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PubMed2005

Measurement of tissue mechanical characteristics to distinguish between benign and malignant prostatic disease.

OBJECTIVES: To investigate the relationship between the morphology and mechanical properties of benign and malignant prostatic tissues measured in vitro. METHODS: Fresh tissue specimens were collected from patients undergoing transurethral resection of the prostate (TURP) for benign or malignant prostatic enlargement. Individual TURP chippings underwent immediate mechanical testing by applying a dynamic compressive strain to the samples. The amplitude ratio (E*) and phase difference (tan delta), measures of tissue elastic and viscous components respectively, were derived. Individual sections from the processed specimens underwent immunohistochemical staining and computerized image analysis was used to measure the morphologic characteristics of each TURP chipping. Linear regression analysis was used to assess correlations between morphologic and mechanical measurements, and the unpaired t test, assuming equal variances, was used to compare the mechanical and morphologic characteristics of benign and malignant prostates. RESULTS: Significant differences were noted between the morphology of the benign and malignant prostates. Tan delta was significantly smaller within the malignant prostates (P = 001). No difference was found between the benign and malignant prostates with respect to E*. Within the malignant prostates, a strong negative correlation was found between the epithelial tissue content and tan delta (R2 = 0.50, P = 0.031). CONCLUSIONS: The results of this study showed that measurable differences exist between the mechanical characteristics of benign and malignant prostatic tissue and provide further evidence that significant correlations exist between prostatic tissue morphology and mechanical characteristics. We believe that the ability to quantify prostatic tissue mechanical characteristics in vivo may be of clinical benefit in the future assessment of prostatic diseases, both benign and malignant.

Aged↗

PubMed1993

Management of concomitant abdominal aortic aneurysm and gastrointestinal malignancy.

Selecting the most appropriate surgical approach for patients with abdominal aortic aneurysm (AAA) and gastrointestinal malignancy remains controversial. In an attempt to develop guidelines for the management of patients with these two simultaneous lesions, a retrospective review of patients who had concomitant AAA and gastrointestinal malignancy was undertaken. During the period from January 1985 to February 1993, 229 patients with AAA were admitted to our hospital. Among these, 19 patients (8%) had a gastrointestinal malignancy together with AAA and were divided into 2 groups. Group I was composed of 11 patients who underwent either a 1- or a 2-stage operation for both lesions. Group II was composed of eight patients who either underwent an operation for one lesion (six patients) or did not have any operation (two patients). Among group I, six patients underwent the two-stage operation. In four of the six patients, the malignancy was resected first. In the remaining two patients, the aneurysmectomy was performed first, because, in one patient, the aneurysm was more than 6 cm in diameter, and, in the other patient, the aneurysm was a saccular type. Among group I, five patients (two patients with gastric cancer, and one patient each with esophageal cancer, rectal cancer, and malignant lymphoma of the stomach) underwent a one-stage operation. In three of the five patients (two patients with gastric cancer and one patient with esophageal cancer), simultaneous resection was carried out by using segregated approaches, namely, the retroperitoneal approach for AAA and the transperitoneal approach for malignancy. Although the clinical characteristics of the patients were different, 8 of the 11 patients (73%) in group I are still alive, whereas only 1 of the 8 patients (13%) in group II is still alive. The principles of our surgical approaches for concomitant AAA and gastrointestinal malignancy are as follows: (1) The lesion that absolutely indicated urgent surgery was resected first. (2) If both lesions were asymptomatic, the malignancy was resected first. (3) Simultaneous resection using different approaches was useful in some patients with concomitant upper early gastrointestinal malignancy. (4) Both lesions need to be resected eventually for better long-term survival.

Aortic Aneurysm, Abdominal↗

PubMed1996

Mucin-hypersecreting tumors of the pancreas: assessing the grade of malignancy preoperatively.

BACKGROUND: Mucin-hypersecreting tumor of the pancreas (MHST) is a unique variant of pancreatic tumor, where mucin was excreted from the patulous orifice of the enlarged ampulla of Vater and the main pancreatic duct was dilated with excessive mucin. It is difficult to differentiate preoperatively between benign and malignant variants. PATIENTS AND METHODS: A total of 18 patients with an MHST were retrospectively reviewed to identify possible indicators of malignancy. The 18 tumors consisted of 9 benign lesions (hyperplasia or adenoma with mild to moderate atypia), 2 borderline disorders (adenoma with severe atypia), and 7 malignant diseases (unequivocal adenocarcinoma). RESULTS: The age, sex, and site of origin demonstrated no significant difference among the three groups. One of the 9 patients with the benign lesion was diabetic, while 4 of the 7 patients with the malignant variant were diabetic (P<0.05). All 9 benign lesions were confined to the side branch, while 4 of the 7 malignant diseases were located in the main pancreatic duct (P<0.05). The mean greatest diameters of these three variants were 3.2 cm, 3.3 cm, and 6.6 cm, respectively. The mean greatest diameter of the main pancreatic duct in the 7 malignant disorders were larger than in the 9 benign conditions (9.7 versus 5.4 mm, P <0.05). The mean diameter of the mural nodules in the 7 malignant tumors were larger than in the 9 benign lesions (20.5 versus 5.1 mm, P <0.05). The serum and mucin carcinoembryonic antigen and carbohydrate antigen 19-9 levels showed no substantial difference between the benign and malignant variants. CONCLUSIONS: The presence of diabetes, large tumors (> or = 5 cm), marked dilatation of the main pancreatic duct (> or = 10 mm), main pancreatic duct type, and large mural nodules (> or = 10 mm) is strongly suggestive of a malignant variant of the MHST.

Adenocarcinoma↗

PubMed1997

Second malignant neoplasms in children after treatment of soft tissue sarcoma.

Currently, approximately 67% of children diagnosed with cancer can be expected to survive more than 5 years. Among the most significant late effects of cancer therapy is the development of second malignant neoplasm (SMN). This study was performed to identify the factors associated with the development of second malignant neoplasms after treatment for soft tissue sarcomas in childhood. Retrospectively the charts of 20 children who developed second malignant neoplasms after treatment for primary childhood soft tissue sarcoma were reviewed. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment, family histories (when available), and outcome were recorded. The mean age of the patients (10 boys, 10 girls) was 8.5 years of age (range, 1 to 20 years). Most primary tumors were rhabdomyosarcoma (14/20) and occurred in an extremity (10/20). Ninety percent of the patients (18/20) had a complete response to treatment of the primary cancer. Eleven out of 20 received combined chemotherapy and radiation therapy. The most common secondary malignancy was a bone sarcoma (6/20), followed by brain tumors (n = 3), leukemia (n = 2), and other sarcomas (n = 2). Four of the bone sarcomas developed in the field of radiation treatment. Median follow-up was 16 years (range, 1 to 26 years). The median time to development of a SMN was 11.4 years (range, 1.5 to 21 years). Survival after a second malignancy was only 30%. Two patients developed a third malignant neoplasm. The occurrence of a secondary malignancy represents a serious complication of childhood cancer. Certain tumors are related directly to treatment such as osteosarcoma within irradiated fields and secondary leukemias or lymphomas after certain chemotherapy regimens. Combined radiotherapy and chemotherapy may play an additive role in the development of second malignant neoplasms. Genetic factors may predispose affected patients to the development of both primary and secondary malignancies. Close surveillance of children previously treated for childhood cancers is warranted.

Adolescent↗

PubMed1998

High incidence of malignancies in patients with dermatomyositis and polymyositis: an 11-year analysis.

OBJECTIVES: Dermatomyositis and polymyositis (DM/PM) are associated with neoplasms. The aim of the present study is to compare our experience in Israel with other published data. METHODS: Thirty-five adult patients with DM/PM, admitted to Sheba Medical Center during the 11-year interval between 1984 and 1994, were studied for the prevalence and features of malignant diseases. Patients with DM/PM alone and with DM/PM and malignancy were identified by using the hospital computer system. The manifestations of DM/PM and features of the malignant diseases were abstracted from the patients' charts. The presence or absence of malignancy and the type of cancer were verified in the National Cancer Registry. RESULTS: There were 15 men and 20 women. The mean age at the onset of the disease was 53 +/- 18 years. A total of 15 had PM and 20 DM. Malignancies occurred in four patients with PM (27%) and in nine with DM (45%) a frequency 12.6 times higher than in the general population. In six patients, the malignancy and the DM/PM were diagnosed simultaneously; in four before and in three after the appearance of the DM/PM. Hematologic, gastrointestinal, breast, ovarian, and lung tumors, malignant melanoma, and metastatic carcinoma of unknown primary were found among our patients. Eight DM/PM patients with malignancy died during the study period of infection, pulmonary embolism, and tumor spread. CONCLUSIONS: Our study found that DM/PM is associated with high rates of malignancy and mortality.

Adult↗

PubMed1979

Malignant fibrous histiocytoma of bone and osteosarcoma. A comparative light and electron microscopic study.

Malignant fibrous histiocytomas are well-described tumors of the soft tissues. Recent investigations have shown that malignant histiocytoma may also occur as a primary bone tumor. However, difficulties may arise to distinguish malignant histiocytoma of bone from other malignant bone tumors, such as osteosarcoma. In the present study, the ultrastructure of five cases of malignant fibrous histiocytoma of bone is compared with that of osteosarcoma. The results show that malignant fibrous histiocytoma is composed mainly of histiocytic cells and fibroblastic cells. In addition, xanthomatous cells, undifferentiated cells, and giant cells may be observed. By contrast, the predominant cell type in osteosarcoma is the neoplastic osteoblast, characterized by abundant rough endoplasmic reticulum. Signs of matrix calcification in the intercellular matrix between the collagen fibrils are regularly observed in osteosarcoma, but not in malignant histiocytoma. From these results it is concluded that the ultrastructure of malignant fibrous histiocytoma arising in bone is morphologically identical with the soft tissue counterpart of this tumor. The components of the tumor are derived from neoplastic histiocytes. This cytogenesis differs from that of osteosarcoma, which is derived from neoplastic osteoblasts. Therefore, from the ultrastructural point of view, malignant fibrous histiocytoma of bone should be accepted as a distinct histologic entity among bone tumors.

Adolescent↗

PubMed1997

Malignant salivary gland tumours in Sweden 1960-1989--an epidemiological study.

Epidemiological data from the Swedish Cancer Registry of new cases of malignant major and accessory salivary gland tumors in Sweden between 1960 and 1989 are presented, including the total number and the age-standardised incidence rate per 1 million population, by site and sex, I(s). An analysis of the various histopathological types of malignant salivary gland tumours in the different sublocations is also given. A comparison is made between the three 10-year periods 1960-1969, 1970-1979 and 1980-1989 regarding total number and I(s). The total number of new malignant major salivary gland tumors was 2557, representing approximately 85 new cases per year and 0.3% of all new diagnosed cancers in Sweden. In addition, approximately 25 new cases per year of malignant accessory salivary gland tumors were reported. If all malignant salivary gland tumours were considered, the most common location was found in the parotid glands with a relative frequency of 57.5%, and the next most common site was malignant accessory salivary gland tumours with 22.6%. I(s) was 10.2 for the major and 3.0 for the accessory salivary glands. No major difference between the examined 10-year periods was found concerning the relative frequency, and no statistically significant difference in I(s) was found between the examined 10-year periods, except for a statistically significant decrease in the I(s) between the time periods 1960-1969 and 1980-1989 for the multiple or unspecified malignant salivary glands from 0.5 to 1.4. A difference in the distribution of various histopathological types of malignant salivary gland tumours was observed between the different time periods. This was particularly valid for the diagnoses adenoid cystic carcinomas and mucoepidermoid carcinomas which increased in number and the diagnosis malignant salivary gland tumours of mixed type, which decreased in number during the examined time periods.

Adenoma, Pleomorphic↗

PubMed1989

Malignant cell glycoproteins and glycolipids.

The cell surface is involved in cell growth and division, cell-cell interaction, communication, differentiation and migration, and other processes likely to be involved in malignant transformation and/or the metastatic spread of cancer. Although there are many alterations of glycoproteins and glycolipids on the malignant cell surface, it is unclear whether these alterations are epiphenomena or an integral part of the malignancy process. This article reviews the recent literature and some earlier studies relevant for understanding emerging concepts and trends with respect to malignant cell glycoconjugates. Emphasis is on structural alterations of the carbohydrate portions of malignant cell glycoproteins and glycolipids and on the enzymes (glycosyltransferases and glycosidases) involved in their metabolism. Practical applications derived from malignant cell glycoconjugate studies are discussed briefly with respect to the diagnosis, staging, monitoring, and treatment of malignant disease. The review concludes by indicating which research areas on malignant cell glycoconjugates are likely to be fruitful in increasing our basic understanding of, and ability to deal effectively with, malignant disease.

Animals↗

PubMed1976

Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition.

Tumour antigen-induced inhibition of leucocyte adherence was modified for use in glass test tubes (Tube LAI assay) for the study of cell-mediated anti-tumour immunity to human malignant melanoma. Peripheral blood leucocytes (PBL) of 20 out of 25 patients (80%) with active malignant melanoma responded to an extract of malignant melanoma with LAI, whereas only 4-5% of 475 control subjects showed a response. The malignant melanoma patients reacted to both allogeneic and autologous extracts of malignant melanoma which indicates a common cross-reacting antigen. Malignant melanoma patients did not respond to unrelated tumour extracts. The LAI was mediated by PBL (monocytes) "armed" with cytophilic anti-tumour antibody specific for the sensitizing tumour antigen. The anti-tumour response of the malignant melanoma patients was dependent on the stage of the cancer, and 11 out of 13 Stage I patients had a positive NAI, whereas patients with disseminated cancer had decreased response. The diminished LAI in patients with large tumour burdens appeared to be the result of release of tumour antigen systemically. Also, surgery and chemotherapy depressed LAI. Although LAI was depressed after surgical excision of the cutaneous melanoma, most patients showed LAI 1-3 months later. Tumour-free melanoma patients monitored for one year by the Tube LAI assay showed a decline in their anti-tumour immunity 5-6 months after surgery. The NAI was low or negative after the 8th post-surgical month in tumour-free patients. Patients with residual malignant melanoma showed persistent or recurrent LAI after the 8th post-surgical month. LAI reactivity monitored after "curative" surgery for malignant melanoma may assist in determining whether the patient is tumour-free or has a recurrence.

Antigens, Neoplasm↗

PubMed1985

HNK-1+ cells in non-Hodgkin's lymphoma: lack of relation with transferrin receptor expression on malignant cells.

It has been proposed that Natural Killer (NK) cell activity is involved in host defence against neoplasia, and that NK cells react with or recognize the transferrin receptor (TrR) on target cells. HNK-1 expression has been related to NK cell function. Therefore, in 118 cases of non-Hodgkin's lymphoma (NHL) we studied the occurrence and distribution of HNK-1+ cells by immunohistochemistry, and simultaneously assessed the expression of TrR on malignant cells. In NHL of intermediate or high grade malignancy there was uniform expression of TrR on malignant cells. In low grade malignancy NHL, only lymphocytic and lymphoplasmacytoid lymphomas were TrR negative, except for faint staining of proliferation centres. In 23 cases of follicular lymphoma, 9 showed the absence of HNK-1+ cells in neoplastic follicles. In 16/23 cases HNK-1+ cells were present around follicles or in interfollicular areas: 8 of these cases revealed a higher density of HNK-1+ cells at this site than inside the follicles. In 22/26 cases with high grade malignancy NHL, HNK-1+ cells were absent or present in small density, which is different from the presence in higher density in low grade malignancy NHL. We conclude that (i) TrR expression on NHL cells is not obligatory related with histological class or malignancy grade of the tumour, and that (ii) HNK-1+ cells are not universally present in areas of malignant cells, in particular in follicular lymphoma and in NHL of high grade malignancy.

Antibodies, Monoclonal↗

PubMed2000

Teratomatous genotype detected in malignancies of a non-germ cell phenotype.

Originating from post-meiotic germ cells, mature ovarian teratomas (MOT) are genetically homozygous tumors within heterozygous hosts. MOT may be associated with malignant tumors of a non-germ cell phenotype (so-called malignant transformation). Based on the presence of in situ changes, some cases have been hypothesized to arise from teratomatous tissue. However, other malignancies associated with mature teratomas, such as sarcomas, may originate from either teratomatous elements or preexisting somatic ovarian tissue. Eight cases of MOT containing various histologic types of malignancy, including four squamous cell carcinomas, two sarcomas, one thyroid carcinoma, and one carcinoid tumor, were selected for study. Using selective tissue microdissection and PCR-based analysis of the extracted DNA, we compared the genotypic pattern of the mature teratomatous components to the associated malignant neoplasm with a random panel of highly informative genetic markers for different chromosomes. In all eight cases, genetic analysis of the malignant component revealed a homozygous genotype. In seven cases, the genetic profiles of mature teratomas and the associated malignant tumors were identical, suggesting a direct pathogenetic relationship between these lesions. In one case, the malignant component revealed homozygosity of different alleles compared with mature teratoma, suggesting independent teratomatous growth processes. This finding indicates that some ovarian malignancies of the non-germ cell phenotype arise in teratoma and fall into the spectrum of germ cell tumors.

DNA, Neoplasm↗

PubMed2003

Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma.

The overall incidence of osteosarcoma is low. However, the occurrence of osteosarcoma in a setting of multiple primary tumours is not infrequent, although population-based incidence numbers are unknown. The occurrence of osteosarcoma and other malignancies is frequently related to treatment, and can also be the result of genetic predisposition as in patients with retinoblastoma, Li-Fraumeni syndrome, Werner syndrome and Rothmund-Thomson syndrome. The aim of our study is to establish the incidence of osteosarcoma associated with other malignancies in a populationwide study and to find out if these osteosarcomas have a specific subtype, that could draw attention to a genetic predisposition to malignancy. A list of all patients registered in the Dutch National Pathology Register, named PALGA, with a diagnosis of osteosarcoma between 1975 and May 2000 was retrieved. All patients with another malignancy besides osteosarcoma were selected. All patients registered in the same period with a tonsillectomy served as a control for the occurrence of malignancy in a normal population. In a second step, only osteosarcoma patients with a history of retinoblastoma or a malignancy before the age of 46 years, since these are most probable to have a hereditary cancer syndrome, were retained for further analysis. The osteosarcomas were subtyped as common, chondroblastic, fibroblastic, teleangiectatic, anaplastic, osteoclast-rich or small cell. As a control for osteosarcoma subtypes the data of 570 patients entered in two studies from the European Osteosarcoma Intergroup (EORTC/MRC) were used. Of all 938 patients registered with the diagnosis of osteosarcoma, 66 had a history of multiple primary tumours. Four patients had a surface osteosarcoma, three an extraskeletal osteosarcoma and 59 had intramedullar high-grade osteosarcoma. Of this last group, one patient was known with Rothmund-Thomson syndrome, one had retinoblastoma and 30 had their malignancies before the age of 46. Of these 32 patients, 17 had osteosarcoma of the long bones. Especially women seem to be more susceptible for the development of multiple primaries. In nine patients, the histological subtype could be assessed by revision of available histological slides. All of these patients had an osteosarcoma subtype other than common as opposed to 29% in the control group of the European Osteosarcoma Intergroup. It is concluded that although the incidence of osteosarcoma is low, the occurrence of another malignancy in osteosarcoma patients is higher than in the normal population. Specifically, osteosarcoma patients have a relative risk of 2.4 (95% confidence interval 1.88-3.07) to develop another malignancy. A noncommon subtype of osteosarcoma should draw attention to a possible genetic predisposition of the patient involved.

Adolescent↗

PubMed2002

Differentiation between malignant and benign follicular adnexal tumours of the skin by DNA image cytometry.

BACKGROUND: We have demonstrated in previous studies that DNA image cytometry (DNA ICM) can be helpful in detecting malignancy in sebaceous tumours of the Muir-Torre syndrome and sweat gland tumours. However, little is known about DNA ICM in cutaneous adnexal tumours with follicular differentiation. OBJECTIVES: To study a larger series of benign and malignant follicular adnexal tumours with DNA ICM. METHODS: We studied 13 malignant follicular tumours (seven trichilemmal carcinomas, five malignant proliferating pilar tumours, one pilomatrix carcinoma) and 55 benign follicular tumours (four tumours of the follicular infundibulum, seven Winer's pores, eight trichilemmomas, two trichofolliculomas, 16 trichoepitheliomas, 13 pilomatrixomas, five trichoblastomas) by DNA ICM. All cases were clear-cut as malignant or benign, respectively, on histopathological criteria. The stemline interpretation according to Böcking et al. (DNA distribution in gastric cancer and dysplasia. In: Precancerous Conditions and Lesions of the Stomach, Zhang YC, Kawai K, eds. Berlin: Springer-Verlag, 1993: 103-20) was performed in all cases. In addition, 5[c]-exceeding events (5cEE) and the 2[c] deviation index (2cDI) were calculated, except in one histopathologically benign tumour, which revealed euploid polyploidization, as the analysis of 5cEE and 2cDI is not valid in that case. RESULTS: A 2cDI threshold of 0.24 proved to be the most reliable marker for the distinction between malignant and benign follicular tumours. On the basis of this feature, all malignant and benign tumours were correctly classified. A specificity of 100% was achieved by all three interpretation methods, but the sensitivity of 2cDI for the detection of malignant tumours was superior to the analysis of 5cEE (sensitivity 77%) and to the stemline interpretation (sensitivity 23%). CONCLUSIONS: DNA ICM may be helpful in distinguishing between malignant and benign follicular tumours.

Aneuploidy↗

PubMed1998

Cellular proliferation and nuclear ploidy assessments augment established prognostic factors in predicting malignancy in testicular Leydig cell tumours.

AIMS: Testicular Leydig cell tumours are rare. Although most behave benignly approximately 10% are malignant. Clinicopathological features have been described which have some value in predicting malignant behaviour, although as with other endocrine tumours uncertainties remain in many individual cases. Our aim was to determine the clinicopathological features of 20 testicular Leydig cell tumours. We wished to investigate whether, in addition to established clinicopathological features, the MIB1 index and/or flow cytometric analysis of nuclear DNA content are of value in predicting malignancy. We also wished to investigate the frequency of p53 protein accumulation in these neoplasms. METHODS AND RESULTS: Twenty testicular Leydig cell tumours were studied and the clinical case notes examined. Histological sections were assessed by pathologists involved in the study. Pathological features evaluated included: tumour size, extratesticular extension, nuclear pleomorphism, mitotic activity, necrosis and vascular invasion. Immunohistochemical staining was performed with the anti-p53 monoclonal antibody DO-7 and the cell proliferation marker MIB1. A flow cytometric analysis of nuclear DNA content was also performed. Three tumours behaved in a malignant fashion with the development of metastases. Another had morphological features of malignancy but the patient died a short time after diagnosis from unrelated causes. These four neoplasms were larger than benign tumours, often contained areas of necrosis and sometimes exhibited vascular invasion. They generally exhibited greater nuclear pleomorphism and a higher mitotic rate than benign tumours. Three of the four malignant tumours had a high MIB1 index (20-50%) and the fourth exhibited DNA aneuploidy by flow cytometry. Two malignant tumours showed increased expression of p53 protein, with approximately 50% of nuclei staining with DO-7. All benign tumours had a low MIB1 index (0-2%) and a diploid DNA profile, except for one case where there was DNA aneuploidy. There was little or no staining of benign tumours with DO-7. CONCLUSIONS: The study confirms that large size, marked nuclear pleomorphism, high mitotic rate, necrosis and vascular invasion are important factors in predicting malignant behaviour in testicular Leydig cell tumours. Additional prognostic value may be derived from the MIB1 index and flow cytometry. Accumulation of p53 protein, through mutational or other events, may be important in malignant progression in these tumours.

Adult↗

PubMed1998

Type 1 protein tyrosine kinases in benign and malignant breast lesions.

AIMS: To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues. METHODS AND RESULTS: Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found. CONCLUSION: Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours.

Adult↗

PubMed2003

Synchronous diffuse malignant mesothelioma and carcinomas in asbestos-exposed individuals.

AIMS: The development of synchronous diffuse malignant mesothelioma and carcinoma in individuals exposed to asbestos is rare. We report nine cases and discuss the medico-legal implications. METHODS AND RESULTS: Five hundred patients seeking compensation for asbestos-related diffuse malignant mesothelioma were reviewed with access to post-mortem data. The study group comprised cases in which a second (non-mesothelial) neoplasm was identified. The study group comprised eight males, one female, mean age 68 years (range 60-75). All individuals gave a history of asbestos exposure. Synchronous malignant mesothelioma with carcinoma was identified in 9/500 (1.8%). Eight malignant mesotheliomas were pleural, one was primary peritoneal in origin. By morphological subtyping there were four epithelioid, three biphasic and two sarcomatoid mesotheliomas. In 6/9 (67%) the second tumour was a primary bronchogenic carcinoma (three adenocarcinomas, two squamous cell carcinomas and one small-cell carcinoma). In 3/9 (33%) the second tumour was a non-bronchogenic carcinoma (colonic, pancreatic and breast ductal adenocarcinoma). No other neoplasms were identified in the cohort of malignant mesotheliomas studied. Five persons had pathological evidence of asbestosis (four had bronchogenic carcinomas, one colorectal adenocarcinoma). Two persons with non-bronchogenic carcinomas had identifiable asbestos bodies but no interstitial fibrosis. In two cases the second neoplasms (primary bronchogenic squamous cell and small-cell carcinomas) were associated with diffuse interstitial fibrosis but no asbestos bodies were seen on light microscopy. In each case transmission electron microscopic mineral analysis revealed an asbestos fibre burden within the background population range for control subjects and well below that seen in cases of established asbestosis. These cases were considered to represent cryptogenic fibrosing alveolitis in subjects with a history of asbestos exposure. CONCLUSIONS: Synchronous malignant mesothelioma with carcinomas in asbestos-exposed workers is rare and identified in 1.8% of 500 malignant mesotheliomas in this series. In most cases the carcinoma represents a primary bronchogenic neoplasm. Primary lung carcinomas are recognized to be asbestos related only when occurring in association with asbestosis. In this series this combination (bronchogenic carcinoma and asbestosis) was seen in four (0.8%) cases. In post-mortem cases for possible malignant mesothelioma it is important to identify any other neoplasia and determine whether it is related to asbestos. Their presence impact upon anticipated life expectancy and in the presence of malignant mesothelioma will affect the compensation settlement.

Adenocarcinoma↗

PubMed2002

An algorithm including results of gray-scale and power Doppler ultrasound examination to predict endometrial malignancy in women with postmenopausal bleeding.

OBJECTIVE: To determine if power Doppler ultrasound examination of the endometrium can contribute to a correct diagnosis of endometrial malignancy in women with postmenopausal bleeding and endometrium > or = 5 mm. METHODS: Eighty-three women with postmenopausal bleeding and endometrium > or = 5 mm underwent gray-scale and power Doppler ultrasound examination using predetermined, standardized settings. Suspicion of endometrial malignancy at gray-scale ultrasound examination (endometrial morphology) was noted, and the color content of the endometrium at power Doppler examination was estimated subjectively (endometrial color score). Computer analysis of the most vascularized area of the endometrium was done off-line in a standardized manner. Stepwise multivariate logistic regression analysis was carried out to determine which subjective and objective ultrasound and power Doppler variables satisfied the criteria to be included in a model to calculate the probability of endometrial malignancy. RESULTS: Endometrial thickness, vascularity index (vascularized area/endometrial area), and use of hormone replacement therapy (HRT) satisfied the criteria to be included in the model used to calculate the 'objective probability of endometrial malignancy'. Endometrial morphology, endometrial color score and HRT use satisfied the criteria to be included in the model to calculate the 'subjective probability of malignancy'. Endometrial thickness > or = 10.5 mm had a sensitivity with regard to endometrial cancer of 0.88 and a specificity of 0.61. At a fixed sensitivity of 0.88, the specificity of the 'objective probability of malignancy' (0.81) was superior to all other ultrasound and power Doppler variables (P = 0.001-0.02). The 'objective probability of malignancy' detected more malignancies at endometrium 5-15 mm than endometrial morphology (5/7 vs. 1/7, i.e. 0.71 vs. 0.14; P = 0.125) with a similar specificity (49/57 vs. 51/57, i.e. 0.86 vs. 0.89). CONCLUSION: Power Doppler ultrasound can contribute to a correct diagnosis of endometrial malignancy, especially if the endometrium measures 5-15 mm. The use of regression models including power Doppler results to estimate the risk of endometrial cancer deserves further development.

Aged↗

PubMed2003

Hematologic malignancies in patients with cryoglobulinemia: association with autoimmune and chronic viral diseases.

OBJECTIVE: To determine the prevalence and clinical characteristics of hematologic malignancies occurring in a large series of patients diagnosed with cryoglobulinemia, and to study their association and overlap with autoimmune and/or chronic viral diseases. METHODS: We retrospectively analyzed the occurrence of hematologic malignancies in 607 patients diagnosed with cryoglobulinemia in a single institution. Clinical, histologic, and serologic characteristics of patients were recorded on a protocol form. Hematologic malignancies were diagnosed according to the Revised European-American Lymphoma/World Health Organization classification criteria. RESULTS: Of the total cohort of 607 patients with cryoglobulinemia, we retrospectively identified 27 patients (5%) in whom a hematologic malignancy was diagnosed, including 24 (89%) lymphoproliferative and 3 (11%) myeloid malignancies. Fifteen (56%) were men and 12 (44%) women, with a median age at diagnosis of hematologic malignancy of 67 years (range, 44 to 88 years). The identified hematologic malignancies were non-Hodgkin lymphoma (n = 18), Hodgkin lymphoma (n = 2), chronic lymphocytic leukemia (n = 2), and 1 case each of multiple myeloma, Waldenström macroglobulinemia, Castleman disease, chronic myeloid leukemia and myelodysplastic syndrome. Of the 18 patients with non-Hodgkin lymphoma, there was a predilection for specific histologic types (diffuse large B-cell lymphoma in 8 cases and small lymphocytic lymphoma in 4) and a higher frequency of a primary extranodal origin in 6 (33%) cases. Conditions associated with hematologic malignancies were hepatitis C virus (HCV) infection in 14 patients (52%) and systemic autoimmune diseases in 13 (48%), with both HCV and systemic autoimmune disease in 6 cases (22%). CONCLUSIONS: Hematologic neoplasia associated with cryoglobulinemia is defined by a clear predominance of lymphoproliferative disorders (mainly non-Hodgkin lymphoma), with substantial extranodal involvement and an elevated presence of immunologic markers. HCV infection is the main etiologic factor associated with hematologic malignancies in patients with cryoglobulinemia, followed by specific systemic autoimmune diseases such as Sjögren syndrome and systemic lupus erythematosus, highlighting the close relationship between lymphoproliferation, autoimmunity, and viruses.

Adult↗