the implication of different pathways leading to a multidrug resistance phenotype. However, these cell lines shared two common rearrangements: an unbalanced translocation der(8)t(8;13)(p22;q?) and a deletion of the 11p. These chromosomal imbalances could reflected the acquisition of the chemoresistance (der(8)) or the loss of tumorigenicity properties (del(11p)). Colour figure can be viewed on <a target="_blank" href="http://www.esacp.org/acp/2003/25&#x2010;3/struski.htm">http://www.esacp.org/acp/2003/25&#x2010;3/struski.htm</a>.

St&#xe9;phanie Struski

Martine Doco&#x2010;Fenzy

Michael Koehler

Ilse Chudoba

Francis Levy

Linda Masson

Nicole Michel

Evelyne Ulrich

Nadine Gruson

Jean B&#xe9;nard

G&#xe9;rard Potron

Pascale Cornillet&#x2010;Lefebvre

Cytogenetic Evolution of Human Ovarian Cell Lines Associated with Chemoresistance and Loss of Tumorigenicity

Feature extraction is a crucial step in most cytometry studies. In this paper a systematic approach to feature extraction is presented. The feature sets that have been developed and used for quantitative cytology at the Laboratory for Biomedical Image Analysis of the GSF as well as at the Center for Image Analysis in Uppsala over the last 25 years are described and illustrated. The feature sets described are divided into morphometric, densitometric, textural and structural features. The latter group is used to describe the eu&#x2010; and hetero&#x2010;chromatin in a way complementing the textural methods. The main goal of the paper is to bring attention to the need of a common and well defined description of features used in cyto&#x2010; and histometrical studies. The application of the sets of features is shown in an overview of projects from different fields. Finally some rules of thumb for the design of studies in this field are proposed. Colour figures can be viewed on <a target="_blank" href="http://www.esacp.org/acp/2003/25&#x2010;1/rodenacker.htm">http://www.esacp.org/acp/2003/25&#x2010;1/rodenacker.htm</a>.

Karsten Rodenacker

Ewert Bengtsson

A Feature Set for Cytometry on Digitized Microscopic Images

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Analytical Cellular Pathology provides a forum for pathologists and medical practitioners working in the cellular pathology field. Topics covered include cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, and immunopathology.

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Chief Editor&nbsp;Professor Dimitrios Karamichos&nbsp;focuses on investigating corneal wound healing and dystrophies with a particular interest in the effect of transforming growth factor-β3 or TGF- β3 on corneal stromal cells and their extracellular environment.

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Analytical Cellular Pathology - Table of contents 2003

title

Analytical Cellular Pathology provides a forum for pathologists and medical practitioners working in the cellular pathology field. Topics covered include cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, and immunopathology.

Analytical Cellular Pathology