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Small cell carcinoma versus other lung malignancies: diagnosis by fine-needle aspiration cytology.

BACKGROUND: When a diagnosis of small cell carcinoma is reached in a patient with a lung mass, a surgical treatment approach is no longer considered and chemotherapy becomes the treatment of choice. The aim of this study is to compare the diagnostic accuracy of fine-needle aspiration cytology in the diagnosis of small cell carcinoma with the diagnoses of other lung malignancies. The capacity of this technique to distinguish between these two categories is assessed. METHODS: Two hundred fifty-nine consecutive transthoracic fine needle aspirations of lung tissue from 235 patients with histologic diagnosis of malignancy were reviewed. The aspirates were performed over a 10-year period at the University of Miami/Jackson Memorial Medical Center, Miami, Florida. Two hundred and forty-two fine-needle aspirations from 221 patients yielded satisfactory smears and were included in the study. Fourteen patients were excluded. The cytologic diagnoses were classified into 5 categories: 1) small cell carcinoma (18 smears, 7%); 2) other lung malignancies (158 smears, 65%); 3) suspicious for malignancy (19 smears, 8%); 4) inflammatory process (7 smears, 3%); and 5) negative for malignancy (40 smears, 17%). RESULTS: The histologic diagnoses were divided into two groups: small cell carcinomas (29 smears, 12%), and other lung malignancies (213 smears, 88%). The efficiency of fine-needle aspiration cytology in the diagnosis of these two groups was 96% versus 88%, respectively, with an equal specificity of 100%, and a sensitivity of 67% versus 81%. Once the diagnosis of malignancy was established, fine-needle aspiration cytology was found to be highly accurate in distinguishing small cell carcinoma from other neoplasms. CONCLUSION: We conclude that fine-needle aspiration cytology of the lung is an accurate diagnostic tool for the diagnosis of lung malignancies and is an excellent technique for distinguishing small cell carcinoma from other malignant neoplasms. It can be used with confidence to select treatment modalities and to avoid unnecessary surgeries in patients with lung malignancies.

Adult↗

Malignancies in HIV-infected children at Siriraj Hospital.

BACKGROUND: Some malignancies such as Kaposi's sarcoma, non-Hodgkin's lymphoma (NHL) are one of the acquired immunodeficiency syndrome (AIDS)-defining illnesses. With the improving survival of patients with AIDS due to better prevention and treatment of infectious complications, there may well be an increase in AIDS-related malignancies. OBJECTIVE: To study malignancies in human immunodeficiency virus (HIV)-infected children in view of demographic data, HIV disease status, characters of malignancies, and treatment outcome. METHOD: Retrospective study was performed in HIV-infected children with malignancies at Siriraj Hospital from January 1995 to October 2001. RESULTS: During the 6 year and 10 month period, there were 7 HIV-infected children (2 boys, 5 girls) with malignancies. Mean age at diagnosis of malignancies was 3 years 7 months (2 years 6 months-5 years). Hepatomegaly and lymphadenopathy were the most common presenting symptoms. All patients had NHL stage III or IV. Burkitt's lymphoma was the predominant type. Six patients were treated with appropriate chemotherapy and one patient also received antiretroviral therapy. Only one patient with large cell lymphoma stage IV who received both antiretroviral and chemotherapy has survived to date. Five patients died during chemotherapy treatment and one patient died before receiving chemotherapy. Causes of death of these patients were infections. One of them with Burkitt's lymphoma stage III also had central nervous system (CNS) relapse at the time of death. Mean survival time after diagnosis with malignancies was 11 months (15 days-3 years 1 month). CONCLUSION: NHL is the most common malignancy in HIV-infected children at Siriraj Hospital. Age at presentation of NHL in these children is younger than their non-HIV counterpart. Outcome of treatment is poor. Adjustment protocol for treatment of malignancy in HIV-infected children combined with antiretroviral therapy for controlling HIV infection should be studied further.

Age Distribution↗

[Malignant blue nevus: clinicopathologic study with AgNOR measurement. Seven cases].

BACKGROUND: Malignant blue nevus is a very rare tumor. Argyrophilic nucleolar organizer regions (AgNORs) have been reported to be both a diagnostic and prognostic clue in various tumors, especially if standardized using an image analysis systems. PATIENTS AND METHODS: Seven cases of malignant blue nevus were retrospectively recorded between 1974 and 1999, and their clinical and pathological features described. Using an image analysis system, AgNOR measurements were studied in all cases. These results were compared with those obtained in 10 cases of commun blue nevus, 10 cases of cellular blue nevus and 10 cases of malignant melanoma. RESULTS: The most frequent location of malignant blue nevus was the scalp. Clinically, the tumor generally consisted of a blue nodule, 2.5 cm in diameter. There was no single histopathological criterion for the diagnosis of malignant blue nevus. AgNOR measurement was significantly higher in malignant blue nevus in comparison with commun blue nevus (p<0.0004) or cellular blue nevus (p<0.012), whereas there was no difference between malignant blue naevus and malignant melanoma (p > 0.50). DISCUSSION: Our results confirm the severe prognosis of malignant blue nevus and highlight the necessity of removing all blue tumours located on the scalp. AgNOR measurement using an image analysis system appears to be a useful tool for the diagnosis of malignant blue nevus, but further studies remain necessary.

Adolescent↗

[Imaging of gastrointestinal stromal tumor (GIST): relation between CT findings and grade of malignancy].

PURPOSE: To report the relation between CT findings and the grade of malignancy in gastrointestinal stromal tumor (GIST), especially the uncommitted type of GIST. MATERIALS AND METHODS: A total of 14 patients with histologically proven GIST (uncommitted type) underwent CT. Tumors were divided into three grades. HISTOLOGICALLY: Benign (mitotic index [MI] < 2/10 high-power fields [HPF]), borderline (2/10 HPF < or = MI < or = 5/10 HPF), and malignant (5/10 HPF < MI). We evaluated tumor size, cystic component, margin, and early enhancement. RESULTS: All benign tumors were smaller than 5 cm, and most malignant tumors reached 5 cm. The size of borderline tumors was between the sizes of benign and malignant tumors. No benign tumors had cystic components, whereas all borderline and malignant tumors except for one case had cystic components. Only two huge malignant tumors had unclear margins. The relation between early enhancement and the grade of malignancy showed no tendency, but all duodenal tumors showed marked early enhancement irrespective of grade. CONCLUSION: The grade of malignancy of GIST (uncommitted type) and size, presence of cystic components, and margin were highly correlated. That is, 1) tumors smaller than 5 cm with no cystic components can be diagnosed as benign, whereas 2) tumors that have cystic components are borderline or malignant. 3) Tumors that have cystic components and unclear margin can be diagnosed as actively malignant.

Aged↗

[Evaluation of transvaginal ultrasonography-color Doppler energy imaging in surveillance of gynecologic malignant tumors after operation].

BACKGROUND & OBJECTIVE: Transvaginal ultrasonography (TVS) and color Doppler energy imaging (CDE) have been already applied in ultrasonography diagnosis extensively, but articles about the methods in surveillance of gynecologic malignant tumors after operation are few. The objective of this study was to evaluate TVS-CDE in surveillance of gynecologic malignant tumors after operation. METHODS: Fifty-four cases of gynecologic malignant tumors after operation, which were doubted as recurrent malignant tumors in clinic, were scanned with transabdominal ultrasonography (TAS), TVS, and TVS-CDE. The results were compared with that of pathology. Then their sensitivity, specificity,and accuracy were calculated, and the accuracy was compared by Chi-square test. RESULTS: Forty-three cases were diagnosed as malignant tumors by TAS; Forty-six cases were diagnosed as malignant tumors by TVS,and the positions, sizes, characteristics of the recurrent malignant tumors could be depicted visually. Forty-seven cases were diagnosed as malignant tumors by TVS-CDE; Not only the blood flow characteristics of masses,but also more diagnostic information than TVS were provided. The sensitivity was 81.3%, 91.7%, and 95.9%, respectively; the specificity was 33.3%,66.7%, and 83.3%, respectively; the accuracy was 75.9%, 88.9%, and 94.4%, respectively. Obviously, the accuracy of both TVS and TVS-CDE was higher than that of TAS(P< 0.05), but the accuracy of TVS and TVS-CDE was similar (P >0.05). CONCLUSION: TVS-CDE is helpful in the diagnosis of gynecologic malignant masses. It will be more effective in surveillance of recurrent gynecologic malignant tumors if it combined with CDE.

Adult↗

[Comparison of cytological and histological analysis of gastric mucosa biopsy in diagnosing malignant diseases].

The aim of this study was to determine the value of cytological analysis of an imprint of gastric mucosa biopsy compared to the histological evaluation, in diagnosing malignant diseases of gastric mucosa. In this study 70 patients, with changes of gastric mucosa endoscopically suspect of malignancy were included. Biopsy and imprint of gastric mucosa were performed in order to obtain morphological diagnosis. In the investigated group 46 patients (65.7%) were male, 24 patients (34.2%) were female, mean age 60 years (36-83). In 34 patients endoscopy finding suggested malignancy, in 23 endoscopy finding was described as gastric ulcer, in three as duodenal ulcer, in five as polyp, and in five as gastritis. In 42 patients malignancy was proved by pathohistological examination while in imprint smears of gastric mucosa biopsy the diagnosis of malignancy was made in 46 patients. In five patients malignant cells were found on cytological examination of imprint smears, and pathohistological examination did not find malignant tumour. In one patient malignant tumour was found on pathohistological examination, and cytological examination of an imprint smear did not find malignant cells. The results indicate that cytological examination of an imprint smear of gastric mucosa biopsy is satisfactory for proving malignant changes. In case of positive cytological and negative pathohistological analysis, it is recommended to repeat biopsy and imprint cytology in order to obtain morphological diagnosis.

Adult↗

[The value of FDG-PET/CT in the evaluation of patients with a pulmonary nodule and a previous malignant disease].

BACKGROUND: Patients with primary malignant disease undergoing oncological surveillance, upon completion of their treatment, are a unique population that is gradually growing. Therefore, the number of patients with a pulmonary nodule and a previous malignant disease has increased over recent years. In order to select appropriate management for these patients, a few questions should be answered: Is it a malignant lesion? Secondly, is it primary or metastatic? Is it the only one? In the past, several imaging and invasive diagnostic procedures were used to clarify theses uncertainties. However, in many cases the results were equivocal and it was difficult to establish treatment policy. In recent years PET/CT-FDG was found to be specific, sensitive and accurate in the evaluation and staging of patients with primary malignant disease. In this study we analyzed the accuracy and value of PET/CT-FDG in patients with primary malignant disease and an indeterminate pulmonary nodule. METHODS: Patients with primary malignant disease in the past and undefined pulmonary nodule/s were recruited. Computerized retrospective screening was performed. The specificity, sensitivity, positive and negative predictive value of PET/CT-FDG were calculated. The influence of the PET results on the clinical policy was evaluated. RESULTS: Forty one patients with previous malignant disease entered the study. PET/CT-FDG was positive in 15 cases. In 13 patients (87%) the FDG positive nodule was found to be malignant. In 26 patients the PET/CT was negative. In 19 (73%) diagnosis of non-malignant nodule was confirmed. The positive and negative predictive value of PET/CT-FDG for metastatic disease was 87% and 91% respectively and the accuracy 86%. CONCLUSIONS: The results of the present study demonstrate that PET/CT-FDG is a very valuable tool in the evaluation of patients with previous primary malignant disease and a pulmonary nodule. This imaging technique was able to clarify most of the thoracic surgeon's uncertainties and provided enough data to choose the optimal treatment strategy.

Fluorodeoxyglucose F18↗

Molecular mechanisms of malignant conversion in skin carcinogenesis.

The elucidation of the cellular and molecular events involved in progressive stages of malignant transformation has been enhanced by the development of new in vitro and in vivo model systems. In the model of chemically induced mouse skin tumors, multiple benign squamous papillomas precede the development of an occasional squamous cell carcinoma. The incidence of carcinomas can be substantially enhanced by treating papilloma-bearing mice with mutagens such as urethane, nitroquinoline-N-oxide, or cisplatinum suggesting that a distinct genetic event is responsible for malignant conversion. The malignant phenotype is characterized by a marked reduction in the transcription of specific epidermal differentiation markers, a pattern which is useful for the early diagnosis of malignant conversion. Cells expressing a benign phenotype can be obtained by introducing the v-ras oncogene into primary epidermal cells or by culturing cells from benign tumors induced by chemical carcinogens in vivo. Benign epidermal tumor cells in culture are good recipients for exogenous DNA and can be used to detect genes involved in malignant conversion. Transfection studies reveal that transforming constructs of the fos oncogene induce malignant conversion, whereas myc and adenovirus E1A oncogenes do not. Malignant tumors induced by fos transfection do not express differentiation-specific epidermal markers and secrete transin and urokinase, proteases characteristic of malignant skin tumors. Introduction of v-ras and v-fos oncogenes into cultured normal epidermal cells is sufficient to produce the malignant phenotype. Alone the v-fos oncogene does not detectably alter the normal phenotype of recipient cells. These studies imply that a limited number of genetic changes is sufficient to produce squamous malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Multiplicity of transforming growth factors in human malignant effusions.

Human malignant effusions were found to contain transforming growth factor (TGF) activity capable of stimulating anchorage independent growth of nontransformed rodent fibroblasts. Bio-Gel P-60 chromatography of acid-ethanol extracts demonstrated the presence of three populations of TGF activities in 57% of malignant effusions. Two activities were similar to those of TGF alpha and TGF beta as judged by their size (Mr approximately equal to 6,000 and approximately equal to 25,000, respectively), biological activity (ability to stimulate anchorage independent growth of NRK fibroblasts in the absence or presence of epidermal growth factor, respectively), and capacity to competitively inhibit binding of 125I-labeled epidermal growth factor to A-431 membranes and 125I-TGF beta to baby hamster kidney fibroblasts, respectively. In addition a third factor which stimulated anchorage independent growth of nontransformed rodent fibroblast and human colonic epithelial cells was also recovered following Bio-Gel P-60 chromatography of extracts from several cytology positive human malignant effusions of patients with colonic and breast carcinoma as well as other malignancies. The latter malignant effusion related transforming growth factor was not present in benign or cytology negative effusions. Malignant effusion related TGF factor was inactivated by sulfhydryl reducing agents, heat, and trypsin treatment but was stable in 1% acetic acid and ethanol. Partial purification was accomplished by chromatography of an acid-ethanol extract on Bio-Gel P-60 followed by high performance liquid chromatography with C18-mu Bondapak to yield a nearly pure protein with apparent molecular weights of 64,000 by sodium dodecyl sulfate-polacrylamide gel electrophoresis when run in nonreducing conditions and 32,000 when run in reducing conditions. Malignant effusion related TGF was able to stimulate anchorage independent growth of nontransformed fibroblasts in the absence of other growth factors. It did not competitively inhibit binding of 125I-labeled epidermal growth factor, 125I-TGF beta, or 125I-labeled platelet derived growth factor. Therefore, this factor isolated from human malignant effusions may be distinct from previously described transforming growth factors. Collectively these observations indicate that human malignant effusions contain a multiplicity of transforming growth factors. It is possible that the malignant effusion related transforming growth factors play a role or reflect the metastatic growth properties of various tumors.

Animals↗

The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions.

This study presents data on 3,011 pleural and peritoneal effusion specimens that were examined over a three-year period (1982 to 1984). Totals of 812 (44%) of 1,846 pleural and 423 (36%) of 1,165 peritoneal specimens were positive for malignant cells. While 535 patients had malignant pleural effusions, 254 patients had malignant peritoneal effusions, and 57 had both malignant pleural and peritoneal effusions. The most common primary neoplasms causing malignant pleural effusions were carcinomas of breast (24%) and lung (19%) and lymphoreticular neoplasms (16%). The most common primary neoplasms causing malignant peritoneal effusions were carcinomas of ovary (32%) and breast (13%) and lymphoreticular neoplasms (7%). There was an average interval of more than 30 months between the histologic diagnosis of the primary neoplasm and the diagnosis of malignant effusions in patients with carcinoma of breast, lymphoreticular neoplasm and malignant melanoma. The average time until death following the diagnosis of a malignant effusions was five months or less, except for patients with carcinoma of the breast and carcinoma of the ovary. One hundred twenty-five patients (15%) presented with malignant effusions caused by neoplasms of unknown primary sites. The most common primary neoplasms that were later diagnosed were, in decreasing order of frequency, carcinoma of the ovary, carcinoma of the lung and lymphoreticular neoplasms.

Adolescent↗

[Frequency of malignant non-Hodgkin's lymphomas in biopsy material. A retrospective study].

The biopsy material of the Institute of Pathology of the Medical Academy of Erfurt, GDR, from January 1967 to February 1978 has been reinvestigated for malignant non-Hodgkin's lymphomas which were reclassified according to the Kiel classification (Gérard-Marchant et al. 1974). We observed 122 (72.6%) low grade malignant lymphomas and 46 (27.4%) high grade malignant lymphomas. 17 cases remained unclassifiable. The median age ranged between 47.6 years (lymphoblastic malignant lymphoma) and 65.8 years (centrocytic malignant lymphoma). The sex ratio shows a predominance of males for all types of low grade malignant lymphomas. Only the immunoblastic malignant lymphoma in the group of high grade malignant lymphomas has a predominance in females. The survival of patients with high grade malignant lymphomas shows a good correspondence to the data given in the literature, whereas patients suffering from low grade malignant lymphomas have a distinctly worse prognosis in our material in comparison to literature data.

Adolescent↗

Small bowel tumors: an analysis of tumor-like lesions, benign and malignant neoplasms.

The clinical records of 72 patients with 73 small bowel tumors diagnosed over a period of 25 years were reviewed. The tumors consisted of 23 tumor-like lesions, 17 benign neoplasms and 33 malignant neoplasms, the mean size of which were 2.1 cm, 5.2 cm and 7.7 cm in diameter, respectively. The tumor-like lesions and benign neoplasms were found even in children, while the malignant neoplasms were observed in patients 43 years old or over. The most common tumor-like lesion was aberrant pancreatic tissue. The common benign neoplasms were leiomyoma, lipoma and adenoma. The malignant neoplasms consisted of adenocarcinoma, malignant lymphoma and leiomyosarcoma. Regardless of tumor type or tumor location, the lesions 4 cm or larger often caused abdominal symptoms. Most of the lesions less than 4 cm caused no symptoms, but the malignant lesions of this size in the ileum elicited abdominal symptoms in all patients. The presence of lesions was diagnosed preoperatively in 26.1% of patients with tumor-like lesions, 47.1% with benign neoplasms and 48.5% with malignant neoplasms. Resection was performed in all but one patient with tumor-like lesions and benign neoplasms. Among malignant lesions, the resectability rate was 80.0% for adenocarcinoma and 100% for both malignant lymphoma and leiomyosarcoma. However, the patients with malignant lesions showed a poor prognosis. In conclusion, it is important to recognize small bowel tumors--especially malignant lesions--as a rare but possible cause of abdominal symptoms and thereby to contribute to the early detection and successful management of small bowel tumors.

Adenocarcinoma↗

[Medical treatment of malignant hypercalcemia].

Hypercalcemia is one of the life-threatening paraneoplastic syndromes and urgent medical treatments are needed since malignant hypercalcemia progresses very rapidly. The intravenous administration of sufficient quantities of isotonic saline sometimes with loop diuretic agents is the first and fundamental step in the management of malignant hypercalcemia. As hormonal therapeutic agents for malignant hypercalcemia, calcitonin and/or glucocorticoid are the usual candidates. Calcitonin exerts calcium-lowering effects both through its direct inhibitory effect on osteoclastic bone resorption and prevention of calcium reabsorption from renal tubulus. Among the anticalcemic agents available, calcitonin has the most rapid onset of action; the hypocalcemic effects appear within a few hours after administration. But continued usage diminishes its effect which is called the "escape phenomenon". The usual dosage of calcitonin is 80-160 unit/day. Glucocorticoid alone has sometimes calcium-lowering effects for malignant hypercalcemia, even in the case of solid cancer such as lung cancer, though the mechanism is not clear. In lymphocytic proliferative disorders, a direct inhibitory effect on the proliferation of malignant cells accounts for the calcium-lowering effects. Glucocorticoid is known to prolong the calcium-lowering effect of calcitonin. So, the combination of calcitonin and glucocorticoid is the most effective hormonal treatment for malignant hypercalcemia. Calcitonin is used for initial several days and glucocorticoid (30-40 mg/day) is continued along with calcitonin from the beginning of the treatment. Most effective and safe hypocalcemic agents for malignant hypercalcemia are the newly developed bisphosphonate compounds, which are not yet available in Japan. These agents interact chemically with hydroxyapatite on the bone surface and prevent osteoclastic function and activity. According to the data of our own investigation, pamidronate, one of the relatively new generation of bisphosphonates, showed clearly hypocalemic effects for malignant hypercalcemia due to various kinds of malignancy by one intravenous administration (30-60 mg) without any adverse effect. In near future, the combination of calcitonin and bisphosphonates will also be the most effective medical management for malignant hypercalcemia in Japan.

Aged↗

Increased risk of malignancy in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus is a chronic, multisystem, autoimmune disorder that primarily affects women. Morbidity and mortality have improved for lupus patients during the last 15 years. An increased risk of malignancy in patients with lupus has been shown in some, but not all studies. The purpose of this study was to ascertain cancer risk in lupus patients by linking two disease registries. METHODS: Participants in the Chicago Lupus Cohort included 616 women with lupus who were residents of Cook County, Illinois. They were seen during 1985-1995 at 4 University, inner city, and suburban inpatient and outpatient clinics in Chicago. Malignancies occurring in these subjects during the study interval, 1985-1995, were identified from the Illinois State Cancer Registry by matching name, birthdate, and social security number. Standardized incidence ratios (SIRs) were estimated for all malignancies in this cohort of lupus patients using age, gender, and all race or race-stratified specific cancer incidence data from Cook County, Illinois. RESULTS: The registry linkage study with the Illinois State Cancer Registry documented that 30 women with lupus had a malignancy. The expected number of malignancies for women in the lupus cohort was 15.0. There were 8 cases of breast cancer and 4 each of lung and cervical cancer. In the remaining 14 women, 12 different types of cancers were noted. The SIR and 95% confidence interval (CI) for malignancy for all women with lupus in the study were 2.0 (1.4, 2.9) and lung cancer was the only individual cancer increased in all women--SIR and 95% CI were 3.1 (1.3, 7.9). In the analysis stratified by race, the risk of malignancy (SIR and 95% CI) was increased in Caucasian women, 2.3 (1.4, 3.9). Breast cancer was the only individual cancer increased in Caucasian women with lupus with an SIR and 95% CI of 2.9 (1.4, 6.4). CONCLUSIONS: Lupus patients have an increased risk of malignancy. Breast, lung, and gynecological malignancies were the most common malignancies observed in the cohort and breast cancer was significantly increased in Caucasian women.

Adult↗

Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex.

BACKGROUND: The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, skin, and kidney. Malignant tumors also can occur in patients with tuberous sclerosis, particularly in the kidney, although they occur less frequently than benign tumors. The types of malignancy that occur in TSC have not been characterized fully. METHODS: Clinical and pathologic features of 8 malignant tumors from 6 TSC patients ranging in age from 22 months to 21 years are reviewed. Six tumors were renal, one was from the inguinal region, and one was from the brain. The tumors were analyzed for loss of heterozygosity (LOH) in the chromosomal regions of the TSC1, TSC2, and VHL genes. RESULTS: Three patients (ages 7, 8, and 20 years) had renal cell carcinomas (RCCs). Two of these patients had multifocal RCCs. All three patients with RCC also had prominent multifocal dysplasia of renal cyst epithelium. Two patients (ages 20 and 21 years) had malignant angiomyolipomas (1 renal and 1 inguinal). One patient (age 22 months) had a Grade 4 giant cell astrocytoma (glioblastoma multiforme). LOH in the region of the TSC2 gene was found, either in the malignant tumor or in benign tumors, in all five patients whose DNA could be analyzed. CONCLUSIONS: Children with TSC, as well as adults with the disease, are at risk for developing malignant tumors. Two types of renal malignancy occur in TSC: RCC, which appears to arise from dysplastic renal cyst epithelial cells, and malignant angiomyolipoma. Tumors cytologically similar to malignant angiomyolipomas also may occur at extrarenal sites. LOH analyses suggest that the majority of patients with TSC who develop malignant tumors have germline TSC2, rather than TSC1, gene mutations.

Adult↗

Detection of hyperdiploid malignant cells in body cavity effusions by fluoresence in situ hybridization on ThinPrep slides.

BACKGROUND: Benign body cavity effusions sometimes cannot be distinguished from malignant ones by conventional cytology. The authors performed fluorescence in situ hybridization (FISH) on ThinPrep slides using chromosome specific probes to see if hyperdiploid malignant cells could be detected in 20 body cavity effusions. The results were then compared with those of conventional cytology. METHODS: A total of 20 body cavity effusions from 19 patients were studied using conventional cytology and FISH. Probes specific for chromosomes 3, 8, 10, and 12 were used to detect hyperdiploidy on ThinPrep slides (Cytyc Corporation, Boxborough, MA). RESULTS: A total of 13 patients had malignant conditions (either prior history of malignancy or the presence of malignancy anywhere in the body). Conventional cytology and FISH were both positive in 5 of these patients (6 samples) and negative in 2 patients. The results for one sample were inconclusive by both methods. There were 5 discrepant cytology-FISH results in patients with malignant conditions. One sample was positive by FISH and negative by cytology, one was positive by FISH and "atypical" by cytology, and three were inconclusive by FISH and negative by cytology. FISH results were either negative (in 4 samples) or inconclusive (in 2 samples) in the 6 patients with benign conditions. CONCLUSIONS: FISH can detect hyperdiploid malignant cells in body cavity effusions and is especially useful when the major cell population consists of malignant cells that cannot be differentiated from mesothelial or "atypical" cells. It is less useful in detecting a small population of malignant cells hidden in an inflammatory or reactive cell background. More studies are needed to establish diagnostic criteria further and to assess the clinical usefulness of this procedure.

Adult↗

Detection of cancer cells in effusions from patients diagnosed with gynaecological malignancies. Evaluation of five epithelial markers.

The detection of malignant cells in pleural, peritoneal, and pericardial fluids of cancer patients marks the presence of metastatic disease and is associated with a grave prognosis. We evaluated five epithelial markers for the detection of cancer cells in 94 fresh pleural, peritoneal and pericardial effusions. Eighty-four of the samples were regarded as adequate for analysis after evaluation of cytological smears, including 61 samples from patients known to have gynaecological neoplasms. The other 23 samples were from patients with various non-gynaecological malignancies or tumours of unknown origin. Our control cases were 10 fallopian tubes not affected by any malignancy and 12 malignant mesotheliomas. Cell blocks from all cases were stained for CA-125, BerEP4, carcinoembryonic antigen (CEA), BG8 (Lewis Y blood antigen), and B72.3 (TAG-72). Fifty-one of 84 cases were diagnosed as malignant or suggestive of malignancy in cytological smears and/or cell block sections. However, staining for epithelial markers highlighted the presence of malignant cells in 7 additional cases. When membrane staining was evaluated, the sensitivity of the markers studied in detecting malignant cells was as follows: CA-125: 88%, BerEP4: 78%, CEA: 26%, BG8: 86%, B72.3: 79%. Membrane positivity for CEA, B72.3 and BerEP4 was not detected in reactive mesothelial cells. However, membranous staining in mesothelial cells was evident in 13% and 31% of cases with the use of BG8 and CA-125, respectively. Weak cytoplasmic staining for CEA was observed in mesothelial cells in 2 cases. When Ber-EP4, B72.3, and BG8 staining results in cancer cells were combined, the following sensitivity levels were observed: BG8+B72.3: 91%; BG8+Ber-EP4: 90%; B72.3+Ber-EP4: 93%; BG8+Ber-EP4+B72.3: 95%. The detection of malignant cells in effusions is facilitated by the use of immunocytochemistry using a wide panel of antibodies. BerEP4 and B72.3 appear to be the best markers when both sensitivity and specificity are considered, followed by BG8, while CEA and CA-125 have a limited role in the detection of metastases from gynaecological tumours owing to the low sensitivity of the former and the low specificity of the latter. Analysis of all staining results should be based on a thorough morphological examination.

Adolescent↗

Soluble HLA class I molecules in malignant pleural and peritoneal effusions and its possible role on NK and LAK cytotoxicity.

PURPOSE: To examine the amount of sHLA-I in malignant pleural and peritoneal effusions and its possible role in natural immune defense. METHODS: Three groups of patients (75 patients with malignancy, 21 with infection, and 27 with other diseases) were studied for sHLA-I value using an ELISA method. Cytolytic activity of freshly isolated pleural and peritoneal effusion-associated lymphoid (EAL) cells from 14 of cases with malignancy were examined and compared to that of ten non-cancerous patients. EAL cells were co-cultured with the autologous cell-free effusions immediately after collection and 3 days after incubation with IL-2. RESULTS: The mean value of sHLA-I in effusions was 1.01+/-1.36 micro g/ml, 0.97+/-1.20 micro g/ml, and 0.49+/-0.45 micro g/ml, respectively. Despite higher mean sHLA-I levels in malignant and infected patients, no significant difference between these groups was observed ( P >0.05). Generally, the amount of sHLA-I in peritoneal effusions was higher than that for pleural effusions, but the difference was not significant. There were also no statistical differences in the sHLA-I levels between sub-groups of patients with malignancy. EAL cells' killing activity in malignant and infected effusions was 68.15+/-11.73 and 78.28+/-14.41, respectively ( P=0.08). No correlation between sHLA-I level and NK activity of EAL cells from the patients was found. Almost all malignant cases after exposure to cell-free effusions displayed an increase in NK activity (from 68.66+/-11.13 to 74.2+/-12.39, P=0.042) and a decrease in LAK activity (74.5+/-18.30 vs 67.72+/-16.46, P=0.040). Whereas, the same experiment performed for non-malignant effusions showed a decrease in both NK activity and LAK activity. Changes in NK and LAK activity were not correlated with the amount of sHLA-I in the effusions. CONCLUSION: The presence of sHLA-I, particularly in malignant effusions, suggests a role for these molecules in tumor immunity in the peritoneal or plural environment; however, at least with these group of patients, sHLA-I appears not to be a unique determining factor on EAL cells' killing activity.

Ascitic Fluid↗