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S G Silverberg

Publications and source records attributed to S G Silverberg.

At least 37 records · Page 2Linked to original sources
PubMed1999

Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas.

To assess the hypothesis that oral contraceptives (OCs) increase the risk of cervical adenocarcinomas, we conducted a six-center case-control study of 124 patients with adenocarcinomas, 139 with squamous cell carcinomas, and 307 population controls. Women between the ages of 18 and 69 who were newly diagnosed with cervical adenocarcinomas between 1992 and 1996 were eligible. Healthy female controls and a second case group of incident cervical squamous cell carcinomas were matched to the adenocarcinoma cases. All participants were interviewed regarding OCs, other risk factors for cervical carcinoma, and utilization of cytological screening, and a PCR-based test determined HPV genotype of cervical samples for both case groups and controls. Use of OCs was positively and significantly associated with adenocarcinomas and positively but weakly associated with squamous cell carcinomas. Associations between OCs and invasive adenocarcinomas (n = 91), squamous cell carcinoma in situ (n = 48), and invasive squamous cell carcinomas (n = 91) disappeared after accounting for HPV infection, sexual history, and cytological screening, but a positive association remained between current use of OCs and cervical adenocarcinoma in situ (n = 33). This association persisted after stratification by screening and sexual history and after restriction according to HPV status, but small numbers made it difficult to exclude detection bias, selection bias, or residual confounding by HPV as potential explanations Current OC use was associated with cervical adenocarcinomas in situ, but we saw no other evidence that OCs independently increase the risk of cervical carcinomas.

Adenocarcinoma↗
PubMed1998

Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up.

BACKGROUND: Most published series of ovarian carcinoma find a correlation between histologic grade and survival, but the grading system used commonly is not specified, and several different systems exist, some of which use different criteria for different histologic types. However, several studies have shown marked interobserver variability in distinguishing among the histologic types of ovarian carcinoma. The authors attempted to derive a universal grading system for all invasive ovarian carcinomas (IOC), based on the Nottingham system for grading all types of mammary carcinoma. METHODS: The authors studied 461 patients with IOC of different histologic types and clinicopathologic stages who were treated in a uniform manner between 1980 and 1994 with surgery and cisplatin-based chemotherapy. All slides were reviewed and the tumors graded as follows: Architectural pattern (predominant): Glandular = 1, Papillary = 2, and Solid = 3; Nuclear pleomorphism: Slight = 1, Moderate = 2, and Marked = 3; Mitotic activity (mitotic figures per 10 high-power fields [1 HPF = 0.345 mm2]) in most active region: 0-9 = 1, 10-24 = 2, and > or = 25 = 3; Grade 1 = total score (adding three values obtained earlier) 3-5, Grade 2 = 6 or 7, and Grade 3 = 8 or 9. RESULTS: Tumor grade correlated with survival in both early and advanced stage disease and for all major histologic types of IOC except clear cell carcinoma (CCC). Results for CCC approached but did not reach clinical significance. By multivariate analysis, only this tumor grade and performance status were significant in Stage I/II IOC. For Stage III/IV tumors, the new tumor grade also was significant, as were performance status, residual tumor size, response to chemotherapy, and mucinous (unfavorable) or transitional cell (favorable) histologic type. International Federation of Gynecology and Obstetrics grade (based primarily on architectural features) did not correlate significantly with survival except in Stage III/IV serous and Stage I/II mucinous carcinomas. CONCLUSIONS: The new grading system reported is simple, reproducible (among the current study authors), and useful for all histologic types and clinical stages of IOC. Further testing for reproducibility and clinical utility is recommended.

Carcinoma↗
PubMed1998

Interobserver variability in the classification of proliferative breast lesions by fine-needle aspiration: results of the Papanicolaou Society of Cytopathology Study.

This study evaluates the applicability of the published cytologic criteria in the categorization of proliferative breast lesions by assessing the diagnostic accuracy and interobserver reproducibility of a panel of experts. Twelve breast fine-needle aspiration (FNA) specimens of biopsy-proven nonproliferative breast lesion (NPL) (1 case), proliferative lesions without atypia (PL) (7 cases), proliferative lesion with atypia (PLA) (1 case), and low-nuclear grade ductal carcinoma in situ (DCIS) (3 cases) were selected. Six FNAs were Papanicolaou (PAP) and 6 were Diff-Quik-stained (DQ). Six expert cytopathologists classified the smears using a summary of published criteria as a guideline. All 6 participants rendered the same cytologic diagnosis in 2/12 (16%) cases. The agreement among the 6 raters was low (Kappa = 0.35). Cytohistologic correlation was achieved in 26/72 (36%) FNA diagnoses. The correlation of the PAP-stained cases was better than the DQ: 17/36 (47%) PAP and 9/36 (25%) DQ correlated. Improving the correlation was achieved by amalgamation of NPL and PL into "low risk" and PLA and DCIS into "high risk" categories: 47/72 (65%) FNA diagnoses then correlated with histology [29/36 (81%) PAP and 18/36 (50%) DQ]. We conclude that the cytologic criteria of proliferative breast lesions need to be further defined and assessed. Consideration should be given to minimizing the number of diagnostic categories and adopting a terminology that has a direct effect on patient management.

Adult↗
PubMed1998

Toward the development of a universal grading system for ovarian epithelial carcinoma. I. Prognostic significance of histopathologic features--problems involved in the architectural grading system.

OBJECTIVE: Because there is no universally accepted grading system for ovarian epithelial carcinoma, we attempted to compare the prognostic utility of the individual components used in some systems--both architectural and cytologic features, as well as mitotic activity and histologic tumor type--to determine which of these components fit best with survival. METHODS: We studied 461 patients with invasive ovarian carcinoma who had uniform treatment, complete clinical data including staging and follow-up, and slides available for review. Each tumor was assigned a histologic subtype, architectural grade (based on whether the predominant pattern was glandular, papillary or solid), nuclear grade, mitotic count, and FIGO grade (based on the system for endometrial carcinoma). These features were compared with each other and with tumor stage and survival. RESULTS: The architectural grade, nuclear grade, and mitotic count were independent variables both in stage I/II and stage III/IV disease. Each of them correlated with survival for most combinations of histologic type and stage. By multivariate analysis, in stage I/II cancer, nuclear grade and architectural grade were significantly correlated with survival, mitotic count showed only a trend, and FIGO grade did not correlate. In stage III/IV disease, nuclear grade, architectural grade 3, and mitotic count were significant, and FIGO grade was not. CONCLUSION: The new architectural grading system proposed worked better than the FIGO system in this study. Furthermore, it could be applied to all histologic subtypes of carcinoma. The nuclear grade and mitotic count were also independent of each other, correlated with survival, and could be utilized for all histologic types. These data support the development of a grading system which combines these architectural, nuclear, and mitotic features and can be applied regardless of the histologic type of carcinoma, modeled after the Nottingham system for grading of breast carcinoma.

Carcinoma↗
PubMed1998

Mammographic-histopathologic correlation of large-core needle biopsies of the breast.

Large-core (14g) needle biopsy (CNB) of the breast is a new diagnostic modality increasingly being used to evaluate patients with mammographic abnormalities. Two hundred twenty-four CNBs were performed on 198 patients. Surgical follow-up was available in 64 cases (28.6%). Overall concordance rate was 93.8% (60 of 64 cases). Of the four discordant cases, two were diagnosed as atypical ductal hyperplasia (ADH) on CNB; on excision, these cases showed cribriform ductal carcinoma in situ (DCIS); two remaining cases, diagnosed on CNB as ADH versus DCIS, showed invasive carcinoma (DCIS with invasive component and infiltrating cribriform carcinoma, respectively) on excisional biopsy. Malignancy, primary (52) or metastatic (5), was identified in 57 cases (25.4%); 47 of these patients underwent surgical excision, and the diagnosis was confirmed in all of these cases. Of 51 cases with radiographic evidence of microcalcifications, 48 (94%) had microcalcifications in the CNB: 30 (62.5%) were benign, 11 (22.9%) were malignant, and 7 (14.6%) were diagnosed as ADH. In the remaining three cases (1.3%), only benign breast tissue without microcalcifications was seen, and the lesion was considered to have been missed. Biopsy specimens were obtained from 173 lesions because of the presence of a mass: 125 (72.3%) were benign, 45 (26%) were malignant, and 3 (1.7%) were diagnosed as ADH. Follow-up was available in 118 patients with benign lesions: all were mammographically stable or decreased at 6 or 12 months; no follow-up was available for the remaining patients. CNB of the breast is a highly sensitive (96.9%) and specific (100%) technique for management of patients with mammographic abnormalities. The histologic findings should be correlated with the mammographic appearance, and an attempt should be made to achieve a specific diagnosis in all lesions, particularly masses. The diagnosis of ADH should always prompt excisional biopsy because of a high frequency of false-negative results caused by sampling errors or underestimation.

Adolescent↗
PubMed1998

Endometrial polyps: a comparison study of patients receiving tamoxifen with two control groups.

Many reports describe an increased frequency and unusual features of endometrial polyps and carcinomas in women treated with tamoxifen (TMX) for breast cancer. Postmenopausal women with endometrial polyps were identified by computer search of pathology files from 1990 to 1996. Medical records were reviewed, and patients were divided into three groups: 28 receiving TMX for breast cancer, 23 receiving hormone replacement therapy (HRT), and 28 untreated controls (UC). Cumulative doses (CDs) of TMX were calculated. Histologic slides of polyps were reviewed blindly and evaluated for size, metaplasias, vascularity, fibrosis, and inflammation. Carcinomas were found in 3 TMX, no HRT, and 1 UC patient. Atypical hyperplasias were found in 1 TMX, 0 HRT, and 1 UC patient. Mean polyp size was larger in the TMX group (2.9 cm) than in the HRT (1.05 cm) and UC (1.35 cm) groups, and stromal fibrosis was more prominent in TMX-related and larger polyps. Mucinous metaplasias were observed more frequently in the patients receiving TMX. No other differences were noted. The two TMX patients in whom low-grade carcinomas developed and the one with atypical hyperplasia had independent risk factors. CDs for these patients were 32.9, 36.5, and 17.6 g, respectively. A high-grade carcinoma developed in a TMX patient without constitutional risk factors at a CD of 94.9 g. On the basis of a literature review and these results, low-grade carcinomas developing after relatively low CDs of TMX may be at least partially attributable to other risk factors. The association between poorly differentiated and nonendometrioid tumors with higher TMX CDs is still speculative, but the current study suggests that they may be related to TMX. A statistically significant increase in the frequency of thyroid replacement use by TMX patients is also noted.

Aged↗
PubMed1997

Loss of heterozygosity on chromosome 11q13 in lobular lesions of the breast using tissue microdissection and polymerase chain reaction.

Demonstration of identical allelic loss on chromosome 11q13 in synchronous in situ (DCIS) and invasive ductal (IDC) breast carcinoma has provided molecular evidence of the progression of DCIS to IDC. We investigated loss of heterozygosity (LOH) at chromosome 11q13 in the spectrum of "marker/premalignant" and "malignant" lobular lesions of the breast, including atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and infiltrating lobular carcinoma (ILC). Thirty-eight cases with various combinations of ALH, LCIS, and ILC were studied. Synchronous ductal lesions were present in 9 of 38 cases. Areas of interest were specifically isolated by tissue microdissection. The extracted DNA was amplified by polymerase chain reaction (PCR) and analyzed with two polymorphic markers for chromosome 11q13 (INT2 and PYGM). LOH at 11q13 was identified in ILC and LCIS in approximately one third of informative cases. LCIS in association with ILC showed a loss in 50% of cases, whereas pure LCIS in the absence of ILC had a much lower frequency of LOH, which was comparable to that of pure ALH. These results suggest that LOH on chromosome 11q13 may play an important role in development of ILC, similar to that of IDC from DCIS/ADH. Additionally, frequent LOH in ILC and LCIS associated with ILC and a significantly lower and comparable frequency of LOH in LCIS without ILC and ALH implies that genetic alteration(s) on chromosome 11q13 may be important in the transition of LCIS to ILC. LOH was detected in three of nine synchronous ductal lesions (one IDC and two DCIS), confirming our earlier findings and indicating that lobular and ductal neoplasia in the breast show some similar genetic changes. We hypothesize that LOH may help in separating morphologically similar yet genetically different subgroups of ALH and LCIS into one group with genetic changes and an increased potential to progress to invasive cancer and another group, the "marker" lesions of LCIS/ALH, that remain stable or possibly regress.

Breast Neoplasms↗
PubMed1997

Telomerase expression in normal endometrium, endometrial hyperplasia, and endometrial adenocarcinoma.

Telomerase activity has been detected in a broad range of human cancers and its expression could be an important step in tumor progression. Here, telomerase activity by the telomeric repeat amplification protocol in cases of benign endometrium, endometrial hyperplasia, and endometrial adenocarcinoma was tested. Telomerase expression was detected in 13 of 14 cases of proliferative phase endometrium, in 7 of 12 cases of secretory phase endometrium, but was not detected in any of 7 cases of atrophic endometrium. Three of three cases with evidence of luteal phase defect and one of four cases of chronic endometritis also expressed telomerase activity. Hyperplastic endometrium was positive for telomerase in 13 of 17 cases. Telomerase activity was detected in 40 of 48 cases of endometrial adenocarcinoma, which included 36 of 43 cases of endometrioid adenocarcinoma and four of five cases of papillary serous carcinoma. The detection of telomerase in endometrial adenocarcinoma was not associated with either architectural grade, myometrial invasion, or stage. There was statistically significant association, however, between telomerase activity in benign atrophic endometrium versus any endometrial abnormality in women 52 years of age or older.

Adenocarcinoma↗
PubMed1996

K-ras point mutations in endometrial carcinoma: effect on outcome is dependent on age of patient.

Mutations involving the K-ras proto-oncogene are believed to play an important role in the mechanism of tumorigenesis for many human cancers and occur in 10-30% of endometrial carcinomas. In the present study 221 cases of endometrioid endometrial carcinoma obtained from Japanese patients with average follow-up of 41 months were examined for point mutations in codon 12 of K-ras through use of the polymerase chain reaction. In 103 cases lymph node dissection had been performed. K-ras mutations were significantly associated with the presence of lymph node metastases (P < 0.04). Since endometrial carcinoma in premenopausal women generally behaves less aggressively than tumors of similar histologic grade arising in postmenopausal patients, we evaluated the effect of K-ras mutation on outcome in patients stratified into three different age categories (<53 years, premenopausal; 54-59 years, perimenopausal; >60 years, postmenopausal). In the postmenopausal age group (>60 years), the presence of K-ras mutations was statistically significantly associated with patients who died or experienced recurrence (41.2% vs 13.0%; P < 0.03). This was related to a dramatic (greater than eightfold; P = 0.011) increase in the likelihood of adverse outcome between the premenopausal and postmenopausal states for patients whose tumors contained mutant K-ras. These findings point to a possible role for K-ras activation in the mechanism(s) responsible for more aggressive clinical behavior of endometrioid endometrial cancer that is observed in postmenopausal patients.

Adult↗
PubMed1996

Microinvasion in low malignant potential tumors of the ovary.

The presence of microinvasion (Mi) has not previously been investigated in nonserous low malignant potential (LMP) tumors of the ovary. In serous LMP tumors (SLMP), Mi has not worsened the prognosis compared with usual SLMP in previous reports. In a retrospective clinicopathologic review of 126 cases of serous and mucinous LMP (MLMP) tumors of the ovary, the authors identified 14 cases with Mi: seven of 72 SLMP, four of 44 mucinous intestinal LMP (MILMP), and three of 10 mucinous müllerian LMP (MMLMP). Tumors with Mi resembled usual LMP histologically except for small foci (up to 0.2 cm) in the stroma consisting predominantly of single cells or small clusters of cells, sometimes in a cribriform pattern. In SLMP-Mi, the cells had eosinophilic cytoplasm, and the stromal reaction was minimal/absent. In MILMP-Mi and MMLMP-Mi, nuclear staining was paler; the stroma often showed a fibrous reaction or edema, especially in MILMP-Mi. All 14 patients had follow-up (2.2 to 18.6 years) and were without evidence of disease. Careful screening of both mucinous and serous ovarian LMP can show Mi. Mi foci should be distinguished from true stromal invasion, pseudoinvasion, endothelial cells, decidual cells and histiocytes, and pseudomyxoma in mucinous LMP. Mi does not seem to worsen prognosis in MLMP and SLMP tumors of the ovary.

Adult↗
PubMed1996

Placental site nodule occurring in a fallopian tube.

The placental site nodule (PSN), a recently described benign lesion of intermediate trophoblast, is usually an incidental finding in younger women. It is a well-circumscribed, round to oval lesion that is extensively hyalinized and immunohistochemically stains for cytokeratin, placental alkaline phosphatase (PLAP), human placental lactogen (HPL) and, focally, for human chorionic gonadotropin (HCG) and epithelial membrane antigen (EMA). Thus far, the cases reported have been found in endometrial curettage or hysterectomy specimens. The pathogenesis of PSN is yet to be ascertained; however, there is wide acceptance of the fact that it represents a remnant of the placental implantation site. If this is indeed the case, it should not be surprising to find PSN occurring at sites of ectopic gestation. We describe herewith a case in which PSN was found in a fallopian tube segment resected in a postpartum tubal ligation.

Adult↗
PubMed1996

Advanced stage transitional cell carcinoma of the ovary.

Primary transitional cell carcinoma (TCC) of the ovary has been recently recognized as a separate subtype of epithelial cancer. It has been proposed that recognition of such tumors is important on clinical grounds because of a favorable response to chemotherapy and an improved patient survival. The authors reviewed the histological and clinicopathologic findings of 58 patients with advanced stage (stages III and IV) ovarian cancer with a view to determining the frequency of TCC and confirming the favorable prognosis. Of these cases, 15 (26%) were reclassified as TCC; 13 were predominantly TCC, and 2 had a mixed pattern with approximately 50% of the tumor being TCC. TCC patients ranged in age from 44 to 70 years of age (mean, 57). Ten of the patients had stage III disease, and five were stage IV. The tumor was unilateral in 2 cases and bilateral in 11 (2 unknown). Tumor size varied between 3 and 23 cm. Of the stage III patients, five were optimally debulked, and five had residual disease. All patients received the same type of chemotherapy. The median overall survival was 28 months. There was no significant difference in the clinical outcome of patients with TCC compared with that of patients with serous carcinomas. These data suggest that TCC does not confer a favorable prognosis or better response rate to chemotherapy.

Adolescent↗
PubMed1996

Proliferative activity of postmenopausal endometriosis: a histopathologic and immunocytochemical study.

Histological features of 21 cases of postmenopausal endometriosis as well as the corresponding eutopic endometrium were studied. Immunocytochemical analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 nuclear antigen was also performed on the endometriotic lesions as well as the corresponding endometrium. All the cases studied were complicated by various other gynecologic diseases, making the preoperative diagnosis of endometriosis unlikely. Histologically, the endometriotic foci contained both epithelial and stromal components mostly lacking atrophic features in contrast to the corresponding eutopic endometrium. The endometriotic lesions and the corresponding endometrium exhibited immunoreactivity with ER in both the glands and stroma. The stromal cells of endometriotic lesions revealed positive PR staining, whereas those of the eutopic endometrium were either negative or weakly positive for PR, but the epithelial components of both were positive for PR. The positivity of Ki-67 antigen tended to be higher in the stroma of the postmenopausal endometriosis than in the eutopic endometrial stroma. Endometriotic lesions appear to remain biologically active, with proliferative activity as well as retained hormonal responsiveness, even in the low-estrogen milieu of the postmenopausal age.

Adult↗
PubMed1996

Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma.

The in situ formation of estradiol plays an important role in the development and biological behavior of human breast cancer Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD type 1) are two principal enzymes involved in in situ estradiol production. We evaluated the expression of aromatase and 17 beta-HSD type 1 by immunohistochemistry in 41 cases of invasive breast carcinoma (19 lobular and 22 ductal). We then examined the correlation among the expression of these enzymes, estrogen (ER) and progesterone (PR) receptor status, Ki67 labeling index of carcinoma cells, age, and the clinical stage of the patients. Marked aromatase immunoreactivity was observed in stromal cells around carcinomatous glands in 32 of 41 cases (78%), and 17 beta-HSD type 1 immunoreactivity was detected in carcinoma cells in 23 of 41 cases (56%). There was a significant correlation observed between expression of 17 beta-HSD type 1 and aromatase in invasive lobular carcinoma (P = 0.0119), but not in invasive ductal carcinoma. There was an inverse correlation between aromatase and ER status in invasive ductal carcinoma (P = 0.0213), but not in invasive lobular carcinoma. No other correlations were observed among 17 beta-HSD type 1, aromatase, PR, ER, clinical stage, age, and Ki67 labeling indexes. Aromatase and 17 beta-HSD are not always expressed simultaneously in human breast carcinoma, but their simultaneous expression is more frequent in invasive lobular carcinoma than invasive ductal carcinoma. Consequently, different mechanisms may be involved in the regulation of expression of these two enzymes in human breast carcinoma.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

DNA analysis and S-phase fraction determination by flow cytometric analysis of infiltrating lobular carcinoma of the breast.

Flow cytometric analysis was performed on 50 infiltrating labular carcinomas (ILCs) of the breast from 50 patients with clinical follow-up (average duration, 4.1 yr) who had been treated between 1976 and 1991. The patients were classified as alive with no evidence of disease, alive with disease, or dead of disease. Ploidy and S-phase fraction (SPF) were compared with clinical outcome, histologic pattern (classical versus variant patterns), nuclear grade 1 or 2, axillary lymph node status, tumor size, percentage of signet ring cells, and estrogen receptor status. There was no association between aneuploid or diploid ILC and disease recurrence (of those patients classified as alive with no evidence of disease plus dead of disease, 4 (40%) of 10 were aneuploid and 15 (38%) of 40 were diploid), survival (of those classified as alive with no evidence of disease plus alive with disease, 9 (90%) of 10 were aneuploid and 36 (90%) of 40 were diploid), or any of the other factors evaluated. However, ILCs with a high SPF were more likely to recur than those with a low SPF (a high SPF was found in 9 [56%] of 16; a low SPF was found in 9 [30%] of 30), but this relationship was not statistically significant (P = 0.08). When only diploid ILCs were considered, there was a statistically significant association between high SPF and recurrence (a high SPF was found in 9 [64%] of 14, a low SPF was found in 6 [24%] of 25, P = 0.033). After the stratification of the diploid ILCs by the stage of disease, this relationship persisted only in Stage 1 (recurrence: a high SPF was found in 3 [75%] of 4; a low SPF was found in 1 [9%] of 11, P = 0.033). There was no association between SPF and any of the other factors evaluated. Our study indicates that ILC is usually diploid and that SPF may be a prognostic indicator that is limited to Stage 1 disease.

Breast Neoplasms↗
PubMed1995

Mature cystic teratomas of the ovary with intestinal wall structures harboring intestinal- type epithelial neoplasms.

Mature cystic teratomas of the ovary frequently contain intestinal-type tissues, but these rarely organize into complete intestinal walls, including all layers, and even more rarely develop secondary neoplasms. The present report documents two mature teratomas with formation of complete segments of intestinal wall, one also containing a benign mucinous cystadenoma of the appendiceal type and the other an intestinal-type adenocarcinoma infiltrating into the neoplastic bowel wall but not the surrounding ovarian parenchyma. The latter patient is alive and well 5 years after surgery. These cases expand the repertoire of secondary neoplasms, benign and malignant, developing in mature cystic teratomas.

Adenocarcinoma↗