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PubMed2004

Cyst fluid analysis for the differential diagnosis of pancreatic cysts.

Pancreatic cystic neoplasms comprise a pathologically heterogeneous group with many shared clinical features. We assessed the reliability of cyst fluid analysis for the differential diagnosis of pancreatic cysts. Cyst fluid was obtained by fine-needle aspiration from 78 pancreatic cysts. The lesions studied consisted of 17 mucinous cystic tumors (MCTs), 13 serous cystadenomas (SCAs), 5 solid pseudopapillary tumors (SPTs), 8 intraductal papillary mucinous tumors (IPMTs), 6 ductal adenocarcinomas (ACAs) with cystic degeneration, and 29 pseudocysts (PCs). Epithelial cells were observed in 27 (81%) of 33 successful aspirates of cystic neoplasms. Cytologic diagnosis was possible in 5 (31%) out of 16 MCTs. Mucicarmine staining was positive in five out of nine MCTs, one out of one ACA, and one out of two IPMTs, but in none of the SCAs, SPTs, or PCs. Cyst fluid carcinoembryonic antigen (CEA) levels of more than 467 ng/mL had a 87% sensitivity and a 98% specificity for detecting MCTs, and amylase levels of more than 479 U/L had a 73% sensitivity and a 90% specificity for detecting PCs. In conclusion, cyst fluid analysis for cytology, mucin staining, CEA, and amylase levels are useful in the differential diagnosis of pancreatic cysts.

Amylases↗
PubMed1979

Characterization of the carcinoembryonic antigen activity associated with cyst fluids of mucinous ovarian cystadenocarcinoma.

Cyst fluids from mucinous cystadenocarcinoma of the ovary show significant concentrations of carcinoembryonic antigen (CEA) activity. This CEA activity was compared to several colon CEA standards with respect to size, concanavalin A binding, and immunological activity. CEA activity in unfractionated ovarian cyst fluid was indistinguishable from CEA standards by gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The cyst fluid CEA activity showed identity with various CEA standards by double immunodiffusion in agar gels and by radioimmune competition assay. Attempts to purify the cyst fluid CEA by perchloric acid extraction prior to gel filtration chromatography were unsuccessful. The yield of soluble CEA activity following perchloric acid extraction averaged 10%, and in one cyst fluid, qualitative changes were noted in the soluble antigenic activity. Ovarian cyst fluid CEA activity was bound by concanavalin A-Sepharose 4B and specifically eluted with competing monosaccharide. Lectin affinity chromatography and gel filtration chromatography over Sepharose 4B and Sephadex G-200 can be used to purify cyst fluid CEA from whole fluid or lyophilized and reconstituted samples.

Carcinoembryonic Antigen↗
PubMed1990

Cyst fluid proteases.

The precise origin of breast cyst fluid remains obscure. Molina has presented evidence that type II cysts (high Na/K ratio) may be transudative, that is, partly derived from plasma elements which enter through gap junctions, while Type I cysts (high K/Na ratio) are primarily secretory. In transudative cysts, plasma protease inhibitors may be present, but the balance between protease and its inhibitors may fluctuate as a result of as yet undetermined circumstances. An imbalance between the protease activity of cyst fluid and its inhibitors may be involved in the pathogenesis of breast gross cystic disease. Accumulation of protein fragments with resistant bonds would produce an elevated oncotic pressure causing a shift of fluid into the cyst capsule. Albumin is a good substrate for the protease, which may account for its low concentration in cyst fluid. The major protease fraction closely corresponds to the progesterone binding protein (GCDFP-24) described by Haagensen. Affinity columns containing aprotinin or benzamidine ligands retain the protease which can then be eluted with 0.5 M NaCl. The HD1 protease and progesterone binding protein are either tightly complexed or are the same protein. Cyst fluid is a complex mixture of biomolecules. If the progesterone binding protein is a protease, many questions must be answered concerning the influence of cyst fluid steroids, lipids, anions, and cations on enzyme action. Determination of the amino acid sequence of HD1 may help elucidate the source of the enzyme and its relationship to other tissue proteases. Human plasma contains inhibitors of this protease activity. When pooled, dialyzed plasma was mixed with pooled, dialyzed cyst fluid, the ratio of plasma/cyst fluid at which all activity was inhibited was 6/1. A comparison of the rate of cleavage of three 14C-protein substrates shows that cyst fluid proteases cleave in a characteristic manner, distinct from either trypsin or calpain. A simple method for semiquantitative estimation of protease activity in cyst fluid is described which utilizes prestained Coomassie blue-albumin containing agarose gel plates. All cyst fluids tested had protease activity but showed variability in their ability to cleave 14C-albumin by a factor of 4. There is much direct and indirect evidence that proteases are involved in the cancer process. In view of the higher than normal incidence of breast cancer in women who have had gross cystic breast disease, the possibility exists that an imbalance between these proteases and their inhibitors is somehow involved.

Exudates and Transudates↗
PubMed1993

Cyst fluid analysis in the differential diagnosis of pancreatic cysts. A comparison of pseudocysts, serous cystadenomas, mucinous cystic neoplasms, and mucinous cystadenocarcinoma.

Pancreatic cystic lesions include inflammatory pseudocysts, benign serous tumors, and mucinous neoplasms, some of which are malignant. Clinical and radiologic indices are often inadequate to discriminate reliably among these possibilities. In an attempt to develop new preoperative diagnostic criteria to assist in decisions regarding therapy, the authors have performed cyst fluid analysis for tumor markers (carcinoembryonic antigen: CEA, CA 125, and CA 19.9), amylase content, amylase isoenzymes, relative viscosity, and cytology on 26 pancreatic cysts. The cases included nine pseudocysts, five serous cystadenomas, 4 mucinous cystic neoplasms, 7 mucinous cystadenocarcinomas, and one mucinous ductal adenocarcinoma with cystic degeneration. Carcinoembryonic antigen levels were high (> 367) in all benign and malignant mucinous cysts, but were low (< 23) in the pseudocysts and benign serous cystadenomas, an indication that CEA discriminates between mucinous and nonmucinous cysts (p < 0.0001). Values for CA 125 were high in all malignant cysts, low in pseudocysts, and variable in mucinous cystic neoplasms and serous cystadenomas. Levels of Ca 19.9 were nondiscriminatory. Cyst fluid amylase and lipase content were variable but were generally high in pseudocysts and low in cystic tumors. Amylase isoenzyme analysis was useful to differentiate pseudocysts from cystic tumors. Measurement of the relative viscosity in cyst fluid showed high (> serum viscosity) values in 89% of mucinous tumors and low values (< serum) in all pseudocysts and serous cystadenomas (p < 0.01). Cytologic analysis of cyst fluids was of limited value in differentiating pseudocysts from serous cystadenoma, but in seven of eight mucinous tumors provided useful diagnostic information and correctly classified three of five malignant tumors. The authors conclude that cyst fluid analysis can provide a preoperative classification of these diagnostically difficult lesions. The combination of viscosity, CEA, CA 125, and cytology can reliably distinguish malignant cystic tumors and potentially premalignant mucinous cystic neoplasms from pseudocysts and serous cystadenomas. Amylase content with isoenzyme analysis is useful to identify pseudocysts.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1997

Increased concentration of vascular endothelial growth factor/vascular permeability factor in cyst fluid of enlarging and recurrent thyroid nodules.

Human thyrocytes produce vascular endothelial growth factor (VEGF), a potent angiogenic factor, also known as vascular permeability factor (VPF), which increases vascular permeability. Based on the assumption that VEGF/VPF is involved in fluid accumulation in thyroid cysts, we determined the VEGF/VPF concentration in cyst fluids of thyroid nodules from 79 patients. VEGF/VPF was found to be abundantly present in the cyst fluids (0.02-183 ng/mL). There was no significant difference of VEGF/VPF concentration in the cyst fluid obtained from thyroid adenoma or from adenomotous goiter with cystic degeneration. Immunoreactive VEGF/VPF in cyst fluid was eluted mainly at 45 kDa, and stimulated endothelial cell proliferation, which was partially blocked by anti-VEGF/VPF antibody. The VEGF/ VPF concentration in the cyst fluid obtained from patients who required repeated aspiration or underwent surgical resection because of recurrent accumulation (84.8 +/- 58.3 ng/mL, mean +/- SD, n = 18) was significantly higher than that in the cysts that regressed or disappeared after a single aspiration (4.3 +/- 4.4 ng/mL, n = 12, P < 0.001). These in vitro and clinical findings suggest that VEGF/VPF is at least partly involved in the accumulation of cyst fluid in thyroid nodules, and that a high VEGF/VPF concentration predicts rapid accumulation of the cyst fluid, possibly necessitating interventional treatment.

Adenoma↗
PubMed1992

Relationships between androgen and estrogen sulfates in breast cyst fluid.

In 28 breast cyst fluids obtained from 20 patients (age 29-65 years) sodium, potassium and the sulfates (S) of estrone (E1), estradiol (E2), dehydroepiandrosterone (DHEA) and androsterone (A) were determined. The radioimmunoassays (RIA) used were validated for this particular biological fluid. According to electrolyte ratio (Na+/K+) the cyst fluids were subdivided into two groups: the first with low (less than 3) (n = 16) and the other with high (greater than 3) (n = 12) values. Markedly higher steroid sulfate levels were observed in the first group, the mean levels being: 147.7 nmol/l, 54.6 nmol/l, 108.1 mumol/l and 158.0 mumol/l for E1S, E2S, DHEAS and AS respectively. The mean levels in the second group were: 13.6 nmol/l, 6.7 nmol/l, 68.8 mumol/l and 33.6 mumol/l for E1S, E2S, DHEAS and AS, respectively. In the first group only E1S and E2S levels were significantly correlated (r = 0.51; P less than 0.05). Conversely, the steroid sulfate levels were significantly correlated with each other in the group with high electrolyte ratio. These data have confirmed preceding results and have clearly shown that breast cyst fluids with low electrolyte ratio contain more E2S than the other group. This finding might be correlated with the fact that patients with these breast cysts lined by with apocrine epithelium may be at a greater risk of breast cancer than those with the other type.

Adult↗
PubMed1987

Trimethoprim-sulfamethoxazole in cyst fluid from autosomal dominant polycystic kidneys.

Cyst infection in patients with autosomal-dominant polycystic kidney disease (ADPKD) is often refractory to therapy, in part because of the limited entry of commonly used antibiotics into cyst fluid. To study the efficacy of trimethoprim-sulfamethoxazole in cyst infection, cyst fluid was obtained by percutaneous aspiration or at surgery from eight patients with ADPKD receiving trimethoprim-sulfamethoxazole. Cysts were categorized as nongradient or gradient by cyst-fluid sodium concentration. Trimethoprim-sulfamethoxazole concentrations within cysts were determined and cyst fluid inhibitory and bactericidal titers were assessed in vitro against Escherichia coli, Proteus mirabilis and Streptococcus fecalis. The mean cyst fluid trimethoprim and sulfamethoxazole concentrations were 15.2 micrograms/ml and 42.5 micrograms/ml, respectively. Preferential accumulation of trimethoprim was observed in gradient cysts, exceeding serum levels more than eightfold. Sulfamethoxazole penetrated cysts to a lesser extent, with concentrations ranging from 10 to 70 percent of the serum level. Cyst fluid sampled prior to trimethoprim-sulfamethoxazole administration (control) demonstrated no antibacterial activity, while cyst fluid inhibitory and bactericidal titers following antibiotic administration were 1:32 or greater in most instances. These studies indicate that trimethoprim-sulfamethoxazole is likely to be efficacious in the treatment of cyst infection in polycystic kidneys.

Adult↗
PubMed2000

Increased concentrations of nitrate and nitrite in the cyst fluid suggesting increased nitric oxide synthesis in solitary bone cysts.

The etiology and treatment of a solitary bone cyst have remained undefined. Surgical treatments have not been encouraging, because a less invasive corticosteroid-injection treatment has afforded good results. However, there has been little scientific rationale supporting corticosteroid treatment. In recent reports, bone-resorbing factors, including matrix metalloproteinases, prostaglandins, interleukin-1, and oxygen free radicals, have been demonstrated in the cyst fluid. To better elucidate the pathophysiology of the solitary bone cyst, we examined the activities of nitric oxide and cytokines in the cyst fluid as well as in the cyst membrane. The levels of nitrate and nitrite were significantly higher in the cyst fluid than in serum. Immunostaining of cells in the stroma and lining cells of the cyst wall was strongly positive for inducible nitric synthase. The levels of interleukin-6 and interleukin-1beta in the cyst fluid were elevated, and cells in the cyst membrane were positive for tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. Cultured cells from the cyst membrane were induced in the production of nitrate and nitrite in response to cytokine treatment. These findings suggest that the solitary bone cyst was in a state favorable for the production of nitric oxide.

Adolescent↗
PubMed1994

Oncostatin M, interleukin 2, interleukin 6 and interleukin 8 in breast cyst fluid.

Women with breast cysts lined by apocrine epithelium (intracystic Na/K < 3) may have a higher risk of developing breast cancer than those whose breast cysts are lined by "flattened" epithelium (intracystic Na/K < 3). In this study, the concentrations of the cytokines, oncostatin M (OSM), interleukin 2 (IL-2), interleukin 6 (IL-6) and interleukin 8 (IL-8) were measured in breast cyst fluid, OSM, IL-2 and IL-6 having been shown to have growth-inhibitory actions on tumour cells. All cytokines were measured by "sandwich" enzyme immunoassays. IL-2 was not detectable in breast cyst fluid. OSM, IL-6 and IL-8 concentrations were significantly higher in the high-electrolyte-ratio group. Although significant positive correlations were found between OSM and IL-6, OSM and IL-8, OSM and Na/K, IL-6 and IL-8, IL-6 and Na/K and IL-8 and Na/K when all samples were analysed together, analysis of the correlations between these analytes in each subgroup separately suggests that the control of production of these cytokines or the mechanism of entry into cyst fluid is likely to be different for the 2 cyst types. The significantly higher intracystic concentrations of OSM and IL-6 in the high-electrolyte-ratio group may partly explain the lower risk of breast cancer in this group of women.

Breast Neoplasms↗
PubMed1983

Neonatal ovarian cyst: prenatal diagnosis and analysis of the cyst fluid.

Ovarian cysts of clinical significance are uncommon in the fetus and neonate. The authors diagnosed a large fetal cyst prenatally by ultrasound scan and removed it in the neonatal period. Analysis of the fluid obtained from the cyst demonstrated a capacity of the fetal ovary to synthesize estrogen and progesterone.

Estradiol↗
PubMed1995

Immunodiagnosis of Taenia saginata in cattle using hydrophobic antigens from T. hydatigena metacestode cyst fluid.

Hydrophobic fractions isolated from cyst fluid of Taenia hydatigena metacestodes, obtained from naturally infected goats from Tanzania, were used in an indirect ELISA and in immunoblot (Western or dot blot) procedures. The use of the most hydrophobic fractions of the cyst fluid proved to result in a better diagnostic discrimination in ELISA than the more hydrophilic fractions. Best diagnostic ratio between responses from T. saginata infected and non-infected cattle was achieved when using horse-radish peroxidase-labelled sheep antibovine IgG1 as the conjugate. When the hydrophobic fractions of T. hydatigena cyst fluid were employed as antigen in ELISA, no cross-reaction took place with sera from cattle infected with Fasciola hepatica, Ostertagia ostertagi, Cooperia oncophora, Dictyocaulus viviparus, Sarcocystis cruzi or a mixture of D. viviparus, Trichostrongylus axei and Eimeria. Using the Western blot technique, specific low molecular weight components (M(r) 10-18 kDa) of the hydrophobic fractions of the cyst fluid were reactive with sera from 14 of the 21 calves infected with T. saginata for 60 days. Also, hydrophobic fractions of T. hydatigena cyst fluid were dotted onto strips of filter membranes and reacted specifically with sera from 21 calves infected with T. saginata. This technique resulted in the highest sensitivity, detecting 17 of the 21 calves infected with T. saginata. Calves harbouring as few as 16, 26, 43, 53 and 74 cysts could be detected. Thirteen calves harbouring between 74 and 2,545 cysts were all detected. However, 4 calves harbouring 2, 22, 52 and 66 cysts, respectively, were not detected. The potential of using a dot blot technique in large scale investigations in the tropics is present. However, before accepting any of the three tests in the tropical environment, a broader spectrum of helminth infections should be evaluated for their eventual cross-reactivity.

Animals↗
PubMed1999

Cyst fluid cytology and chemical features in a case of lymphoepithelial cyst of the pancreas: A rare and difficult preoperative diagnosis.

Most pancreatic cysts (90%) are inflammatory pseudocysts. Approximately 10% of pancreatic cysts are neoplasms, including serous cystadenomas, and mucinous tumors, some of which are malignant. Analysis of pancreatic cyst fluid obtained by percutaneous or endoscopic fine-needle aspiration is increasingly being used for the preoperative diagnosis of pancreatic or peripancreatic cysts. However, cyst fluid chemical and cytologic features in less common types of pancreatic cysts have not been reported. Lymphoepithelial cyst of the pancreas is exceedingly rare, and only occasional individual reports have described cyst fluid findings. We report on a case of lymphoepithelial cyst of the pancreas developing in a middle-aged man. Cyst fluid aspirated under radiological guidance showed elevated levels of carcinoembryonic antigen (CEA), CA19-9, CA 125, and amylase, and a viscosity greater than that of serum. A cell block preparation of a fine-needle aspiration showed tissue fragments with a keratinized squamous lining and a lymphocytic infiltrate in the wall, and abundant background keratinous debris. The cytologic and biochemical findings in this case exhibit similarities to the findings reported in other reports, and may represent a recognizable pattern on cyst fluid analysis.

Amylases↗
PubMed1977

Comparative antigenic characterisation of Echinococcus granulosus and Taenia hydatigena cyst fluids by immunoelectrophoresis.

Hydatid cyst fluid from Echinococcus granulosus (HCF) and cyst fluid from Taenia hydatigena (TCF) cysts were compared in reciprocal immunoelectrophoresis (IEP) tests using homologous and heterologous antisera which were free of antibodies to host serum contaminants. The antigens for the E granulosus arc 5 were demonstrated in TCF. Antibody activity to these and other antigens common to HCF and TCF was removed from homologous antisera by absorptions with the heterologous antigenic preparation. Antigens not shared by the two metacestodes fluids were then demonstrated by IEP tests. These findings are discussed in terms of their significance to phylogenetic and immunodiagnostic studies of these parasites in their immediate hosts.

Animals↗
PubMed1994

[Concentrations of B2-microglobulin and Tamm-Horsfall protein in cyst fluid and urinary excretion of these proteins in patients with simple renal cysts].

The existing classifications of simple renal cysts are based on cyst fluid sodium concentration or cyst fluid/plasma sodium ratio. The present study aimed to assess: 1) the usefulness of cyst fluid concentrations of beta-2-microglobulin (beta-2-MG) as a marker of proximal tubules function and Tamm-Horsfall protein (THP) as a marker of distal tubules function to define the origin of renal cysts (proximal or distal); and 2) the function of proximal and distal tubules in patients with simple renal cysts. 31 patients with simple renal cysts and 10 healthy subjects were examined. Basing on the cyst fluid/plasma sodium ratio, 25 cysts were classified as of proximal origin and 6 as of undetermined origin. In all patients cyst fluid and plasma concentrations of beta-2-MG, erythropoietin, sodium, potassium and total protein were assessed. Urinary excretion of beta-2-MG and THP was also estimated and fractional excretion of beta-2-MG was calculated. The concentration of beta-2-MG in fluid obtained from cysts of proximal origin were significantly higher than in fluid from cysts of undetermined origin (2.26 +/- 0.36 vs. 0.65 +/- 0.13 mg/l, p = 0.0004). Concentrations of THP (6.85 +/- 1.21 vs. 3.14 +/- 1.06 micrograms/ml, p < 0.05), erythropoietin (500.6 +/- 176.8 vs. 42.0 +/- 17.7 mU/ml, p < 0.05) and potassium (4.39 +/- 0.07 vs. 3.13 +/- 0.44 mmol/l, p < 0.05) were also higher in fluid from proximal cysts than in fluid from cysts of undetermined origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1995

Evaluation of cyst fluid analysis in the diagnosis of pancreatic cysts.

The pre-operative differential diagnosis of pancreatic cystic lesions is often difficult because of the lack of reliable clinical or radiological criteria. In order to improve the pre-operative recognition of these lesions, we performed cyst fluid analysis for enzymes (amylase and lipase), tumour markers (CEA, CA 19-9, CA 125, CA 72-4), and cytology in 52 pancreatic cysts. The cases included 21 pseudocysts, 12 mucinous cystic neoplasms, 7 ductal carcinomas, 7 benign lesions, and 5 rare malignancies observed from 1989 to 1994. Cyst fluid amylase, lipase, CEA, and CA 19-9 were variable and not discriminant between the groups. CA 125 fluid levels were high in 63% of malignant cysts. CA 72-4 fluid levels were significantly higher in mucinous cystic tumours than in pseudocysts (p < 0.0001), showing 95% specificity in detecting mucinous or malignant cysts. Cytology showed a sensitivity of 61% and a specificity of 100%. CA 72-4 determination raised the sensitivity of cytology to 92% in detecting mucinous or malignant cysts. This study confirms the low sensitivity of cytologic examination and low amylase specificity in distinguishing cystic neoplasms from pseudocysts. Cyst tumour markers assay is useful to improve the sensitivity of cytology, and CA 72-4 shows the best specificity in detecting (pre)malignant neoplasms.

Adenocarcinoma, Mucinous↗
PubMed1988

Apocrine cells in breast cyst fluid and their relationship to cyst type: a morphometric study.

The morphology of apocrine cells exfoliated in breast cyst fluid (BCF) was studied in 78 BCF samples obtained from 39 premenopausal patients with gross cystic disease who were bearing two simultaneously aspirated cysts. 57/78 samples showed cell clusters suitable for computer-assisted cytometry. This was performed on 5820 cells using a Leitz Texture Analysis System (TAS). We measured the surface areas of cytoplasm, nucleus and nucleolus; we also calculated the nuclear/cytoplasmic (N/C), nuclear/nucleolar (N/n) ratios and the nuclear roundness factor (RF). Cysts were divided according to the cationic pattern of BCF: Type I, K+/Na+ greater than 1.5; Type II, K+/Na+ less than 0.66. The cytometric analysis was made on 47 samples of Type I and 10 samples of Type II. At the light microscope, no difference was apparent between the apocrine cells coming from Type I or Type II cysts. Cytometric measurements showed significant differences for the apocrine cells aspirated from Type I vs. Type II cysts for the mean cytoplasmic area (97.13 +/- 24.28 S.D. mu2 vs. 59.66 +/- 14.90 S.D. mu2, respectively) and the mean nucleolar area (4.35 +/- 0.99 S.D. mu2 vs. 2.75 +/- 0.71 S.D. mu2, respectively). Our data do not allow the inference of apocrine changes in the epithelium lining the cysts simply from the cationic pattern of BCF. The significantly wider cytoplasm and nucleoli of the apocrine cells aspirated from Type I cysts could reflect different functional stages of these particular cells.

Adult↗