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Extrauterine endometrial stromal sarcoma: A pathologic study of 63 cases with clinical correlation
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Abstracts / Gynecologic Oncology 125 (2012) S3–S167
expression group) and 48.54 (+/− 7.91 normal expression group). 31 tested positive for loss of expression and 129 retained normal expression. Loss of expression group showed statistical difference, with a greater incidence of Grade III tumors in this group (p = 0.0013) and less Grade I tumors (p = 0.0020), greater depth of myometrial invasion (p = 0.0019), greater incidence of positive lymph node metastases (p = 0.0157), and positive lymphvascular space involvement (p = 0.0020). Lower BMI was noted in the loss of expression group as well (p = 0.0001), with 48% having normal to underweight BMI at time of diagnosis versus 23% in the normal expression group. No patients in the loss of expression group had BMI N 40, although 35% of the normal expression group had BMI N 40. Conclusions: The DNA mismatch repair mechanism primarily involves 2 functional pairs of genes. MSH6 and MSH2 recognize and bind to mismatched DNA sequences. MLH1 and PMS2 excise and repair the mismatched nucleotides. Loss of function of DNA mismatch repair genes has been reported in 30% of patients with endometrial cancer. This loss of function may be attributed to germline mutations, spontaneous mutations, or epigenetic silencing of the MLH1 promoter region and is associated with poor prognostic features in premenopausal and perimenopausal patients with endometrial cancer. Women with loss of gene expression tended to have lower BMI at time of surgery. There are no significant differences in subgroups with MSH6/MSH2 loss of expression and MLH1/PMS2 loss of expression. Long-term follow-up is necessary to evaluate for differences in survival of these patients. doi:10.1016/j.ygyno.2011.12.393
393 Assessment of patients with endometrioid adenocarcinoma (EC) of the uterus falling in the ‘gap’ between PORTEC 1 high intermediate risk and GOG 99 high intermediate risk (HIR) E. Nugent, E. Bishop, C. Mathews, K. Moxley, R. Mannel, J. Walker, K. Moore, L. Landrum, D. McMeekin. University of Oklahoma, Oklahoma City, OK. Objective: Several models for predicting risk of recurrence and need for postoperative treatment in EC have been described. In PORTEC 1 and GOG 99, age and uterine factors define HIR. Risk of recurrence is similar between these studies, both predicting ~ 23% to 27% risk of recurrence for HIR pts treated with surgery alone. Controversy exists when patients have uterine factors meeting 1 rather than both risk model assessments of HIR (termed 'gap' patients). The objective of this study was to determine how meeting HIR for either GOG 99 or PORTEC HIR criteria affects recurrence and survival compared to meeting both models' HIR criteria. Methods: A retrospective review of patients undergoing complete surgical staging for clinical stage 1 EC was performed from 1996 through 2008. Patients were categorized as meeting eligibility for PORTEC 1 and for having HIR inclusion criteria (presence of 2 factors: age N 60, grade 3, greater than 50% DOI). Pts were also classified as having met GOG 99 inclusion criteria and having HIR features (age N70 +1 factor, age 50–70 +2 factors, any age +3 factors: grade 2 or 3, LVSI, N50% DOI), irrespective of nodal status(LN). Uterine factors, recurrence rates, nodal positivity rates, PFS, and OS were compared in those patients meeting a single HIR criterion to those meeting both HIR models. Results: We identified 352 clinical stage 1 patients. 66 patients met PORTEC HIR criteria. The frequency of LN positivity in HIR patients was 19.7% and recurrence rate was 27.3%. 188 patients met HIR for GOG 99, with 34.6% lymph node positivity and 28.3% recurrence rate. 80 patients met either GOG 99 HIR or PORTEC 1 HIR but not both (71 and 9 patients,
respectively). Gap patients had a recurrence rate of 14.5% and a nodal positivity rate of 33.8%. Compared to patients meeting both HIR models, gap patients were significantly less likely to recur (p=0.0016), had less myometrial invasion(p b 0.0001), and lower stage (p= 0.0002). There was no difference in grade, cervical involvement, LVSI, or nodal status between patients meeting 1 or 2 HIR models. 48-month PFS and OS were improved in gap patients (81.1% vs 55.3%, p = 0.0007 and 80.3% vs 59.3%, p = 0.0005, respectively). Conclusions: Patients meeting either GOG 99 HIR or PORTEC HIR but not both have an improved prognosis compared to those meeting the criteria of both HIR models. The patients have a substantial risk of nodal involvement and a relatively high rate of recurrence, potentially affecting patient counseling and adjuvant treatment. doi:10.1016/j.ygyno.2011.12.394
394 Extrauterine endometrial stromal sarcoma: A pathologic study of 63 cases with clinical correlation R. Masand, E. Euscher, M. Deavers, A. Malpica. The University of Texas, MD Anderson Cancer Center, Houston, TX. Objective: Extrauterine endometrial stromal sarcoma (EESS) is an uncommon tumor that occurs in patients (pts) over a wide age range and frequently in association with endometriosis. The non-gynecologic symptoms/signs at presentation, the extrauterine location, and confounding pathologic features can pose a diagnostic challenge. The purpose of this study is to evaluate the clinical and pathologic findings of 63 such cases. Methods: Sixty-three cases of EESS from a period of 20 yrs were retrieved from the pathology database. Clinical information was obtained from the pts' charts and questionnaires sent to physicians. The following clinical parameters were recorded: pts' age, clinical presentation, treatment (tx), recurrences and current status. In 46 cases, slides were re-reviewed. The following pathologic parameters were recorded: size and location, gross and microscopic features, and evidence of endometriosis. Results: The pts' ages ranged from 27 to 87 yrs (median 50). The most common symptoms/signs were: abdominal/pelvic mass or pain, vaginal bleeding, and gastrointestinal symptoms. Tumor size ranged from 1.2 to 24.5 cm. The most common sites of involvement included ovaries (24), bowel wall (27), abdomen/peritoneum (37), pelvis (20), and vagina (6). Multiple sites of involvement were present in 34 cases. 42/45 cases had a classic microscopic pattern and 1 had dedifferentiation; 16 had vascular invasion. Endometriosis was noted in 29/63 cases. In 25% of cases, an initial diagnosis other than ESS was made: GIST, leiomyosarcoma, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and various sex cord stromal tumors. 61/63 pts had cytoreductive surgery, 31/48 had hormonal tx, 13/45 had chemotx, and 7/45 had radiation tx. Follow-up ranged from 5 to 336 months; 14 cases were lost to follow-up. 29 pts had recurrent disease; the time to recurrence ranged from less than 12 mos to 192 mos (median 42 mos). 7 pts died of disease (DOD) with a median of 70 mos from dx to death, 14 pts are alive with disease, and 27 pts are alive without disease. Conclusions: EESS is commonly associated with endometriosis and tends to be indolent with a propensity for recurrence. Most pts are treated with cytoreductive surgery with or without additional hormonal therapy. Chemotherapy and radiation tx are reserved for pts with disease progression and multiple recurrences. 6/7 pts who DOD had bowel involvement and 1 had dedifferentiation. No histologic parameters correlated with the clinical behavior of these tumors. doi:10.1016/j.ygyno.2011.12.395
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
expression group) and 48.54 (+/− 7.91 normal expression group). 31 tested positive for loss of expression and 129 retained normal expression. Loss of expression group showed statistical difference, with a greater incidence of Grade III tumors in this group (p = 0.0013) and less Grade I tumors (p = 0.0020), greater depth of myometrial invasion (p = 0.0019), greater incidence of positive lymph node metastases (p = 0.0157), and positive lymphvascular space involvement (p = 0.0020). Lower BMI was noted in the loss of expression group as well (p = 0.0001), with 48% having normal to underweight BMI at time of diagnosis versus 23% in the normal expression group. No patients in the loss of expression group had BMI N 40, although 35% of the normal expression group had BMI N 40. Conclusions: The DNA mismatch repair mechanism primarily involves 2 functional pairs of genes. MSH6 and MSH2 recognize and bind to mismatched DNA sequences. MLH1 and PMS2 excise and repair the mismatched nucleotides. Loss of function of DNA mismatch repair genes has been reported in 30% of patients with endometrial cancer. This loss of function may be attributed to germline mutations, spontaneous mutations, or epigenetic silencing of the MLH1 promoter region and is associated with poor prognostic features in premenopausal and perimenopausal patients with endometrial cancer. Women with loss of gene expression tended to have lower BMI at time of surgery. There are no significant differences in subgroups with MSH6/MSH2 loss of expression and MLH1/PMS2 loss of expression. Long-term follow-up is necessary to evaluate for differences in survival of these patients. doi:10.1016/j.ygyno.2011.12.393
393 Assessment of patients with endometrioid adenocarcinoma (EC) of the uterus falling in the ‘gap’ between PORTEC 1 high intermediate risk and GOG 99 high intermediate risk (HIR) E. Nugent, E. Bishop, C. Mathews, K. Moxley, R. Mannel, J. Walker, K. Moore, L. Landrum, D. McMeekin. University of Oklahoma, Oklahoma City, OK. Objective: Several models for predicting risk of recurrence and need for postoperative treatment in EC have been described. In PORTEC 1 and GOG 99, age and uterine factors define HIR. Risk of recurrence is similar between these studies, both predicting ~ 23% to 27% risk of recurrence for HIR pts treated with surgery alone. Controversy exists when patients have uterine factors meeting 1 rather than both risk model assessments of HIR (termed 'gap' patients). The objective of this study was to determine how meeting HIR for either GOG 99 or PORTEC HIR criteria affects recurrence and survival compared to meeting both models' HIR criteria. Methods: A retrospective review of patients undergoing complete surgical staging for clinical stage 1 EC was performed from 1996 through 2008. Patients were categorized as meeting eligibility for PORTEC 1 and for having HIR inclusion criteria (presence of 2 factors: age N 60, grade 3, greater than 50% DOI). Pts were also classified as having met GOG 99 inclusion criteria and having HIR features (age N70 +1 factor, age 50–70 +2 factors, any age +3 factors: grade 2 or 3, LVSI, N50% DOI), irrespective of nodal status(LN). Uterine factors, recurrence rates, nodal positivity rates, PFS, and OS were compared in those patients meeting a single HIR criterion to those meeting both HIR models. Results: We identified 352 clinical stage 1 patients. 66 patients met PORTEC HIR criteria. The frequency of LN positivity in HIR patients was 19.7% and recurrence rate was 27.3%. 188 patients met HIR for GOG 99, with 34.6% lymph node positivity and 28.3% recurrence rate. 80 patients met either GOG 99 HIR or PORTEC 1 HIR but not both (71 and 9 patients,
respectively). Gap patients had a recurrence rate of 14.5% and a nodal positivity rate of 33.8%. Compared to patients meeting both HIR models, gap patients were significantly less likely to recur (p=0.0016), had less myometrial invasion(p b 0.0001), and lower stage (p= 0.0002). There was no difference in grade, cervical involvement, LVSI, or nodal status between patients meeting 1 or 2 HIR models. 48-month PFS and OS were improved in gap patients (81.1% vs 55.3%, p = 0.0007 and 80.3% vs 59.3%, p = 0.0005, respectively). Conclusions: Patients meeting either GOG 99 HIR or PORTEC HIR but not both have an improved prognosis compared to those meeting the criteria of both HIR models. The patients have a substantial risk of nodal involvement and a relatively high rate of recurrence, potentially affecting patient counseling and adjuvant treatment. doi:10.1016/j.ygyno.2011.12.394
394 Extrauterine endometrial stromal sarcoma: A pathologic study of 63 cases with clinical correlation R. Masand, E. Euscher, M. Deavers, A. Malpica. The University of Texas, MD Anderson Cancer Center, Houston, TX. Objective: Extrauterine endometrial stromal sarcoma (EESS) is an uncommon tumor that occurs in patients (pts) over a wide age range and frequently in association with endometriosis. The non-gynecologic symptoms/signs at presentation, the extrauterine location, and confounding pathologic features can pose a diagnostic challenge. The purpose of this study is to evaluate the clinical and pathologic findings of 63 such cases. Methods: Sixty-three cases of EESS from a period of 20 yrs were retrieved from the pathology database. Clinical information was obtained from the pts' charts and questionnaires sent to physicians. The following clinical parameters were recorded: pts' age, clinical presentation, treatment (tx), recurrences and current status. In 46 cases, slides were re-reviewed. The following pathologic parameters were recorded: size and location, gross and microscopic features, and evidence of endometriosis. Results: The pts' ages ranged from 27 to 87 yrs (median 50). The most common symptoms/signs were: abdominal/pelvic mass or pain, vaginal bleeding, and gastrointestinal symptoms. Tumor size ranged from 1.2 to 24.5 cm. The most common sites of involvement included ovaries (24), bowel wall (27), abdomen/peritoneum (37), pelvis (20), and vagina (6). Multiple sites of involvement were present in 34 cases. 42/45 cases had a classic microscopic pattern and 1 had dedifferentiation; 16 had vascular invasion. Endometriosis was noted in 29/63 cases. In 25% of cases, an initial diagnosis other than ESS was made: GIST, leiomyosarcoma, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and various sex cord stromal tumors. 61/63 pts had cytoreductive surgery, 31/48 had hormonal tx, 13/45 had chemotx, and 7/45 had radiation tx. Follow-up ranged from 5 to 336 months; 14 cases were lost to follow-up. 29 pts had recurrent disease; the time to recurrence ranged from less than 12 mos to 192 mos (median 42 mos). 7 pts died of disease (DOD) with a median of 70 mos from dx to death, 14 pts are alive with disease, and 27 pts are alive without disease. Conclusions: EESS is commonly associated with endometriosis and tends to be indolent with a propensity for recurrence. Most pts are treated with cytoreductive surgery with or without additional hormonal therapy. Chemotherapy and radiation tx are reserved for pts with disease progression and multiple recurrences. 6/7 pts who DOD had bowel involvement and 1 had dedifferentiation. No histologic parameters correlated with the clinical behavior of these tumors. doi:10.1016/j.ygyno.2011.12.395