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W F Symmans

Publications and source records attributed to W F Symmans.

32 records · Page 2Linked to original sources
PubMed1998

Stereotaxic aspiration biopsy in the evaluation of mammographically detected clustered microcalcification.

BACKGROUND: Stereotaxic fine-needle aspiration biopsy (SFNA) of mammographically detected nonpalpable lesions of the breast provides accurate diagnosis and may eliminate many unnecessary excisional biopsies of areas of microcalcification. METHODS: SFNA of microcalcification of indeterminate radiologic significance was performed on 125 patients (1991-1994), yielding 130 specimens (2 sites in 2 patients and bilateral aspirations in 3 patients). Stereotaxic localization was performed, and samples from within the area of microcalcification were obtained using 22-gauge needles. Smears stained with a Giemsa-type stain were prepared and studied by a cytopathologist during the procedure to determine the adequacy of each specimen. RESULTS: Of 130 specimens, 104 (80%) were cytologically benign, 13 (10%) were atypical, 6 (4.6%) were suspicious, and 7 (5.3%) were malignant. All malignant diagnoses were confirmed by subsequent operative biopsy. Follow-up was available in 74 of 104 benign cases (71%): surgical excisions (all benign) in 8 cases and follow-up mammograms at 6 months to 5.8 years in 66 cases (no radiologic change in 64 cases and 2 [1.9%] cases with new radiologic findings [SFNAs of the new radiographic abnormality revealed adenocarcinoma in both]). CONCLUSIONS: SFNA is a reliable and cost-effective method of evaluating indeterminate microcalcification; however, mammographic follow-up is indicated because of the possibility of subsequent and independent cancers.

Adult↗
PubMed1998

Malignant melanoma metastatic to the breast: a report of seven cases diagnosed by fine-needle aspiration cytology.

BACKGROUND: Metastases to the breast from extramammary primary tumors are uncommon. Malignant melanoma is one of the most common neoplasms to secondarily involve the mammary parenchyma. METHODS: Seven cases of malignant melanoma metastatic to the breast diagnosed by fine-needle aspiration biopsy are presented. RESULTS: The cytologic findings of malignant melanoma metastatic to the breast usually are straightforward on aspiration cytology. However, knowledge of a prior history of melanoma is crucial to make an accurate diagnosis. CONCLUSIONS: Malignant melanoma metastatic to the breast can be diagnosed reliably by fine-needle aspiration cytology, thus avoiding radical and unnecessary surgery.

Adult↗
PubMed1998

Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice.

We tested the antineoplastic effect of the farnesyltransferase inhibitor L-744,832 in mammary and lymphoid tumors overexpressing the N-ras proto-oncogene in transgenic mice. Mice bearing mammary tumors were randomly assigned to receive daily 40 mg/kg s.c. injections of this compound (experimental group, n = 6) or vehicle (control group, n = 6) per day for 5.5 weeks. Treatment with the compound significantly reduced the mammary tumor mean growth rate in the experimental group (-0.7 mm3/day), as compared with the control group (+28.2 mm3/day; P < 0.001). There was a significant difference in lymphoma incidence at the end of the treatment between the experimental (0 of 6) and the control (3 of 6) groups (P < 0.05). Therefore, this compound is effective in treating in vivo mammary carcinomas and lymphomas in which an activated N-Ras pathway drives tumorigenesis. The number of apoptotic figures in mammary tumors was significantly higher (P = 0.04) in the experimental (14.7 +/- 8.1) than it was in the control (5.7 +/- 3.5) group, indicating that apoptotic induction could contribute to the mechanism of antitumor activity of this compound. We analyzed the level of processing of N-Ras and H-Ras after immunoprecipitation and Western blotting of protein extracts obtained from mammary tumors treated with L-744,832 or vehicle, either in vivo or in vitro (after primary culture of the same tumors), and from several in vitro treated control cell lines. In all compound-treated mammary tumors and cell lines, H-Ras was mostly unprocessed (more so after in vitro than after in vivo treatment), whereas N-Ras remained mostly processed. Both H-Ras and N-Ras remained fully processed in all vehicle-treated samples. These findings are consistent with a less intense antineoplastic effect of the treatment with the compound in our N-ras model than the effect previously reported for the same compound in H-ras transgenics. In addition, the finding that, in compound-treated mammary tumors, the N-Ras protein remains mainly processed suggests that, in our model, other proteins in addition to Ras may be a target for the compound. Our results and the previous findings of frequent N-ras activation in human hematopoietic malignancies support a role for L-744,832 in the treatment of lymphomas and of mammary carcinomas with an activated N-Ras pathway, as well as the testing of a farnesyl protein transferase inhibitor in humans to establish its clinical relevance.

Alkyl and Aryl Transferases↗
PubMed1996

Activated N-ras oncogene and N-ras proto-oncogene act through the same pathway for in vivo tumorigenesis.

We compared the tumorigenic effects of the N-ras oncogene and the N-ras proto-oncogene in lymphoid and mammary tissues in an in vivo model. For this purpose, we generated transgenic mice with high levels of N-ras oncogene or N-ras proto-oncogene expression, driven by the complete mouse mammary tumor virus LTR (MMTV-LTR) (MMTV/N-rasT and MMTV/N-rasN constructs) and transgenic mice with low levels of N-ras oncogene or N-ras proto-oncogene expression, driven by a truncated MMTV-LTR (TMTV/N-rasT and TMTV/N-rasN constructs). We show that both, the N-ras proto-oncogene and the N-ras oncogene with a C:G-->A:T mutation at codon 61, lead to identical tumor types: lymphoblastic T-cell lymphomas, cleaved B-cell lymphomas and poorly differentiated mammary carcinomas. Nevertheless, there were quantitative differences in tumor incidence and latency and in transgene expression among N-ras oncogene and N-ras proto-oncogene transgenics. Despite these differences in tumor kinetics, the predisposition to identical tumor types is in agreement with the idea that the N-ras oncogene and the N-ras proto-oncogene act through the same pathway for in vivo tumorigenesis in B-cells, T-cells or mammary epithelial cells.

Animals↗
PubMed1996

Transfected neu oncogene induces human prostate cancer metastasis.

c-erb B2/neu has been demonstrated to be a transforming oncogene in both rodent and human prostatic epithelial cells. To understand the potential role of neu in human prostatic cancer progression, we used a transfer procedure to determine whether neu amplification/overexpression leads to increased tumor growth and metastasis. We chose an androgen-independent human prostatic epithelial cell line, PC-3, as the target for gene transfer. PC-3 cells were cotransfected with pSVneu-T (a point-mutated rat neu oncogene construct) and pSV2neo, and single-cell cloned. Fifty cell clones were isolated and characterized, of which two neu-transfected clones (N17 and N35) and a neo control clone (C32) were studied extensively with respect to neu gene integration, levels of neu mRNA and protein expression, anchorage-independent growth, and tumorigenic and metastatic potential. Results showed that: 1) Clone N35 contained 70 copies of the neu oncogene and a high level of neu mRNA transcripts. It acquired increased anchorage-independent growth potential in vitro and increased tumorigenicity in vivo. 2) Clone N17 contained 10 copies of the neu oncogene and a low level of neu mRNA transcripts. It did not acquire additional capability for anchorage-independent growth and tumorigenic potential as compared to the controls. 3) Despite an increased level of neu mRNA transcripts present in clone N35, there was no corresponding increase of the steady-state levels of neu protein in this particular clone. 4) When administered subcutaneously, none of the cell clones tested, including the control neomycin-resistant clone, acquired metastatic potential. However, clone N35 exhibited marked metastatic potential when administered orthotopically; this cell clone was found to disseminate widely to the lymph nodes, kidney, skeletal muscle, lung, liver, and bone. 5) When neu-transfected cell subclones from N35-induced primary and metastatic lymph node, kidney, and bone tumors were analyzed for cytoskeletal, extracellular matrix, and cell adhesion protein expression, the bone metastatic subclone exhibited increased levels of vimentin and collagen IV and decreased levels of cytokeratin and ICAM-1. These results, taken together, suggest that neu transfection induces secondary changes, which, rather than neu protein per se, are responsible for the acquisition of tumorigenic and metastatic potential of prostate cancer cells when an appropriate host microenvironment is present.

Animals↗
PubMed1995

Breast cancer heterogeneity: evaluation of clonality in primary and metastatic lesions.

Breast cancers often contain different clones of tumor cells. Attention to the cellular properties of breast cancer metastases may identify characteristics in primary tumors that are associated with metastasis. Such characteristics could include DNA content, cell proliferation, abnormal oncogene expression, or relative cell population (clonal dominance). We examined DNA ploidy (image analysis), proliferation index (proliferating cell nuclear antigen-1 immunostaining), and expression of Her-2/neu oncoprotein in 17 invasive breast cancer samples (36 primary tumor samples) and 82 corresponding regional metastases. In all samples the primary tumor was multiclonal (usually biclonal) by DNA ploidy analysis. In approximately 90% of metastatic DNA clones (30 of 34) the corresponding clone was identified in a primary tumor sample representing 25% or more of the tumor cell population (significant clone). A majority DNA clone (> or = of tumor cell population) existed in 60% (21 of 36) of primary tumor samples and in 70% (60 of 82) of metastases (30% diploid v 70% nondiploid in both groups). In approximately 50% of metastases (37 of 82) an unexpected majority clone was identified (not a majority in any primary tumor sample) and the ratio of diploid to nondiploid clones also was 30% to 70%. However, in 80% of majority metastatic clones (46 of 60) that clone was a significant primary tumor clone. Proliferation index was quite variable in primary tumor samples and in corresponding metastases. Overexpression of Her-2/neu oncoprotein in the primary tumor of seven of 10 patients also was identified in all corresponding metastases in five of seven patients and in some metastases in two of seven patients. The metastases in three Her-2/neu-negative patients were all negative. We conclude that (1) DNA clones are stable after metastasis, (2) clonal majorities in metastases reflect clones identified in primary tumors, (3) different metastatic clones from an individual tumor can establish clonal majorities, (4) neither diploid nor aneuploid cells have a metastatic advantage in breast cancer, (5) proliferation indices are heterogeneous, and (6) overexpression of Her-2/neu is usually consistent between primary tumors and corresponding metastases.

Breast Neoplasms↗
PubMed1991

Changes in nurse cell nuclei during synchronous infection with Trichinella spiralis.

The rate of enlargement of nuclei was determined on 4-microns-thick sections of synchronously infected mouse thigh muscle. Normal muscle nuclei had a geometric mean volume of 84 microns and a range of 42-170 microns 3. At days 5, 6, 7, 8, and 10 and 6 mo after infection, mean nuclear volume was 177 (100-315) microns 3, 254 (140-462) microns 3, 278 (172-447) microns 3, 681 (407-1,138) microns 3, 512 (326-804) microns 3, and 509 (298-870) microns 3, respectively. Size of nuclei for any given day followed a log normal distribution. On days 7 and 8 after infection, 31% of enlarged nuclei had 2 nucleoli, whereas only 15% had 2 nucleoli on day 10. One percent of enlarged nuclei in 6-mo-old nurse cells had double nucleoli. The number of enlarged nuclei in 6-mo-old nurse cells was determined from serial sections of infected tongue muscle. Each nurse cell contained an average of 40 enlarged nuclei. Sixty-four percent of nurse cells examined (n = 55) had between 30 and 60 enlarged nuclei. However, there was great variation in the range (7-142). These results are discussed in relation to the development of the nurse cell.

Animals↗
PubMedDate not supplied

Plasmacytoma of the breast. A report of two cases diagnosed by aspiration biopsy.

BACKGROUND: Extramedullary plasmacytoma of the breast is an uncommon neoplasm, occurring either as a solitary tumor or as evidence of disseminated multiple myeloma. CASE: Two cases of plasmacytoma of the breast were diagnosed by fine needle aspiration cytology. Aspiration smears showed a dispersed population of plasmacytoid cells with eccentric nuclei, abundant cytoplasm and the characteristic paranuclear hof. CONCLUSION: The clinical, cytologic and immunophenotypic features of plasmacytoma are characteristic, and the importance of distinguishing these neoplasms from primary mammary tumors is important to avoid unnecessary surgery.

ADP-ribosyl Cyclase↗
PubMedDate not supplied

Apoptotic index from fine needle aspiration cytology as a criterion to predict histologic grade of non-Hodgkin's lymphoma.

OBJECTIVE: To investigate whether the assessment of apoptotic index (AI) from fine needle aspiration (FNA) smears of non-Hodgkin's lymphomas (NHL) is reliable and has potential utility as a criterion to predict histologic grade. STUDY DESIGN: AI was independently determined by four cytopathologists as a percentage from routine FNA smears in 96 NHLs and 15 lymphoid hyperplasias. Working formulation (WF) grades from corresponding surgical biopsies were modified to include mantle zone-derived NHLs as intermediate grade and to make diffuse large cell NHL a separate category called "high" grade, whereas WF high grade NHLs were called "very high" grade. Histologic grades were also derived from the Revised European American Lymphoma (REAL) classification. AI was compared with histologic grade using the unpaired, two-tailed Student t test. These data were used to determine potential thresholds for AI that separate lower from higher grade NHLs. RESULTS: Measurements of AI strongly correlated between cytopathologists (median r = .93). Low and intermediate grade NHLs had indistinguishable AIs, whereas higher grade NHLs had significantly higher AIs. Appropriate potential AI thresholds between low or intermediate grade and higher grade NHLs were in the range of 1.5-2.5% (modified WF) and 1-2% (REAL). CONCLUSION: There is excellent interobserver reliability in the measurement of AI from FNAs of NHLs. Higher AIs distinguish higher from lower grade NHLs. Diffuse large cell NHLs had AIs that were similar to WF high grade NHLs.

Apoptosis↗
PubMedDate not supplied

Aspiration cytology of signet-ring cell lymphoma. A case report.

BACKGROUND: Signet-ring cell lymphoma is a rare subtype of non-Hodgkin's lymphoma, composed of vacuolated cells with a signet-ring cell appearance. We found only two cases that had been reported as diagnosed by fine needle aspiration biopsy. CASE: A 61-year-old female had signet-ring cell lymphoma diagnosed by computed tomography-guided aspiration biopsy. Smears of aspirates from her retroperitoneal mass contained a population of small to medium-sized, angular lymphoid cells; lymphoglandular bodies; and an abundance of signet-ring cells. The signet-ring cells were negative for cytokeratin and positive for leukocyte common antigen and CD20, a B-cell marker. Monoclonality for lambda light chain determinant was noted, and a diagnosis of signet-ring cell lymphoma of the B-cell type was made. A core biopsy specimen confirmed the diagnosis. CONCLUSION: Signet-ring cell lymphoma should always be considered in the differential diagnosis of tumors composed of signet-ring cells.

Antigens, CD↗
PubMedDate not supplied

Pancreatic endocrine tumor with signet ring cell features: a case report with novel ultrastructural observations.

The case of a malignant pancreatic endocrine neoplasm with an unusual signet ring cell appearance is reported. The tumor was resected from a 30-year-old man with a 4.0-cm tumor in the body of the pancreas diagnosed by computerized tomographic (CT) scan. The resected tumor had a unique morphology characterized by numerous mucin-negative, signet ring cells, which were argyrophilic and immunoreactive for cytokeratin (CAM 5.2), chromogranin, synaptophysin, neuron specific enolase, and gastrin. Dense-core neurosecretory-type granules and numerous cytoplasmic lamellar inclusions were identified by electron microscopy. These inclusion bodies consisted of multilayered concentric osmiophilic lamellae (myelin figures), which most likely represent an abnormal accumulation of degenerating organelles. Two years later, the patient developed an abdominal recurrence of the tumor, confirming its malignant behavior. This case expands the spectrum of pancreatic endocrine tumors to include an aggressive signet ring cell tumor with a novel ultrastructural basis.

Abdominal Neoplasms↗
PubMedDate not supplied

Transformation of follicular lymphoma. Expression of p53 and bcl-2 oncoprotein, apoptosis and cell proliferation.

Transformation in follicular lymphoma represents an abrupt transition in tumor biology. The protein product of the bcl-2 oncogene is overexpressed in most follicular lymphomas and inhibits apoptosis. The protein product of the p53 oncogene prevents cell proliferation and induces apoptosis and is overexpressed in the dysfunctional (mutated) form. We studied 15 transformed lymphomas (large cell type), 7 follicular lymphomas before transformation and 2 control groups of follicular center cell lymphomas with no evidence of transformation (9 small cleaved cell and 10 de novo large cell lymphomas). High p53 expression (> or = 45% cells) was detected by immunostaining in 9/15 transformed lymphomas as compared with 0/10 de novo large cell lymphomas and 1/7 follicular lymphomas. Overexpression of bcl-2 (> or = 50% cells) was similar in transformed (11/15) and de novo large cell lymphomas (6/10). The apoptotic index was high (> or = 2%) in all transformed and large cell lymphomas and low in all follicular lymphomas and in the control group of small cleaved cell lymphomas. The apoptotic index in the transformed lymphomas appeared to be independent of bcl-2 expression and was sometimes paradoxically high in the presence of both p53 and bcl-2 overexpression. The apoptotic index was weakly associated with bcl-2 expression in de novo large cell lymphomas. Expression of p53 did not correlate with proliferation index. Our results indicate that p53 overexpression is a specific step associated with transformation and may occur shortly before it. This is not seen in de novo large cell lymphoma. Furthermore, the high apoptotic index in transformed lymphomas often occurs despite overexpression of bcl-2 and p53, implying that other factors may induce apoptosis in these tumors.

Apoptosis↗
PubMedDate not supplied

Meningeal meningiomatosis in a child: case report.

We report a child with multifocal meningeal lesions demonstrating mixed meningiomatous histologic features. This lesion appears to have evolved over seven years, starting with a brief episode of garbled speech, nausea, and headache at 4.5 years of age. The child was then asymptomatic until 9 when she presented with bilateral leg weakness, in addition to her prior presenting symptoms and communicating hydrocephalus. Meningeal biopsies of two lesions were performed 18 months later. Immunohistochemistry and electron microscopy were needed to substantiate the histologic diagnosis. Radiation therapy to the craniospinal axis and corticosteroids were of some benefit, but more aggressive therapeutic modalities became necessary. The nosology of this lesion is discussed.

Adolescent↗