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Diffuse alveolar damage. Morphologic features in bronchoalveolar lavage fluid
Beskow CO; Drachenberg CB; Bourquin PM; Britt EJ; Simsir A; Gunev I; Papadimitriou JC
OBJECTIVE: To evaluate the overall cytologic characteristics of diffuse alveolar damage (DAD) in bronchoalveolar lavage (BAL) specimens in search of features that could be useful in cytologic diagnosis. STUDY DESIGN: We evaluated BAL samples from patients with DAD obtained simultaneously with transbronchial biopsies (n = 8) or open lung biopsies (n = 2) or within 24 hours of autopsy (n = 2). The material was processed routinely for cytologic and histologic evaluation. RESULTS: The smears were moderately to highly cellular. All cases had large numbers of alveolar macrophages and/or desquamated alveolar cells. The epithelial component displayed various degrees of nuclear atypia. Some epithelial clusters were three-dimensional, with peripheral cells showing clear cytoplasm, protruding outwards and resembling hobnails. Other aggregates appeared two-dimensional, as sheets of cells with flattened and dense cytoplasm (squamotized). Both types of cell clusters were often associated with dense, basophilic or amphophilic, amorphous extracellular material. Counterparts of all the cytologic features were observed in the histologic material, including atypia of the alveolar lining with hobnailing, squamotization, amorphous extracellular material and hyaline membranes. CONCLUSION: The cytologic features of BAL represent a constellation of alveolar cell injury. Based on these features, DAD can be correctly diagnosed or suggested in BAL samples in the appropriate clinical setting
PMID: 10934959
ISSN: 0001-5547
CID: 22754
Human polyoma virus in renal allograft biopsies: morphological findings and correlation with urine cytology
Drachenberg CB; Beskow CO; Cangro CB; Bourquin PM; Simsir A; Fink J; Weir MR; Klassen DK; Bartlett ST; Papadimitriou JC
Human polyoma virus (PV) interstitial nephritis occurs in immunosuppressed patients after reactivation of latent virus in renal epithelium. Currently, there is neither general consensus about the incidence of clinically significant PV infection in renal transplants nor conclusive evidence determining its significance in the long-term graft outcome. We evaluated 601 renal transplant biopsy specimens (from 365 patients) by routine light microscopy and immunoperoxidase stains with antibody against SV40 (which cross reacts with PV). We also examined urine samples from 200 patients (100 obtained concurrently with a renal biopsy in patients presenting with acute graft dysfunction and 100 from patients with stable graft function). Electron microscopic evaluation was performed in 50 renal biopsy specimens and in 23% of all urine samples. PV was identified in 1.8% biopsy specimens (1.9% of patients). PV interstitial nephritis showed the typical viral cytopathic changes in tubular epithelial cells associated with marked tubular damage and a disproportionately mild degree of tubulitis. There was no difference in the incidence of PV in the urine of patients with acutely deteriorating versus stable renal function (18% and 19%, respectively); however, urines with large numbers of infected cells (> 10/cytospin) and inflammatory changes in the sediments corresponded invariably to patients with acute allograft dysfunction (8 of 8), and in most cases to biopsy specimens showing PV interstitial nephritis (7 of 8). Based on these findings, urine samples seem to be the most sensitive and cost-effective screening method for PV infection; only urine samples with inflamed sediments and abundant infected cells correlate with clinically significant disease. In these cases, examination of a renal biopsy is indicated. Immunohistochemical stains are useful to confirm the presence of PV but do not increase the sensitivity of diagnosis of PV if this is not already suspected on routine light microscopy. In our material, immunostains were helpful ruling out the presence of PV in a small number of biopsy specimens (2%) that showed markedly reactive tubular cells resembling PV infection. Most patients with PV interstitial nephritis responded to decreased immunosuppression; however, the decay in graft function (based on creatinine slopes) was significantly more rapid in these patients than in matched controls. Evidence of PV infection should be systematically sought in renal biopsy specimens and urine samples from renal allograft recipients
PMID: 10452511
ISSN: 0046-8177
CID: 22755
Immunophenotypic analysis of non-Hodgkin's lymphomas in cytologic specimens: a correlative study of immunocytochemical and flow cytometric techniques
Simsir A; Fetsch P; Stetler-Stevenson M; Abati A
Most Non-Hodgkin's lymphomas(NHL) can be accurately diagnosed and classified based on morphologic and immunophenotypic findings on cytologic specimens. Immunophenotyping can be accomplished via immunocytochemistry (IC) or flow cytometry (FC). We reviewed our experience with 98 cytology specimens (70 fine-needle aspirates [FNA] and 28 effusions) that were submitted for immunophenotyping utilizing both IC and FC between January 1992 and December 1997 for the diagnosis of NHL. Eighty-five percent of the cases were immunophenotyped by both techniques. Among these there were only two discrepancies between IC and FC, yielding a 98% correlation rate. Of the 98 cases, 11% could not be immunophenotyped by FC and 4% could not be immunophenotyped by IC. The advantage of IC is the preservation of cytomorphology, which results in the requirement for a lower number of neoplastic cells and a limited, targeted panel of antibodies. This is especially useful in predominantly necrotic lymphomas in which only a few well-preserved neoplastic cells may be present, rendering the specimen inadequate for immunophenotyping by FC. The advantages of FC are in the detection of a small population of monoclonal cells in a background of reactive cells (particularly useful in effusion samples in which the predominant cell population is often reactive T lymphocytes), increased diagnostic precision through evaluation of objective parameters, and the use of multiple markers with dual labelling. We conclude that IC and FC are both excellent methods for immunophenotyping of cytology specimens and can be used interchangeably depending on the institutional expertise and availability
PMID: 10319228
ISSN: 8755-1039
CID: 22756
E-cadherin, N-cadherin, and calretinin in pleural effusions: the good, the bad, the worthless
Simsir A; Fetsch P; Mehta D; Zakowski M; Abati A
The distinction between reactive mesothelial cells (RMC), malignant mesothelioma (MM), and metastatic adenocarcinoma (ACA) in pleural effusions may be impossible based on morphology alone. E-cadherin, N-cadherin, and calretinin are newly described immunocytochemical markers which can potentially be utilized for facilitating this distinction. E-cadherin and N-cadherin are calcium-dependent intercellular adhesion molecules expressed in epithelial cells and mesenchymal/mesothelial cells, respectively. The differential expression of E-cadherins in epithelial cells and N-cadherins in mesothelial cells has been utilized to differentiate reactive mesothelial cells, MMs and ACAs. Calretinin is a calcium-binding protein within the family of EF-hand proteins. It is abundantly expressed in peripheral and central nervous tissues, and has been shown to consistently immunoreact with mesothelial cells. We studied cell block sections from 77 pleural effusions (22 RMC, 26 MM, and 29 ACA) to investigate the potential immunocytochemical use of anti-E-cadherin, anti-N-cadherin, and anti-calretinin antibodies for differentiating between RMC, MM, and ACA in pleural effusions. A modified avidin-biotin peroxidase complex (ABC) method was used. E-cadherin immunostaining was observed in 14% of RMC, 46% of MMs, and 97% of ACAs. A distinct membrane staining pattern was seen in ACAs. The pattern of staining was cytoplasmic in all reactive RMC and varied from membrane to cytoplasmic in MMs. Anti-N-cadherin immunoreacted with 77% of RMC, 35% of MMs, and 48% of ACAs. Twenty-seven percent of RMC, 58% of MMs, and 31% of ACAs immunoreacted with anti-calretinin. Based on these results, we conclude that anti-E-cadherin is a potentially useful marker in the distinction of ACA cells from RMC. However, it is not as useful for the distinction of ACA and MM. Anti-N-cadherin and anti-calretinin did not reliably distinguish between reactive mesothelial, MM, and ACA cells in pleural effusions
PMID: 10086235
ISSN: 8755-1039
CID: 22757
Late fatal adenovirus pneumonitis in a lung transplant recipient [Case Report]
Simsir A; Greenebaum E; Nuovo G; Schulman LL
Adenovirus (ADV) is increasingly recognized as a cause of morbidity and mortality in transplant recipients, but ADV pneumonitis has rarely been reported after lung transplantation. The few reported instances of ADV pneumonitis occurred mostly in children immediately after lung transplantation suggesting 'primary' infection. We report a fatal case of ADV pneumonitis occurring in an adult, 4 years after unilateral lung transplantation, in whom the premortem diagnosis was not determined. Autopsy revealed severe necrotizing bronchitis, bronchiolitis, and interstitial pneumonitis. Characteristic smudgy intranuclear inclusions, immunohistochemistry for viral protein, in situ hybridization for viral genome, and postmortem lung cultures established ADV as the etiologic agent. ADV can cause fatal, occult respiratory infection in adult lung transplant recipients, remote from transplant surgery
PMID: 9500642
ISSN: 0041-1337
CID: 22759
Additional mimics of mucinous mammary carcinoma: fibroepithelial lesions
Simsir A; Tsang P; Greenebaum E
To determine the origin and nature of mucinlike material in fine-needle aspiration (FNA) smears of the breast in noncancerous breast lesions, we studied breast FNA smears from four patients. All smears contained epithelial cells floating in a mucinlike background, which raised suspicion for mucinous (colloid) carcinoma. Mucicarmine stain was performed on one smear from each case. Subsequent tissue biopsy specimens were studied using mucicarmine, periodic acid-Schiff with and without diastase, and alcian blue stains at pH 2.7 and 0.9 on selected tissue sections. Correlation of the cytologic and histologic findings of each lesion was performed. The mucinlike background in all four FNA smears stained strongly with mucicarmine. Corresponding biopsy specimens revealed pseudoangiomatous hyperplasia in the first case, fibroadenoma and atypical ductal hyperplasia in the second, benign phyllodes tumor in the third, and fibroadenoma in the fourth. Each lesion in cases 1 to 3 was associated closely with fibrocystic changes. In case 4, cystic changes were located within the fibroadenoma. On tissue sections of all four cases, the cyst contents and 10% to 50% of normal lobule and duct contents stained with mucicarmine, indicating that the cyst contents were the most probable source of mucin in the FNA smears. The presence of pools of mucicarmine-positive material in FNA smears of the breast is not an exclusive feature of mucinous carcinoma; mucicarmine-positive mucin can arise from benign cystic changes as well as from normal lobules and ducts
PMID: 9583888
ISSN: 0002-9173
CID: 22758
CA-125 and carcinoembryonic antigen assay vs. cytodiagnostic experience in the classification of benign ovarian cysts
Pinto MM; Greenebaum E; Simsir A; Kleinman GM; Portnoy LM; Garfinkel R
OBJECTIVE: To compare the relative strengths of two factors involved in making an accurate differentiation between functional and epithelial ovarian cysts, along with their combination: (1) the cytologist's level of experience in interpreting ovarian cytology, (2) the use of the tumor markers carcinoembryonic antigen (CEA) and CA-125 in cyst fluid, and (3) a combination of (1) and (2). STUDY DESIGN: Papanicolaou-stained sediments from fluid aspirated from 31 resected ovarian cysts (6 functional and 25 epithelial) were blindly and independently evaluated by five pathologists with varying experience in ovarian cytology. Cyst fluid supernatant was used for CEA, enzyme-linked immunosorbent assay, and CA-125 radioimmunoassay; CEA levels > 5 ng/mL or CA-125 > 5,000 U/mL were considered elevated. Cysts were categorized cytologically and histologically as functional or epithelial and by tumor markers as 'neither elevated' or 'either or both elevated' (EBE). RESULTS: The agreement of histologic diagnosis with each pathologist's cytologic diagnosis ranged from 53% to 84% (53%, 71%, 83%, 82%, 84%), corresponding to increasing level of experience. The percentage of agreement with EBE was 77%, whereas combined experienced pathologist's diagnosis and EBE was 87%. Kappa equaled .45 for experienced cytopathologist's diagnosis or EBE alone. Kappa equaled .53 when the pathologist or EBE diagnosed an epithelial cyst, indicating results unlikely to occur by chance. CONCLUSION: The distinction of functional from epithelial ovarian cysts is best achieved by combining measurement of the tumor markers CEA and CA-125 with a high level of cytopathology experience
PMID: 9305384
ISSN: 0001-5547
CID: 22760
Biliary stent replacement cytology
Simsir A; Greenebaum E; Stevens PD; Abedi M
Using fluoroscopic guidance, polyethylene biliary stents are replaced endoscopically or percutaneously when bile duct stenosis recurs. To improve the sensitivity of conventional biliary cytology, we examined cells recovered from removed stents. Biliary stents removed endoscopically from each of 11 patients were rinsed with saline; next, the rinse was centrifuged and the sediment smeared and Papanicolaou stained. Three patients with choledocholithiasis had biliary stent replacement cytology (BSRC) to exclude a neoplastic etiology. Eight patients with clinicoradiologic evidence of hepatobiliary or pancreatic carcinoma had BSRCs performed for pathologic documentation of carcinoma. BSRC from six of eight patients with clinicoradiologically malignant biliary strictures contained malignant cells, predominantly in loose clusters, but also singly (sensitivity 75%, specificity 100%; positive predictive value 75%, negative predicative value 60%). Reparative epithelial atypia was also present in all cases. BSRC from two patients with clinicoradiological evidence of carcinoma of the biliary region and from three with choledocholithiasis contained only bile pigment, leukocytes, and benign epithelial cells. The sampling of cells which have accumulated on, or in biliary stents, improves the sensitivity of biliary cytology. This is most applicable when 1) a patient is inoperable, 2) tissue biopsy is neither feasible nor diagnostic, 3) prior brush, suction, percutaneous, or endoscopic needle aspiration cytology is inconclusive, and 4) permanent metal stent is needed
PMID: 9099544
ISSN: 8755-1039
CID: 22761
Malignant granular cell tumor: a case report and review of the recent literature [Case Report]
Simsir A; Osborne BM; Greenebaum E
We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The tumor occurred in the infratemporal fossa of a 30-year-old man, extended to the left orbital base, into the foramen ovale, and invaded the mandible. A granular cell tumor (GCT) was diagnosed by fine-needle aspiration and core needle biopsy of the mass. The patient underwent a radical subtotal debulking procedure followed by radiotherapy. He is alive with recurrent disease 12 months after presentation. Cytologically, the aspirated material was abundantly cellular showing large polygonal cells with ample granular eosinophilic cytoplasm, eccentric nuclei, and often prominent nucleoli. Histologically, the tumor consisted of solid sheets of similar cells that stained strongly with S-100 protein, neuron-specific enolase (NSE), and vimentin. There was moderate nuclear pleomorphism and broad zones of necrosis. Four mitotic figures per 100 high-power field (HPF) were counted. By electron microscopy, the cytoplasm of the tumor cells was filled with lysosomes. Although, some observers advocate that the diagnosis of a MGCT should be reserved for cases in which lymph node and/or distant organ metastasis is evident, we believe malignancy ought to be considered in any GCT with aggressive clinical course defined by persistent local recurrence and destruction of neighboring structures. Nuclear pleomorphism, necrosis, and presence of any mitotic activity should indicate malignancy
PMID: 8760023
ISSN: 0046-8177
CID: 22762
Analysis of fatal pulmonary hantaviral infection in New York by reverse transcriptase in situ polymerase chain reaction [Case Report]
Nuovo GJ; Simsir A; Steigbigel RT; Kuschner M
The purpose of this study was to analyze the histological distribution of polymerase chain reaction (PCR)-amplified hantaviral cDNA in three cases of fatal hantaviral infection that occurred 2 years ago in Long Island, NY. The three otherwise healthy patients had a rapid death characterized by fever and pulmonary failure and were identified from the autopsy files at University Hospital, Stony Brook. Six autopsy controls with either no pulmonary disease (three) or fatal pneumonitis of known etiology (three) were also studied. PCR-amplified hantaviral cDNA was detected in the lung tissue of the three cases and none of the six controls using the reverse transcriptase in situ PCR technique. In the positive cases, viral RNA was detected in approximately 20% of pneumocytes and alveolar endothelial cells as determined with a consensus and Four Corners-specific primer pair. Infected endothelial cells were identified in a wide variety of other sites, but at rates much lower than in the lungs. The selective localization of the viral RNA in many pneumocytes and pulmonary endothelial cells using a highly sensitive PCR-based test demonstrates a correlation between direct viral infection in the lung and the disease process
PMCID:1861712
PMID: 8774123
ISSN: 0002-9440
CID: 22763