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R Nayar

Publications and source records attributed to R Nayar.

At least 19 recordsLinked to original sources
PubMed2005

Perinucleolar compartment prevalence has an independent prognostic value for breast cancer.

The perinucleolar compartment (PNC) is a multicomponent nuclear structure enriched with RNAs transcribed by RNA pol III and RNA binding proteins. Studies in cultured cells showed an association between PNC and transformed phenotype. To evaluate the relationship between structure and malignancy in vivo, we examined PNC prevalence (the percentage of cells containing at least one PNC) in normal and cancerous paraffin-embedded breast tissues using immunohistochemistry against a PNC-associated protein. Five hundred nuclei in the most active area of each sample were scored for PNC prevalence. The results show that PNC prevalence significantly correlates with the progression of breast cancer (by the criteria of staging). PNC prevalence in primary tumors, lymph nodes, and distant metastases shows a stepwise increase from a median of 23% in primary tumors to approximately 100% in distant metastases. In addition, univariate and multivariate (controlling for tumor size and grade) analyses show that early-stage patients with invasive ductal carcinomas containing a higher PNC prevalence have a significantly poorer prognosis. These findings link PNC prevalence with the progression of breast cancer in vivo and suggest that PNC-containing cells have metastatic advantages. These findings also show the potential of PNC prevalence as a prognostic marker for breast cancer.

Aged↗
PubMed2001

Replicative stress after allogeneic bone marrow transplantation: changes in cycling of CD34+CD90+ and CD34+CD90- hematopoietic progenitors.

To further characterize hematopoietic "replicative stress" induced by bone marrow transplantation (BMT), the cell-cycle status of CD90+/- subsets of marrow CD34+ cells obtained 2 to 6 months after transplantation from 11 fully chimeric recipients was examined. Cycling profiles, derived by flow cytometry after staining with Hoechst 33342 and pyronin Y, were compared with those of 14 healthy marrow donors. Primitive CD34+CD90+ cells represented a smaller proportion of CD34+ cells in recipients (10% +/- 4% versus 19.6% +/- 5.3% in donors; P <.0001) and were more mitotically active, with the proportion of cells in S/G2/M nearly 4-fold higher than in donors (15.6% +/- 3% and 4.4% +/- 1.6%, respectively; P <.0001). By comparison, there was a modest increase in the proportion of CD34+CD90- progenitors in S/G2/M after BMT (10.9% +/- 1% vs 9.6% +/- 2% in donors; P =.04). Replicative stress after BMT is borne predominantly by cells in a diminished CD34+CD90+ population.

Adult↗
PubMed2001

Adenocarcinoma in colonic brushing cytology: High-grade dysplasia as a diagnostic pitfall.

Cytologic evaluation of brushing specimens obtained from the colon may be useful in the diagnosis of neoplastic and inflammatory lesions, as previous studies have reported favorable sensitivity and specificity figures for this procedure. In this study, we report our experience with 80 colonic brushings examined over a 5-yr period. Thirty cases received an atypical or malignant cytologic diagnosis. Nineteen of 20 cases diagnosed cytologically as adenocarcinoma revealed adenocarcinoma on biopsy; one case showed only adenomatous epithelium on biopsy and subsequent resection. Cases diagnosed cytologically as "atypical" or "adenomatous" showed adenocarcinoma, adenoma, and inflammatory conditions upon biopsy. Slides from 30 atypical/malignant cases were retrospectively reviewed for a number of cytomorphologic features and were correlated with the histologic diagnosis. Cases from histologically confirmed adenocarcinoma tended to show greater degrees of altered nuclear polarity, nuclear pleomorphism, membrane irregularities, and chromatin pattern alterations than those from histologically proven adenomatous or inflammatory lesions. The most likely cause of a false-positive diagnosis in this setting is sampling of an adenoma with high-grade dysplasia which fails to meet histologic criteria for adenocarcinoma (invasion of the underlying muscularis mucosae). Thus, in the second part of the study, we examined histologic sections from surgically excised adenomas to determine the frequency with which profound nuclear atypia is at least focally present, potentially resulting in a false-positive cytology diagnosis upon brushing. Slides from 51 cases were reviewed; cytologic atypia beyond that typically observed in adenomas was not observed in 43% of cases. However, profound nuclear atypia was present in 6% of cases; cytologic evaluation of a brushing specimen from these lesions may have resulted in a false-positive diagnosis of adenocarcinoma, despite the histologic diagnosis of adenoma with severe dysplasia. The remaining cases demonstrated intermediate degrees of atypia. These findings serve to quantitate the frequency with which cytohistologic discrepancies might be expected for mass lesions of the colon.

Adenocarcinoma↗
PubMed2001

Differences in cell cycle kinetics of candidate engrafting cells in human bone marrow and mobilized peripheral blood.

Patients undergoing hematopoietic stem cell transplantation (HSCT) with mobilized peripheral blood (MPB) engraft quicker than those receiving bone marrow (BM). Our objective was to determine whether candidate engrafting cells--primitive hematopoietic progenitors (PHPs)--from MPB and BM exhibit different responses to cytokines that could explain this observation. We compared the cell cycle kinetics and ex vivo expansion of PHP-enriched cells obtained from MPB (n = 12) and BM (n = 10) by fluorescence-activated sorting of CD90+, AC133+ or CD38(dull) subsets of pre-selected CD34(+) cells. Cell cycle status, before and after 40 hours of serum-free culture with a cytokine cocktail, was assessed by multiparameter flow cytometry following incubation with Hoechst 33342 and pyronin Y. We found that 0.2% +/- 0.3% of MPB CD34(+)CD90(+) cells were in S/G(2)/M phases at hour 0, compared with 5% +/- 2.5% of those from BM (p = 0.0001), and 86.3% +/- 9.7% were in G(0), compared with 65.3% +/- 10% of those in BM (p = 0.0001). After 40 hours of culture, CD34(+)CD90(+) cells from MPB were more mitotically active than those from BM, with 29% +/- 4.9% in S/G(2)/M and 20% +/- 11.4% in G(0), compared to 19% +/- 6.5% (p = 0.001) and 39.2% +/- 22% (p = 0.027) of cells from BM. There was greater expansion of both total CD34(+) cells and the CD90(+) subset from MPB samples (p = 0.001 and 0.0001, respectively). Results from PHPs defined on the basis of AC133 expression correlated well with results obtained in CD90(+) subsets (r(2) = 0.81; p = 0.014).MPB PHPs appear to be primed for a greater acceleration in mitotic activity upon cytokine exposure. This qualitative difference may contribute to the earlier engraftment seen after HSCT using MPB grafts.

AC133 Antigen↗
PubMed2001

Cytologic differential diagnosis of papillary pattern in breast aspirates: correlation with histology.

Papillary neoplasms, fibroadenoma, fibrocystic change, low-grade ductal carcinoma, and apocrine carcinoma are among "gray zone" lesions in breast cytology. They often have cellular smears with a papillary or pseudopapillary pattern. To better define cytologic criteria useful in distinguishing these entities, we correlated them with histology. Papanicolaou and giemsa stained smears from 33 aspirates and their corresponding histology were reviewed. Of these, 28 had an initial cytologic diagnosis or suspicion of papillary neoplasm, while five cases were not diagnosed cytologically as papillary but the histologic diagnosis was a papillary neoplasm. Cytologic features evaluated included cellularity, architecture, apocrine/single/columnar cells, nuclear atypia, intranuclear inclusions, calcifications, background, myoepithelial cells, and bipolar, naked nuclei. Discriminating cytologic features grouped by final histologic diagnosis were as follows: Papillary neoplasm (14 cases): Hemorrhagic/cystic background, 3-dimensional papillary clusters, columnar cells, and fibrovascular cores. Myoepithelial cells within clusters and background naked, bipolar nuclei were inconspicuous. Fibroadenoma (4 cases): Two-dimensional branching clusters often with folding, moderate myoepithelial cells in clusters, moderate to numerous background bipolar nuclei, often forming doublets in smear background, cellular stroma. Ductal carcinoma (11 cases): Papillary ductal carcinoma in situ in 5 of 11 cases, cribriform/tubular architecture in 6 of 11. Absence or paucity of myoepithelial within clusters and background bipolar nuclei was noted. Fibrocystic change (4 cases): Two-dimensional clusters, moderate myoepithelial cells within clusters, and moderate bipolar nuclei in the background. The presence and quantity of myoepithelial cells, bipolar naked nuclei in the background, and ductal cell architecture were the only consistently useful cytologic features in distinguishing breast lesions with a papillary pattern. Ann Diagn Pathol 5:34-42, 2001.

Adult↗
PubMed2001

Diagnostic challenges in aspiration cytology of the salivary glands.

The main goal of fine-needle aspiration (FNA) of salivary gland lesions is to assist the clinician in the management of patients who present with a mass lesion. Cytologic examination aims to determine, if a process is inflammatory and/or reactive, benign or malignant neoplasm and if possible renders a specific diagnosis. It has been argued that in the area of salivary gland tumors, surgical management relies less heavily on a specific preoperative diagnosis, because almost all neoplastic salivary gland lesions will undergo surgical excision. However, knowing beforehand if a lesion is malignant or benign, will aid in planning surgery and may prompt or postpone decisions for surgical intervention. The salivary glands are unique in their histologic complexity and morphological variability of tumors, which is reflected in the cytologic material. In addition to the overlapping morphologic patterns of salivary gland tumors, they also represent relatively rare lesions, thus making it more difficult to acquire diagnostic expertise in FNA. Other than approaching salivary gland tumors by a description of single entities in their benign and malignant categories, we favor a more practical approach to diagnosis based on the key morphologic features noted in FNAs. This article addresses differential diagnoses according to the predominant cytologic presentation with attention to the cell type and size, nature of the cytoplasm, and the smear background.

Adenocarcinoma↗
PubMed2001

Thyroid aspiration cytology: a "cell pattern" approach to interpretation.

The key to the interpretation of thyroid fine needle aspiration is largely dependent on the recognition of various morphologic patterns of epithelial cells, usually follicular cells, and background elements, such as colloid. These morphologic patterns consist of 3 parts: 1) The arrangement of cells with respect to one another, 2) The cytologic features of individual cells, and 3) The presence of background elements. The cellular arrangements generally encountered in fine needle aspiration of the thyroid include the follicular patterns (macro-/normo-follicular and micro-follicular), the papillary pattern, the syncytial pattern, the dispersed cell pattern, and the cystic pattern. This article approaches some of the differential diagnostic challenges encountered while interpreting thyroid aspiration cytology by focusing first on the overall cellular arrangement to generate a differential diagnosis and then narrowing that differential by assessing cellular features of individual cells and the presence of background elements.

Biopsy, Needle↗
PubMed2000

Thyroid plasmacytoma mimicking medullary carcinoma: a potential pitfall in aspiration cytology.

Extramedullary plasmacytoma (EMP), a malignant neoplasm of the soft tissues composed of plasma cells, may occur either as a solitary plasma-cell tumor (primary EMP) or as a manifestation of multiple myeloma (secondary EMP). We report on the aspiration cytology findings of an intriguing case of EMP of the thyroid that was initially misinterpreted as medullary carcinoma on clinical and cytologic examination. A major contributing cause for the cytologic misinterpretation was the presence of amyloid in the aspirate and the clinical impression of a "thyroid mass." Based on this experience, we suggest that EMP should be considered in the differential diagnosis of a neck mass that yields discohesive cells associated with amyloid/amyloid-like material. Clinical correlation and immunocytochemistry are crucial in avoiding pitfalls in this situation.

ADP-ribosyl Cyclase↗
PubMed2000

Hyaline globules in renal cell carcinoma and hepatocellular carcinoma. A clue or a diagnostic pitfall on fine-needle aspiration?

The cytologic similarity to hepatocellular carcinoma (HCC) of 2 cases of granular renal cell carcinoma (RCC) with hyaline globules (HGs) prompted us to evaluate the frequency of HGs in RCC and HCC and the association between cell type, differentiation, and malignant potential of these 2 neoplasms and the presence of HGs. We studied fine-needle aspirates from 23 cases of RCC (primary, 7; metastatic, 16) and 23 cases of primary HCC and noted anatomic site, tumor cell type, and presence, quality, and quantity of HGs. Fuhrman nuclear grade was assigned to RCC and overall differentiation to HCC cases. RCC cell type was granular (7), mixed (4), and clear (12). HCC cases were granular (22) and clear (1). Morphologically similar, predominantly intracytoplasmic HGs were identified in 4 RCCs and 10 HCCs. All 4 RCCs with HGs were at metastatic sites, granular cell type, and high Fuhrman grade. HGs showed no association with differentiation of HCC. While HGs are seen more commonly in HCC than in RCC, their presence in an adenocarcinoma should bring renal origin into consideration. The presence of HGs in metastatic granular RCC, particularly in the liver, can lead to misinterpretation as primary HCC.

Adult↗
PubMed1999

Increased nuchal translucency in trisomy 13 fetuses at 10-14 weeks of gestation.

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10-14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10-14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT.

Chromosomes, Human, Pair 13↗
PubMed1999

Engraftment of gene-marked hematopoietic progenitors in myeloma patients after transplant of autologous long-term marrow cultures.

We conducted a phase I hematopoietic stem cell (HSC) gene-marking trial in patients undergoing autologous blood or marrow stem cell transplant for the treatment of multiple myeloma. Between 500 and 1000 ml of bone marrow was harvested from each of 14 myeloma patients and 1 syngeneic donor. A mean of 3.3x10(9) cells per patient were plated in 20 to 50 long-term marrow culture (LTMC) flasks and maintained for 3 weeks. LTMCs were exposed on days 8 and 15 to clinical-grade neo(r)-containing retrovirus supernatant (G1Na). A mean of 8.23x10(8) day-21 LTMC cells containing 5.2x10(4) gene-marked granulocyte-macrophage progenitor cells (CFU-GM) were infused along with an unmanipulated peripheral blood stem cell graft into each patient after myeloablative therapy. Proviral DNA was detected in 71% of 68 tested blood and bone marrow samples and 150 of 2936 (5.1%) CFU-GM derived from patient bone marrow samples after transplant. The proportion of proviral DNA-positive CFU-GM declined from a mean of 9.8% at 3 months to a mean of 2.3% at 24 months postinfusion. Southern blots of 26 marrow and blood samples were negative. Semiquantitative PCR analysis indicated that gene transfer was achieved in 0.01-1% of total bone marrow and blood mononuclear cells (MNCs). Proviral DNA was also observed in EBV-transformed B lymphocytes, in CD34+ -enriched bone marrow cells, and in CFUs derived from the latter progenitors. Gene-modified cells were detected by PCR in peripheral blood and bone marrow for 24 months after infusion of LTMC cells. Sensitivity and specificity of the PCR assays were independently validated in four laboratories. Our data confirm that HSCs may be successfully transduced in stromal based culture systems. The major obstacle to therapeutic application of this approach remains the overall low level of genetically modified cells among the total hematopoietic cell pool in vivo.

Bone Marrow Cells↗
PubMed1999

Anaplastic spindle-cell squamous carcinoma arising in association with tall-cell papillary cancer of the thyroid: A potential pitfall.

Transformation of a differentiated thyroid carcinoma is an infrequent occurrence and is usually associated with a dismal prognosis. Following a long-standing history of papillary carcinoma of the thyroid, the patient in the present report developed anaplastic thyroid carcinoma. The anaplastic component initially arose in the setting of papillary carcinoma with tall-cell features, represented a very small proportion of the tumor, and was overlooked at the time of the original diagnosis. Several years later, the patient developed a recurrent neck mass. Fine-needle aspiration (FNA) of this mass revealed a population of atypical spindle cells arranged singly and in papillary clusters which lacked the classical cytologic features of papillary carcinoma of the thyroid. Histology of the resected mass revealed an unusual and recently described subtype of thyroid carcinoma, termed "anaplastic spindle-cell squamous carcinoma," which has been reported as occurring in association with tall-cell papillary carcinoma. The FNA findings of this unusual subtype of anaplastic thyroid carcinoma are presented. Diagn. Cytopathol. 1999;21:413-418.

Biopsy, Needle↗
PubMed1999

CD109 is expressed on a subpopulation of CD34+ cells enriched in hematopoietic stem and progenitor cells.

CD109 is a monomeric cell surface glycoprotein of 170 kD that is expressed on endothelial cells, activated but not resting T-lymphocytes, activated but not resting platelets, leukemic megakaryoblasts, and a subpopulation of bone marrow CD34+ cells. Observing an apparent association between CD109 expression and the megakaryocyte lineage (MK), we sought to determine whether CD109 was expressed on MK progenitors. In fetal bone marrow (FBM), a rich source of MK progenitors, CD109 is expressed on a mean of 11% of CD34- cells. Fluorescence activated cell sorting (FACS) of FBM CD34+ cells into CD109+ and CD109- fractions revealed that the CD34+CD109+ subset contained virtually all assayable MK progenitors, including the colony-forming unit-MK (CFU-MK) and the more primitive burst-forming unit-MK (BFU-MK). The CD34+CD109+ subset also contained all the assayable burst-forming units-erythroid (BFU-E), 90% of the colony-forming units-granulocyte/macrophage (CFU-GM), and all of the more primitive mixed lineage colony-forming units (CFU-mix). In contrast, phenotypic analysis of the CD34+CD109- cells in FBM, adult bone marrow (ABM) and cytokine-mobilized peripheral blood (MPB) demonstrated that this subset comprises lymphoid-committed progenitors, predominantly of the B-cell lineage. CD109 was expressed on the brightest CD34 cells identifiable not only in FBM, but also in ABM and MPB indicating that the most primitive, candidate hematopoietic stem cells (HSC) might also be contained in the CD109+ subset. In long-term marrow cultures of FBM CD34+ cells, all assayable cobblestone area forming cell (CAFC) activity was contained within the CD109+ cell subset. Further phenotypic analysis of the CD34+CD109+ fraction in ABM indicated that this subset included candidate HSCs that stain poorly with CD38, but express Thy-1 (CD90) and AC133 antigens, and efflux the mitochondrial dye Rhodamine 123 (Rho123). When selected CD34+ cells were sorted for CD109 expression and Rho123 staining, virtually all CAFC activity was found in the CD109+ fraction that stained most poorly with Rho123. CD34+ cells were also sorted into Thy-1 CD109+ and Thy-1 CD109+ fractions and virtually all the CAFC activity was found in the Thy-1+CD109+ subset. In contrast, the Thy-1-CD109+ fraction contained most of the short-term colony-forming cell (CFC) activity. CD109, therefore, is an antigen expressed on a subset of CD34+ cells that includes pluripotent HSCs as well as all classes of MK and myelo-erythroid progenitors. In combination with Thy-1, CD109 can be used to identify and separate myelo-erythroid and all classes of MK progenitors from candidate HSCs.

Adult↗
PubMed1999

Immunoreactivity of ductal cells with putative myoepithelial markers: A potential pitfall in breast carcinoma.

The identification of an intact layer of myoepithelial cells (MECs) located between epithelial cells and the basal lamina is useful in differentiating benign breast lesions and carcinoma in situ from invasive breast carcinoma. In the present study we used three antibodies considered to be putative markers of MECs (S100 protein, muscle-specific actin [HHF-35], and smooth muscle actin [SMA]) in 100 formalin-fixed, paraffin-embedded histologic sections of breast in an attempt to compare their value in demonstrating MECs in benign breast tissue and breast carcinomas. We concluded that for identifying MECs in benign breast tissue, SMA appears to be the most reliable, followed closely by HHF-35, but S100 is very unreliable for this purpose. In breast carcinoma, all three stains showed variable cross-reactivity with myofibroblasts, being greatest with SMA. A significant number of tumor cells in ductal carcinoma, both intraductal and invasive, stain with these markers and this "cross-reactivity" is extremely high with HHF-35. Thus, immunohistochemistry should be interpreted cautiously in differentiating benign, in situ, and invasive breast neoplasms. The "cross-reactivity" also suggests the possibility of myoepithelial differentiation and/or high actin content of breast tumor cells.

Actins↗