Prognostic value of the trichorhinophalangeal syndrome-1 (TRPS-1), a GATA family transcription factor, in early-stage breast cancer.

BACKGROUND: TRPS-1 is a new GATA transcription factor that is differentially expressed in breast cancer (BC) where it been found recently to regulate epithelial-to-mesenchymal transition (EMT). PATIENTS AND METHODS: We carried out a quantitative immunohistochemistry (qIHC) analysis of TRPS-1 expression in 341 primary-stage I-III BC samples in relation to patient clinical characteristics as well as its prognostic value, especially in an estrogen receptor-positive (ER+) subgroup. RESULTS: Higher TRPS-1 expression was significantly associated with a number of clinical and pathological characteristics as well as with improved overall survival (OS) and disease-free survival (DFS). Among stage I/II ER+ BC patients who received endocrine therapy alone, those with high TRPS-1 expression had significantly longer OS and DFS. There was also a strong association between TRPS-1 levels and the EMT marker E-cadherin in the ER+ invasive ductal carcinoma cases. Analysis of gene expression data on a panel of BC lines found that TRPS-1 expression was low or absent in BC lines having enriched mesenchymal features. CONCLUSIONS: Our data indicated that TRPS-1 is an independent prognostic marker in early-stage BC and a new EMT marker that can distinguish patients with ER+ BC who will respond longer to adjuvant endocrine therapy.

Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death, reflecting the need for better understanding the oncogenesis, and developing new diagnostic and therapeutic targets for the malignancy. Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have malfunctioning roles in tumorigenesis. Our recent study demonstrated that small nucleolar RNA 42 (SNORA42) was overexpressed in lung tumors. Here, we investigate the role of SNORA42 in tumorigenesis of NSCLC. We simultaneously assess genomic dosages and expression levels of SNORA42 and its host gene, KIAA0907, in 10 NSCLC cell lines and a human bronchial epithelial cell line. We then determine in vitro functional significance of SNORA42 in lung cancer cell lines through gain- and loss-of-function analyses. We also inoculate cancer cells with SNORA42-siRNA into mice through either tail vein or subcutaneous injection. We finally evaluate expression level of SNORA42 on frozen surgically resected lung tumor tissues of 64 patients with stage I NSCLC by using quantitative reverse transcriptase PCR assay. Genomic amplification and associated high expression of SNORA42 rather than KIAA0907 are frequently observed in lung cancer cells, suggesting that SNORA42 overexpression is activated by its genomic amplification. SNORA42 knockdown in NSCLC cells inhibits in vitro and in vivo tumorigenicity, whereas enforced SNORA42 expression in bronchial epitheliums increases cell growth and colony formation. Such pleiotropy of SNORA42 suppression could be achieved at least partially through increased apoptosis of NSCLC cells in a p53-dependent manner. SNORA42 expression in lung tumor tissue specimens is inversely correlated with survival of NSCLC patients. Therefore, SNORA42 activation could have an oncogenic role in lung tumorigenesis and provide potential diagnostic and therapeutic targets for the malignancy.

Identification of putative oncogenes in lung adenocarcinoma by a comprehensive functional genomic approach.

Amplification and overexpression of putative oncogenes confer growth advantages for tumor development. We used a functional genomic approach that integrated simultaneous genomic and transcript microarray, proteomics, and tissue microarray analyses to directly identify putative oncogenes in lung adenocarcinoma. We first identified 183 genes with increases in both genomic copy number and transcript in six lung adenocarcinoma cell lines. Next, we used two-dimensional polyacrylamide gel electrophoresis and mass spectrometry to identify 42 proteins that were overexpressed in the cancer cells relative to normal cells. Comparing the 183 genes with the 42 proteins, we identified four genes - PRDX1, EEF1A2, CALR, and KCIP-1 - in which elevated protein expression correlated with both increased DNA copy number and increased transcript levels (all r > 0.84, two-sided P < 0.05). These findings were validated by Southern, Northern, and Western blotting. Specific inhibition of EEF1A2 and KCIP-1 expression with siRNA in the four cell lines tested suppressed proliferation and induced apoptosis. Parallel fluorescence in situ hybridization and immunohistochemical analyses of EEF1A2 and KCIP-1 in tissue microarrays from patients with lung adenocarcinoma showed that gene amplification was associated with high protein expression for both genes and that protein overexpression was related to tumor grade, disease stage, Ki-67 expression, and a shorter survival of patients. The amplification of EEF1A2 and KCIP-1 and the presence of overexpressed protein in tumor samples strongly suggest that these genes could be oncogenes and hence potential targets for diagnosis and therapy in lung adenocarcinoma.

Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.

PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.

DNA image analysis combined with routine cytology improves diagnostic sensitivity of common bile duct brushing.

BACKGROUND: Cytologic evaluation of common bile duct brushings has a low sensitivity for diagnosing malignancy because of scant cellularity, poor cellular preservation, or sampling errors occur. The aim of this study was to evaluate whether cytology combined with image analysis improves the diagnostic accuracy of bile duct brushing in comparison with cytology alone. METHODS: Forty-nine specimens of bile duct brushings obtained from 45 patients during endoscopic retrograde cholangiopancreatography were evaluated using cytology and image analysis. Specimens were classified as negative, atypical, suspicious, or malignant by using cytologic evaluation. DNA histograms were classified as diploid (D), broad diploid (BD), aneuploid (A), or tetraploid (T). Degree of hyperploidy (DH), representing cells with a DNA content > 5C was evaluated using a cutoff value of > or = 1%. Final diagnosis of cancer was based on tissue specimens that were obtained by fine-needle aspiration or surgical biopsy and clinical fol- low-up. RESULTS: Thirty-four patients ultimately proved to have a malignancy. Cytology revealed 19 negative cases, 15 atypical cases, 9 suspicious cases, and 6 malignant cases. Together, suspicious and malignant cytology cases yielded a sensitivity of 44% and a specificity of 100% for a cytologic diagnosis of cancer. The DNA histogram pattern was D in 24 cases, BD in 9 cases, and A in 16 cases. BD and A patterns were significantly associated with malignancy (P < 0.001). A DH > or = 1% was noted in 22 cases. DH alone had a sensitivity of 62% and a specificity of 91% and was significantly associated with malignancy (P < 0.004). Atypical cytology alone had a false-negative rate of 29%, but in combination with a DH > or = 1%, the false-negative rate decreased to 7%. Additionally, when the authors combined atypical, suspicious, and malignant cytology with a DH > or = 1%, the diagnostic sensitivity increased to 88%, but the specificity decreased to 73%. CONCLUSIONS: Combined cytology and image analysis of bile duct brushing increased diagnostic sensitivity compared with cytology alone. The findings suggest that image analysis may help select patients having atypical cytology who should undergo a more rigorous evaluation for malignancy. A larger prospective study of the usefulness of combined cytology and image analysis of bile duct brushing is warranted.

Primary effusion lymphoma in an HIV-negative patient with no serologic evidence of Kaposi's sarcoma virus.

Primary effusion lymphoma (PEL) is a newly described high-grade B cell lymphoma which develops in association with Kaposi's sarcoma-associated herpesvirus (KSV) in human immunodeficiency virus (HIV)-infected individuals. We hereby describe a very unusual presentation of PEL that developed in the abdominal cavity of an HIV negative, KSV negative patient with a 1-year history of refractory ascites due to alcohol-related liver cirrhosis. Possible factors aiding lymphomagenesis in the cirrhotic state are discussed.

Detection of chromosome 11q13 breakpoints by interphase fluorescence in situ hybridization. A useful ancillary method for the diagnosis of mantle cell lymphoma.

We assessed cytologic specimens from 11 mantle cell lymphomas (MCLs) and 32 other B-cell non-Hodgkin lymphomas (NHLs) for 11q13 breakpoints using a 2-color fluorescence in situ hybridization (FISH) assay that uses an 11q13 probe centered on the CCND1 gene and a centromeric chromosome 11 probe (CEP11). The number of nuclei in 200 cells were counted, and results were expressed as an 11q13/CEP11 ratio. All MCLs showed a high percentage of interphase nuclei with 3 or more 11q13 signals (mean, 74.8%; range 57%-90%). In contrast, in other B-cell NHLs the mean percentage of cells with 3 or more 11q13 signals was 9.2%. All MCLs had an elevated 11q13/CEP11 ratio (mean, 1.38). The mean ratio for other B-cell NHLs was 0.99. Two non-MCL cases, 1 large B-cell and 1 B-cell unclassified NHL, had high 11q13/CEP11 ratios of 1.15 and 1.30, respectively. Conventional cytogenetic analysis performed on the former case revealed a t(5;11)(q31;q13). Interphase FISH analysis using 11q13 and CEP11 probes is a convenient ancillary method for assisting in the diagnosis of MCL. This commercially available assay is simple to use on cytology or imprint specimens, and results can be obtained within 24 hours.

The detection of telomerase activity in patients with adenocarcinoma of the pancreas by fine needle aspiration.

Telomerase activation in differentiated cells is associated with cell immortalization. Detection of telomerase expression in cancer provides a potential biomarker to be evaluated in the diagnosis and prognosis of cancer patients. Analysis of telomerase activity in biopsy specimens may serve as a useful marker for the diagnosis of pancreatic adenocarcinoma. This study was conducted to determine if telomerase could be detected in fine needle aspirates from patients with pancreatic carcinoma. The telomeric repeat amplification protocol (TRAP) assay was used to determine telomerase activity from pancreatic cancer cell lines, paired tumor/normal human pancreatic tissues and specimens obtained at the time of diagnostic fine-needle aspiration (FNA) biopsies. In this report, we demonstrate that: i) telomerase activity is present in pathologically confirmed pancreatic cancer specimens, but absent in matched adjacent areas of normal pancreatic tissues; ii) telomerase activity is present in FNA samples obtained at the time of CT-guided FNA of pancreatic adenocarcinomas; and iii) this activity can be detected in material normally discarded during FNA slide preparation. Activation of telomerase can be identified in FNA specimens obtained at the time of routine cytologic diagnosis. These findings may be useful for further diagnostic or therapeutic investigations of telomerase activity in pancreatic carcinoma.

Numeric chromosomal abnormalities in small lymphocytic and transformed large cell lymphomas detected by fluorescence in situ hybridization of fine-needle aspiration biopsies.

BACKGROUND: Chromosomal abnormalities in some lymphomas are associated with a poor prognosis. Trisomy 12 and deletions of chromosome 13 have been described in small lymphocytic lymphoma (SLL). To determine whether chromosomal aberrations could be detected by fluorescence in situ hybridization (FISH) on fine-needle aspiration biopsies (FNABs), we analyzed and compared specimens from seven patients with SLL and nine patients with a history of SLL that had transformed to large cell lymphoma. METHODS: DNA probes specific to chromosome 12 and the chromosome 13/RB-1 gene locus were used for in situ hybridization on interphase cell nuclei. The cytologic features, ploidy, proliferation index, and conventional cytogenetic analysis findings were correlated with the FISH results. RESULTS: Trisomy 12 was detected in 2 (29%) of the 7 cases of SLL and 2 (22%) of the 9 cases of transformed large cell lymphoma. Deletion of chromosome 13/RB-1 was present in 3 (43%) of 7 cases of SLL and 3 (33%) of 9 cases of transformed large cell lymphoma. CONCLUSIONS: This study showed that interphase cytogenetic analysis by FISH is feasible on FNAB specimens. Trisomy 12 and deletions of chromosome 13/RB-1 were present in some cases of SLL and transformed large cell lymphoma, and the presence of these chromosomal abnormalities did not correlate with transformation to a higher grade of lymphoma.

Macrophagelike vacuolated renal tubular cells in the urine of a male with osmotic nephrosis associated with intravenous immunoglobulin therapy. A case report.

BACKGROUND: Osmotic nephrosis is a form of renal tubular injury that has been found in patients treated with intravenous immunoglobulin (IVIG). CASE: A 46-year-old male who had two courses of chemotherapy for acute myelogenous leukemia was found to have refractory thrombocytopenia. After IVIG (Sandoglobulin 12%, Novartis) administration (1 g/kg) for five consecutive days, the patient became oliguric and eventually anuric on the fifth dose. Hemodialysis was initiated, and urine production was noted on day 2 of hospitalization. Routine cytologic examination of fresh, voided urine showed numerous macrophagelike, bland epithelial cells with abundant, multivacuolated cytoplasm. Cytokeratin immunostain revealed positivity, thus confirming the epithelial origin of these cells. CONCLUSION: To our knowledge, this is the first such case reported in the English-language cytology literature. Awareness of a patient's clinical history may be helpful in avoiding an incorrect diagnosis. Urine cytology may be useful in obtaining an early diagnosis of osmotic nephrosis in patients receiving high-dose IVIG therapy that may eliminate the need for a renal biopsy.

Intraoperative evaluation of tissue perfusion in high-risk patients by invasive and noninvasive hemodynamic monitoring.

OBJECTIVE: Although invasive monitoring has not been effective in late stages after organ failure has occurred, early postoperative monitoring revealed differences in survivor and nonsurvivor patterns and provided goals for improving outcome. We searched for the earliest divergence of survivor and nonsurvivor circulatory changes as an approach to earlier preventive therapy. The aim was to describe the intraoperative time course of circulatory dysfunction in survivors and nonsurvivors among high-risk elective surgery patients using both the thermodilution pulmonary artery catheter (PAC) and multicomponent noninvasive monitoring. DESIGN: Prospective intraoperative description of circulatory dysfunction. SETTING: University-run county hospital. PATIENTS: Two hundred nine consecutively monitored high-risk elective surgery patients. MEASUREMENTS AND MAIN RESULTS: We evaluated the data of high-risk elective surgery patients using both PAC and multicomponent noninvasive monitoring. The latter consisted of the following: a) an improved bioimpedance method for estimating cardiac output; b) the standard pulse oximetry to screen for pulmonary problems; c) transcutaneous oxygen and carbon dioxide tension sensors to evaluate tissue perfusion; and d) routine noninvasive blood pressure and heart rate. The current noninvasive impedance cardiac output estimations closely approximated those of the thermodilution method; r2 = .74, p < .001; the precision and bias was -0.124 +/- 0.75 L/min/m2. Outcome measures included intraoperative description of circulatory patterns of high-risk surgical patients who survived compared with nonsurvivors. Hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous oxygen, high transcutaneous carbon dioxide tensions, low oxygen delivery, and low oxygen consumption developed intraoperatively gradually over time; the abnormalities were more pronounced in the nonsurvivors than in the survivors. CONCLUSIONS: The survivors had slightly higher mean arterial pressure, cardiac index, and mixed venous oxygen saturation, as well as significantly higher oxygen delivery, oxygen consumption, transcutaneous oxygen tension, and transcutaneous oxygen tension/FIO2 ratios, than did the nonsurvivors. The data suggest that blood flow, oxygen delivery, and tissue oxygenation of the nonsurvivors became inadequate toward the end of the operation. Noninvasive monitoring provides similar information to that of the PAC; both approaches revealed low-flow and poor tissue perfusion that were worse in the nonsurvivors. The continuous on-line real-time displays of hemodynamic trends facilitate early recognition of acute circulatory dysfunction.

Quantitative analysis of transforming growth factor beta 1 and 2 in ovarian carcinoma.

Transforming growth factor beta (TGF-beta) is an important family of cytokines that may promote tumor growth in vivo through several mechanisms including interference with antitumor T-cell immune responses, alteration of factors in the stroma and matrix, and the promotion of angiogenesis. TGF-beta isotypes have been detected in malignant and normal ovarian tissues. We have determined by quantitative immunohistochemistry the density of TGF-beta1, TGF-beta2, and human leukocyte antigen (HLA) Class I and Class II antigens on malignant cells in paired primary and metastatic specimens from 10 patients with ovarian carcinoma. Cryostat sections of specimens from the carcinomas and from normal ovaries of three women of similar age without ovarian cancer were stained respectively with specific antibodies to TGF-beta1, TGF-beta2, and HLA Class I and II antigens, and with isotype-matched control antibodies. Antigen density was quantitated blindly as mean absorbance on a SAMBA 4000 image analyzer. TGF-beta1 and TGF-beta2 were overexpressed in both primary and metastatic tumor specimens in comparison with normal ovarian tissue. No statistical correlation was found between the expression of TGF-beta1 or TGF-beta2 and HLA class I or HLA class II, which suggests that TGF-beta isotypes could have effects on the immune system other than down-modulation of these HLA molecules. Furthermore, the lack of association between levels of TGF-beta expression and the reduced expression of HLA molecules could suggest that tumor cells expressing both HLA and TGF-beta may be suitable targets for adaptive immunotherapy. Additional studies are necessary to determine whether TGF-beta expressed by ovarian cancer cells merits evaluation as a therapeutic target.

Image analysis of papillary thyroid carcinoma fine-needle aspirates: significant association between aneuploidy and death from disease.

BACKGROUND: Papillary thyroid carcinoma is the most common thyroid malignancy in the U.S. As many as half of patients with papillary carcinoma present with cervical lymph node metastases at the time of diagnosis. Metastatic disease involving cervical lymph node tissue has not historically been proven to correlate with a more aggressive course; however, distant metastases worsen prognosis. METHODS: Diagnostic fine-needle aspiration (FNA) smears from 26 primary and metastatic papillary carcinomas underwent Feulgen reaction and were studied by image analysis to determine DNA pattern, proliferation index, and the percentage of cells with DNA content >5C. The medical records of all the patients were reviewed for metastatic disease pattern and survival data. For metastatic pattern, two groups were defined: 1) confined to thyroid/local lymph node metastases/soft tissues of the neck involved by tumor, and 2) distant metastases. RESULTS: Among the 26 patients, 16 had "nonaggressive" DNA patterns described as diploid, abnormal diploid, or tetraploid, and 10 had "aggressive" DNA patterns described as aneuploid. Only 2 of the 16 patients in the "nonaggressive" DNA pattern group developed distant metastases, whereas 5 of the 10 patients in the aneuploid group developed distant metastatic disease. In addition, none of the 16 patients with "nonaggressive" DNA patterns died of disease, whereas 3 of the 10 individuals with DNA histograms interpreted as aneuploid did die of metastatic disease complications. CONCLUSIONS: Aneuploidy identified by image analysis of FNA of papillary thyroid carcinoma is significantly associated with death from papillary carcinoma (log rank test, P=0.027).

Urinary nuclear matrix protein 22 (NMP22): a diagnostic adjunct to urine cytologic examination for the detection of recurrent transitional-cell carcinoma of the bladder.

This study compares urine nuclear matrix protein 22 (NMP22) immunoassay and conventional urine cytologic examination for detecting recurrent transitional-cell carcinoma (TCC) of the urinary bladder. One hundred twenty-eight urine specimens from 107 patients with a history of TCC of the urinary bladder were studied. NMP22 immunoassay and conventional cytologic examination were performed on each specimen. The NMP22 and cytology results were then compared with the results of subsequent cystoscopies/surgical biopsies performed over a 6-mo follow-up period. The sensitivity of urine cytologic study for predicting recurrent TCC was 60%, while the sensitivity of NMP22 assay was 47%. When both NMP22 assay results and the cytologic interpretation were positive for TCC, the positive predictive value of the combined tests was 74%. When both tests showed negative results, the negative predictive power was 81%. Our findings suggest that urine NMP22 assay may represent a useful diagnostic adjunct to conventional urine cytologic examination for the detection of recurrent TCC of the urinary bladder.

Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members.

In a series of 111 patients with squamous cell carcinoma (SCC), we used immunohistochemistry to examine the expression levels of four epidermal growth factor receptor (EGFR) family members (EGFR, HER-2/neu, HER-3, and HER-4). Expression of the EGFR members was not significantly associated with tumor size. However, their expressions (except for HER-4) were significantly associated with the presence of lymph node metastasis, and all of them were significantly associated with distant metastasis. We further examined the association between the expression levels of the EGFR members and the survival rates in 47 oral SCC patients whose detailed clinical follow-ups were available. The expression of all EGFR members was significantly associated with shortened patient survival, and the association was strongest for HER-2/neu. Furthermore, the combination of HER-2, HER-3, and EGFR but not HER-4 significantly improved the predicting power. The expression level of HER-2/neu was significantly correlated with that of EGFR or HER-3. Similar coexpression patterns were also observed in three oral SCC cell lines studied, but not in four other head and neck SCC cell lines. Taken together, these results indicated that expression levels of EGFR, HER-2/ neu, and HER-3 may help predict the outcome of patients with oral SCC.

Relationship among cystectomy, microvessel density and prognosis in stage T1 transitional cell carcinoma of the bladder.

PURPOSE: The selection of therapy for stage T1 bladder cancer is controversial, and reliable biomarkers that identify patients likely to require cystectomy for local disease control have not been established. We evaluated our experience with T1 bladder cancer to determine whether early cystectomy improves prognosis, and whether microvessel density has prognostic value for T1 lesions and could be used for patient selection. MATERIALS AND METHODS: We retrospectively reviewed the records of 88 patients with T1 transitional cell carcinoma of the bladder. Patient outcome was correlated with therapeutic intervention. Paraffin embedded tissue from 54 patients was available for factor VIII immunohistochemical staining for microvessel density quantification. RESULTS: Median followup was 48 months (range 12 to 239). Of the patients 34% had no tumor recurrence. The rates of recurrence only and progression to higher stage disease were 41 and 25%, respectively. The survival of patients in whom disease progressed was diminished (p = 0.0002). Grade did not predict recurrence or progression nor did cystectomy provide a survival advantage. Microvessel density did not correlate with recurrence or progression. CONCLUSIONS: Patients with T1 bladder cancer have a high risk of recurrence and progression. Tumor progression has a significant negative impact on survival. Neither grade nor early tumor recurrence predicted disease progression. Because early cystectomy did not improve patient outcome, we suggest reserving cystectomy for patients with progression or disease refractory to local therapy. Microvessel density is not a prognostic marker for T1 bladder cancer and has no value in selecting patients with T1 disease for cystectomy.

Fine-needle aspiration of 154 parotid masses with histologic correlation: ten-year experience at the University of Texas M. D. Anderson Cancer Center.

BACKGROUND: Clinical and radiologic assessment of parotid masses cannot distinguish reliably between benign and malignant lesions. The utility of fine-needle aspiration (FNA) of parotid masses at a cancer referral center (where clinicians may be especially adept at diagnosing parotid gland malignancies) remains controversial. METHODS: Between January 1986 and June 1996, 482 parotid glands were resected at the University of Texas, M. D. Anderson Cancer Center (MDACC). A preoperative FNA result was available for 147 of these resections (30%), (corresponding to 154 preoperative FNAs). The results of 154 consecutive preoperative FNAs were compared with the corresponding histopathologic diagnoses. RESULTS: Histologic evaluation revealed 76 malignant tumors and 78 benign lesions (67 neoplastic and 11 nonneoplastic). The FNA smear was nondiagnostic in two benign and two malignant cases. The cytologic diagnosis was true-positive in 61 cases (82% sensitivity), and true-negative in 65 cases (86% specificity). There were 11 false-positive results. Eight of these cases were classified as false-positive because they were suspicious for malignancy; five of the eight were outside cases. In addition, there were 13 false-negative results (6 metastatic lesions, 3 low grade mucoepidermoid carcinomas, 2 acinic cell carcinomas, and 2 carcinoma ex pleomorphic adenomas) (9%). Fifty-one of the malignant lesions (84%) and 60 of the benign lesions (92%), including 93% of the benign tumors, were classified accurately. Ten of ten lymphoma cases in this series were identified correctly. CONCLUSIONS: FNA of parotid masses at a major referral cancer center has a sensitivity of 82%, a specificity of 86%, and an overall diagnostic accuracy of 84%. FNA plays an important role in the preoperative and postoperative assessment of parotid masses by aiding in the evaluation of tumors in poor surgical candidates and unresectable tumors, and by identifying metastases from other sites, reticuloendothelial tumors, and nonneoplastic inflammatory conditions.

Thymic neoplasia as represented by fine needle aspiration biopsy of anterior mediastinal masses. A practical approach to the differential diagnosis.

OBJECTIVE: To evaluate the cytomorphology of thymoma and to discuss the potential diagnostic pitfalls and a practical approach, which sometimes uses ancillary studies, in distinguishing various lesions of anterior mediastinal masses. STUDY DESIGN: A review of 25 fine needle aspiration (FNA) specimens of anterior mediastinal masses of thymic origin from 24 patients. RESULTS: The FNA diagnoses were thymoma in 16 aspirates, thymic/poorly differentiated carcinoma in 2, necrotic fluid/debris in 2, small lymphocytic proliferation in 2, hyperplastic thymic tissue in 1, benign cyst in 1, and scant tissue in 1. In 22 cases that had histologic confirmation, the diagnoses of 19 (86%), including 14 thymomas, concurred with the FNA diagnoses. Sampling error was responsible for the discrepancy in the remaining three cases. The cytologic evaluation of thymoma revealed a characteristic dual population of predominantly small lymphocytes and occasional large, atypical lymphocytes intimately admixed with relatively bland epithelial cells. Differential diagnoses of thymoma in the mediastinal aspirates included a variety of entities, depending on which component predominated. CONCLUSION: FNA of anterior mediastinal thymic lesions generally yields adequate cellular tissue with distinct cytologic and immunophenotypic features that enable precise classification. Caution in interpretation should be taken when the FNA yields only necrotic fluid or scanty material or when the patient is younger than the typical age range for thymoma. When the FNA diagnosis is coupled with clinical and radiographic findings, a definitive diagnosis can be generally rendered without open biopsy.