Desmosomes in verrucous carcinoma of the head and neck.

Verrucous carcinoma (VC) is a variant of squamous cell carcinoma (SCC), characterised by its inability to metastasize. In contrast, hybrid carcinomas, composed of VC and foci of conventional SCC, harbour a metastatic potential. Correct pathohistological diagnosis is therefore crucial for the choice of treatment. There is mounting evidence that desmosomes are involved in several aspects of carcinogenesis. Previous studies have shown an altered expression of desmosomal components in conventional SCC, which was associated with tumour behaviour, but no data have been found on desmosomes in VC. We therefore analysed the expression of desmosomal components in biopsy samples of 21 cases of VC and 5 cases of hybrid carcinoma of the head and neck in comparison to 23 cases of conventional SCC and 47 samples of normal squamous epithelium of similar localisation, using immunohistochemistry and real-time reverse-transcription polymerase chain reaction. We found that the expression patterns of desmosomal components in VC were fairly similar to those in normal epithelium but differed significantly from those in conventional SCC. Immunohistochemical reactions against desmosomal components disclosed the foci of SCC in hybrid carcinomas. In conclusion, we believe that expression patterns of desmosomal components in VC are consistent with its less aggressive behaviour. Differential expression of desmosomal components between VC and SCC makes some desmosomal components potentially useful in the diagnostics of VC, especially for the detection of hybrid carcinoma.

MicroRNA miR-1 is up-regulated in remote myocardium in patients with myocardial infarction.

MicroRNAs are small regulatory RNA molecules that mediate regulation of gene expression, thus affecting a variety of physiological, developmental and pathological conditions. They are believed to be new promising therapeutic targets. In recent studies two muscle-specific microRNAs were discovered to contribute to heart diseases and development: miR-1 and miR-133, but there is little data on their expression patterns in human myocardial infarction. We performed simultaneous expression analysis of miR-1, miR-133a, miR-133b in samples of infarcted tissue and remote myocardium from twenty- four patients with acute myocardial infarction. MicroRNA expression was analysed using quantitative real-time PCR and compared to the expression patterns in myocardium of eight healthy adults who died in accidents. We found ~3.8-fold miR-1 up-regulation in remote myocardium when compared to infarcted tissue or healthy adult hearts. As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients. In addition, miR-133a/b down-regulation in infarcted tissue and remote myocardium was observed, indicating miR-133a/b involvement in the heart response to myocardial infarction. We conclude that miR-1 and miR-133 seem to be important regulators of heart adaptation after ischaemic stress.

Salivary gland tumours as second neoplasms: two cases and literature review.

OBJECTIVES: Patients who survive malignant tumours have an increased risk of second neoplasms, including those of the salivary glands. Mucoepidermoid carcinoma of the parotid gland is by far the most common type of second salivary gland tumour; other types have rarely been reported. We describe here two patients with a second tumour of the salivary glands. CASE REPORTS: The first patient was a 22-year-old woman with a low grade mucoepidermoid carcinoma of the parotid gland, which developed 21 years after completion of chemoradiotherapy for acute lymphoblastic leukaemia. The second patient was a 40-year-old woman with an epithelial-myoepithelial carcinoma of the buccal mucosa, which arose 11 years after treatment for two malignant neoplasms - retroperitoneal liposarcoma and squamous cell carcinoma of the uterine cervix. CONCLUSIONS: It is mandatory that survivors of cancer should be monitored carefully, so that the complications related to their previous disease and therapy are detected early and managed properly.

Granulocytic sarcoma in a patient with essential thrombocythemia presented as acute spinal cord compression--case report and review of the literature.

Granulocytic sarcoma (GS) is a rare solid tumor of myeloid origin, which usually precedes or occurs concurrently with myeloid leukemia, or with other types of myeloproliferative and myelodysplastic disorders. Spinal affections of GS have been described but are uncommon, particularly in association with essential thrombocythemia. We present a case of a 75-year-old woman with a long history of essential thrombocythemia who developed 2 tumors: 1 in the bodies of T3 - 6 vertebras extending epidurally, and the other in the right frontal lobe, adherent to dura, thus, mimicking meningioma. The patient died because of massive pulmonary thrombembolia. Microscopical and immunohistochemical features of spinal and intracranial tumor samples obtained at autopsy were consistent with the diagnosis of GS with focal megakaryocytic differentiation. Clinicians and pathologists should be aware of this rare tumor being so diverse in its clinical presentation, as well as in microscopical and immunohistochemical features. Careful evaluation of morphology, in conjunction with immunohistochemistry for evidence of myeloid differentiation are required to avoid frequent errors in diagnostics of GS. The suggested panel includes chloroacetate esterase, myeloperoxidase, lysozyme, CD117, CD43, CD79a and CD3. Only early correct diagnosis will enable proper treatment which may be successful despite the highly malignant potential of GS.

Pseudovascular adenoid squamous-cell carcinoma of the oral cavity--a report of two cases.

Informed consent was obtained for the publication of the patients' details in this report. Two cases of pseudovascular adenoid squamous-cell carcinoma (SCC) in the oral cavity are described, which were characterised by acantholysis of the tumour cells, with formation of anastomosing spaces and channels mimicking an angiosarcoma. Both tumours contained foci of SCC suggesting the correct diagnosis: in one patient conventional SCC, and in the other, a spindle-cell carcinoma. The pathogenesis of pseudovascular adenoid SCC is unknown. Our cases were characterised by loss of immunohistochemical expression of E-cadherin, one of the major adhesion molecules of epithelial cells. Pseudovascular adenoid SCC is suggested to be pathogenetically related to the loss of E-cadherin expression, leading to the loss of tumour cell-cell adhesion.

Inflammatory myofibroblastic tumour of paranasal sinuses with fatal outcome: reactive lesion or tumour?

Inflammatory myofibroblastic tumours (IMTs) are clinicopathologically distinctive but biologically controversial entities, which have been described in the lungs, abdomen, retroperitoneum, and extremities, but rarely affect the head and neck region. IMT usually follows a benign clinical course after radical excision, but invasive, locally recurrent, and metastatic forms of abdominal and mediastinal IMT have also been described. This report describes a case of IMT of the paranasal sinuses with a fatal outcome. A 22 year old woman was admitted to hospital as a result of epistaxis. Computed tomography scan and magnetic resonance imaging showed an expansive process in the paranasal sinuses, extending into the nasal cavity, orbita, and endocranium. The tumour progressed despite several surgical procedures. Radiotherapy, corticosteroids, and chemotherapy were unsuccessful, and the patient died four years after diagnosis, as a result of extensive intracranial spread of the tumour. This is the first known case of an IMT of the head and neck region with a fatal outcome. It shows that the aggressive behaviour of IMTs is not limited to abdominal and mediastinal locations, and supports recent observations that at least a subset of IMTs represents true neoplasia rather than reactive myofibroblastic proliferation.

Expression of tenascin and fibronectin in benign epithelial hyperplastic lesions and squamous carcinoma of the larynx.

BACKGROUND: Tenascin (T) and fibronectin (FN) are glycoprotein components of the extracellular matrix presumably involved in cancer progression. We analyzed their expression in epithelial hyperplastic lesions (EHL) and squamous carcinoma (SC) of the larynx. MATERIALS AND METHODS: Samples from resected larynges of 30 patients with SC, and laryngeal biopsies of 28 patients with EHL, SC or benign reactive conditions were included. Immunohistochemistry was performed with antibodies against T and FN. RESULTS: T and FN gradually increased with the grade of EHL and were markedly increased in the majority of SC. In SC, expression of T and FN correlated with the degree of desmoplasia but was inversely related to the density of lymphocytic stromal infiltration and the differentiation of SC. T and FN were also positive in benign reactive conditions. CONCLUSION: T and FN immunostaining provides useful information on epithelial-stromal interaction in laryngeal EHL and SC but should not be regarded as a reliable stromal marker of malignancy. Our results supported the postulated diversified nature of the tumor stroma.

Wegener's granulomatosis in the upper respiratory tract.

Wegener's granulomatosis is a distinct clinico-pathological entity characterised by necrotising vasculitis of small arteries and veins in conjunction with the formation of granuloma in the upper and lower respiratory tracts, and glomerulonephritis. The vast majority of patients have antineutrophil cytoplasmic antibodies in the serum with a characteristic cytoplasmic pattern. However, in early phases of the disease only the upper respiratory tract may be affected, clinical and histological features may be nonspecific, and antineutrophil cytoplasmic antibodies not present. In this paper we present four patients with involvement of the upper respiratory tract suspicious for early Wegener's granulomatosis. We emphasise the significance of clinical, histological and serological parameters in the early detection of Wegener's granulomatosis.

Amyloidosis of the larynx.

Amyloidosis of the larynx is an uncommon disease and mainly a local occurrence. Hoarseness is the prevalent symptom. Surgical excision of the amyloid masses is the treatment of choice. In the present paper, the authors describe seven cases treated in the last twenty years.

Clinical applicability of the Ljubljana classification of epithelial hyperplastic laryngeal lesions.

The diagnosis, prognosis, and choice of treatment of various laryngeal lesions depends almost entirely on the interpretation of changes in the covering epithelium. These abnormalities, referred to as epithelial hyperplastic laryngeal lesions, have been graded according to the Ljubljana classification into simple, abnormal and atypical (risky epithelium) hyperplasia and carcinoma in situ. The aim of this study was to evaluate the clinical applicability and prognostic value of this classification and to determine the incidence of malignant transformation. A retrospective clinical-pathological analysis was performed in a series of 4167 patients with 4574 biopsies, treated from 1979 to 1994. Simple (benign prickle cell) hyperplasia was the predominant grade in nodules, polyps, Reinke's oedema, granulomas, and papillomas, accounting for 37.6-68.6% of cases. In chronic laryngitis, abnormal (benign basal cell) hyperplasia was predominant with 43.9% of cases. Atypical ('risky') hyperplasia was observed almost exclusively in patients with chronic laryngitis (16.1%) and papillomas (10.1%), and only exceptionally in patients with vocal cord nodules (0.9%) and Reinke's oedema (0.3%). The percentage of malignant transformation in atypical hyperplasia was 11.6% (13/112 patients in 2-12 years), while in simple and abnormal hyperplasia, it was 0.3% (8/2920 patients in 1.5-11 years). The data support the concept of the Ljubljana classification dividing epithelial hyperplastic laryngeal lesions into benign (simple and abnormal hyperplasia), potentially malignant (atypical hyperplasia) lesions and carcinoma in situ.

The Ljubljana classification: a practical strategy for the diagnosis of laryngeal precancerous lesions.

There is no internationally accepted classification of epithelial hyperplastic laryngeal lesions (EHLL). The majority of current classifications follow criteria similar to those commonly used for cervical epithelial lesions. However, the different etiology of laryngeal cancer and its particular clinical and histologic features necessitate a grading system more appropriate to this region. The Ljubljana classification of EHLL was devised in 1971 to cater to this requirement. Detailed criteria for histologic grading in this classification were formulated by a working group on EHLL of the European Society of Pathology in 1999. The system recognizes four grades: simple and abnormal hyperplasia are benign categories; atypical hyperplasia ("risky" epithelium) is potentially malignant, and carcinoma in situ actually malignant. The main features by which the proposed grading system differs from other classifications are: 1. the distinction between benign and potentially malignant lesions; 2. the positive separation of carcinoma in situ from atypical hyperplasia; 3. the lack of prognostic significance for any surface keratin layer. The eventual outcome of EHLL patients so graded justifies the proposal for separating the lesions into a benign group, showing malignant transformation in only 0.9% of cases, from a potentially malignant group showing malignant transformation in 11% of cases. For diagnostically difficult cases, supplementary techniques such as those using morphometry, immunohistochemical and molecular biology are advised to improve the accuracy of diagnosis and predictions of their biological behavior.

Angiomyolipoma of the kidney--an immunohistochemical study.

The study included 25 patients with angiomyolipoma of the kidney. None of them had any signs of tuberous sclerosis. Serious clinical complications such as massive hemorrhage (2/25) and hydronephrosis (2/25) were documented in four patients. Concomitant adenoma of the adrenal gland and renal cell carcinoma were found in one patient each. All tumors consisted of a differing mixture of mature adipose tissue, smooth muscle cells and blood vessels, with thickened walls devoid of elastic lamina. Immunohistochemically, the smooth muscle cells stained strongly with antibodies against vimentin, desmin and actin, as well as HMB-45 and NKI/C3. Immunohistochemical staining for NKI/C3 was stronger and more diffusely distributed. These two markers proved to be very useful in the diagnosis of angiomyolipoma, when only needle biopsy specimens are available.

Unfavorable course of minimal change nephrotic syndrome in children with intrauterine growth retardation.

BACKGROUND: Intrauterine growth retardation (IUGR) is associated with higher morbidity and mortality not only in perinatal life but also in later life. The purpose of our study was to determine whether IUGR has any effect on the course of minimal change nephrotic syndrome (MCNS) in children. METHODS: Forty children who were between 1 and 16 years old at the onset of MCNS, who have been followed for at least three years and for whom we were able to obtain birth weights and gestational ages, were included. The diagnosis of MCNS was predicted on the basis of clinical and laboratory features, and in 11 children (27.5%) the diagnosis was confirmed by renal biopsy. IUGR was defined as birth weight below the tenth percentile for gestational age. RESULTS: Five children (12.5%) had signs of IUGR at birth. In children with IUGR, we observed a higher mean number of relapses (10.4 vs. 3.3, P < 0.001) and a higher incidence of steroid dependency (80% vs. 21%, P < 0.02) than in children without IUGR. Other differences between children with and those without IUGR included more frequent treatment with cytotoxic agents and cyclosporine, and a higher incidence of renal biopsy in children with IUGR. CONCLUSION: Our study demonstrated an unfavorable course of MCNS in children with IUGR. IUGR could therefore enable early identification of those children who are at risk of becoming frequent relapsers and of developing steroid dependency. This, however, should be confirmed in a larger number of patients.

Effect of intrauterine growth retardation on the clinical course and prognosis of IgA glomerulonephritis in children.

Intrauterine growth retardation (IUGR) resulting in a reduced number of nephrons is one of the nonimmune mechanisms that have been recently proposed as contributing to the progression of renal diseases. The purpose of our study was to determine whether IUGR has any effect on the clinical course and prognosis of IgA glomerulonephritis (IgA GN) in children. Fifty children with biopsy-proven IgA GN, who were followed for at least 3 years, were included. Six of the 50 children (12%) had signs of IUGR at birth, defined as birth weight below the 10th percentile for gestational age. There were no significant differences in initial clinical presentation between children with IUGR and those without IUGR. However, in kidney biopsy specimens, we found a significantly higher mean percentage of sclerotic glomeruli in children with IUGR than in those without IUGR (33 vs. 13%, p < 0.015). At the end of the follow-up period, we observed a significantly higher incidence of arterial hypertension in children with IUGR than in those without IUGR (50 vs. 11 %, p < 0.05). Other differences between the two groups of children were not statistically significant. In conclusion, our study demonstrated an increased risk of the development of arterial hypertension and glomerulosclerosis in children with IgA GN who had suffered from IUGR with a birth weight below the 10th percentile for gestational age. IUGR may therefore help to identify early in the course of IgA GN those children who are at higher risk of an unfavorable course.

Malignant rhabdoid tumor of the liver diagnosed by fine needle aspiration cytology. A case report.

BACKGROUND: Primary malignant rhabdoid tumor (MRT) of the liver is a rare tumor of early infancy, with a grim prognosis. CASE: A 17-month-old female presented with a palpable mass in the upper right side of the abdomen. Ultrasonographically guided fine needle aspiration biopsy of the tumor contained malignant cells with medium-sized, vesicular nuclei; prominent nucleoli; and well-defined cytoplasm exhibiting paranuclear, dense inclusions. These inclusions reacted positively with cytokeratin and vimentin. Ultrastructural examination showed the presence of intermediate cytoplasmic filaments. CONCLUSION: Cytomorphologic and immunocytochemical characteristics permit the preoperative differentiation of MRT from other malignant tumors of childhood. That facilitates treatment planning and precludes unnecessary surgical intervention.

Epidermal growth factor receptor, c-erbB-2 and p53 overexpressions in epithelial hyperplastic lesions of the larynx.

An immunohistochemical analysis of overexpression of epidermal growth factor receptor (EGFR), c-erbB-2, and p53 proteins was performed on 43 biopsies of laryngeal epithelial hyperplastic lesions (EHLL), classified according to the Kambic-Lenart classification, and in 11 cases of laryngeal carcinoma (SCCL). The aim of the present study was to determine whether there is a correlation between the staining patterns of these proteins and different grades of EHLL, and to reveal their possible prognostic value. We compared the staining patterns of atypical hyperplasia adjacent to cancer with the same type of lesions which have not turned malignant. p53 and EGFR overexpressions were detected in 28/54 (52%) and 33/54 cases (61%), respectively, and tend to increase with the degree of epithelial changes. The intensity of staining in various grades of EHLL adjacent to cancer was more pronounced than the same type of lesions which have not progressed to cancer. c-erbB-2 was weakly positive in the majority of cases, and changed from predominantly membranous in simple hyperplasia to cytoplasmic staining in abnormal and atypical hyperplasias. There was no significant statistic correlation between the amount of positive cells for all proteins and the grade of epithelial abnormalities. We conclude that the overexpression of each biomarker itself adds little predictive value over routine histomorphology, and cannot be regarded as a reliable prognostic factor for EHLL. However, the histologic characteristics of atypical hyperplasia together with the immunostaining patterns of EGFR and p53 up to two-thirds or more of the epithelial thickness could be considered a reliable pattern which correlates with the progression to cancer.

Human papillomavirus infection and expression of p53 and c-erbB-2 protein in laryngeal papillomas.

Laryngeal papilloma (LP) is the most frequent benign laryngeal epithelial tumor caused by human papillomaviruses (HPV) types 6 and 11. In the present study, we were interested in whether we can find any prognostic markers which might reflect the biological behavior of the covering epithelium in LP. We focused our attention on the determination of HPV infection, the detection of p53 protein, and c-erbB-2 protein in 24 biopsy specimens of LP. We confirmed the HPV 6 and 11 etiology in 23 of 24 LP. In these lesions the overexpression of p53 protein increased with the grade of epithelial abnormalities. The distribution of positive cells changed from scattered and focal, in simple and abnormal hyperplasia, to diffuse in atypical hyperplasia. It has been shown that in the presence of HPV types 6 and 11 found in LP, p53 can still preserve its tumor suppressor activity. Infection with HPV types 6 and 11 might therefore account for the significantly lower rate of malignant transformation in LP. Two staining patterns for c-erbB-2 protein were observed in the hyperplastic epithelium covering LP: membranous and cytoplasmic. With the increasing grade of epithelial abnormalities, cytoplasmic staining became predominant, and c-erbB-2 positivity sometimes occupied the whole epithelial thickness. This may represent either an alteration in the processing stability of the c-erbB-2 mRNA, gene amplification, or even an artefact.

Contribution to the pathogenesis of radiation-induced injury to large arteries.

We report a case of a 35-year-old man who died of a brain infarct 20 months after radiotherapy for carcinoma of the tonsil with metastases to the cervical lymph nodes. Histology revealed mild atherosclerosis, necrotizing vasculitis, and occlusive thrombosis of the internal carotid artery. Significant changes were observed in the vasa vasorum: swelling and detachment of the endothelium, subendothelial oedema, hyaline change, fibrinoid necrosis of the vessel walls with mononuclear cellular infiltration, accompanied by focal haemorrhages and chronic inflammation in the periadventitial soft tissue. We believe that these changes of the vasa vasorum and necrotizing vasculitis are causally related and that vasculitis represents focal ischaemic necroses with inflammatory reaction. Our findings support the hypothesis, based on experimental studies, that injury to the vasa vasorum is an important mechanism in the development of radiation-induced vasculopathy of large arteries. They also suggest an evolution of the injury to the vasa vasorum and periadventitial tissue from the early lesions described in our patient, to late stages resulting in dense periadventitial fibrosis as reported previously. We suggest that injury to the vasa vasorum and the consequent ischaemic lesions of the arterial wall are morphological features distinguishing radiation-induced arterial injury from spontaneous atherosclerosis.