Primary Pancreatic Lymphoma Evaluated by Fine-Needle Aspiration.

OBJECTIVES: Primary pancreatic lymphoma (PPL) is rare, mimicking pancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. The aim of this study is to evaluate the clinical, radiologic, and pathological characteristics of PPL diagnosed by fine-needle aspiration (FNA) in our institution. METHODS: Patient clinical, radiologic, and pathological information was collected from the electronic health record system. RESULTS: In total, 11 of 4,353 pancreatic FNAs met the criteria. The most common clinical symptom was jaundice, followed by abdominal pain, weight loss, and diarrhea. Abnormal laboratory findings included elevated alkaline phosphatase, total bilirubin, lactate dehydrogenase, and cancer antigen 19-9. Abnormal radiologic findings included pancreatic mass, biliary dilatation, vessel encasement, and common bile duct encasement and thickening. Five patients underwent more than 1 tissue sampling procedure before the final diagnosis of lymphoma. Final pathologic diagnosis included 7 large B-cell lymphomas and 4 follicular lymphomas. Flow cytometric analysis was performed on 9 specimens, and all demonstrated an aberrant monoclonal B-cell population. CONCLUSIONS: PPL mimics PDAC clinically and radiologically and could be a challenge for pathologic diagnosis if lymphoma is not included in the differential diagnosis during immediate evaluation. If lymphoma is suspected during immediate evaluation, PPL could be reliably diagnosed by FNA with the aid of ancillary studies.

Endobronchial ultrasound-guided transbronchial needle aspiration biopsy is useful evaluating mediastinal lymphadenopathy in a cancer center.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy is used to stage mediastinal lymph nodes in cancer patients to optimize treatment strategies. In this retrospective study, the authors determined the utility of EBUS-TBNA biopsy in the evaluation of mediastinal lymphadenopathy at a high-volume cancer center. MATERIALS AND METHODS: The pathology database was searched for all patients who had undergone EBUS-TBNA biopsy of mediastinal lymph nodes over a one-year period. Cytologic diagnoses were correlated with clinical histories, subsequent resection, and clinical follow-up data. RESULTS: Of 928 lymph node samples, 226 (24%) were diagnosed as malignant, 4 (0.4%) were suspicious for malignancy, 9 (1%) were atypical, 640 (69%) were benign, and 47 (5%) were insufficient for evaluation. In 89 (9.6%) cases, the patients had surgical resection. There was one false positive, in which the primary tumor contained infiltrating lymphocytes, had been sampled. There were five false-negative cases, which resulted from sampling errors, including two with micrometastases. The sensitivity, specificity, and positive and negative predictive value rates for EBUS-TBNA biopsy in the evaluation of mediastinal lymph nodes were 68.7% and 98.6% and 91.6% and 93.5%, respectively on a per lymph node basis. The overall clinical sensitivity, specificity, and positive and negative predictive value rates after one year clinical/radiological and histologic follow-up were 97%, 99.3%, 96.7% and 99.4%, respectively. CONCLUSIONS: EBUS-TBNA biopsy is a sensitive and specific method for evaluating mediastinal lymphadenopathy in patients with lung and other primary tumors.

A Proposal for the Performance, Classification, and Reporting of Lymph Node Fine-Needle Aspiration Cytopathology: The Sydney System.

BACKGROUND: The evaluation of lymph nodes (LN) by fine-needle aspiration cytology (FNAC) is routinely used in many institutions but it is not uniformly accepted mainly because of the lack of guidelines and a cytopathological diagnostic classification. A committee of cytopathologists has developed a system of performance, classification, and reporting for LN-FNAC. METHODS: The committee members prepared a document that has circulated among them five times; the final text has been approved by all the participants. It is based on a review of the international literature and on the expertise of the members. The system integrates clinical and imaging data with cytopathological features and ancillary techniques. The project has received the endorsement and patronage of the International Academy of Cytology and the European Federation of the Cytology Societies. RESULTS: Clinical, imaging, and serological data of lymphadenopathies, indications for LN-FNAC, technical procedures, and ancillary techniques are evaluated with specific recommendations. The reporting system includes two diagnostic levels. The first should provide basic diagnostic information and includes five categories: inadequate/insufficient, benign, atypical lymphoid cells of undetermined/uncertain significance, suspicious, and malignant. For each category, specific recommendations are provided. The second diagnostic level, when achievable, should produce the identification of specific benign or malignant entities and additional information by utilizing ancillary testing. CONCLUSION: The authors believe that the introduction of this system for performing and reporting LN-FNAC may improve the quality of the procedure, the report, and the communication between cytopathologists and the clinicians. This system may lead to a greater acceptance and utilization of LN-FNAC and to a better interdisciplinary understanding of the results of this procedure.

Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer.

PURPOSE: The study aims to evaluate the efficacy and toxicity of fenretinide in preventing tumor recurrence in patients with transitional cell carcinoma (TCC) of the bladder. EXPERIMENTAL DESIGN: We conducted a multicenter phase III, randomized, placebo-controlled trial of fenretinide (200 mg/day orally for 12 months) in patients with non-muscle-invasive bladder TCC (stages Ta, Tis, or T1) after transurethral resection with or without adjuvant intravesical Bacillus Calmette-Guerin (BCG). Patients received cystoscopic evaluation and bladder cytology every 3 months during the 1-year on study drug and a final evaluation at 15 months. The primary endpoint was time to recurrence. RESULTS: A total of 149 patients were enrolled; 137 were evaluable for recurrence. The risk of recurrence was considered to be "low" in 72% (no prior BCG) and intermediate or high in 32% (prior BCG) of the evaluable patients. Of the lower-risk group, 68% had solitary tumors and 32% had multifocal, low-grade papillary (Ta, grade 1 or grade 2) tumors. The 1-year recurrence rates by Kaplan-Meier estimate were 32.3% (placebo) versus 31.5% (fenretinide; P = 0.88 log-rank test). Fenretinide was well tolerated and had no unexpected toxic effects; only elevated serum triglyceride levels were significantly more frequent on fenretinide (versus placebo). The Data Safety and Monitoring Board recommended study closure at 149 patients (before reaching the accrual goal of 160 patients) because an interim review of the data showed a low likelihood of detecting a difference between the two arms, even if the original accrual goal was met. CONCLUSIONS: Although well tolerated, fenretinide did not reduce the time-to-recurrence in patients with Ta, T1, or Tis TCC of the bladder.

Up-regulation of 14-3-3zeta in lung cancer and its implication as prognostic and therapeutic target.

A functional genomic approach integrating microarray and proteomic analyses done in our laboratory has identified 14-3-3zeta as a putative oncogene whose activation was common and driven by its genomic amplification in lung adenocarcinomas. 14-3-3zeta is believed to function in cell signaling, cycle control, and apoptotic death. Following our initial finding, here, we analyzed its expression in lung tumor tissues obtained from 205 patients with various histologic and stage non-small cell lung cancers (NSCLC) using immunohistochemistry and then explored the effects of specific suppression of the gene in vitro and in a xenograft model using small interfering RNA. The increased 14-3-3zeta expression was positively correlated with a more advanced pathologic stage and grade of NSCLCs (P = 0.001 and P = 0.006, respectively) and was associated with overall and cancer-specific survival rates of the patients (P = 0.022 and P = 0.018, respectively). Down-regulation of 14-3-3zeta in lung cancer cells led to a dose-dependent increased sensitivity to cisplatin-induced cell death, which was associated with the inhibition of cell proliferation and increased G2-M arrest and apoptosis. The result was further confirmed in the animal model, which showed that the A549 lung cancer cells with reduced 14-3-3zeta grew significantly slower than the wild-type A549 cells after cisplatin treatment (P = 0.008). Our results suggest that 14-3-3zeta is a potential target for developing a prognostic biomarker and therapeutics that can enhance the antitumor activity of cisplatin for NSCLC.

Cytologic Evaluation of Positron Emission Tomography-Computed Tomography-Positive Lymph Nodes Sampled by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: Experience at a Large Cancer Center.

CONTEXT.­: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is routinely used to evaluate mediastinal lymph nodes (LNs), especially for cancer staging. There are limited large studies evaluating the cytologic, radiologic, and clinical features of 18F-fluorodeoxy glucose positron emission tomography-computed tomography-positive (PET-CT+) LNs. OBJECTIVE.­: To compare cytologic, radiologic, and clinical features of PET-CT+, cytology-malignant (PET-CT+/Cyto+) and PET-CT+, cytology-benign (PET-CT+/Cyto-) LNs. DESIGN.­: The pathology database was searched for cases of mediastinal LNs obtained by EBUS-TBNA from January 1, 2015 to December 31, 2015. The cytologic, radiologic, and clinical features were collected for all PET-CT+ LNs. RESULTS.­: Of 2267 mediastinal LNs obtained by EBUS-TBNA during this period, 577 LNs met the criteria. Of the latter, 263 (46%) were PET-CT+/Cyto+ and 314 (54%) were PET-CT+/Cyto-. All of the patients with PET-CT+/Cyto+ results had a prior or concurrent diagnosis of malignancy as compared to 89% of patients with PET-CT+/Cyto- results. Of the 224 patients with PET-CT+/Cyto+ LNs, 177 (79%) had metastases from lung primary, 43 (19%) had metastases from nonlung primaries, and 7 (3%) had lymphoma. Average LN size was larger in the PET-CT+/Cyto+ group than in the PET-CT+/Cyto- group (14.6 mm versus 9.58 mm), and mean standardized uptake value in PET-CT+/Cyto+ LNs was higher than that of PET-CT+/Cyto- LNs (10.05 versus 5.99). Significant cytologic findings in PET-CT+/Cyto- cases were necrosis and granulomatous inflammation, including 3 cases with fungal organisms. CONCLUSIONS.­: PET-CT positivity alone was nonspecific for malignancy and insufficient to guide management of patients with mediastinal adenopathy, but specificity could be improved when combined with LN size and standardized uptake value.

Accuracy of diagnosing mantle cell lymphoma and identifying its variants on fine-needle aspiration biopsy.

BACKGROUND: Mantle cell lymphoma (MCL) is an incurable B-cell lymphoma portending an aggressive clinical course; the blastoid and pleomorphic morphological variants have an even worse prognosis. In addition, patients with classic morphology and a high proliferation index (HPI), also have reduced survival. Although variants have been defined, to the authors' knowledge the ability to detect these subtypes by fine-needle aspiration biopsy (FNAB) has not been described. METHODS: MCL cases diagnosed by lymph node FNAB with concurrent core needle biopsy were reviewed from 146 patients, accounting for 172 specimen pairs. FNAB and core needle biopsy diagnoses were compared to determine concordance rates. Flow cytometric immunophenotype and Ki-67 rates were evaluated. RESULTS: The classic subtype was diagnosed in 58% of cases (99 of 172 pairs) and variant morphology was diagnosed in 42% of cases (73 of 172 pairs) by histology. Twenty-nine patients presented with variant morphology whereas 28 underwent transformation. A nontraditional immunophenotype including loss of CD5 or FMC-7 and expression of CD23 and CD10 was found in 44% of variants (29 of 66 variants) and 19% of classic subtypes (18 of 94 classic subtypes) (P = .0008). Ki-67 rates averaged from 56% to 76% for blastoid and pleomorphic cases, 53% to 55% for MCL-HPI cases, and 17% to 19% for classic cases. The sensitivity and specificity to detect MCL variants by FNAB were 74% and 93%, respectively. CONCLUSIONS: The accuracy of diagnosing MCL is high when adequate samples for cytomorphology and flow cytometry are obtained. Subtyping variants by cytomorphology alone has challenges, but overall demonstrates high sensitivity and specificity. The performance of Ki-67 on cytology specimens is useful for detecting MCL with HPI.

Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer.

Detection of lung cancer by sputum cytology has low sensitivity but is noninvasive and, if improved, could be a powerful tool for early lung cancer detection. To evaluate whether the accuracy of diagnosing lung cancer by evaluating sputa for cytologic atypia and genetic abnormalities is greater than that of conventional cytology alone, automated scoring of genetic abnormalities for 3p22.1 and 10q22.3 (SP-A) by fluorescence in situ hybridization (FISH) and conventional cytology was done on sputa from 35 subjects with lung cancer, 25 high-risk smokers, and 6 healthy control subjects. Multivariate analysis was performed to select variables that most accurately predicted lung cancer. A model of probability for the presence of lung cancer was derived for each subject. Cells exfoliated from patients with lung cancer contained genetic aberrations and cytologic atypias at significantly higher levels than in those from control subjects. When combined with cytologic atypia, a model of risk for lung cancer was derived that had 74% sensitivity and 82% specificity to predict the presence of lung cancer, whereas conventional cytology achieved only 37% sensitivity and 87% specificity. For diagnosing lung cancer in sputum, a combination of molecular and cytologic variables was superior to using conventional cytology alone.

Gain of the 3q26 region in cervicovaginal liquid-based pap preparations is associated with squamous intraepithelial lesions and squamous cell carcinoma.

BACKGROUND: Chromosomal aberrations have been documented in cervical carcinomas, especially chromosome 3q. The human telomerase RNA gene (hTERC) is located in the chromosome 3q26 region, and its product, telomerase, is involved in the maintenance of chromosome length and stability. Upregulation of telomerase is in general associated with tumorigenesis. In this study, cervicovaginal specimens were analyzed by fluorescence in situ hybridization (FISH) for gain of chromosome 3q26 containing hTERC, and FISH findings were compared with the cytologic and histologic diagnoses. METHODS: Slides prepared from 66 liquid-based preparations from cervical specimens with cytologic diagnoses of negative for squamous intraepithelial lesion or malignancy (NILM, n=4), atypical squamous cells of undetermined significance (ASC-US, n=15), low-grade squamous intraepithelial lesion (LSIL, n=20), high-grade squamous intraepithelial lesion (HSIL, n=24), or cervical squamous cell carcinoma (SCCA, n=3) were analyzed for aberrations of 3q26 using a commercially available two-color FISH probe. The results of the cytologic analysis and those of concurrent or subsequent biopsies, when available, were compared with the FISH-detected 3q26 abnormalities. The Wilcoxon rank-sum test was used to assess associations between 3q26 gains and diagnoses. RESULTS: Gain of 3q26 was significantly associated with the cytologic diagnosis (p<0.0001). Patients with HSIL or SCCA cytology diagnoses had significantly higher percentages of cells with 3q26 gain than did patients with NILM or ASC-US cytologic diagnoses. CONCLUSIONS: FISH can be performed on cervicovaginal liquid-based preparations to detect gain of 3q26. Gain of 3q26 is associated with HSIL and SCCA. This test may be an adjunct to cytology screening, especially high-risk patients.

Cytologic features, immunocytochemical findings, and DNA ploidy in four rare cases of epithelioid hemangioendothelioma involving effusions.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) involving serous effusion is extremely rare, and the diagnosis can be challenging. DNA ploidy quantitation of EHE in effusion fluids has not been previously described in the English-language literature. METHODS: Specimens of cytological diagnosed with EHE in effusion fluids between 2002 and 2009 were retrieved from the pathology files at MD Anderson Cancer Center. A total of four cases of EHE involving or arising from effusion fluids were found, and we reviewed cytospin, smears, cell block sections, and immunostained slides. DNA image analysis for ploidy and proliferation evaluation was performed on a destained, papanicolaou-stained slide from each case. RESULTS: The tumor cells were epithelioid with prominent cytoplasmic vacuolization and intracytoplasmic inclusions, which could resemble reactive mesothelial cells, mesothelioma, or adenocarcinoma. The tumor cells were positive for endothelial markers. DNA image analysis in three of the four cases revealed predominantly diploid and tetraploid subpopulations, with few aneuploid cells and fairly low proliferation indices, and these patients had fairly prolonged survival. CONCLUSIONS: DNA image analysis is useful for differentiating EHE from reactive mesothelial cells and high-grade carcinoma. For accurate diagnosis of EHE in effusion fluids, cytologic features should be considered together with clinical history and ancillary studies.

Efficacy of telecytopathology for preliminary assessment of fine-needle aspirations performed at a remote facility.

INTRODUCTION: The need for real time anatomic pathology services has grown as healthcare systems, traditionally found at large medical centers, expand into smaller communities. The placement of a pathologist is not cost-, time-, or resource-efficient. Telecytopathology can provide rapid offsite evaluation of cytology tissues. This study evaluated the accuracy rate of rendered preliminary assessments for telecytopathology of ultrasound (US)-guided fine-needle aspirations (FNAs) for an offsite facility by comparing preliminary assessment results with the final diagnosis. MATERIALS AND METHODS: The pathology database was searched for telecytopathology US-guided FNAs with rapid offsite evaluation performed at a regional care center from August 2014 to June 2016. A total of 674 consecutive US-guided FNAs from 444 patients were obtained. FNA sites included lymph node (345 cases), breast (178 cases), thyroid gland (71 cases), and others (80 cases). RESULTS: Preliminary assessments of the 674 FNAs were adequate/benign in 275 (41%) cases, adequate/malignant in 182 (27%) cases, adequate/further review needed in 162 (24%) cases, indeterminate/borderline cellularity in 37 (5%) cases, and nondiagnostic in 18 (3%) cases. Final FNA diagnoses rendered included 391 (58%) negative for malignancy, 205 (30%) malignant, 34 (5%) atypical/suspicious for malignancy, 26 (4%) indeterminate cellularity-favor benign, and 18 (3%) nondiagnostic specimens. Concurrent core biopsy was performed in 42 cases and 83 cases were triaged for ancillary studies. The majority (99%) of US-guided FNAs demonstrated concordant preliminary assessments with the final diagnoses. A major discrepancy occurred in 1 case; 5 cases had minor discrepancies. CONCLUSIONS: Remote facility telecytopathology can be utilized as an accurate modality in guiding appropriate tissue acquisition and final diagnosis.

Fine-needle aspiration biopsy findings in patients with small lymphocytic lymphoma transformed to hodgkin lymphoma.

Although small lymphocytic lymphoma (SLL) is an indolent lymphoma, approximately 5% of cases can transform to a higher-grade lymphoma, rarely Hodgkin lymphoma (HL). We report the fine-needle aspiration (FNA) results of 6 cases of SLL/chronic lymphocytic leukemia (CLL) that transformed to HL. FNA findings were correlated with the histologic features and clinical follow-up. The patients included 5 men and 1 woman, ranging in age from 49 to 72 years at the time of SLL/CLL diagnosis with time for development of HL ranging from 0 to 95 months (mean, 49.3 months). The FNA diagnoses were SLL with HL transformation (2 cases), SLL with large atypical cells (1 case), and atypical lymphoid proliferation with large atypical cells (3 cases). Flow cytometry performed in 5 cases (2 FNA specimens) demonstrated a monoclonal B-cell population with CD19/CD5 coexpression. The presence of large atypical mononucleated and binucleated cells in lymph node FNA specimens from patients with SLL/CLL with progressive adenopathy should raise the possibility of transformation to HL. In these cases, histologic confirmation is always recommended, not only to differentiate HL transformation from other entities but also for subclassification of HL.

Sensitivity of fine-needle aspiration biopsy for diagnosing and grading follicular lymphomas using a multiparameter approach in a cancer center.

OBJECTIVES: The diagnosis and grading of follicular lymphomas (FLs) by fine-needle aspiration biopsy (FNAB) has not been systematically compared with core needle biopsy (CNB). We evaluated the sensitivity of FNAB in diagnosing and grading FLs using a multiparameter approach in a large cancer center. METHODS: We retrospectively identified CNBs of lymph nodes diagnosed as FL that also had a concurrently acquired FNAB on the same site. The majority of cases had flow cytometric analysis and these results were available for interpretation of both the FNAB and CNB. RESULTS: Out of 342 patients, CNB diagnoses included 291 (85%) low-grade (LG) FLs, 30 (9%) high-grade (HG) FLs, and 21 (6%) non-graded FLs/other. FNAB diagnoses included 194 (57%) LG FLs, 19 (6%) HG FLs, 93 (27%) non-graded FLs, 9 (3%) large B-cell lymphomas (LBCL) of follicle center origin, and 27 (7%) insufficient for diagnosis/other. Review of non-graded FLs showed 45% LG, 35% indeterminate due to polymorphous lymphoid cells with increased numbers of large cells, and 20% scant cellularity. Sensitivity of FNAB for diagnosing FL was 89%, and 66% for LG FL. The latter increased (94%), however, when grading was performed. CONCLUSION: FNAB is highly sensitive for diagnosing FLs when cellular material for cytomorphology and flow cytometric analysis is obtained, and grading is feasible for most LG FLs. A subset of FLs composed of a polymorphous lymphoid population with increased numbers of large cells may be more difficult to grade, and HG FLs can be difficult to distinguish from CD10-positive diffuse LBCLs.

Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior.

The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA's effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type.

RNA silencing of S-phase kinase-interacting protein 2 inhibits proliferation and centrosome amplification in lung cancer cells.

The S-phase kinase-associated protein-2 (SKP2) plays a key role in ubiquitin-mediated proteolysis, which results in the progression of cells from a quiescence to proliferative state. SKP2 is overexpressed in a variety of tumors. In this study, we used small interfering RNAs (siRNAs) to inhibit the SKP2 expression in lung cancer cells and thereby investigate the role of SKP2 in lung tumorigenesis. Three lung cancer cell lines were transfected with siRNAs targeted against SKP2. SKP2-siRNAs specifically and efficiently reduced the levels of the SKP2 protein by 90% 48 h after transfection in all cell lines. In the A549 and H1792 cells, p27 expression was increased and the increase was inversely proportional to the level of SKP2; cell proliferation was reduced to 12 and 28%, respectively; apoptosis was increased to 36 and 30%, respectively; 36 and 28% of cells accumulated in the sub-G1 phase, respectively; and the population of cells in the G1 phase was decreased to 37 and 41%, respectively. In addition, the SKP2-depleted A549 and H1792 cells showed decreased levels of cyclin E/CDK2. Correspondingly, only 4 and 6% of the treated A549 and H1792 cells had multiple centrosomes, respectively, compared with 43 and 46% of the control cells, respectively. These results imply that SKP2 plays an oncogenic role in lung cancer and that SKP2 silencing may be useful in the treatment of lung cancer.

Surfactant protein A gene deletion and prognostics for patients with stage I non-small cell lung cancer.

PURPOSE: The present study was conducted to determine clinical relevance of surfactant protein A (SP-A) genetic aberrations in early-stage non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: To determine whether SP-A aberrations are lung cancer-specific and indicate smoking-related damage, tricolor fluorescence in situ hybridization with SP-A and PTEN probes was done on touch imprints from the lung tumors obtained prospectively from 28 patients with primary NSCLC. To further define the clinical relevance of SP-A aberrations, fluorescence in situ hybridization was done on both tumor cells and adjacent bronchial tissue cells from paraffin-embedded tissue blocks from 130 patients NSCLC for whom we had follow-up information. RESULTS: SP-A was deleted from 89% of cancer tissues and the deletion was related to the smoking status of patients (P < 0.001). PTEN was deleted from 16% in the cancer tissues and the deletion was not related to the smoking status of patients (P > 0.05). In the cells isolated from paraffin-embedded tissue blocks, SP-A was deleted from 87% of the carcinoma tissues and 32% of the adjacent normal-appearing bronchial tissues. SP-A deletions in tumors and adjacent normal-appearing bronchial tissues were associated with increases in the risk of disease relapse (P = 0.0035 and P < 0.001, respectively). SP-A deletions in the bronchial epithelium were the strongest prognostic indicators of disease-specific survival (P = 0.025). CONCLUSIONS: Deletions of the SP-A gene are specific genomic aberrations in bronchial epithelial cells adjacent to and within NSCLC, and are associated with tumor progression and a history of smoking. SP-A deletions might be a useful biomarker to identify poor prognoses in patients with NSCLC who might therefore benefit from adjuvant treatment.

Fine needle aspiration cytology of a low grade myxoid renal epithelial neoplasm: a case report.

BACKGROUND: Recently, several case reports have described a rare but distinct subtype of renal tumor, referred to as a "low grade renal epithelial neoplasm," that appears to have a better prognosis than conventional renal cell carcinoma does. This report describes the cytologic features of this tumor as determined by fine needle aspiration (FNA) biopsy. CASE: A 53-year-old woman with a history of lymphoma had a renal mass incidentally discovered on an abdominal computed tomographic scan performed for lymphoma restaging. Results of an FNA biopsy showed relatively uniform, medium-sized tumor cells with moderate amounts of finely vacuolated or wispy cytoplasm and indistinct cell borders. The nuclei were primarily round with coarse chromatin and had prominent nucleoli. In the cell block preparation, the tumor cells showed a tubular architecture and an abundant myxoid matrix. The patient underwent a partial nephrectomy. The tumor was classified as a low grade myxoid renal epithelial tumor. CONCLUSION: This unusual kidney tumor appears to have distinctive cytomorphologic features, including a uniform population of epithelial cells with round nuclei, an abundant myxoid matrix and tubular architecture.

Use of mailed urine specimens in diagnosing urothelial carcinoma by cytology and DNA image analysis.

OBJECTIVE: To evaluate the usefulness of urine specimens collected via a mailer system and analyzed by cytology and DNA ploidy for the detection of urothelial carcinoma (UC). STUDY DESIGN: We retrospectively reviewed the diagnoses of 91 mailed urine specimens received from 72 patients, 67% of whom had a history of UC. The specimens were fixed in an equal volume of 50% ethanol solution before being mailed. The cytologic findings were interpreted in conjunction with DNA ploidy image analysis. We compared these initial diagnoses with those of follow-up examinations, including biopsies, cystoscopic findings and urinary cytology/DNA ploidy analyses. In addition, to examine the quality of the mailed samples, 3 cytopathologists performed a blinded assessment of cytologic slides of 20 mailed and 17 fresh urinary samples for bacterial overgrowth, urothelial degeneration, and presence of proteinaceous material and crystals. RESULTS: Follow-up was available for 68 of the 91 mailed specimens. The sensitivity for detecting UC using mailed urine specimens that were analyzed by both cytology and DNA ploidy was 61%, while specificity was 92%. The levels of bacterial overgrowth and urothelial degeneration in the mailed specimens were not significantly greater than in the fresh specimens (p>0.05). The levels of proteinaceous material and crystals were significantly higher in the mailed specimens (p<0.05). CONCLUSION: The results of combined cytology and DNA ploidy image analysis by using mailed urine samples were comparable to those of fresh urine specimens for the detection of UC reported in previous publications. The increase in crystals and proteinaceous material did not impede diagnostic interpretation. The mailing system is a reliable and convenient method of monitoring and triaging patients with UC or related symptoms.

Multiple pancreatic metastases from malignant melanoma: Conclusive diagnosis with endoscopic ultrasound-guided fine needle aspiration.

Pancreatic metastases are rare, ranging from 2% to 5% of pancreatic malignancies. Differentiating a primary pancreatic malignancy from a metastasis can be difficult due to similarities on imaging findings, but is crucial to ensure proper treatment. Although transabdominal ultrasound, computed tomography, and magnetic resonance imaging provide useful images, endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is often needed to provide a cytologic diagnosis. Here, we present a unique case of malignant melanoma with pancreatic metastases. It is important for clinicians to recognize the possibility of melanoma metastasizing to the pancreas and the role of EUS with FNA in providing cytological confirmation.

Pulmonary artery intimal sarcoma diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration.

Intimal sarcoma of the pulmonary artery is a rare intraluminal malignant neoplasm that has an aggressive biological behavior, and early diagnosis may improve patient outcome. We describe a case of pulmonary artery intimal sarcoma diagnosed on cytologic material obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy with rapid on-site evaluation (ROSE). The aspirate showed loosely cohesive clusters of pleomorphic malignant spindled and epithelioid cells. An immunostain panel did not demonstrate any definitive mesenchymal or epithelial differentiation. The tumor's intraluminal origin was supported by radiographic imaging studies. Subsequently, the patient received preoperative chemotherapy and underwent tumor resection with reconstruction. This report describes the cytomorphologic features of this rare intravascular tumor and demonstrates how EBUS-TBNA with ROSE was instrumental in obtaining optimal cytologic sampling for ancillary studies, thus expediting the management.