Biomedical subjects

Stefan E Pambuccian

Publications and source records attributed to Stefan E Pambuccian.

At least 19 recordsLinked to original sources

PubMed2006

Genes associated with early development, apoptosis and cell cycle regulation define a gene expression profile of adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is an uncommon salivary gland malignancy characterized by indolent yet relentless growth that exhibits inherent resistance to systemic chemotherapy, surgical salvage and conventional radiotherapy. We used microarray analysis to characterize gene expression changes associated with ACC. Eight ACC patient specimens were compared with normal parotid gland tissue and the ACC3 cell line. Differentially expressed genes were identified (512 total) using supervised analysis methods and functional categories assigned using OntoExpress. Genes associated with morphogenesis, neurogenesis, proliferation and apoptosis characterized ACC tumors. Genes associated with saliva production and immune response characterized normal parotid tissues while the ACC3 cell line expressed genes primarily associated with proliferation, chromosome maintenance and the cell cycle. These results demonstrate that ACC tumors express genes associated with early developmental processes including morphogenesis and neurogenesis implicating oncogenic events that result in dedifferentiation of normal salivary glands.

Adult↗

PubMed2006

Disaggregation and invasion of ovarian carcinoma ascites spheroids.

BACKGROUND: Malignant ascites often develops in advanced stages of ovarian carcinoma, consisting of single and aggregated tumor cells, or spheroids. Spheroids have commonly been used as tumor models to study drug efficacy, and have shown resistance to some chemotherapies and radiation. However, little is known about the adhesive or invasive capabilities of spheroids, and whether this particular cellular component of the ascites can contribute to dissemination of ovarian cancer. Here, we examined the invasive ability of ascites spheroids recovered from seven ovarian carcinoma patients and one primary peritoneal carcinoma (PPC) patient. METHODS: Ascites spheroids were isolated from patients, purified, and immunohistochemical analyses were performed by a pathologist to confirm diagnosis. In vitro assays were designed to quantify spheroid disaggregation on a variety of extracellular matrices and dissemination on and invasion into normal human mesothelial cell monolayers. Cell proliferation and viability were determined in each assay, and statistical significance demonstrated by the student's t-test. RESULTS: Spheroids from all of the patients' ascites samples disaggregated on extracellular matrix components, with the PPC spheroids capable of complete disaggregation on type I collagen. Additionally, all of the ascites spheroid samples adhered to and disaggregated on live human mesothelial cell monolayers, typically without invading them. However, the PPC ascites spheroids and one ovarian carcinoma ascites spheroid sample occasionally formed invasive foci in the mesothelial cell monolayers, suggestive of a more invasive phenotype. CONCLUSION: We present here in vitro assays using ascites spheroids that imitate the spread of ovarian cancer in vivo. Our results suggest that systematic studies of the ascites cellular content are necessary to understand the biology of ovarian carcinoma.

Journal Article↗

PubMed2006

Cytologic-histologic correlation of screening and diagnostic Papanicolaou tests.

The Pap test (PT) is most commonly used as a screening test; however, it is often also used as a "diagnostic test," usually in patients of known or suspected lesions. As we have recently shown that the yield of atypical interpretations in diagnostic Pap tests (DPTs) is nearly five times greater than the yield for screening Pap tests (SPTs), we speculated that the PT might function differently when used in each population. The University of Virginia's cytologic-histologic correlation results for PTs, accessioned between 4 January 2003 and 11 December 2003, were reviewed. PTs were considered as SPTs or DPTs, depending on the billing codes used by referring physicians. Using the original diagnosis, results were compared for SPTs and DPTs using chi-square testing. There were 1,311 PTs (776 DPTs and 535 SPTs), which had histologic follow-up within a 7-mo period. Of SPTs interpreted as negative (242), 11 (4.5%) showed SIL or worse and 3 (1.2%) showed HSIL or worse on follow-up biopsy. Of SPTs interpreted as ASC (133), 59 (44.3%) showed SIL or worse and 16 (12.0%) showed HSIL or worse on follow-up biopsy. Of SPTs interpreted as LSIL (117), 65 (55.5%) showed SIL or worse and 17 (14.5%) showed HSIL or worse on follow-up biopsy. Of SPTs interpreted as HSIL (38), 31 (81.6%) showed SIL or worse and 23 (60.5%) showed HSIL or worse on follow-up biopsy. Of SPTs interpreted as glandular lesions (AGC, adenocarcinoma, etc.) (4), 3 (75%) showed HSIL or malignancy. Of DPTs interpreted as negative (261), 69 (26.4%) showed SIL or worse and 10 (3.8%) showed HSIL or worse on follow-up biopsy. Of DPTs interpreted as ASC (166), 75 (45.2%) showed SIL or worse and 22 (13.3%) showed HSIL or worse on follow-up biopsy. Of DPTs interpreted as LSIL (227), 146 (64.4%) showed SIL or worse and 31 (13.7%) showed HSIL or worse on follow-up biopsy. Of DPTs interpreted as HSIL (119), 105 (87.4%) showed SIL or worse and 84 (70.6%) showed HSIL or worse on follow-up biopsy. Of DPTs interpreted as glandular lesions (AGC, adenocarcinoma, etc.) (3), 3 (100%) showed HSIL or malignancy. Overall, DPTs were more likely than SPTs to show SIL or HSIL on follow-up biopsy (P < 0.01), and negative DPTs were more likely than negative SPTs to show SIL or HSIL on follow-up biopsy (P < 0.01, P = 0.01, respectively). Some of this may be a reflection of the increased percentage of LSIL and HSIL results for DPTs. Despite the difference in disease prevalence between women having SPTs and those having DPTs, the PT seems to function relatively the same in both scenarios, except in high risk women with negative DPTs.

Cervix Uteri↗

PubMed2006

Endoscopic ultrasound-guided fine needle aspiration diagnosis of metastatic sex cord tumor with annular tubules: a case report.

The cytologic findings of a paratracheal metastasis from a malignant sex cord tumor with annular tubules (SCTATs) diagnosed by endoscopic ultrasound guided fine needle aspiration are described. Cytologic features of SCTATs include the presence of highly cellular aspirates forming simple and complex rosette-like structures around central rounded hyaline material, small nucleoli, and prominent nuclear grooves. These cytologic findings are clearly distinct from the poorly formed rosette-like structures of granulosa-cell tumors and are reminiscent of the low-power appearance of the cribriform variant of adenoid cystic carcinoma. The fine needle aspiration cytologic features of only two other cases have been previously described and, to the best of our knowledge, this is the first case reporting the cytologic diagnosis of a distant metastasis of a SCTATs by endoscopic ultrasound-guided fine needle aspiration. In this case, the distinctive and characteristic cytologic features have allowed the proper diagnosis of a distant metastasis of SCTATs.

Biopsy, Fine-Needle↗

PubMed2006

Differential gene expression identifies subgroups of ovarian carcinoma.

Papillary serous ovarian carcinoma, the most common type of ovarian cancer, displays different biological behavior in different patients. This heterogeneity cannot be recognized by light microscopy. In this study, gene expression in 29 papillary serous ovarian carcinoma samples (21 invasive tumors and 8 borderline tumors), and 17 nonmalignant tissue types comprising 512 samples, was determined using Affymetrix U_133 oligonucleotide microarrays (Affymetrix, Inc., Santa Clara, Calif) representing approximately 40,000 known genes and expression sequence tags (ESTs). Differences in gene expression were quantified as the fold change in gene expression between the various sets of samples. A set of genes was identified that was over-expressed in the invasive ovarian carcinoma samples compared with the normal ovary samples. Principle component analysis of the set of invasive ovarian carcinomas using this set of genes revealed the existence of 2 major subgroups among the invasive ovarian carcinomas. A series of principle component analyses of the ovarian carcinomas using different gene sets composed of genes involved in different metabolic pathways also revealed the same 2 major subgroups of the invasive ovarian carcinomas. Review of the pathology by a single pathologist in a blinded manner suggested that these 2 subgroups differed in pathologic grade. Genes differentially expressed between the 2 ovarian carcinoma subsets were identified. Examination of gene expression in each ovarian carcinoma subset compared with that in 17 different normal tissue types (512 samples) revealed genes specifically over-expressed in ovarian carcinoma compared with these normal tissues. It is concluded that gene expression patterns may be useful in helping to further classify subtypes of papillary serous ovarian carcinoma that may have clinical significance. In addition, the genes identified as over-expressed in each set of serous ovarian carcinoma compared with normal tissues may represent potential biomarkers and/or targets for therapy.

Adipose Tissue↗

PubMed2006

Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection.

The organized structure of lymphatic tissues (LTs) constitutes a microenvironment referred to as a niche that plays a critical role in immune system homeostasis by promoting cellular interactions and providing access to cytokines and growth factors on which cells are dependent for survival, proliferation, and differentiation. In chronic human immunodeficiency virus type 1 (HIV-1) infection, immune activation and inflammation result in collagen deposition and disruption of this LT niche. We have previously shown that these fibrotic changes correlate with a reduction in the size of the total population of CD4+ T cells. We now show that this reduction is most substantial within the naïve CD4+ T-cell population and is in proportion to the extent of LT collagen deposition in HIV-1 infection. Thus, the previously documented depletion of naïve CD4+ T cells in LTs in HIV-1 infection may be a consequence not only of a decreased supply of thymic emigrants or chronic immune activation but also of the decreased ability of those cells to survive in a scarred LT niche. We speculate that LT collagen deposition might therefore limit repopulation of naïve CD4+ T cells with highly active antiretroviral therapy, and thus, additional treatments directed to limiting or reversing inflammatory damage to the LT niche could potentially improve immune reconstitution.

Adult↗

PubMed2006

Interobserver variability with the interpretation of thyroid FNA specimens showing predominantly Hürthle cells.

Fine-needle aspiration (FNA) is used for the diagnosis and triaging of thyroid lesions. Recently, it has been shown that the pathologic interpretation of selected thyroid specimens can show a high degree of interobserver variability (IV). Because Hürthle cells may be seen in neoplastic and nonneoplastic disease, we investigated whether pathologists consistently interpret FNA specimens from these lesions. In the present study, 22 FNA specimens that showed Hürthle cells as the predominant cell type were reviewed by 7 pathologists. Cytologic features were assessed semiquantitatively. IV was calculated, and individual case diagnoses were compared with cytologic features. IV was high before diagnoses were collapsed into like diagnoses and triage recommendations (k = 0.17, 0.44, and 0.51, respectively). Overall cellularity, number of Hürthle cells, and number of lymphocytes all correlated with collapsed diagnostic agreement, and the number of air-dried rapid Romanowsky-stained slides, overall cellularity, number of Hürthle cells, and number of lymphocytes all correlated with collapsed triage recommendations.

Biopsy, Fine-Needle↗

PubMed2006

Prostatic glands and urothelial epithelium in a seminal vesicle cyst: report of a case and review of pathologic features and prostatic ectopy.

We report a case of a seminal vesicle cyst containing prostatic glands and urothelial epithelium in a patient with no other urogenital anomalies. The detection of prostatic tissue, which is of endodermal origin, in a seminal vesicle cyst, a mesonephric duct derivative, is unusual. We review the pathologic features of seminal vesicle cysts and discuss the histogenesis of prostatic and urothelial tissue.

Adult↗

PubMed2005

Significance of benign endometrial cells in papanicolaou tests from women aged >or=40 years.

BACKGROUND: The 2001 Bethesda System recommends reporting benign endometrial cells (BECs) in women aged >or=40 years and considers these women at risk for endometrial pathology. The current study examines the relative risk of hyperplasia or malignancy conferred by the presence versus the absence of BECs in Papanicolaou (Pap) tests of women aged >or=40 years. METHODS: Women aged >or=40 years represented 29,177 (46.2%) of 63,202 Pap tests obtained over 1 year from a largely suburban screened population. Of these, 866 Pap tests (3%) showed BECs. Over the same 1 year period, 789 women aged >or=40 years had endometrial histologic evaluations between 14 days and 6 months following a Pap test. The Pap tests of 159 women had BECs, and 33 had atypical (n=32) or malignant (n=1) endometrial cells. The 597 remaining women, who had Pap tests without endometrial cells but who had endometrial sampling for other reasons, served as controls. RESULTS: There were nine endometrial hyperplasias (5.7%) and no adenocarcinomas in the BECs group, whereas 34 hyperplasias (5.7%) and 6 adenocarcinomas (1%) were diagnosed in the controls. These differences were not statistically significant, even after restricting the analysis to women aged >or=50 years or to women known to be postmenopausal. CONCLUSIONS: The current study found that women aged >or=40 years with BECs in their Pap tests did not have more endometrial hyperplasias or malignancies when compared with women who had endometrial sampling for reasons other than the presence of endometrial cells in a Pap test.

Adenocarcinoma↗

PubMed2005

Atypical teratoid/rhabdoid tumor of the brain: cytopathologic characteristics and differential diagnosis.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly aggressive neoplasm with a unique cytogenetic profile. Although the clinicopathologic and radiologic features of AT/RT have been described previously, to the authors' knowledge the cytomorphologic profile of this tumor has not been studied well. METHODS: Nine samples of AT/RT from 8 patients were analyzed from the pathology files of 2 large institutions in a 10-year period (1993-2002). Material consisted of slides made from scraping and smearing (SS) or squash preparation (SP) of the tissue cores (six slides), fine-needle aspiration (FNA) (two slides), and cerebrospinal fluid (one slide). Smears were stained with Diff-Quik, Papanicolaou, and hematoxylin and eosin stains. RESULTS: There were 4 males and 4 females who ranged in age from 1-16 years (mean age, 7.1 years). Cytomorphologic features consisted of hypercellularity (eight of eight tumors); predominantly large tissue fragments with tumor cells surrounding proliferating capillaries depicting a "papillary-like" appearance (five of eight tumors); large, round, "plasmacytoid" cells and characteristic "rhabdoid" cells (i.e., intermediate-sized cells with granular to fibrillary, brightly eosinophilic cytoplasm with or without globoid "inclusions"; large, eccentrically located, round-to-reniform nuclei with single prominent nucleoli; eight of eight tumors); small, round, primitive "neuronal-appearing" cells with a high nuclear to cytoplasmic ratio (five of eight patients); and bizarre, multinucleated giant cells (two of eight tumors). Also seen were numerous apoptotic bodies, mitoses, and significant necrosis (seven of eight tumors), and prominent dystrophic calcification (four of eight tumors). CONCLUSIONS: AT/RT is extremely rare. Cytologic examination by SS, SP, or FNA offers a useful alternative to frozen section during intraoperative consultation. Cytomorphologic features are unique and lead to an accurate diagnosis in the right clinicoradiologic context. The differential diagnosis includes medulloblastoma (in cerebellar tumors), primitive neuroectodermal tumor (in suprasellar tumors), choroid plexus carcinoma, and malignant glioma.

Adolescent↗

PubMed2005

The diagnosis of trichomonas vaginalis in liquid-based Pap tests: morphological characteristics.

We investigated the morphological features of Trichomonas vaginalis in liquid-based Papanicolaou (Pap) (LBP) tests, in order to assess the impact of this new slide preparation system on recognition of T. vaginalis organisms. We reviewed 88 LBP test slides previously interpreted as showing T. vaginalis and assessed morphological characteristics of the organisms and the presence of secondary features. Eighty-six of 88 slides showed, at least focally, organisms with cytoplasmic granules, nuclei, and flagella allowing for confident recognition of T. vaginalis. Compared with 58 controls, cases of T. vaginalis were more likely to have squamous cells with perinuclear halos, "ghost cells," and coccobacilli. The lack of a "dirty" background or cytolysis allowed a more straightforward identification of the organisms. We concluded that T. vaginalis organisms are morphologically distinct in LBP tests, which may lead to an increased specificity when they are identified in such tests.

Adolescent↗

PubMed2005

The diagnosis of Trichomonas vaginalis in liquid-based Pap tests: correlation with PCR.

The conventional Papanicolaou smear (CPS) is not considered accurate for the diagnosis of Trichomonas vaginalis (T. vaginalis), and women noted to carry the organism on CPS are recommended to undergo confirmatory testing. Liquid-based preparations have been shown to facilitate the diagnosis of squamous lesions and may also facilitate the diagnosis of T. vaginalis. We used polymerase chain reaction (PCR) to investigate the accuracy of the diagnosis of T. vaginalis by the liquid-based Pap test (LBP). LBP with the diagnosis of T. vaginalis from a 12-mo period were identified. Residual samples from these cases were subjected to PCR for T. vaginalis as were the residual samples of a control group of 195 LBP (including 103 inflammatory LBP and 69 cases of atypical squamous cells) in which T. vaginalis was not diagnosed cytologically. PCR confirmed the presence of T. vaginalis in 50 of 51 (98%) LBP and identified 2 additional cases. Morphologic identification of T. vaginalis on LBP is highly accurate and should not require confirmatory testing.

Animals↗

PubMed2005

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms.

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.

Aged↗

PubMed2005

c-kit expression in adenoid cystic carcinoma does not have an impact on local or distant tumor recurrence.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a neoplasm with unpredictable behavior with frequent late relapses that lacks good prognostic indicators. c-kit tyrosine kinase oncogene has recently been found to be expressed in ACC. The aim of this study is to correlate the expression of c-kit in ACC with clinical follow-up. METHODS: Paraffin sections of 45 cases of ACC diagnosed during a 15-year period were immunostained for c-kit. RESULTS: Seventy-eight percent of tumors stained positive for c-kit. Mean follow-up time was 6 years. No degree/pattern of c-kit expression correlated to local or distant tumor recurrence. However, there was a significant association between surgical margin involvement by tumor and cell membrane expression of c-kit. Staining quality was not affected by storage time. CONCLUSIONS: Our results suggest that expression of c-kit may not serve as a useful marker for predicting outcome in ACC, although they need to be confirmed in a larger patient population with longer clinical follow-up.

Adult↗

PubMed2005

Interobserver variability in thyroid fine-needle aspiration interpretation of lesions showing predominantly colloid and follicular groups.

We studied interobserver variability (IV) in the assessment of thyroid fine-needle aspiration (FNA). We limited our cases to those showing predominantly colloid and follicular cell groups. Twenty cases of thyroid FNA diagnosed by 1 experienced cytopathologist were reviewed by 4 other cytopathologists who made their own diagnoses while unaware of the original diagnoses. Two cytopathologists then assessed the cytologic features of the 20 cases. IV was calculated for noncollapsed and collapsed diagnoses. Diagnoses and observer agreement were compared with cytologic features. There was little correlation among observers regarding the diagnosis of follicular "lesion" vs "neoplasm." IV was somewhat poor before data were collapsed to treatment recommendations (kappa = 0.35) but was relatively good when data were collapsed (kappa = 0.65). Cellularity, cyst change, and amount of colloid correlated with treatment recommendations; no specific features correlated with poor performance. Thyroid FNA shows good interobserver agreement in the diagnoses of lesions showing predominantly colloid or follicular cells (when collapsed). We speculate that IV is poor in some cases owing to difficulty assessing thin colloid, some lack of agreement regarding criteria for adequacy, and a possible "gray zone" that might exist with lesions showing colloid and abundant follicular cells.

Biopsy, Fine-Needle↗

PubMed2005

Ki-67 immunoreactivity in the differential diagnosis of pulmonary neuroendocrine neoplasms in specimens with extensive crush artifact.

The aim of the present study was to evaluate the usefulness of immunohistochemical markers in the differential diagnosis of pulmonary neuroendocrine tumors with particular emphasis on the preservation of immunoreactivity in areas showing crush artifacts. Specimens from 9 carcinoid tumors (CTs) and 13 small cell carcinomas (SCCs) with crush artifact were stained with antibodies to Ki-67, chromogranin A, synaptophysin, and cytokeratin. The immunoreactivity was well preserved in the crushed areas. Ki-67 was expressed in the crushed areas of all SCCs. Reactivity was diffuse or at least present in 25% of the crushed areas. In contrast, the immunoreactive areas in CTs never exceeded 10%. Immunoreactivity for Ki-67, synaptophysin, chromogranin A, and cytokeratin is well preserved in tissue with crush artifacts and can be interpreted reliably. The diagnosis of SCC should be questioned if fewer than 25% of cells show reactivity for Ki-67.

Artifacts↗

PubMed2005

Perivascular epithelioid cell tumor of the oral mucosa.

Perivascular epithelioid cell tumors (PEComas) are a family of tumors defined by the coexpression of melanocytic and muscle markers. Examples have been reported in many organs, soft tissues, and bone. Further expanding the list of locations, we report a case arising in the hard palate. Histologically, the tumor was composed of large elongated or epithelioid cells with granular cytoplasm. Immunohistochemically, tumor cells were positive for HMB-45, Melan A/MART-1, CD10, smooth muscle actin, desmin, and calponin. Ultrastructural examination revealed stage I melanosomes, thin filaments, and dense plaques. Recurrence has not been reported after 20 months. To our knowledge, this is the first detailed description of an intraoral PEComa.

Biomarkers, Tumor↗

PubMed2005

Pulmonary complications after bone marrow transplantation: an autopsy study from a large transplantation center.

CONTEXT: Bone marrow transplantation (BMT) is used to treat various malignant and nonmalignant disorders. Pulmonary complications are some of the most common causes of mortality in BMT recipients. Poor general health and bleeding tendency frequently preclude the use of definitive diagnostic tests, such as open lung biopsy, in these patients. OBJECTIVE: To identify pulmonary complications after BMT and their role as the cause of death (COD). DESIGN: The autopsy and bronchoalveolar lavage (BAL) slides and microbiology studies of BMT recipients from a 7-year period were reviewed. RESULTS: Pulmonary complications were identified in 40 (80%) of the 50 cases. The most common complications were diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH). Pulmonary complications were the sole or 1 of multiple CODs in 37 cases (74%). All complications were more common in allogeneic BMT recipients. In 19 (51%) of the 37 cases in which pulmonary complications contributed to the death, cultures were negative. Both DAD and DAH, complications commonly reported in the early post-BMT period, were seen more than 100 days after BMT in 33% and 12% of cases, respectively. Five (83%) of 6 cases of invasive pulmonary aspergillosis diagnosed at autopsy were negative for fungi ante mortem (by BAL and cultures). CONCLUSIONS: Pulmonary complications are a significant COD in BMT recipients, many of which, especially the fungal infections, are difficult to diagnose ante mortem. The etiology of DAD and DAH is likely to be multifactorial, and these complications are not limited to the early posttransplantation period. Autopsy examination is important in determining the COD in BMT recipients.

Adolescent↗