Papers by Stephanie Wethington
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, Jan 26, 2015
The purpose of this study was to assess the rate of lymph node (LN) metastasis in comprehensively... more The purpose of this study was to assess the rate of lymph node (LN) metastasis in comprehensively staged ovarian clear cell carcinoma (OCCC) clinically confined to the ovary and determine factors associated with LN metastasis. We identified all cases of OCCC treated at 4 institutions from January 1994 through December 2011. We included cases with disease grossly confined to the ovary that had surgical staging performed, including at least 10 LNs sampled. Clinical and pathologic data were abstracted from electronic medical records, and a deidentified data set was compiled and processed at a single institution. Factors potentially associated with LN metastasis were tested. Appropriate statistical tests were performed. We identified 145 eligible cases that met the criteria for this analysis. Median age was 52.9 years (range, 30-81 years), and median total LN count was 19 (range, 10-74). Seven (4.8%) of 145 comprehensively staged cases had LN metastasis; 6 of these cases (4.1%) were iso...
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists, Jan 3, 2015
Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a poor prognosis. It... more Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a poor prognosis. It has histologic features that overlap with other endometrial carcinomas and is frequently misclassified. Accurate classification is crucial, however, to improve treatment options. The objectives of this study were (1) to assess diagnostic interobserver variability among 5 gynecologic pathologists for tumors originally diagnosed as CC or with a component of CC (n=44); (2) to determine the utility of immunohistochemical markers estrogen receptor and HNF-1β; and (3) to detect mutations in select genes. Clinical data and morphologic features were also recorded. Agreement among reviewers was only moderate: only 46% of the original CC remained classified as such. After reclassification, estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC), and 47% of serous carcinomas (SC). Sensitivities of HNF-1β in CC, SC, and EC were 62%, 27%, and 17%, respectively, whereas specif...
International Journal of Gynecological Cancer, 2013
Radical trachelectomy has enabled select women with stage I cervical cancer to maintain fertility... more Radical trachelectomy has enabled select women with stage I cervical cancer to maintain fertility after treatment. Tumor size greater than 2 cm has been considered a contraindication, and those patients denied trachelectomy. We report our trachelectomy experience with tumors measuring 2 to 4 cm. We retrospectively reviewed the medical records of all patients planned for fertility-sparing radical trachelectomy. Largest tumor dimension was determined by physical examination, preoperative magnetic resonance imaging, or pathologic evaluation. No patient received neoadjuvant chemotherapy. Twenty-nine (26%) of 110 patients had stage IB1 disease with tumors 2 to 4 cm. Median age was 31 years (range, 22-40 years), and 83% were nulliparous. Thirteen patients (45%) had squamous cell carcinoma, 12 patients (41%) had adenocarcinoma, and 4 patients (14%) had adenosquamous carcinoma. Thirteen (45%) of 29 patients had positive pelvic nodes. All para-aortic nodes were negative. Owing to intraoperative frozen section, 13 patients (45%) underwent immediate hysterectomy and 1 patient (3%) definitive chemoradiation. Owing to high-risk features on final pathology, 6 patients (21%) who had retained their uterus received chemoradiation. Nine patients (31%) underwent a fertility-sparing procedure. At a median follow-up of 44 months (range, 1-90 months), there was one recurrence. Expanding radical trachelectomy inclusion criteria to women with 2- to 4-cm tumors allows for a fertility-sparing procedure in 30% of patients who would otherwise have been denied the option, with no compromise in oncologic outcome.
Gynecologic Oncology, 2008
Objective. To determine the utility and cost effectiveness of preoperative computed tomography (C... more Objective. To determine the utility and cost effectiveness of preoperative computed tomography (CT) in detecting disease extent in patients with uterine carcinoma.
Gynecologic Oncology, 2009
Review the literature on positive peritoneal cytology in endometrioid endometrial adenocarcinoma,... more Review the literature on positive peritoneal cytology in endometrioid endometrial adenocarcinoma, its prognostic value, proposed treatment strategies, and future avenues of investigation. PubMed search of articles pertaining to stage IIIA endometrioid endometrial adenocarcinoma identified over 50 articles that were reviewed. Low-risk stage IIIA1 was defined as those with grade 1 or 2 disease, no evidence of cervical involvement, myometrial invasion less than 50% and no lymph vascular space invasion (LVSI). Analysis of available data was completed with weighted averages, Student's-t-test and Chi square statistical analyses. Incidence of positive washings is approximately 11%. In low-risk stage IIIA1 endometrial carcinoma patients, the rate of recurrence is 4.1%. In contrast, in high-risk stage IIIA1 endometrial carcinoma patients the rate of recurrence is 32%, a statistically significant difference (p<0.001). Positive peritoneal cytology is associated with an increased incidence of extrauterine disease but is not consistently linked to other high-risk factors such as positive lymph node status, extent of myometrial invasion or LVSI. To date there is no definitive consensus on the prognostic significance of positive peritoneal cytology alone. However, even in the low-risk cohort with stage IIIA1 some patients will recur. Adjuvant therapy for low-risk stage IIIA diseased may or may not be of benefit. High-risk disease should be treated with chemotherapy, radiation or a combination thereof. A prospective, multicenter trial of comprehensively surgically staged patients with stage IIIA endometrial cancer is indicated in order to clearly define prognosis and treatment for these patients.
Gynecologic Oncology, 2012
Gynecologic Oncology, 2012
Conclusions: The addition of TPZ to CIS chemo-radiation did not improve PFS or OS, although defin... more Conclusions: The addition of TPZ to CIS chemo-radiation did not improve PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemo-radiation was tolerable at a modified starting dose. Further evaluation of other combination therapies with radiation in locally advanced cervix cancer is warranted.
Expert Review of Anticancer Therapy, 2008
Ovarian cancer remains one of the most difficult gynecologic cancers to treat, owing to its aggre... more Ovarian cancer remains one of the most difficult gynecologic cancers to treat, owing to its aggressive biology and high relapse rate, as well as the toxic side effects of available chemotherapeutic agents used to treat recurrent disease. Topoisomerase I inhibitors, including topotecan and irinotecan, are some of the most effective and tolerable treatment options for recurrent ovarian cancer. The ideal dosing, timing of administration, role in combination with other chemotherapies or biologics and potential role in up-front therapy remains an area of active research. This article reviews the mechanism of action of topoisomerase I inhibitors and the efficacy, dosing, schedule and toxicity for topotecan, irinotecan, 9-nitrocamptothecin, DX-8951 and 9-aminocamptothecin. Conclusions include a discussion of future avenues of research and ongoing projects.
Cancer, 2008
BACKGROUND. Fallopian tube cancers are rare neoplasms. These malignancies are thought to behave b... more BACKGROUND. Fallopian tube cancers are rare neoplasms. These malignancies are thought to behave biologically and clinically like ovarian cancer. The purpose of this study was to compare the clinical behavior and outcome of fallopian tube and ovarian cancer.
Annals of Surgical Oncology, 2011
Background. Endometrial polyps commonly affect premenopausal and postmenopausal women and carry a... more Background. Endometrial polyps commonly affect premenopausal and postmenopausal women and carry a small risk of cancer. Consensus guidelines to direct the management of women with endometrial polyps are lacking. We examined the risk of malignancy in symptomatic and asymptomatic women with endometrial polyps. Methods. Institutional databases were analyzed to identify women with pathologically confirmed endometrial polyps diagnosed from 2002 to 2007. Demographic, clinical, and pathologic outcomes were reviewed. The most significant pathologic diagnosis was recorded for each subject. Endometrial hyperplasia and cancer were characterized as arising in the polyp or the adjacent endometrium. Factors associated with atypical hyperplasia and cancer were analyzed. Results. A total of 1011 women with endometrial polyps were identified. On pathology review, 964 (95.4%) polyps were reported as benign, 13 (1.3%) as hyperplasia without atypia, 5 (0.5%) as hyperplasia with atypia, and 13 (1.3%) as endometrial cancer. The only clinical or demographic factor associated with atypical hyperplasia and cancer was menopausal status (P = .02). Among premenopausal women the risk of cancer or atypical hyperplasia was 0.9% in patients without bleeding and 1.0% in women with bleeding. In postmenopausal women cancer or atypical hyperplasia was found in 1.9% of patients without bleeding and in 3.8% of women with bleeding.
The American Journal of Surgical Pathology, 2012
It is unknown whether the type and grade of a primary endometrial carcinoma is reliably maintaine... more It is unknown whether the type and grade of a primary endometrial carcinoma is reliably maintained in recurrence. All matched primary and recurrent endometrial carcinomas diagnosed from 2000 to 2010 at our institution were identified; 34 cases had available slides. Histologic classification was performed using modifications to the World Health Organization criteria. Immunohistochemical analysis for p53, p16, progesterone receptor (PR), and DNA mismatch-repair proteins (MMR) (MLH1, MSH2, MSH6, and PMS2) was performed. Endometrioid carcinoma recurrences were mostly local, whereas serous carcinoma recurrences were mostly peritoneal. Compared with endometrioid carcinoma patients, serous carcinoma patients were older, presented at high stage, and had shorter survival. Serous carcinomas were the most common recurrent endometrial carcinoma (18/34 cases). Overall, 21 cases (62%) displayed similar morphology when comparing primary and recurrent carcinomas, whereas 13 displayed discordant morphology. Seven of 13 endometrioid carcinomas (54%) had a morphologically discordant recurrence, compared with 3 of 14 serous carcinomas (21%), 1 of 4 morphologically ambiguous carcinomas (25%), and both mixed epithelial carcinomas. Serous and morphologically ambiguous carcinomas therefore demonstrated relative morphologic fidelity compared with endometrioid carcinomas. Four morphologically discordant cases demonstrated either pure clear cell carcinoma or clear cell features at recurrence. Seven of 23 matched pairs displayed discordant PR results, with 5 cases, including both endometrioid and serous carcinomas, showing diminished PR expression at recurrence. p53, p16, and DNA MMR staining results were generally concordant when evaluating matched pairs, with only occasional exceptions. Sixty-four percent of all pure endometrioid carcinomas and mixed epithelial carcinomas with an endometrioid component showed loss of expression of MLH1 and/or PMS2; no serous carcinoma demonstrated this abnormality. Clinical and immunohistochemical data supported the use of modifications to the World Health Organization diagnostic criteria. More importantly, the data suggest that when confronted with recurrent endometrial carcinoma, particularly a serous carcinoma, it is reasonable to base therapeutic decisions on the type of the primary tumor, especially if sampling or excising the recurrent tumor is problematic. However, in light of the PR results, sampling a recurrent endometrioid carcinoma may be worthwhile if hormonal therapy is planned. Recurrent endometrioid carcinoma may be enriched for tumors with DNA MMR abnormalities.
Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women with BRCA mutation due to inc... more Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women with BRCA mutation due to increased risk of pelvic serous carcinoma. Serous tubal intraepithelial carcinoma (STIC) is a pathologic finding of unknown clinical significance. This study evaluates the clinical outcome of patients with isolated STIC. We retrospectively reviewed the medical records of consecutive patients with a germline BRCA1/2 mutation or a high-risk personal or family history of ovarian cancer who underwent RRSO between January 2006 and June 2011. All patients had peritoneal washings collected. All surgical specimens were assessed using the sectioning and extensively examining the fimbria protocol, with immunohistochemistry when indicated. p53 signature lesions and secretory cell outgrowths were excluded. Of 593 patients who underwent RRSO, isolated STIC was diagnosed in 12 patients (2%). Five patients (42%) were BRCA1 positive, 5 patients (42%) were BRCA2 positive, and 2 patients (17%) had high-risk family history. Preoperatively, all patients with STIC had normal CA-125 levels and/or pelvic imaging results. Seven patients underwent hysterectomy and omentectomy, 6 patients (46%) had pelvic node dissections, and 5 patients (39%) had para-aortic node dissections. With the exception of positive peritoneal washings in 1 patient, no invasive or metastatic disease was identified. No patient received adjuvant chemotherapy. At median follow-up of 28 months (range, 16-44 months), no recurrences have been identified. Among the cases of isolated STIC after RRSO reported in the literature, the yield of surgical staging is low, and short-term clinical outcomes are favorable. Peritoneal washings are the most common site of disease spread. Individualized management is warranted until additional data become available.
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Papers by Stephanie Wethington