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Predicting factors of malignancy in dermatomyositis and polymyositis: a case-control study.

BACKGROUND: An association between dermatomyositis (DM)/polymyositis (PM) and malignancies has been widely reported in the literature. The validity of extensive evaluation for malignancies in those patients has also been questioned for decades. Only limited papers regarding the signs of malignancy and the prognostic factors in DM/PM have been reported. OBJECTIVES: To define the potential risk factors of concomitant neoplastic diseases in patients diagnosed as having DM/PM. METHODS: From 1 April 1983 to 30 June 1999, 147 patients were diagnosed as having probable or definite DM/PM at the Veterans General Hospital, Taichung, Taiwan. We excluded four patients who had preceding neoplastic diseases diagnosed before DM/PM, then retrospectively reviewed the data of the remaining 143 patients and subgrouped the cases as four main types: primary idiopathic DM, primary idiopathic PM, juvenile DM/PM and amyopathic DM (ADM). We next performed univariate analysis using logistic regression to evaluate the possible predictive factors for malignancies, such as mean age at onset, gender, manifestations at onset, association with other connective tissue diseases, initial skin presentations, complications and laboratory data. Then we chose the significant factors for multivariate analysis by logistic regression, to determine the independent risk factors of malignancies in DM/PM patients. RESULTS: Among the 143 patients, DM was the most common type (64%), followed by ADM (14%), juvenile DM/PM (13%) and PM (10%). The mean age at onset overall was 42.4 years. Other connective tissue diseases were present in 22% of all patients, especially PM (50%) and juvenile DM/PM patients (28%). Internal malignancies were present in 13% of patients, and most were associated with DM. Nasopharyngeal carcinomas (NPCs) were the most common tumours. Patients with primary idiopathic DM, with an older age at onset, higher serum creatine phosphokinase levels and male gender, had more chance of developing concomitant malignancies. Those associated with complications, especially interstitial lung diseases, had a lower risk of associated neoplasia. In multivariate analysis, an older age at onset (odds ratio 9.10) and male gender (odds ratio 4.06) were associated with greater risk of developing malignancies. CONCLUSIONS: The two independent predictive factors for malignancy (P < 0.05) in patients with DM/PM were an older age at onset (> 45 years) and male gender. The primary idiopathic DM group was shown to have higher risk of developing internal malignancies, especially NPC. However, this was not identified as an independent predictive factor for concomitant neoplastic diseases in multivariate analysis. In addition, patients who had the complication of interstitial lung disease had a significantly lower frequency of malignancies (P < 0.001).

Adult↗

Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME-1 expression.

Histological diagnosis of malignant mesothelioma and differentiation from adenocarcinoma is often difficult. Definitive pathological confirmation of malignant mesothelioma requires demonstration of an appropriate immunohistochemical phenotype. Selection of an optimum panel of immunohistochemical antibodies for the reliable identification of malignant mesothelioma is hindered by the absence of a specific immunohistochemical label for mesothelioma cells. Recently, we have found that the ovarian carcinoma cell antibody CA125 labels malignant mesothelioma cells, and the antibody HBME-1 has been developed as a sensitive mesothelial cell marker. We have compared the immunohistochemical staining patterns achieved with CA125 and HBME-1 to those obtained using a panel of eight further antibodies in 17 malignant mesotheliomas and 14 primary and secondary adenocarcinomas within lung and pleura. CA125 labelled malignant mesothelioma cells in 15 of 17 cases (88%), and adenocarcinoma cells in seven of 14 cases (50%). HBME-1 labelled mesothelioma cells in all 17 cases (100%) but also labelled adenocarcinoma cells in 10 of 14 cases (71%). BerEP4 positively labelled one malignant mesothelioma but was negative in the remaining 16 cases and positively labelled nine of 14 adenocarcinomas (64%). Monoclonal anti-CEA, AUA-1, CA19.9 and LeuM1 labelled no malignant mesotheliomas and were positive in 10 (71%), nine (64%), eight (57%) and six (43%) of 14 cases of adenocarcinoma, respectively. Diastase-PAS staining detected neutral mucin in none of the malignant mesotheliomas but in 10 (71%) of the 14 adenocarcinomas. We conclude that CA125 and HBME-1 do not label mesothelial cells with sufficient specificity to be useful for differentiating malignant mesothelioma from adenocarcinoma, although negative staining with HBME-1 makes a diagnosis of malignant mesothelioma unlikely. As there remains an absence of a specific positive mesothelial cell marker this distinction is still most reliably made using a panel of antibodies including at least two of the following: anti-CEA, AUA-1, BerEP4, LeuM1 and CA19.9, in combination with histochemical assessment of neutral mucin production.

Adenocarcinoma↗

Adult Henoch-Schönlein purpura associated with malignancy.

OBJECTIVE: Malignancies are among the well-established causes of vasculitis. We studied the association between adult Henoch-Schonlein purpura (HSP) and malignant neoplasms. METHODS: We retrospectively reviewed 14 cases of adult HSP diagnosed during a 6-year period and found a malignant neoplasm in four. Fifteen reports of adult HSP with malignant disease were identified in the literature. These 19 cases were compared with 158 adults who had HSP but no malignancy and who where reported in the literature. RESULTS: Most (63%) of the malignant neoplasms associated with adult HSP were solid tumors: lung, n = 6; prostate, n = 2; breast, n = 1; renal, n = 1; stomach, n = 1; and small bowel, n = 1. Hematologic malignancies (37%) included non-Hodgkin lymphoma, n = 2; Hodgkin disease, n = 2; IgA multiple myeloma, n = 1; myeloproliferative disease, n = 1; and myelodysplastic syndrome, n = 1. Patients with malignancy were older (median age, 59 years), were more likely to be male (M/F = 8.5), had joint involvement more frequently (95%), and had a lower frequency of prior acute infection than those without malignancy. A typical paraneoplastic course was documented in only two cases. CONCLUSIONS: Epidemiological studies are needed to determine the association between adult HSP and malignancy. In practice, it may be wise to suspect a malignancy in men older than 40 years of age who develop HSP in the absence of a precipitating factor. Pathogenic hypotheses involve tumor antigens or abnormal IgA production leading to immune complex formation.

Adult↗

Angiogenically active vascular endothelial growth factor is over-expressed in malignant human and rat prostate carcinoma cells.

Vascular endothelial growth factor (VEGF) is one of the most potent factors for stimulating angiogenesis, an essential process required for expansion of primary tumour and dissemination of malignant cells. To investigate the possible role of VEGF in facilitating metastasis of prostate cancer via stimulating angiogenesis, we have used Northern and slot blotting, reverse transcription polymerase chain reaction, nucleotide sequence analysis and enzyme-linked immunosorbent assay to compare the VEGF expression in series of human and rat cell lines with either benign or malignant characteristics. We have also employed the chick chorioallantoic membrane (CAM) assay to measure the angiogenic activity of the VEGF derived from both benign and malignant cells. The level of VEGF mRNA expressed in the seven malignant human and rat cell lines is 3.5- to 10-fold higher than that expressed in the benign cell lines. The three metastatic variants, generated by transfection of a benign cell line with DNA extracted from prostate carcinoma cells, expressed 2.5 to 5 times more VEGF mRNA than their parental benign cells. While VEGF 121 and 165 were predominantly expressed by both the benign and malignant cells, the transcript representing VEGF 189 isoform was only detected in the malignant cells. At protein level, three human malignant cell lines produced more VEGF (2.7-7.9 ng ml(-1)) than the benign cell line (1.3 ng ml(-1)). CAM assay detected a VEGF-dependent angiogenic activity in the medium from malignant cells, but only a relatively weak VEGF-independent activity in the medium from benign cells. These results demonstrated that malignant cells did over-express VEGF and only the VEGF derived from malignant cells was angiogenically active. Thus, we suggest that the VEGF produced by malignant cells might play an important role in facilitating metastasis of prostatic cancer.

Allantois↗

[Second neoplasms after malignant diseases in childhood].

Since 1980 the German Registry of Childhood Malignancies has been established. In the framework of the long-term follow-up secondary malignancies are reported continually to the registry. An additional retrospective inquiry to all treating clinicians and principal investigators of clinical trials as well as a link to a previously existing pool of secondary malignancies (1) lead to a completion of the data. At the registry now 329 patients with second malignant neoplasms have been observed. 41.3% of them had been developed the first malignancy before the registry started its work in 1980. The most common primary malignancies are acute lymphoblastic leukaemia (ALL, 28.6%), brain tumours (12.2%), and retinoblastomas (8.8%). Compared to the population of the registry retinoblastomas as a secondary malignancy occur in excess (2.5% vs 8.8%). Most common secondary malignancies are brain tumours (20.1%), acute non-lymphoblastic leukaemia (13.1%), osteosarcomas (10.9%), and thyroid carcinomas (6.1%). Hereby especially for thyroid cancer a remarkable deviation from the frequency in the total population of the registry (0.2%) is observed. In 3% of the patients a secondary malignancy appears within a span of 10 years after the primary malignancy. This is a twentyfold increase compared with the cumulative rate of developing a malignancy in the first 10 years of life. Brain tumours after ALL (8.5%) and after other brain tumours (5.8%) and osteosarcomas after retinoblastomas (4.9%) are the most often reported combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Obstetrical deliveries associated with maternal malignancy in California, 1992 through 1997.

OBJECTIVE: This study aims to characterize the rate of occurrence and nature of outcomes associated with obstetrical deliveries in women with malignant neoplasms among 3,168,911 women who delivered in California in 1992 through 1997. DESIGN: The study is a population-based retrospective review of infant birth and death certificates and maternal and neonatal discharge records. Cases of malignant neoplasms associated with obstetrical delivery were attributed to 1 of 3 categories, depending on the earliest documented hospital discharge diagnosis, as follows: "prenatal" if the diagnosis was first documented by hospitalization within 9 months preceding delivery, "at delivery" if the diagnosis was established from the delivery hospitalization, or "postpartum" if the diagnosis was first documented by hospitalization within 12 months after delivery. METHODS: Computer-linked infant birth and death certificates and maternal and neonatal discharge records were used to identify cases and outcomes. Cases of malignant neoplasms were identified by using International Classification of Diseases, Ninth Revision codes (140-208). Noninvasive neoplasms and carcinoma in situ neoplasms were excluded. In analysis of outcomes, the Mantel-Haenszel estimate for adjusted odds ratios was used. RESULTS: Among 3,168,911 obstetrical deliveries over the 6-year span, a total of 2247 cases of primary malignancy were identified. The observed rate of occurrence for primary malignant neoplasms was 0.71 per 1000 live singleton births. Most cases (53.3%) were first documented in the postpartum period as follows: prenatal, 587 cases (0.18 per 1000); at delivery, 462 cases (0.15 per 1000); and postpartum, 1198 cases (0.38 per 1000). The most frequently documented primary malignant neoplasms associated with obstetrical delivery were breast cancer (423 cases, 0.13 per 1000), thyroid cancer (389 cases, 0.12 per 1000), cervical cancer (266 cases, 0.08 per 1000), Hodgkin's disease (172 cases, 0.05 per 1000), and ovarian cancer (123 cases, 0.04 per 1000). Odds ratios for a variety of demographic factors identified maternal age as the most significant risk factor for development of malignant neoplasms (age greater than 40 vs 20-25, odds ratio 5.7, CI 4.6-6.9). Age-adjusted odds ratios for maternal cancer of any type suggested significantly elevated risks for cesarean delivery (odds ratio 1.4, CI 1.3-1.6), blood transfusion (odds ratio 6.2, CI 4.5-8.5), hysterectomy (odds ratio 27.4, CI 20.8-36.1), and maternal postpartum hospital stay greater than 5 days (odds ratio 30.6, CI 27.9-33.6), but not for postpartum maternal death (odds ratio 0.8, CI 0.6-1.0). Odds ratios also suggested significantly elevated risks for premature newborn (odds ratio 2.0, CI 1.8-2.2), very low birth weight (odds ratio 2.9, CI 2.2-3.8), and newborn hospital stay longer than 5 days (odds ratio 2.6, CI 2.4-3.0), but not for neonatal death (odds ratio 1.6, CI 0.8-3.1) or infant death (odds ratio 1.2, CI 0.5-3.3). However, several types of malignant neoplasms did confer significant elevations in risk for neonatal death. Hospital charges for both maternal and neonatal care were significantly elevated in the maternal malignant neoplasm group. CONCLUSION: A lower than expected occurrence rate of obstetrical delivery associated with maternal malignancy was seen when compared with previously published hospital-based reports. Malignant neoplasms associated with obstetrical delivery were most frequently first documented in the postpartum period. Maternal and neonatal morbidity were significantly increased, yet the risk of in-hospital maternal death was not significantly elevated. A significant increase in risk of neonatal death for infants of mothers with cervical cancer was found.

Adult↗

Veterans with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have a markedly increased rate of second malignancy, which is the most common cause of death.

Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have an increased incidence of high-grade lymphoid malignancy. The risk of non-lymphoid second malignancy in this population is not well-defined to date. To test the hypothesis that patients with CLL/SLL have an increased risk of second malignancy, we studied the rate of second malignancy in 132 CLL/SLL patients and compared it to the rate of malignancy (excluding non-melanomatous skin cancer) in the Central Arkansas Veterans Healthcare System population of approximately 38,000 veterans over a period of 11.5 years. The rate of second malignancy, diagnosed concomitantly or after CLL/SLL, and the age-adjusted rate of malignancy calculated from tumor registry reports and demographic data, were used to calculate a Standardized Morbidity Ratio (SMR) with 95% confidence interval (CI). Twenty-one (16%) of the CLL/SLL patients had second malignancies (19 non-lymphoid, 1 Richter's transformation and 1 Hodgkin's disease), which were fatal in 15 (71%) patients. The SMR for the CLL/SLL population was 2.97 (95% CI 1.84-4.55) for second malignancy and 2.69 (95% CI 1.62-4.21) for non-lymphoid second malignancy. This study of a well-defined CLL/SLL population shows a significantly increased risk of second malignancy, which was the primary cause of death for 9% of all CLL/SLL patients (34% of all patient deaths).

Adult↗

Quantitative study of monocyte chemoattractant protein-1 (MCP-1) in cerebrospinal fluid and cyst fluid from patients with malignant glioma.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a 76-amino acid protein that attracts monocytes. In vitro studies have reported high levels of MCP-1 messenger RNA expression, as well as the presence of MCP-1, in malignant glioma cells. PURPOSE: Our purpose was to determine whether an MCP-1 assay could be used in a clinical setting 1) to differentiate malignant from benign gliomas and from nontumor disorders of the central nervous system and 2) to detect subarachnoid dissemination of glioma cells. METHODS: MCP-1 levels in cerebrospinal fluid (CSF) and cyst fluid were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) that we had previously developed. We measured MCP-1 levels in CSF samples from 19 patients with malignant glioma (glioblastoma, 10; anaplastic astrocytoma, six; anaplastic oligodendroglioma, two; and ependymoblastoma, one), nine patients with benign glioma, and seven patients with nontumor disorders of the central nervous system. Cyst fluids from four patients with malignant glioma (anaplastic astrocytoma) were also tested. The correlation between MCP-1 concentration in the CSF and subarachnoid dissemination of malignant glioma cells was also studied. RESULTS: The MCP-1 concentration (mean +/- SE) in CSF samples from patients with malignant glioma (2.3 +/- 0.4 ng/mL) was significantly higher than that from patients with benign glioma (0.6 +/- 0.1 ng/mL) (P < .01) or from patients with no tumor (0.5 +/- 0.1 ng/mL) (P < .01). Furthermore, CSF samples from patients with subarachnoid dissemination of malignant glioma contained significantly higher amounts of MCP-1 than those from patients without dissemination (P < .05). Cyst fluids from four of the patients with malignant glioma contained high concentrations of MCP-1. CONCLUSIONS: These results indicate that MCP-1 is produced by malignant glioma in vivo as well as in vitro and suggest that testing for MCP-1 in CSF may be useful in the clinic to differentiate malignant glioma from benign glioma and to detect subarachnoid dissemination of the tumor cells. IMPLICATIONS: The MCP-1 ELISA in CSF may lead to more accurate diagnosis of malignant glioma and detection of subarachnoid dissemination of tumor cells, facilitating selection of patients with these conditions for appropriate therapy.

Adolescent↗

Outcome in critically ill medical patients treated with renal replacement therapy for acute renal failure: comparison between patients with and those without haematological malignancies.

BACKGROUND: Starting renal replacement therapy (RRT) for acute renal failure in critically ill patients with haematological malignancies is controversial because of the poor outcome and high costs. The aim of this study was to compare the outcome between critically ill medical patients with and without haematological malignancies who received RRT for acute renal failure. METHODS: We retrospectively collected data on all consecutive patients who received RRT for acute renal failure at the Medical Intensive Care Unit (ICU) of a University Hospital between 1997 and 2002, and assessed the impact of the presence of a haematological malignancy on the survival within 6 months after ICU admission by Cox proportional hazard models. RESULTS: Fifty of the 222 (22.5%) consecutive patients with haematological malignancies admitted to the ICU over the study period received RRT for acute renal failure compared with 248 of the 4293 (5.8%) patients without haematological malignancies (P<0.001). Among patients who received RRT, those with haematological malignancies had higher crude ICU (79.6 vs 55.7%, P=0.002) and in-hospital (83.7 vs 66.1%, P=0.016) mortality rates, and a higher mortality at 6 months (86 vs 72%, P=0.018) by Kaplan-Meier estimates compared with those without haematological malignancies. However, after adjustment for the severity of illness and the duration of hospitalization before ICU admission, haematological malignancy by itself was no longer associated with a higher risk of death (hazard ratio 1.04; 95% confidence interval, 0.73-1.54, P=0.78). CONCLUSIONS: Medical ICU patients with haematological malignancies have a higher rate of occurrence of acute renal failure treated with RRT and a higher mortality, compared with those without haematological malignancies. However, the presence of a haematological malignancy by itself is not a reason to withhold RRT in medical ICU patients with acute renal failure.

Acute Kidney Injury↗

Malignancy is increased in ANCA-associated vasculitis.

OBJECTIVE: In the light of previous reports of an association between malignancy and renal vasculitis, we aimed to investigate the association of malignancy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, either Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA), and compare it with the general population and disease control groups comprising patients with systemic lupus erythematosus (SLE) or Henoch-Schonlein purpura (HSP). METHODS: A retrospective review of 200 consecutive patients with WG or MPA was performed. Malignancies preceding or concurrent with vasculitis were recorded and the incidence of malignancy was compared with those in a population of 129 patients with HSP, 333 patients with SLE and a normal population in the West Midlands of the UK. RESULTS: Twenty patients had a diagnosis of malignancy, 14 had MPA and six had WG. Patients with ANCA-associated vasculitis had an increased risk of malignancy compared with HSP patients, of whom six patients had malignancy (relative risk 0.85, confidence interval 0.69-1.05; P = 0.034), or SLE patients, of whom five patients had malignancy (relative risk 0.31, 95% confidence interval 0.14-0.7; P<0.0001). The rate of malignancy compared with an age-matched control group was increased in patients with ANCA-associated vasculitis and HSP (ANCA-associated vasculitis, relative risk 6.02, 95% confidence interval 3.72-9.74; HSP, relative risk 5.25, 95% confidence interval 2.4-11.5). The presence of ANCA was not predictive of malignancy. CONCLUSION: In conclusion, patients with ANCA-associated vasculitis have an increased risk of preceding or concurrent malignancy.

Adult↗

Malignant odontogenic tumors: a 22-year experience.

OBJECTIVES/HYPOTHESIS: Malignant odontogenic tumors are exceedingly rare and arise from odontogenic epithelial residues and odontogenic cysts in the jaw bones. Odontogenic malignancies have various origins. Some develop directly from the remnants of odontogenic epithelium left after completion of dental development; others may result from malignant transformation of a benign odontogenic cyst or ameloblastoma. These lesions are usually locally aggressive with radical surgery being the primary mode of treatment. Because of their rarity, much of the existing information about malignant odontogenic tumors with regard to their origin, clinicopathological features, biological behavior, and therapeutics is derived from case reports or small series. The study represents one of the largest series of malignant odontogenic tumors compiled in a single institution. STUDY DESIGN: Retrospective 22-year review from an Academic Medical Center. METHODS: Twenty cases of reported malignant odontogenic tumors were diagnosed in the authors' institution between 1981 and 2002. All pathological slides were reviewed to reconfirm diagnosis. Malignancy was confirmed based on the following criteria: histological findings of infiltrative growth, atypical cytological features, and focal necrosis or clear evidence of distant metastatic spread. Patient age, race, sex, treatment and outcome were recorded on chart review. RESULTS: Of the twenty reported cases, only nine were actually found to be malignant tumors on re-evaluation. These consisted of four cases of malignant ameloblastomas, two cases of ameloblastic carcinoma, one case of malignant Pindborg tumor (calcifying epithelial odontogenic tumor), one case of odontogenic ghost cell carcinoma, and one case of squamous cell carcinoma arising in an odontogenic keratocyst. The racial demographics were six Caucasian patients, one African American patient, and two Asian patients; seven men and two women represented the gender distribution. Tumors of six cases were located in the mandible, and of three cases, in the maxilla. All cases were treated with radical surgical excision. Two patients died of their disease, three patients were alive and free of disease, and four patients were lost to follow-up. CONCLUSION: Malignant odontogenic tumors are rare. They require a multidisciplinary team to determine proper treatment. Long-term surveillance is mandatory and is accomplished by routine physical examinations, along with serial radiographic imaging.

Adult↗

Prevalence and prediction of malignancy in cytologically indeterminate thyroid nodules.

OBJECTIVE: Controversy surrounds the evaluation of nodules with indeterminate cytology results. Malignancy rates in these nodules are not low. We examined the malignancy rates in nodules that showed follicular neoplasm or atypical cells on cytology and attempted to predict malignancy based on ultrasonographic features. DESIGN AND PATIENTS: We retrospectively analysed 5 years' cytopathology results of fine-needle aspiration biopsy (FNAB) specimens of indeterminate follicular thyroid lesions prior to thyroidectomy. The prevalence of malignancy on final histology was determined. The sonographic features of the thyroid nodules with respect to size, echogenicity, echo structure, border shape and presence of calcification were analysed. RESULTS: A total of 86 patients (15 men, 61 women; mean age 52.1 +/- 12.5 years) with indeterminate cytology underwent thyroidectomy and had histopathological diagnoses. The average nodule was 18.9 +/- 12.3 mm. The prevalence of malignancy in patients with atypical cell cytology was 51.7% (30 of 59), and the prevalence of malignancy in patients with follicular neoplasm cytology was 15% (4 of 27). Malignancy prevalence was higher in patients who had follicular neoplasm cytology with atypical cells than in those without atypical cells (2 of 7 and 2 of 20, respectively). We found no significant correlations between sonographic or clinical features and malignancy in this patient group. Sonographic features and nodule size are not useful predictors of malignancy. CONCLUSION: Until better molecular markers for malignancy are developed, surgical consultation remains necessary after examination of cytologically indeterminate FNAB specimens in patients with follicular thyroid lesions. But in follicular lesions without atypical cells the malignancy rate is low and reassessment later on could be an alternative approach.

Adult↗

Morphometry and digital AgNOR analysis in cytological imprints of benign, borderline and malignant serous ovarian tumours.

AIM: The aim of the study was to determine values of a quantitative morphometry analysis of nuclear characteristics and argyrophilic nucleolar organizer regions (AgNORs) in differential cytodiagnosis of benign, atypically proliferating (borderline) and malignant serous ovarian tumours. METHODS: Cytological imprints of benign (n = 20), borderline (n = 19) and malignant (n = 20) ovarian serous tumours were analysed. A computerized, digital analysis was used to determine morphometric nuclear features, the number and characteristics of single AgNORs, cluster AgNORs, total AgNOR and AgNOR area/nucleus (relative area) ratio. According to their size AgNORs were classified in three categories. A one-way variance analysis and post hoc test (Scheffé) were used for statistical analysis. RESULTS: The morphometric nuclear analysis showed that benign, borderline and malignant serous ovarian tumours are statistically different (P < 0.001) according to the area and outline, the values being highest in malignant tumours and lowest in the borderline group. Digital analysis of AgNORs in benign, borderline and malignant groups showed that the total AgNOR number increases with progression of the lesion (meaning tumour malignancy) significantly (P < 0.001) between benign and malignant as well as between borderline and malignant serous ovarian tumours (P < 0.001). The progression of the lesion malignancy was accompanied by a significant (P < 0.001) progressive increase of the total and relative AgNOR area per nucleus. The AgNOR size increases from benign to malignant tumours and a statistically significant difference (P < 0.001) was observed in all three groups regarding small and large AgNORs. CONCLUSION: Combining different markers of morphometric nuclear characteristics and AgNOR values could improve differential cytodiagnosis of benign, borderline and malignant serous ovarian tumours.

Cystadenocarcinoma, Serous↗

Evaluation of fibronectin as a marker of malignant ascites.

The aim of the study was to assess the accuracy of fibronectin, a glycoprotein, for the diagnosis of malignant ascites and to compare it with conventional parameters. Ascitic fluid samples from 50 patients, 25 with intra-abdominal malignancy and 25 without it were analysed for total protein concentration, fluid/serum protein ratio, glucose concentration, leucocyte count, pH, fibronectin concentration (by ELISA) and for malignant cell cytology. Twenty-two of the 25 patients with ascites and intra-abdominal malignancy had documented peritoneal metastases in group A. The 25 patients with non-malignant ascites constituted group B. Mean values of ascitic fluid fibronectin, for groups A and B were 538 +/- 46 micrograms/mL and 60 +/- 4.92 micrograms/mL, respectively (P less than 0.001). Within the group with malignant ascites, patients who had positive malignant cytology (n = 12) exhibited a significantly higher ascitic fluid fibronectin concentration than patients with negative cytology (P less than 0.05). While mean ascitic fluid protein concentration showed a significant difference (P less than 0.01) between the two groups, there was no difference in respect to ascitic fluid pH, glucose concentration and leucocyte count. Malignant cell cytology was positive in 54.5% of group A patients with no false positive report in group B. The diagnostic accuracy for differentiating malignant from non-malignant ascites was 100% for a fibronectin value of greater than or equal to 110 micrograms/mL as compared with 78.7% for ascitic fluid protein concentration greater than or equal to 0.5 g/dL, 57.4% for leucocyte count greater than or equal to 1000/mm3, 59.6% for pH less than 7.45 and 78.7% for malignant cell cytology.

Abdominal Neoplasms↗

Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumours.

BACKGROUND/AIM: Some endoscopic ultrasonographic (EUS) features have been reported to be suggestive of malignancy in gastrointestinal stromal cell tumours (SCTs). The aim of this study was to assess the predictive value of these features for malignancy. METHODS: A total of 56 histologically proven cases of SCT studied by EUS between 1989 and 1996 were reviewed. There were 42 gastric tumours, 12 oesophageal tumours, and two rectal tumours. The tumours were divided into two groups: (a) benign SCT, comprising benign leiomyoma (n = 34); (b) malignant or borderline SCT (n = 22), comprising leiomyosarcoma (n = 9), leiomyoblastoma (n = 9), and leiomyoma of uncertain malignant potential (n = 4). The main EUS features recorded were tumour size, ulceration, echo pattern, cystic spaces, extraluminal margins, and lymph nodes with a malignant pattern. The two groups were compared by univariate and multivariate analysis. RESULTS: Irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern were most predictive of malignant or borderline SCT. Pairwise combinations of the three features had a specificity and positive predictive value of 100% for malignant or borderline SCT, but a sensitivity of only 23%. The presence of at least one of these three criteria had 91% sensitivity, 88% specificity, and 83% predictive positive value. In multivariate analysis, cystic spaces and irregular margins were the only two features independently predictive of malignant potential. The features most predictive of benign SCTs were regular margins, tumour size < or = 30 mm, and a homogeneous echo pattern. When the three features were combined, histology confirmed a benign SCT in all cases. CONCLUSIONS: The combined presence of two out of three EUS features (irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern) had a positive predictive value of 100% for malignant or borderline gastrointestinal SCT. Tumours less than 30 mm in diameter with regular margins and a homogeneous echo pattern are usually benign.

Adult↗

Evaluation of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) in the detection of malignant peripheral nerve sheath tumours arising from within plexiform neurofibromas in neurofibromatosis 1.

OBJECTIVES: The ability of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) to detect malignant change in plexiform neurofibromas from patients with neurofibromatosis 1 (NF1) was evaluated. METHODS: Eighteen NF1 patients who presented with pain, increase in size, or neurological deficit associated with a plexiform neurofibroma were assessed. Magnetic resonance imaging determined the site and extent of the lesion. Qualitative(18)FDG PET was performed and the standard uptake value (SUV) measured the regional glucose metabolism. Histological confirmation of the diagnosis was obtained in 10 patients. RESULTS: Twenty three plexiform neurofibromas were detected in 18 patients. Seven malignant peripheral nerve sheath tumours, four high grade and three low grade tumours, occurred in five patients. In one patient the clinical and radiological characteristics of the tumour suggested malignancy, but histology was inconclusive. Fifteen benign plexiform neurofibromas were identified in 12 patients and these findings were confirmed histologically in five lesions from four patients. Ten plexiform neurofibromas occurring in eight patients were considered benign on(18)FDG PET and the patients did not undergo surgery. They remained stable or their symptoms improved on clinical follow up (median 9 months). The results of qualitative (18)FDG PET were interpreted as indicating that 13 plexiform neurofibromas were benign and 10 were malignant. No malignant tumours were classified as benign, but two benign tumours were reported as malignant. The SUV was calculated for 20 tumours and was significantly higher in five malignant tumours 5.4 (SD 2.4), than in 15 benign tumours 1.54 (SD 0.7), p=0.002. There was an overlap between benign and malignant tumours in the SUV range 2.7-3.3. CONCLUSIONS: (18)FDG PET is helpful in determining malignant change in plexiform neurofibromas in NF1. Increased separation between benign and malignant lesions could be obtained by calculating the SUV at about 200 minutes after injection of (18)FDG, when the peak activity concentration is obtained in malignant tumours.

Adolescent↗

Doppler sonography of adnexal masses: the predictive value of the pulsatility index in benign and malignant disease.

OBJECTIVE: The purpose of this study was to determine whether pulsed Doppler sonography can be used to distinguish between benign and malignant adnexal masses on the basis of pulsatility index. SUBJECTS AND METHODS: In an 18-month period, all patients in whom an adnexal mass was detected at sonography had further evaluation of the mass by color and pulsed Doppler sonography. Ninety-nine patients with 102 masses that were surgically removed were included in the study. The pulsatility indexes were calculated from the reproducible spectral waveforms generated from flow centrally or peripherally within or immediately adjacent to the mass. Each lesion was categorized on the basis of its gray scale morphologic features as typically benign or indeterminate/malignant in appearance. RESULTS: Of the 102 adnexal masses, 89 were benign and 13 were malignant. In seven of the 89 benign lesions, no flow could be detected, and these were excluded from analysis. Of the remaining 82 benign lesions, 65 showed pulsatility indexes consistently equal to or greater than 1.0, and 17 showed pulsatility indexes of less than 1.0. Ten of the 13 malignant lesions had pulsatility indexes consistently less than 1.0, and three primary malignant tumors had their lowest pulsatility indexes ranging between 1.1 and 1.8. Sixty-five of the 68 masses with pulsatility indexes equal to or greater than 1.0 were benign, for a positive predictive value of 96% for benign disease. Ten of the 27 masses with pulsatility indexes of less than 1.0 were malignant, for a positive predictive value of 37% for malignant disease. Forty-five masses were detected in perimenopausal and postmenopausal patients. In this group, the pulsatility index had a positive predictive value of 88% for benign disease and 47% for malignant disease. In this study, 45 of 49 masses that had a typically benign sonographic appearance had pulsatility indexes equal to or greater than 1.0. All 49 masses had benign histology. In the remaining 46 masses with an indeterminate/malignant sonographic appearance, 20 of 23 with pulsatility indexes equal to or greater than 1.0 were benign, and 10 of 23 with pulsatility indexes of less than 1.0 were malignant. CONCLUSION: Our results show a high positive predictive value of high-impedance flow in benign adnexal disease and a predominance of low-impedance flow in malignant adnexal disease. However, the pulsatility indexes showed considerable overlap between benign and malignant lesions, indicating that Doppler sonography has severe limitations in the differentiation of benign from malignant adnexal disease on the basis of low-impedance flow (pulsatility index < 1.0).

Adenofibroma↗

Portal vein thrombosis in patients with cirrhosis: does sonographic detection of intrathrombus flow allow differentiation of benign and malignant thrombus?

OBJECTIVE: The objective of our study was to determine if the detection by Doppler sonography of blood flow in portal vein thrombi occurring in patients with cirrhosis could be used to distinguish benign from malignant portal vein thrombi. SUBJECTS AND METHODS: Color and duplex Doppler sonographic examinations were performed in 47 patients with proven cirrhosis and portal vein thrombi. The examinations were directed at the detection of continuous or pulsatile flow within the portal vein thrombi. The nature of the portal vein thrombi was proven histologically in 27 patients and by CT findings and clinical history in 20 patients. The frequency, type, and direction of portal vein thrombus flow was evaluated to determine if there was any correlation with the benign or malignant nature of the portal vein thrombi. RESULTS: Of the 47 patients, 26 had malignant portal vein thrombi and 21 had benign portal vein thrombi. Blood flow was detected in 22 of the malignant and in 15 of the benign portal vein thrombi. The blood flow was pulsatile in 16 malignant and three benign portal vein thrombi and continuous in six malignant and 12 benign portal vein thrombi. The direction of the pulsatile flow in the malignant portal vein thrombi was predominantly (13/16) hepatofugal. All continuous flow in both benign and malignant portal vein thrombi was hepatopetal. The detection of pulsatile flow in portal vein thrombi yielded a 62% sensitivity and 95% specificity for the diagnosis of malignant portal vein thrombus. CONCLUSION: The detection by Doppler sonography of pulsatile flow in portal vein thrombi occurring in patients with cirrhosis is a moderately sensitive but highly specific sign for the diagnosis of malignant portal vein thrombus. However, continuous flow can be detected in benign and malignant portal vein thrombus and is thus not useful in differentiating between the two.

Adult↗