Piet J. Slootweg

Morphometric study of histological changes in sublabial salivary glands due to aging process.

The sublabial salivary glands were studied by morphometric methods in 68 healthy volunteers to establish possible changes related to age in those tissue components that are affected in Sjögrens syndrome and connective tissue diseases (and which might stimulate Sjögrens syndrome). There was an increase in the amount of connective tissue and intralobular ducts with age and a corresponding decrease in acinar tissue. During the aging process changes in the intralobular ducts occurred: the outer and inner diameters of these ducts and the thickness of the epithelium decreased, but the ratio of the outer and inner diameters of the ducts remained constant. The amount of diffuse lymphoplasmacytic infiltrate and the vascularity of the tissue remains constant with age. In 15 of the subjects, however, discrete lymphocytic foci were seen and in six of these more than one focus/4 mm2 of salivary tissue was found, which has been described as suggestive of Sjögrens syndrome. The volume percentage of lymphocytic foci is constant during the aging process. The histological features commonly used to diagnose Sjögrens syndrome may occur in normal people, and false positive diagnoses will occur if these criteria are rigidly adhered to. Morphometry may provide more reliable criteria for distinguishing changes induced by inflammation and related to age which occur in salivary tissue.

Multiple Robust Signatures for Detecting Lymph Node Metastasis in Head and Neck Cancer

Genome-wide mRNA expression measurements can identify molecular signatures of cancer and are anticipated to improve patient management. Such expression profiles are currently being critically evaluated based on an apparent instability in gene composition and the limited overlap between signatures from different studies. We have recently identified a primary tumor signature for detection of lymph node metastasis in head and neck squamous cell carcinomas. Before starting a large multicenter prospective validation, we have thoroughly evaluated the composition of this signature. A multiple training approach was used for validating the original set of predictive genes. Based on different combinations of training samples, multiple signatures were assessed for predictive accuracy and gene composition. The initial set of predictive genes is a subset of a larger group of 825 genes with predictive power. Many of the predictive genes are interchangeable because of a similar expression pattern across the tumor samples. The head and neck metastasis signature has a more stable gene composition than previous predictors. Exclusion of the strongest predictive genes could be compensated by raising the number of genes included in the signature. Multiple accurate predictive signatures can be designed using various subsets of predictive genes. The absence of genes with strong predictive power can be compensated by including more genes with lower predictive power. Lack of overlap between predictive signatures from different studies with the same goal may be explained by the fact that there are more predictive genes than required to design an accurate predictor.

Grading systems in head and neck dysplasia: their prognostic value, weaknesses and utility

BackgroundGrading of dysplasia, including head and neck lesions, continues to be a hotly debated subject. It is subjective and lacks intra- and inter-observer reproducibility due to the insufficiency of validated morphological criteria and the biological nature of dysplasia. Moreover, due to the absence of a consensus, several systems are currently employed.ObjectivesThe aims of this review are to:1) Highlight the significance of dysplasia and the importance of a valid method for assessing precursor lesions of the head and neck.2) Review the different histopathological classification systems for grading intraepithelial lesions of the head and neck.3) Discuss and review quality requirements for these grading systems.ConclusionRegarding the different classification systems, data concerning the WHO classification system are the most available in current literature. There is no simple relationship or overlapping between the classification systems. Further studies should be done to see whether other systems have advantages above the current WHO system and to discover indications that could lead to an universal classification system for intraepithelial lesions of the head and neck.

Maintenance of Head and Neck Tumor Gene Expression Profiles upon Lymph Node Metastasis

Spread of cancer and development of solid metastases at distant sites is the main cause of cancer-related deaths. To understand and treat metastases, it is important to determine at which stages the most pivotal steps for development of metastases occur. In head and neck squamous cell carcinoma (HNSCC), metastasis nearly always occurs first in local lymph nodes before development of distant metastasis. Here, we have investigated gene expression patterns in HNSCC lymph node metastases using DNA microarrays. Several types of analyses show that the gene expression patterns in lymph node metastases are most similar to the corresponding primary tumors from which they arose, as long as samples contain sufficient proportions of tumor cells. Strikingly, gene expression patterns of metastatic primary HNSCC are largely maintained upon spread to the lymph node. Only a single gene, metastasis-associated gene 1 (MTA1), was found to show consistently changed expression between a large number of matched primary tumor-lymph node metastasis pairs. The maintained expression pattern includes the predictive signature for HNSCC lymph node metastasis. These results underscore the importance of the primary tumor gene expression profile for development and treatment of metastasis. The findings also agree with the concept that disseminated cancer cells alter the surrounding tissue into a metastatic environment that resembles the primary tumor microenvironment.

Assessment of mandibular invasion of squamous cell carcinoma by various modes of imaging: constructing a diagnostic algorithm

The aim of this study was to determine the optimal combination of preoperative examination methods to predict mandibular invasion by squamous cell carcinoma of the oral cavity. Data were gathered prospectively but evaluated retrospectively. The preoperative results of clinical examination, conventional radiography, bone single photon emission computed tomography (SPECT), computed tomography and magnetic resonance imaging were compared to the histological results of resection specimens from 67 patients with tumours, adjacent or fixed to the mandible, histologically confirmed as squamous cell carcinoma. The examination methods with acceptable sensitivity and specificity were selected and diagnostic algorithms were constructed using all possible combinations. The preferred diagnostic algorithm was found to be either computed tomography or magnetic resonance imaging, followed by a bone SPECT in cases where the first scan is negative. A negative bone SPECT rules out mandibular invasion (100% sensitivity). This algorithm accurately predicted mandibular invasion in 85% of the patients, without yielding false negative results. In this study group, application of such an algorithm would have resulted in a reduction of the number of unnecessary mandibular resections by 50%. The suggested, preferred, diagnostic algorithm shortens the preoperative screening process, avoiding unnecessary costs, as well as considerably reducing the number of unnecessary mandibular resections.

Trends in incidence and mortality of thyroid carcinoma in The Netherlands between 1989 and 2003: Correlation with thyroid fine-needle aspiration cytology and thyroid surgery

A persistent increase in incidence of thyroid carcinoma (TC) has been reported worldwide. The aim of our study was to assess trends in incidence and mortality of TC in The Netherlands between 1989 and 2003 and to examine whether these trends correlate with changes in diagnostic practices such as changes in the number of fine needle aspiration biopsies (FNAB) and/or thyroid surgeries. Population‐based incidence and mortality data were retrieved from the Netherlands Cancer Registry. Data concerning FNAB and thyroid surgeries were obtained through the nationwide network and registry of histo‐ and cytopathology in The Netherlands (PALGA). Overall, the incidence of TC remained unchanged. However, there was a slight increase in incidence of papillary TC of 2.1% per year (p < 0.001) particularly in stage I tumors, possibly, in part, because of a marked increase in use of FNAB. Appropriate iodine intake, reduced radiation exposure and a more conservative diagnostic approach toward asymptomatic thyroid nodules may explain why this increase is less pronounced compared to other countries. Incidence of other subtypes of TC decreased (follicular TC, 1.3% per year, p = 0.02 and anaplastic TC, 7.1% per year, p = 0.006) or remained unchanged (medullary TC). The number of FNABs per year progressively increased from 1,093 in 1989 to 4,123 in 2003, whereas the number of thyroid surgeries decreased from 3,419 in 1989 to 2,825 in 2003. The mortality rates decreased by 2.3% per year (p = 0.01). The decrease in incidence of both follicular and anaplastic TC is assumed to be largely responsible for the decrease in TC mortality rates.

Novel diagnostic modalities for assessment of the clinically node-negative neck in oral squamous-cell carcinoma

Oral squamous-cell carcinomas arise in mucosal linings of the oral cavity and frequently metastasise to regional lymph nodes in the neck. The presence of nodal metastases is a determinant of prognosis and clinical management. The neck is staged by palpation and imaging, but accuracy of these techniques to detect small metastases is low. In general, 30-40% of patients will have occult nodal disease and will develop clinically detectable lymph-node metastases when the neck is left untreated. The choice at present is either elective treatment or careful observation followed by treatment of the neck in patients who develop manifest metastases. These unsatisfying therapeutic options have been the subject of debate for decades. Recent developments in staging of the neck, including expression profiling and sentinel lymph-node biopsy, will allow more personalised management of the neck.

No high-risk HPV detected in SCC of the oral tongue in the absolute absence of tobacco and alcohol—a case study of seven patients

IntroductionIn recent years, there has been an increase in the number of patients with squamous cell carcinoma (SCC) of the mobile tongue in the absence of tobacco and alcohol. The literature suggests that human papilloma virus (HPV) may be involved in the development of SCC of the head and neck, especially in non-smoking and non-drinking patients. In the oral cavity, however, the presence of the HPV genome has been reported with various percentages. This may be due to misclassification of the oropharyngeal tongue as oral cavity subsite and the use of various detection methods.Materials and methodsTherefore, we evaluated the role of HPV in seven consecutive non-smoking and non-drinking patients (2003–2006) with a SCC located at the oral, mobile tongue using in situ hybridization and SPF10Line Blot 25 polymerase chain reaction assays.ResultsNo HPV was detected in these specimens. To further determine whether a relationship exists between HPV and SCC in the absence of tobacco and alcohol, subsequent studies at specific locations are necessary.

Computer assisted analysis of the microvasculature in metastasized and nonmetastasized squamous cell carcinomas of the tongue

Quantification of microvessels in solid malignancies is regarded as a potential test to predict their clinicobiologic behavior. However, discordant results have been reported for head and neck cancer that may be explained by varying methods.

Metastatic potential of an aneurysmal bone cyst

Aneurysmal bone cysts (ABCs) are benign bone tumors consisting of blood-filled cavities lined by connective tissue septa. Recently, the hypothesis that ABCs are lesions reactive to local hemodynamics has been challenged after the discovery of specific recurrent chromosomal abnormalities. Multiple cases of malignant transformation of ABC into (osteo)sarcoma have been described, as well as a number of cases of telangiectatic osteosarcoma which had been misdiagnosed as ABC. We herewith document a case of a pelvic ABC metastatic to the lung, liver, and kidneys. Diagnosis was confirmed by the presence of a break in the USP6 gene, which is pathognomonic for ABC, in a pulmonary metastasis of our patient. Sarcomatous transformation as an explanation for this behavior was ruled out by demonstrating diploid DNA content in both the pulmonary lesion and the primary tumor.