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PubMed1996

Early diagnosis of low grade malignant lymphoma and chronic lymphocytic leukaemia. Verification of morphologically suspected malignancy in blood lymphocytes by flow cytometry.

According to international recommendations, the diagnosis of chronic lymphocytic leukaemia (CLL) is made on the grounds of persistent peripheral lymphocytosis or lymphocytic infiltration of the bone marrow. The appearance of morphologically atypical lymphocytes in low-grade malignant lymphoma (NHL) or CLL is easily overlooked, and is generally not regarded as a diagnostic criterion. We report 12 cases of CLL/NHL who were detected only by morphological screening of routine peripheral blood smears (83,400 blood smears). The diagnosis of CLL/NHL was not suggested by the patients' history, physical or other laboratory findings, and had not been contemplated by the physician in charge. Monoclonality of peripheral lymphocytes was confirmed by immunophenotyping and Southern blotting. The lymphoma was classified histologically according to the International Working Formulation (bone marrow biopsy). A monoclonal lymphatic population was not found by immunophenotyping in the blood of 11 patients whose lymphocytes were morphologically classified as activated-abnormal. However, 3 patients suspected to have NHL/CLL on morphological screening of blood smears had to be classified as benign after immunophenotyping. We conclude that morphological screening of routine blood smears is an inexpensive and easy additional screening method for CLL and low grade malignant NHL.

Aged↗

PubMed1992

Epidemiology of malignant melanoma in central Europe: risk factors and prognostic predictors. Results of the Central Malignant Melanoma Registry of the German Dermatological Society.

The Central Malignant Melanoma Registry (CMMR) of the German Dermatological Society was established in 1983, and 7789 cutaneous malignant melanomas (CMM) were registered by 35 dermatological departments in Germany, Austria and Switzerland until the end of 1989. Population-based incidence rates, risk factors for developing CMM and prognostic parameters for predicting the final outcome were investigated in separate multicenter studies performed by the CMMR. Among the 7789 CMM registered, there was a preponderance of females (57.7%) versus males (42.3%). The age distribution peaked in the 5th and 6th decade of life for both sexes with a mean age of 52 years. The mean detection age was 50 years for superficial spreading melanoma, 53 for nodular melanoma, and 65 for lentigo maligna melanoma. Mean tumor thickness decreased from 2 mm in 1983 to 1.5 mm in 1989, indicating better CMM-awareness of the population and the medical community in this area. 90% of the patients presented with clinical stage I CMM without detectable metastases at first diagnosis. The incidence of CMM in Berlin (West) was assessed based on 960 cases diagnosed between 1980 and 1986. The incidence increased by 49% between 1980-81 and 1985-86, and the age standardized-incidence rate (European standard population) was 9.8 for males and 7.8 for females per 100,000 inhabitants and year in 1985-86. Mortality rates decreased in this period from 3.5 to 2.6 for males and slightly increased for females from 1.2 to 1.6 per 100,000 inhabitants and year. A case control study on the relative risk (RR) for developing CMM revealed the total number of melanocytic nevi (MCN) to be the strongest risk predictor (15x -50x increased RR), followed by the presence of dysplastic MCN (7x increased RR) and the skin type I (2x increased RR). Interestingly, no differences between CMM-cases and controls were found with respect to the history of sunburns or other parameters of sun exposure in this study. Multivariate analysis of 5093 stage I CMM-patients from four departments with long-term follow-up revealed that tumor thickness is the strongest predictor of survival with an almost linear correlation to the risk of death for tumor thickness up to 6 mm with no further increase in mortality for higher tumor thickness. The best classification of tumor thickness for survival prediction was less than or equal to 1 mm, 1.01-2 mm, 2.01-4 mm and greater than 4 mm in our data set on 5093 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1994

Thyroid antibodies in association with thyroid malignancy. I. Simultaneous occurrence of thyroiditis and thyroid malignancy.

Occurrence of thyroid antibodies and thyroiditis in association with thyroid malignancy, suspected malignancy or other thyroid diseases was studied in 177 patients. Retrospective clinical analysis revealed that 137 patients had thyroid carcinoma (108 papillary carcinomas, 10 occult papillary carcinomas, 14 follicular carcinomas, and 5 other carcinomas) and 40 had other thyroid diseases. Thyroid microsomal (AMC) and thyroglobulin antibodies (ATG) were measured by the particle agglutination method. Clinically significant thyroid antibody titers and histological or clinical features of thyroiditis were seen in nine patients with thyroid carcinoma, being equally prevalent in follicular and papillary carcinomas. Taking into account the prevalence of positive AMC antibodies and thyroid carcinoma in Finland, the highest predicted prevalence of simultaneously occurring thyroid carcinoma and thyroiditis in the under 40 age group should be 0.002% and in the over 40 age group 0.006%. In the present material the observed occurrences in corresponding age groups were unexpectedly high (4.7% and 5.2%). The results may partly be due to patient selection, but they also suggest that there might be a link between thyroiditis and thyroid carcinoma.

Adolescent↗

PubMed1976

The "Knapp-Ronne" type of malignant melanoma of the choroid. A haemangioma-like melanoma with a typical clinical picture. So-called "preretinal malignant choroidal melanoma".

Five cases of a rare type of malignant melanoma of the choroid with a typical clinical and histopathological picture are reported. This tumour is characterized by it location near the optic disk,its early growth through the retina, its structure with bloodless and blood-filled cavernous spaces, and its manifestation by a massive haemorrhage into the vitreous. "Historical" cases are mentioned, showing that this rare tumour, occurring in about 1:250 of malignant melanomas of the choroid, has a Scandinavian tradition. The clinical and histopathological details are discussed.

Aged↗

PubMed2003

Upregulation of HMG1 leads to melanoma inhibitory activity expression in malignant melanoma cells and contributes to their malignancy phenotype.

Malignant transformation of melanocytes to melanoma cells closely parallels activation of melanoma inhibitory activity (MIA) expression. We have previously shown that upregulation of MIA occurs on a transcriptional level and involves the highly conserved region (HCR) promoter element. We further observed that the HCR element interacts with the melanoma-associated transcription factor (MATF) and thereby confers strong promoter activation. In this study we identify the peptide sequence of MATF and show that it is identical with the transcription factor HMG1. HMG1 was upregulated in malignant melanoma cells and further activated by hypophosphorylation. Stable antisense-HMG1 expression in melanoma cells led to the reduction of MIA promoter activity and protein expression, indicating that HMG1 is a potent regulator of MIA expression. Interestingly, chromatin immunoprecipitation and electrophoretic mobility shift experiments indicated that HMG1 and the NF-kappa B family member p65 both interact and bind to the HCR promoter element. In summary, our study proves HMG1 and p65 to be important factors in MIA regulation and melanoma progression.

Amino Acid Sequence↗

PubMed1991

Coeliac disease and malignancy of the duodenum: diagnosis by endoscopy, successful treatment of the malignancy, and response to a gluten free diet.

A patient presented with subtotal villous atrophy and a malignant duodenal tumour of uncertain histogenesis. He was successfully treated by resection and chemotherapy and the small bowel mucosa recovered on a gluten free diet. The tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and abdominal computed tomography were normal, thus making this one of the earliest coeliac malignancies diagnosed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Recurrent chromosomal imbalances and structurally abnormal breakpoints within complex karyotypes of malignant peripheral nerve sheath tumour and malignant triton tumour: a cytogenetic and molecular cytogenetic study.

BACKGROUND: Cytogenetic studies of malignant peripheral nerve sheath tumours (MPNSTs) and malignant triton tumours (MTTs) are rare. AIMS: To undertake cytogenetic analysis of these tumours. METHODS: Conventional cytogenetic analysis of 21 MPNSTs and MTTs from 17 patients (nine with peripheral neurofibromatosis (NF1)) was carried out using standard culture and harvesting procedures. For a more precise identification of composite structural rearrangements and marker chromosomes, spectral karyotypic analysis (SKY) was applied to a subset of cases. In addition, EGFR gene copy number was assessed by fluorescence in situ hybridisation (FISH) analysis in a subset of cases. RESULTS: Cytogenetic analysis revealed predominantly complex karyotypes. SKY analysis was useful in further defining many structural anomalies. Structural aberrations most frequently involved chromosomal bands or regions 1p31-36, 4q28-35, 7p22, 11q22-23, 19q13, 20q13, and 22q11-13. Overall, loss of chromosomal material was much more common than gain. Loss of chromosomes or chromosomal regions 1p36 (48%), 3p21-pter (52%), 9p23-pter (57%), 10 (48%), 11q23-qter (48%), 16/16q24 (62%), 17(43%), and 22/22q (48%), and gains of 7/7q (29%) and 8/8q (29%) were most prominent. These gains and losses were distributed equally between MPNST and MTT, demonstrating that these entities are similar with respect to recurrent genomic imbalances. Similarly, none of the recurrent chromosomal breakpoints or imbalances was restricted to either NF1 associated or sporadic MPNSTs. FISH analysis was negative for amplification. CONCLUSIONS: These cytogenetic and molecular cytogenetic findings expand the knowledge of chromosomal alterations in MPNST and MTT, and point to possible recurring regions of interest.

Adolescent↗

PubMed1985

An immunocytochemical study of malignant melanoma and its differential diagnosis from other malignant tumours.

A series of 41 fresh and 36 routinely processed malignant melanomas were immunostained with a panel of 12 monoclonal antibodies reactive against a range of epithelial, lymphoid, and melanoma associated antigens. The aim of the study was to determine whether this panel of antibodies would be useful in diagnostically difficult cases for differentiating melanomas from other tumours, particularly carcinomas and lymphomas. The results confirmed that most unequivocal malignant melanomas can be identified by positivity for S100 protein and for the antigen recognised by antibody NK1/C3, and by negativity for epithelial and lymphoid antigens. The incidence of melanomas expressing cytokeratin antigens was higher, however, particularly in cryostat sections than has previously been reported. It is therefore suggested that a panel of antibodies with more than one marker in each category should be used for identifying melanomas in clinical practice.

Antibodies, Monoclonal↗

PubMed1978

Immunodiagnostics of malignant disease. VI. Electrophoretic mobility test (EMT) in malignant melanoma.

The electrophoretic mobility test (EMT) is an in vitro assay for demonstrating cellular immunity. In the presence of tumor antigens lymphocytes of tumor patients liberate lymphokines, which reduce the charge of indicator particles resulting in a measurable reduction of their eletrophoretic mobility. Lymphocytes of 174 patients were tested by EMT. The antigens used were a basic myelin protein termed encephalitogenic factor (EF) and a 3M KCl extract from melanoma tissue. In 91% of the cancer patients there was a positive lymphocyte response. In contrast to this the controls and non-malignant diseases showed a positive result in only 8.7% of the cases. Using the 3M KCl extract from melanoma tissue as tissue as antigen 1 of the benign controls, 3 patients with nonmalignant diseases and none of the 49 patients with malignant diseases reacted positively, whereas in the melanoma group 86% showed a positive lymphocyte response. The results show the possibility of demonstrating tumor specific immune reaction in the EMT.

Antigens↗

PubMed1986

New primary malignant melanoma, epidermotropism and Indian-file arrangement of metastatic tumor cells in a case with intransit metastases of acral type of malignant melanoma.

Multiple malignant melanocytic lesions developed on a localized area of the thigh in an 80-year-old woman 3 years after excision of a primary malignant melanoma on the left second toe and dissection of left inguinal lymph nodes. Biopsy specimens obtained from 2 small pigmented macules revealed the histologic features of new primary lesions, simulating that of the primary lesion on the toe; no tumor cells were found within vessel lumina. A brown-black papule neighboring one of the macules histologically resembled compound type of melanocytic nevus, but the tumor cells compressed thinned epidermis with focal epidermotropism. Other papules, whose color ranged from light brown to reddish brown, showed metastatic tumor cells only in the dermis. In 3 of them, individual tumor cells were lined up along the collagen bundles, showing an 'Indian-file' arrangement. Such a combination of various histologic features in a case of intransit metastases of acral type of melanoma has not been reported in the literature.

Aged↗

PubMed1985

[DNA oriented automated malignancy diagnosis and malignancy grading in prostatic cancer].

85 patients with prostate cancer and 20 patients with benign prostatic hypertrophy underwent DNA single-cell fluorescence photometry to investigate the possibility of DNA-related automatic diagnosis and grading of prostate cancer. The DNA histograms were analysed statistically by univariate data description, stepwise linear discriminant analysis and regression analysis. The accuracy for the malignancy diagnosis was 85.1%, with 10.6% false-negative and 4.3% false-positive results. The accuracy of the malignancy grading, however, was very poor with only 39.5%.

Biopsy, Needle↗

PubMed1997

Doppler ultrasound in a patient with ovarian Brenner tumor of low malignant potential: comparison with Gray-scale ultrasound, magnetic resonance imaging and tumor marker suggesting malignancy.

We present a postmenopausal patient with giant lower abdominal tumor. Gray-scale ultrasound and magnetic resonance imaging showed typical abnormal morphology suggesting malignancy. The serum CA 125 level was 69 U/ml, and that of CA 19-9 was 2,097 ng/ml. Transvaginal color and pulsed Doppler sonography of the tumor vasculature demonstrated low peak systolic velocity (6.7 cm/s) with low pulsatility (resistance index: 0.49). Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histological diagnosis was ovarian Brenner tumor of low malignant potential. Transvaginal Doppler findings seemed to give specific information for the diagnosis in this case.

Aged↗

PubMed1996

Malignant fibrous histiocytoma and malignant histiocytosis in the dog--convergent or divergent phenotypic differentiation?

Malignant fibrous histiocytoma (MFH) and malignant histiocytosis (MH) are neoplasms with different histologic appearances and consequently a different putative cell of origin. Recently, the biopsy and necropsy services at the University of Pennsylvania have seen many canine soft tissue sarcomas that have the gross and histologic appearances of both MH and MFH within the same animal. A retrospective histologic evaluation of 263 cases diagnosed originally as either MH or MFH reclassified these neoplasms into 77 cases that were exclusively MH, 110 cases exclusively MFH, and 76 cases with features of both MH and MFH. Age, sex, breed predispositions, and distribution of lesions in organs were remarkably similar between the two categories. The hybrid neoplasms containing MH-like and MFH-like regions may be the result of divergent or convergent phenotypic differentiation.

Animals↗

PubMed1993

Immunocytochemical identification of cell types in benign and malignant breast diseases: variations in cell markers accompany the malignant state.

We performed immunocytochemical staining of benign, in situ, and malignant breast disease to identify antigens related to the presence of the major parenchymal cell types of the normal breast. Markers for the epithelial cells, antiserum to epithelial membrane antigen, and three monoclonal antibodies (MAb) to milk-fat globule membranes stained most of the inner cells in benign breast lesions, carcinoma in situ, and invasive carcinomas, but the peripheral cells in benign lesions, as well as in carcinoma in situ, were unstained. MAb to epithelium-specific keratin 18 stained the majority of inner cells in benign breast lesions but comparatively fewer such cells in carcinoma in situ and invasive carcinoma. Markers for the myoepithelial cells, antisera, and MAb to smooth muscle actin and vimentin stained most of the peripheral cells in benign breast lesions and in carcinoma in situ but failed to stain virtually any neoplastic cells in invasive carcinomas. Markers for the basement membrane adjacent to the myoepithelial cells, antiserum, and MAb to laminin and Type IV collagen delineated an intact basement membrane around benign lesions and carcinoma in situ, and fragmented structures in 5-10% of invasive carcinomas; the remaining carcinomas were largely unstained. Markers for both myoepithelial and epithelial cells, keratin MAb PKK2 and LP34, stained most of the inner cells in benign lesions but usually only relatively few malignant cells in carcinoma in situ and invasive carcinomas. Markers for the secretory alveolar cell, MAb to beta- and kappa-casein, stained a few isolated cells in benign lesions, many more inner cells in two such lesions in pregnant females, and none in invasive carcinomas. In conclusion, the myoepithelial cell and, under suitable hormonal conditions, the secretory alveolar cell, are retained in most benign lesions, but they are largely lost in invasive carcinomas.

Adolescent↗

PubMed1998

Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma. PATIENTS AND METHODS: Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present. RESULTS: Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04). CONCLUSION: These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.

Aged↗

PubMed2002

Endoscopic laser treatment in pre-malignant and malignant vocal fold epithelial lesions.

Endoscopic laser treatment was performed in 43 patients with pre-malignant or malignant vocal fold epithelial lesions, 10 were treated with endoscopic laser surgery for dysplasia, 12 for carcinoma in situ (CIS), five for verrucous carcinoma and 16 patients for squamous cell carcinoma (SCC). Thirty-two patients received laser therapy as their first therapy, whereas 11 patients had had previous radiation therapy for laryngeal carcinoma (n = 9) or CIS (n = 2). Recurrence after initial laser therapy necessitating re-treatment (a second laser treatment or radiotherapy) occurred in nine out of 32 patients (28 per cent), thus 23 (72 per cent) were maintained free of disease during the follow-up period. Besides the 32 patients without previous therapy, patients who had already undergone radiation therapy were also included in this study. In this group there were nine patients with SCC, one patient with CIS and one with dysplasia. They all underwent laser therapy. Four were free of disease during follow-up (36 per cent) and seven developed recurrences. Six (58 per cent of all patients with previous radiation therapy) underwent total laryngectomy.

Adult↗

PubMed1998

Diagnostic and prognostic value of biochemical markers in malignant bone disease: a prospective study on the effect of bisphosphonate on pain intensity and progression of malignant bone disease.

Seventy cancer patients with malignant osteolytic bone disease received pamidronate every three weeks for a maximum of six cycles. Bone resorption parameters, urinary calcium excretion, and pain parameters were assessed at baseline and throughout the study. At baseline, 80-95% of patients showed elevated urinary pyridinoline, deoxypyridinoline, Osteomark NTx and serum ICTP levels, whereas only 35% of patients had elevated urinary CrossLaps excretion rates. During bisphosphonate therapy, significant decreases in Osteomark NTx, CrossLaps and calcium excretion were observed, which were not related to the clinical outcome. The baseline levels of bone resorption markers were used to predict the probability of non-progressive bone disease or reduction in pain intensity during bisphosphonate therapy. Significant predictors of non-progressive bone disease were urinary pyridinoline and serum ICTP levels; significant predictors of reduction in pain intensity were urinary free deoxypyridinoline and serum ICTP levels. Our data indicate that serum ICTP levels predict significantly the response to bisphosphonate therapy in patients with advanced malignant osteolytic bone disease. CrossLaps did not predict the clinical outcome, but decreased significantly during bisphosphonate therapy. Our data demonstrate that the different bone resorption markers are reflecting different aspects of bone metabolism, and therefore differ in their diagnostic and prognostic properties.

Aged↗

PubMed2006

Dietary small molecules and large-scale gene expression studies: an experimental approach for understanding their beneficial effects on the development of malignant and non-malignant proliferative diseases.

Epidemiological studies have repeatedly demonstrated a correlation between nutrition, development and the severity of malignant and non-malignant proliferative diseases such as cancer and atherosclerosis. Therefore, the prevention of chronic proliferative diseases through dietary intervention is currently receiving considerable attention. Until now, much of the research is being focused on the cellular and molecular action mechanisms of dietary small molecules explaining their beneficial effects. Dietary chemicals may affect gene expression in several human diseases. However, significant progress has been made and several molecular action mechanisms have been proposed. Alteration of genetical pathways by nutrition, also called "Nutrigenomics", may offer a new approach for understanding the beneficial effects of dietary compounds on the development of severe polygenic diseases, such as cardiovascular disease, diabetes and hypertension. This review focuses on the nutritional genomics of dietary chemicals with a special emphasis on catechins. Catechins belong to the flavonoid family, which are polyphenolic compounds available in foods of plant origin. Several epidemiological studies have reported that consumption of flavonoids, and especially catechins might function as chemopreventive agents against cancer and cardiovascular diseases.

Animals↗