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Background: Failure to detect metastasis to para-aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para-aortic lymph nodes.Methods: Sixty-five patients were enrolled; 60 were available for analysis. Patients with stage IB2-IVA cervical cancer without evidence of para-aortic lymphadenopathy on preoperative CT or magnetic resonance imaging (MRI) were prospectively enrolled. All patients underwent preoperative PET/CT. Laparoscopic extraperitoneal lymphadenectomy was performed from the common iliac vessels to the left renal vein.Results: The median age at diagnosis was 48 years (range, 23-84). The median operative time was 140 minutes (range, 89-252). The median blood loss was 22.5 mL (range, 5-150). The median length of hospital stay was 1 day (range, 0-4). The median number of lymph nodes retrieved was 11 (range, 1-39). Fourteen (23%) patients had histopathologically positive para-aortic nodes. Of the 26 patients with negative pelvic and para-aortic nodes on PET/CT, 3 (12%) had histopathologically positive para-aortic nodes. Of the 27 patients with positive pelvic but negative para-aortic nodes on PET/CT, 6 (22%) had histopathologically positive para-aortic nodes. The sensitivity and specificity of PET/CT in detecting positive para-aortic nodes when nodes were negative on CT or MRI were 36% and 96%, respectively. Eleven (18.3%) patients had a treatment modification based on surgical findings.Conclusions: Laparoscopic extraperitoneal para-aortic lymphadenectomy is safe and feasible. Surgical staging of patients with locally advanced cervical cancer should be considered before planned radiation and chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications., Experimental Design: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model., Results: Of 3,328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs. 60 years nonmutated), had a higher prevalence of endometriosis (27.3% vs. 16.9%), and lower grades (grade 1/2, 43.2% vs. 8.1%, all P < 0.0001). The highest prevalence of KRAS mutation was in mesonephric-like endometrial (100%, n = 9/9), mesonephric-like ovarian (83.3%, n = 5/6), mucinous ovarian (60.4%), and low-grade serous ovarian (44.4%) cancers. After adjustment for age, cancer type, and grade, RAS mutation was associated with worse overall survival [hazard ratio (HR) = 1.3; P = 0.001]. Specific mutations were in KRAS (13.5%), NRAS (2.0%), and HRAS (0.51%), most commonly KRAS G12D (28.4%) and G12V (26.1%). Common co-mutations were PIK3CA (30.9%), PTEN (28.8%), ARID1A (28.0%), and TP53 (27.9%), of which 64.7% were actionable. RAS + MAPK pathway-targeted therapies were administered to 62 patients with RAS-mutated cancers. While overall survival was significantly higher with therapy [8.4 years [(95% confidence interval (CI), 5.5-12.0) vs. 5.5 years (95% CI, 4.6-6.6); HR = 0.67; P = 0.031], this effect did not persist in multivariable analysis., Conclusions: RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered., (©2024 American Association for Cancer Research.)

Extrauterine mesonephric-like carcinoma (ExUMLC) shares histologic, immunohistochemical (IHC), and molecular (MOL) features with endometrial mesonephric-like carcinoma (EnMLC). Its rarity and histologic overlap with Mullerian carcinomas contribute to underrecognition of ExUMLC. Aggressive behavior of EnMLC is well-documented; behavior of ExUMLC is yet to be characterized. This study presents the clinicopathologic, IHC, and MOL features of 33 ExUMLC identified over a 20-year time period (2002-2022) and compares the behavior of this cohort to more common upper gynecologic Mullerian carcinomas (low-grade endometrioid, LGEC; clear cell, CCC; high-grade serous, HGSC) and EnMLC diagnosed over the same time period. ExUMLC patients ranged from 37 to 74 years old (median=59 y); 13 presented with advanced stage (FIGO III/IV) disease. Most ExUMLC had the characteristic mixture of architectural patterns and cytologic features, as previously described. Two ExUMLC had sarcomatous differentiation, 1 with heterologous rhabdomyosarcoma. Twenty-one ExUMLC (63%) had associated endometriosis, and 7 (21%) arose in a borderline tumor. In 14 (42%) cases, ExUMLC was part of a mixed carcinoma representing >50% of the tumor in 12. Twenty-six cases (79%) were incorrectly classified as follows: LGEC or HGEC (12); adenocarcinoma, not otherwise specified (3); HGSC (3); LGSC (2); mixed carcinoma (1); carcinosarcoma, Mullerian type (2); seromucinous carcinoma (1); transitional pattern of HGSC (1); and female adnexal tumor of probable Wolffian origin (1). Three patients had occult synchronous endometrial LGEC. IHC facilitated diagnosis in all cases with an expression of GATA-3 and/or TTF-1 in conjunction with decreased hormone receptor expression in most tumors. MOL testing (n=20) identified a variety of mutations, most frequently: KRAS (15); TP53 (4); SPOP (4); and PIK3CA (4). ExUMLC and CCC were more likely to be associated with endometriosis ( P <0.0001). ExUMLC and HGSC had more recurrences compared with CCC and LGEC ( P <0.0001). Histologic subtype was associated with longer disease-free survival for LGEC and CCC versus HGSC and ExUMLC ( P <0.001). ExUMLC trended towards a similar poor overall survival as HGSC compared with LGEC and CCC, and EnMLC trended to shorter survival compared with ExUMLC. Neither finding reached significance. No differences were seen between EnMLC and ExUMLC with respect to presenting stage or recurrence. Staging, histotype, and endometriosis were associated with disease-free survival, but on multivariate analysis, only stage remained as an independent predictor of outcome. The tendency of ExUMLC to present at an advanced stage and have distant recurrence points to more aggressive behavior compared with LGEC with which it is most frequently confused, underscoring the importance of an accurate diagnosis., Competing Interests: Conflicts of Interest and Source of Funding: Supported by The University of Texas MD Anderson Cancer Center Division of Pathology and Laboratory Medicine Supplemental Research Fund. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

PAX8 is the most commonly used immunomarker to link a carcinoma to the gynecologic tract; however, it lacks specificity. Through mining The Cancer Genome Atlas mRNA expression profile data, we identified SOX17 as a potential specific marker at the mRNA level for gynecologic tumors. To evaluate the utility of this marker in the identification of the gynecologic origin of a given carcinoma, we performed immunochemical staining in a large cohort of ovarian and endometrial cancer cases (n = 416), together with a large cohort of solid tumors from other organs (n = 1544) in tissue microarrays. Similar to PAX8, SOX17 was highly expressed in different subtypes of ovarian carcinoma (97.5% for SOX17 vs 97% for PAX8 in serous carcinoma, 90% vs 90% in endometrioid carcinoma, and 100% vs 100% in clear cell carcinoma), except for mucinous carcinoma (0% vs 27%), and was also highly expressed in different subtypes of endometrial carcinoma (88% vs 84% in endometrioid carcinoma, 100% vs 100% in serous and clear cell carcinoma). SOX17 was not expressed in thyroid and renal cell carcinomas, whereas PAX8 expression was high (86% and 85%, respectively). In addition, SOX17 was expressed at low levels in cervical adenocarcinoma (20%) and had no expression in cervical squamous carcinoma, mesothelioma, and carcinomas from the breast, lung, pancreas, colon, stomach, liver, bladder, and salivary gland. Our data indicate that SOX17 is not only a sensitive but also a specific marker for the origin of ovarian and endometrial carcinomas., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients' median age was 55 years (y) (range: 33 to 79 y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The experience with uterine inflammatory myofibroblastic neoplasms with an unfavorable outcome is limited. We present the clinicopathologic features of 9 such cases, including 8 inflammatory myofibroblastic tumors (IMTs) and 1 epithelioid inflammatory myofibroblastic sarcoma (EIMS). Median patient age for the IMT group was 50.5 years; the patient with EIMS was 43 years old. Patients presented with abnormal uterine bleeding, presumed fibroids, pelvic pain, arthralgia and low-grade fever, as well as an incidental finding. Median tumor size for the IMTs was 8.5 cm. The borders were either infiltrative or well-circumscribed. Histologically, IMTs were purely fascicular or myxoid or showed predominance of one or the other pattern. Seven tumors were spindled, and 1 was both spindled and epithelioid. Tumors had variable nuclear atypia, ranging from grade 1 to 3. All tumors had an inflammatory infiltrate-predominantly lymphocytic, majority had necrosis (62.5%) and none had lymphovascular invasion. 7/8 (87.5%) tumors were positive for ALK-1 by immunohistochemistry (IHC). One tumor was negative for ALK-1 by IHC but was positive for ALK fusion by fluorescence in situ hybridization and had TNS1-ALK fusion by next-generation sequencing (NGS). Three other tumors with NGS testing showed one of the following ALK-fusion partners: FN1, DCTN1, and IGFBP5. The EIMS had infiltrative borders, myxoid and hyalinized patterns, epithelioid cells, and no lymphovascular invasion. This tumor was ALK-1 positive by IHC, had ALK rearrangement by fluorescence in situ hybridization and RANBP2-ALK fusion by NGS. Extrauterine disease at time of diagnosis was noted in 2/8 (25%) of IMTs, and in the single case of EIMS. Seven patients had surgery as primary treatment, 1 patient had neoadjuvant chemotherapy and 1 patient declined treatment. Patients with recurrence were treated with a combination of chemotherapy, targeted therapy, radiotherapy or hormonal therapy. Most patients (71.4%) recurred within 24 months (mos). Two thirds of patients were alive with disease at last follow up (mean 43.6 mos). The patient with EIMS was alive with disease at 22 mos. IMT referral cases were initially diagnosed as smooth muscle tumors in 87.5% of cases; while the EIMS was diagnosed as high-grade endometrial stromal sarcoma. Lack of consideration of IMT in the differential diagnosis of smooth muscle tumors with myxoid features can result in misdiagnosis and under-utilization of targeted therapy in these patients., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including "adhesion-like" appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Müllerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

DPC4 immunohistochemistry (IHC) is usually part of the work-up of mucinous neoplasms in the ovary where the distinction between an ovarian primary and metastatic pancreaticobiliary adenocarcinoma (PanACa) must be made. Although DPC4 IHC is lost in about 55% (46%-61%) of PanACas and typically retained in most primary ovarian mucinous neoplasms, no study has evaluated the expression of this marker in a large cohort of neoplasms arising in or involving gynecologic (GYN) organs. In this study, we retrospectively analyzed the expression of DPC4 IHC in a total of 251 tumors and lesions related to the GYN tract in which DPC4 IHC stain was performed during the initial pathology evaluation. Of these, 138 were primary GYN tumors and lesions, 31 were metastatic GYN tumors involving non-GYN sites, and 83 were metastatic non-GYN tumors involving the GYN tract. We identified 27 cases with loss of DPC4 IHC expression of which 20 cases met the inclusion criteria (i.e. clinical information was available to determine the site of tumor origin). We observed that loss of DPC4 nuclear expression was most commonly seen in tumors of endocervical origin (n=7), of which 5 were gastric-type cervical adenocarcinomas (GCxACa) and 2 were usual-type cervical adenocarcinomas, either primary or metastatic. This was followed by tumors of the pancreaticobiliary tract (n=5), ovary (n=2), and appendix (n=1). In addition, 1 gastric-type vaginal adenocarcinoma (GVaACa) also showed loss of DPC4. Our findings indicate that in female patients with mucinous neoplasms involving the ovary or other sites, with loss of DPC4 by IHC, and negative pancreaticobiliary imaging, the possibility of an occult GCx/GVaACa, and rarely an ovarian primary must be considered., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Molecular findings in ovarian, fallopian tube, and peritoneal high-grade serous carcinoma (HGSCa) are emerging as potential prognostic indicators. The chemotherapy response score (CRS) has been proposed as a histologic-based prognostic factor in patients with HGSCa treated with neoadjuvant chemotherapy (NACT). No study details the relationship between the mutational landscape of HGSCa and the CRS. This study addresses this issue using next-generation sequencing (NGS). We retrospectively identified 25 HGSCas treated with NACT and pathology material available to calculate the CRS. All cases had NGS on the primary debulking specimen post-NACT. The three-tier Böhm CRS was applied to the omentum or adnexa and calculated as a combined score. Tumor mutation burden (TMB) and TP53 variant allele frequency (VAF) were calculated and used in correlative analysis. All cases had at least one mutation, most commonly TP53 (25 cases, 100%). Other mutations were BRCA2 (one case, 4%), ARID1A (two cases, 8%), and 1 (4%) of each of the following: ERBB2, NTRK3, STK11, NTRK2, TSC1, PIK3CA, NF1, NOTCH3, CDK2, SMAD4, and PMS2. TMB ranged from 2.58 to 7.75 (median 3.84). There was no statistically significant relationship between the TMB and omental CRS, R-squared = 0.011 (P = 0.62); adnexal CRS, R-squared = 0.005 (P = 0.74); or with the combined CRS, R-squared = 0.009 (P = 0.65). Statistically significant correlation was found between the TP53 VAF and the omental CRS (R-squared = 0.28, P = 0.007), adnexal CRS (R-squared = 0.26, P = 0.01), and the combined CRS (R-squared = 0.33, P = 0.0026). The TP53 VAF was adjusted for percent of tumor present on the slide resulting in an average per cell TP53 mutational load, resulting in similar results with a statistically significant correlation between the average per cell TP53 mutational load and the omental CRS (R-squared = 0.27, P = 0.02), adnexal CRS (R-squared = 0.16, P = 0.05), and the combined CRS (R-squared = 0.23, P = 0.02). In summary, NGS confirmed TP53 mutations in all cases of HGSCa. TMB showed no correlation with the CRS. TP53 VAF and average per cell TP53 mutational load showed significant correlation with the CRS, whether graded on the adnexa or omentum or as a combined score, indicating concordance between molecular and histological findings following NACT., (Copyright © 2021. Published by Elsevier Inc.)

Targeted anti-human epidermal growth factor receptor 2 (HER2) therapy has recently been proven to improve progression-free and overall survival of patients with advanced stage or recurrent endometrial serous carcinoma. To date, no specific pathology HER2 testing or scoring guidelines exist for endometrial cancer. However, based on evidence from the recent successful clinical trial and comprehensive pre-trial pathologic studies, a new set of HER2 scoring criteria have been proposed for endometrial serous carcinoma-distinct from the existing breast and gastric cancer-specific criteria. We present the first study assessing interobserver agreement of HER2 scores using the proposed serous endometrial cancer-specific scoring system. A digitally scanned set of 40 HER2-immunostained slides of endometrial serous carcinoma were sent to seven gynecologic pathologists, who independently assigned HER2 scores for each slide following a brief tutorial. Follow-up fluorescent in situ hybridization (FISH) for HER2 gene amplification was performed on cases with interobserver disagreement when a 2+ HER2 score was assigned by at least one observer. Complete agreement of HER2 scores among all 7 observers was achieved on 15 cases, and all but one case had an agreement by at least 4 observers. The overall agreement was 72.3% (kappa 0.60), 77.5% (kappa 0.65), and 83.3% (kappa 0.65), using four (0 to 3+ ), three (0/1+ , 2+ , 3+ ), or two (0/1+ , 2/3+ ) HER2 scoring categories, respectively. Based on the combination of HER2 immunostaining scores and FISH, the interobserver disagreement may have potentially resulted in a clinically significant difference in HER2 status only in three tumors. We conclude, that the proposed serous endometrial cancer-specific HER2 scoring criteria are reproducible among gynecologic pathologists with moderate to substantial interobserver agreement rates comparable to those of previously reported in breast and gastric carcinomas. Our findings significantly strengthen the foundation for establishing endometrial cancer-specific HER2 scoring guidelines in the future.

Vulvar high-grade neuroendocrine carcinomas (HGNECs) are rare and primarily thought to represent Merkel cell carcinoma (MCC). We present the clinicopathologic features of 16 such cases, the largest series to date. Patients were most often White, postmenopausal, and symptomatic from a palpable vulvar mass/nodule. Tumors ranged from 0.7 to 6 cm and most commonly involved the labium majus. Majority of the cases were pure HGNECs (15/16) with small cell (SC) morphology (14/16); 2 were large cell neuroendocrine carcinomas, of which 1 was combined with moderately differentiated adenocarcinoma. All tumors expressed synaptophysin. Of the 14 HGNECs with SC morphology, 6 were CK20-positive MCCs with characteristic CAM5.2 and neurofilament (NF) expression. Five of these MCCs were positive for Merkel cell polyoma virus large T-antigen (MCPyVLTAg). In contrast, 6 HGNECs with SC morphology were negative for CK20, NF, and MCPyVLTAg and classified as SCNECs. High-risk human papilloma virus was positive in all SCNECs and negative in all MCCs. One case of HGNEC with SC morphology could not be entirely characterized due to lack of tissue for ancillary testing. Five of 12 (42%) cases had a discrepant diagnosis initially rendered. Most patients (10/15) presented with International Federation of Gynecology and Obstetrics stage III or IV disease. Usual sites of metastasis included inguinal lymph node, liver, bone, and lung. Twelve patients underwent surgery with adjuvant chemotherapy and/or radiation therapy, 1 received adjuvant immunotherapy, and 1 patient received neoadjuvant chemotherapy followed by surgery and adjuvant radiation therapy. Median overall survival was 24 months (range: 7 to 103 mo), and overall 5-year survival was 12% (95% confidence interval: 1% to 39%). In summary, vulvar HGNECs are rare, aggressive neoplasms that can be further subclassified into MCC, SCNEC, and large cell neuroendocrine carcinoma. CK20, CAM5.2, NF, TTF-1, MCPyVLTAg, and high-risk human papilloma virus facilitate the distinction of MCC from SCNEC. Proper identification of vulvar HGNECs is critical for patient management., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin-stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.

Lynch syndrome (LS) is associated with an increased risk for colorectal, endometrial, and ovarian carcinomas in women. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy (RRHSO) has been shown to be a cost-effective form of management and prevention of gynecological malignancies in patients with LS. Studies of incidental gynecologic malignancies identified in RRHSO are limited. In addition, recommendations on optimal handling of this type of specimen have ranged from submitting for microscopic examination the entire endometrium, fallopian tubes and ovaries to submitting only routine representative sections of these organs. In this study, we present the clinicopathologic findings of 29 cases of LS patients that underwent risk-reducing gynecologic surgery at our institution over a period of 13 yr. Clinical-pathologic information was obtained from the patients' charts and pathology reports. Significant pathologic abnormalities were identified in 17% (5/29) of cases, all showing endometrial hyperplasia. Four of them with atypical and 1 without atypical. All of our cases with endometrial pathology had significant findings on preoperative endometrial sampling. To further study the recommendation of in toto submission of the endometrium, ovaries and fallopian tubes and the utility of preoperative endometrial sampling, we undertook a literature review of all the reported cases of incidental pathologic findings identified in RRHSO. The findings of our cohort and the literature reviewed support in toto submission of endometrium, and adnexal structures in the absence of gross lesions. In addition, our findings show a definite benefit for preoperative endometrial sampling as part of the workup for LS patients undergoing RRHSO.

Endometrial mesonephric-like carcinomas (MLCa) are uncommon with <50 reported cases thus far. Previous studies have characterized the histologic, immunohistochemical, and molecular features of MLCa; however, there is limited information with respect to outcome. This single-institution study of 23 uterine MLCas characterizes the behavior of such a neoplasm. Uterine MLCas (2004-present) had review of histologic features, immunohistochemical results, molecular profile, and clinical information (stage, treatment, follow-up). The behavior of MLCa was compared with low-grade endometrioid carcinomas (ECas) and uterine serous carcinomas (USCs) treated at our institution from 2004 to present. All MLCas had a mixture of previously described architectural and cytologic features most notably ductal and/or tubular architecture (21/23), nuclei resembling those of papillary thyroid carcinoma (18/23), and at least focal intraluminal eosinophilic secretions (20/23). Immunoperoxidase studies facilitated diagnosis in 22 cases: CD10, 10/10; calretinin, 5/15; estrogen receptor (≥10% nuclei), 6/21; progesterone receptor, 1/15; GATA-3, 15/16; TTF-1, 11/16. Fourteen of 17 tested cases had a KRAS mutation (7 as the only alteration; 7 with additional mutations including PIK [n=5]; PTEN [n=2], CTNNB1 [n=1]).One case had mutations in PTEN, PIK, and CTNNB1 without KRAS; 2 cases had no detectable somatic mutation. Overall, 48% of patients presented with International Federation of Gynecology and Obstetrics (FIGO) stage 3 or 4 disease with the following uterine risk factors: >50% myometrial invasion, 20/23; lymphovascular space invasion, 16/23; cervical stromal invasion, 7/23. Twenty patients had adjuvant therapy (7 radiation only; 13 chemotherapy±radiation), whereas 3 patients had either unknown or declined therapy. Follow-up was known for 21 patients: 17 patients had recurrences or never achieved remission with the lung being the most common recurrence site (n=9); 7 patients died of disease. The median progression-free survival was 18.2 months for MLCa compared with 183 months for ECa and 67.1 months for USC. The median overall survival for MLCa was 70.6 months compared with 139.1 months for USC (median survival for ECa not reached). Uterine MLCa is uncommon with most tumors recognized by architectural heterogeneity, vesicular, overlapping nuclei with grooves, and eosinophilic luminal secretions. The typical immunoprofile includes low to absent expression of hormone receptors but at least focal expression of GATA-3 and/or TTF-1. Most tested cases had a KRAS mutation although genetic mutations typically associated with ECa are not uncommon. Compared with more commonly encountered types of ECa, MLCa is more aggressive with a tendency towards earlier and distant recurrence.

The chemotherapy response score (CRS) is used to score histopathologic response to neoadjuvant chemotherapy (NACT) of patients with extrauterine high-grade serous carcinoma. This study was undertaken to determine if the CRS in the omentum, adnexa or when combined correlates with (1) progression-free survival (PFS) or overall survival (OS), (2) laparoscopic score of abdominal disease, (3) Cancer antigen 125 levels, (4) BRCA status, and (5) platinum-resistant disease. A total of 158 cases were retrospectively collected that received NACT between April 2013 and February 2018 at a single institution. The 3-tier Böhm CRS system was applied to the omentum and adnexa. Survival outcomes between scored subgroups were analyzed using Cox proportional hazards regression. Spearman rank correlation analyses were used to assess CRS and clinical data. A total of 119 cases were treated only with carboplatin/paclitaxel. Omental CRS was: 1 (23 cases, 19.3%), 2 (65 cases, 54.6%), and 3 (31 cases, 26.1%), whereas adnexal CRS was: 1 (50 cases, 42%), 2 (48 cases, 40.3%) and 3 (21 cases, 17.6%). The omental CRS was significantly associated with PFS as a 2-tier score (hazard ratio [HR]=0.612, 95% confidence interval [CI]: 0.378-0.989, P=0.045) but not associated with the PFS using the 3-tier score or with OS using either system. Adnexal CRS was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.49, 95% CI: 0.263-0.914, P=0.025) and 2-tier scores (HR=0.535, 95% CI: 0.297-0.963, P=0.037). The combined score was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.348, 95% CI: 0.137-0.88, P=0.026) and 2-tier scores (HR=0.364, 95% CI: 0.148-0.896, P=0.028). No CRS system used associated with laparoscopic assessment of disease. CRS in the omentum had no significant association with platinum resistance; however, the adnexal CRS 1/2 were 3 times as likely to develop platinum resistance compared with CRS 3 (relative risk=3.94, 95% CI: 1.03-15.09, P=0.046). The CRS, when used on the omentum, adnexa, and as a combined score, was significantly associated with PFS but not with OS. Adnexal CRS 1/2 are more likely to develop platinum-resistant disease. Therefore, the use of this pathology parameter may be useful for clinical management.

Assessment of pelvic, para-aortic or inguinal lymph nodes (LNs) provides not only important prognostic information, but also determines the need for adjuvant treatment. Sentinel lymph node (SLN) biopsy has the potential to provide this prognostic information, while reducing morbidity compared with extended LN dissection. This review discusses the clinical and pathological aspects of SLN biopsy in gynaecological cancer., (© 2019 John Wiley & Sons Ltd.)

Ovarian germ cell tumors are a histologically diverse group of neoplasms with a common origin in the primitive germ cell. The vast majority are represented by mature cystic teratoma. In the minority are malignant germ cell tumors including immature teratoma, dysgerminoma, yolk sac tumor, embryonal cell carcinoma, and choriocarcinoma. This article reviews the histologic and immunohistochemical features of the most common ovarian germ cell tumors. The differential diagnoses for each are discussed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Endometrial cancer is the most common gynecologic neoplasm in developed countries; however, updated universal guidelines are currently not available to handle specimens obtained during the surgical treatment of patients affected by this disease. This article presents recommendations on how to gross and submit sections for microscopic examination of hysterectomy specimens and other tissues removed during the surgical management of endometrial cancer such as salpingo-oophorectomy, omentectomy, and lymph node dissection-including sentinel lymph nodes. In addition, the intraoperative assessment of some of these specimens is addressed. These recommendations are based on a review of the literature, grossing manuals from various institutions, and a collaborative effort by a subgroup of the Endometrial Cancer Task Force of the International Society of Gynecological Pathologists. The aim of these recommendations is to standardize the processing of endometrial cancer specimens which is vital for adequate pathological reporting and will ultimately improve our understanding of this disease.

Objectives: This study aimed to evaluate the impact of radiation therapy on outcomes for patients with uterine carcinosarcoma (UC)., Methods/materials: We retrospectively reviewed the records of 155 women with stage I (98), II (11), or III (46) UC who underwent total abdominal hysterectomy/bilateral salpingo-oophorectomy at our institution between 1990 and 2011. Survival rates were assessed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were performed., Results: Seventy-six patients (49%) received radiation therapy: 38 (50%) had vaginal cuff brachytherapy (VBT) alone and 38 had external beam radiation therapy (EBRT) ± VBT. Seventy patients (45%) received chemotherapy (12 concurrent, 49 adjuvant, 9 both). The 5-year overall survival rate was 48.6% (stage I, 53.8%; II, 30.0%; and III, 42.5%). The disease-specific survival (DSS) rate was 57.2% (stage I, 60.9%; II, 44.4%; and III, 51.8%). Patients treated with EBRT had a higher 5-year pelvic disease control rate (88.3%) than did patients treated with VBT only (67.4%) or no radiation (71.2%; P = 0.04). In stage III patients, EBRT was associated with higher 5-year pelvic disease control (90.0% vs 55.5%, P = 0.046), DSS (64.6% vs 46.4%, P = 0.13), and overall survival (64.6% vs 34.0%, P = 0.04) rates. For all 155 patients, age at least 65 years, cervical involvement, and lymph vascular space invasion were correlated with lower DSS on univariate and multivariate analyses. In addition, treatment with concurrent chemoradiation therapy was independently associated with a higher DSS rate on multivariate analysis., Conclusions: Patients with UC have a high rate of relapse in the regional nodes and distant sites. External beam radiation therapy improves locoregional control in all stages and may improve survival in stage III patients who are at the highest risk of pelvic relapse.

Objective: The role of sentinel lymph node (SLN) biopsy alone for staging of early-stage cervical cancer remains controversial. We aimed to determine the validity of this technique in women with early-stage cervical cancer., Methods: We retrospectively reviewed women with early-stage cervical cancer who underwent SLN mapping followed by complete pelvic lymphadenectomy as part of initial surgical management from August 1997 through October 2015. All modes of surgical approach were included. Lymphatic mapping was performed using blue dye, technetium-99m sulfur colloid (Tc-99), and/or indocyanine green (ICG). We determined SLN detection rates, sensitivity and negative predictive value., Results: One hundred eighty-eight patients were included, and 35 (19%) had lymph node metastases. At least one SLN was identified in 170 patients (90%), and bilateral SLNs were identified in 117 patients (62%). The majority of SLNs (83%) were found in the pelvis. There was no difference in detection rates between mapping agents, surgical approach, patients with and without prior conization or between patients with tumors <2cm and ≥2cm. The detection rate for bilateral SLNs was significantly lower in women with body mass index (BMI)>30kg/m 2 than in women with lower BMI (p=0.03). Metastatic disease in sentinel nodes was detected by H&E staining in 78% of cases and required ultrastaging/immunohistochemistry in 22% of cases. Only one patient had a false-negative result, yielding a sensitivity of 96.4% (95% CI 79.8%-99.8%) and negative predictive value of 99.3% (95% CI 95.6%-100%). The false-negative rate was 3.6%., Conclusions: In these women with early-stage cervical cancer, SLN biopsy had very high sensitivity and negative predictive value. We believe it is time to change the standard of care for women with early-stage cervical cancer to SLN biopsy only., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Extragonadal germ cell tumors are uncommon, and although they morphologically resemble their gonadal counterparts, unexpected gonadal presentation increases the potential for erroneous diagnoses. Yolk sac tumor is a malignant germ cell tumor characterized by an extraembryonic yolk sac line of differentiation, and relative to other germ cell tumors, is characterized by varied and diverse histologic patterns. When occurring outside of typical age parameters or in extragonadal locations, the histologic variability of yolk sac tumor and its tendency to mimic somatic tumors pose diagnostic challenges. Because extragonadal yolk sac tumor of the vulva is very rare, with only isolated case reports and small series in the literature, it is often not considered in the differential diagnosis. As both prognosis and management of yolk sac tumor differ significantly from those of somatic tumors, accurate diagnosis is essential. This review discusses histologic features of extragonadal yolk sac tumor, addresses somatic tumors arising in the vulva for which yolk sac tumor may be confused, and provides guidance with respect to the use of immunohistochemistry in the diagnosis of yolk sac tumor.

We present the clinicopathologic features of 15 cases of extragonadal yolk sac tumor (EGYST) detected in female patients and reviewed at our institution from 1988 to 2016. We recorded: patient age, clinical presentation, tumor location, FIGO stage (where applicable), histologic patterns including presence/absence of Schiller-Duval bodies, other germ cell or somatic components, immunoperoxidase results, treatment, and outcome. Patients' ages ranged from 17 to 87 (median, 62) years and presentation included: abnormal uterine bleeding, 12; hematuria, 1; labial mass, 1; abdominal pain, 1. Primary sites were as follows: uterus (11), vagina (1), vulva (1), bladder (1), and peritoneum (1). Seven patients presented at FIGO stage III or IV. The following histologic patterns were observed: microcystic/reticular (7), glandular (8), solid (8), papillary (5), and hepatoid (1). An admixture of histologic patterns was present in 10 cases. Schiller-Duval bodies were seen in only 3 (23%) cases. Eight cases (46%), all uterine primaries, had associated somatic components, and 2 (15%) had a second germ cell component. In 13/14 (93%) cases, the yolk sac tumor component was either missed or misclassified as adenocarcinoma. Immunoperoxidase studies facilitated the diagnosis in all cases as follows: SALL4, 12/12; CDX2, 10/12; α fetoprotein, 7/14; glypican-3, 9/10; cytokeratin 20, 5/9 (rare cells); cytokeratin 7, 3/12 (nondiffuse); PAX8, 2/9 (variable expression). All patients received chemotherapy and all except 1 underwent surgical resection. Follow-up from 5 to 86 months was available for 13 patients: 5 died of disease, 6 are alive with disease, and 2 have no evidence of disease. EGYST arising in the female pelvis of peri/postmenopausal patients may be associated with a somatic component and represent either somatically derived YST or YST differentiation within a somatic carcinoma. EGYST in younger patients is likely a true germ cell neoplasm, and may respond to germ cell appropriate chemotherapy. The benefit of germ cell appropriate chemotherapy in somatically derived EGYST is less clear. Awareness that the presence of glandular or microcystic patterns may lead to under-recognition or misdiagnosis of EGYST in combination with immunomarkers for germ cell and yolk sac differentiation will facilitate the diagnosis.

Undifferentiated carcinoma of the endometrium (UCAe) is an aggressive, underrecognized high-grade carcinoma that can occur either in pure form or in conjunction with low-grade endometrioid adenocarcinoma (i.e. dedifferentiated carcinoma). The typical solid growth pattern of UCAe can create a diagnostic dilemma as it is frequently misinterpreted as the solid component of an endometrial carcinoma or as a sarcoma. In addition, the high nuclear:cytoplasmic ratio, high mitotic index, and geographic necrosis are reminiscent of basal-like carcinoma of breast (BLCB). This study was undertaken to determine the role of a selected group of immunomarkers in the distinction of UCAe from other endometrial carcinomas, and assess the expression of DNA mismatch repair proteins, and surrogate BLCB immunomarkers in this type of tumor. Cases of UCAe were stained with antibodies against keratin cocktail, CK8/18, PAX-8, and estrogen receptor: 35 cases; progesterone receptor and Her-2/neu: 33 cases; CD44, e-cadherin, p16, and p53: 32 cases; and CK5/6, EGFR, and c-Kit: 18 cases. In addition, mismatch repair protein markers MLH1, MSH2, MSH6, and PMS2 were performed in 34 cases. We found that PAX-8 expression was lost in most cases (83%). In addition, estrogen and progesterone receptors were negative in 83% and 82% of cases, respectively. Seventy-seven percent of cases were positive for keratin cocktail and keratin 8/18, whereas only 11% of cases were positive for keratin 5/6. p16 was diffusely positive in 34% of cases, whereas p53 was expressed in >75% of the tumor cells in 31% of cases. MLH1 and PMS2 were concurrently lost in 50% of cases, whereas MSH2 and MSH6 were lost in 1 case (3%). E-cadherin and CD44 were completely lost in 50% of cases, whereas Her-2/neu was negative in all cases. EGFR was negative in 67% of cases, whereas 22% of cases showed diffuse membranous staining for this marker. UCAe is a high-grade carcinoma of Müllerian origin which tends to be negative for PAX-8. The loss of this marker appears to be a more reliable discriminator than the loss of keratin expression in the differential diagnosis with endometrioid carcinoma or serous carcinoma. UCAe tends to be diffusely positive for p53, but patchy positive for p16. Although UCAe appears to share not only some histologic features with BLCB, but also some of its immunohistochemical features (loss of estrogen receptor, progesterone receptor, and Her-2/neu, a tendency to loose e-cadherin and to express CD44), UCAe appears not to be related to BLCB because it usually lacks the expression EGFR, CK5/6, and c-Kit.

Neuroendocrine carcinoma (NECa) of the endometrium is an uncommon tumor. In this study, we present the clinicopathologic features of 25 such cases. The patients ranged in age from 37 to 87 years (median, 57 y) and most commonly presented with vaginal bleeding. The tumors were either pure NECa (10) or mixed with other histotypes (15), most commonly endometrioid carcinoma. The NECas were large cell type (15), small cell type (4), or a mixture of both (6). NECa was underrecognized in 89% of referral/consultation cases. All tumors were positive for ≥1 neuroendocrine marker (chromogranin, synaptophysin, CD56). Additional immunohistochemical (IHC) studies were obtained in 18 cases, with positive results as follows: keratin cocktail (17), diffuse p16 (6), PAX-8 (6), CD117 (6), and TTF-1 (1). Mismatch-repair protein expression by IHC was abnormal in 8 of 18 cases (6 MLH1/PMS2 loss; 1 MSH2/MSH6 loss; 1 MSH6 loss). According to FIGO staging, cases were distributed as follows: I (6), II (2), III (10), and IV (7). All patients underwent surgical treatment, and 20 patients received adjuvant therapy. Twelve patients died of disease (mean survival 12.3 mo). Eleven patients were alive 5 to 134 months after diagnosis, including 7 who achieved a 5-year survival (3 stage I; 4 stage III). In summary, most of our endometrial NECas were large cell type, mixed with other histotypes, and underrecognized. These tumors tend to be PAX-8 negative and may be associated with microsatellite instability. The recognition of NECa may have an impact on the treatment of the patients affected by this disease. Although NECa usually has an aggressive behavior, 28% of our patients survived at least 5 years.

Ovarian low-grade serous carcinoma (LGSC) is an entity with distinct pathologic and clinical features. The number of studies on this type of tumor is limited. In this article, we present our experience with 33 cases of ovarian LGSC with primary surgical treatment at our institution. For comparison, a cohort of ovarian high-grade serous carcinoma (HGSC) was also studied. Clinical information was obtained from the patients' charts or from the treating physicians. Hematoxylin and eosin slides were reviewed of 28 available LGSCs, and the following parameters were recorded: presence/absence of a serous borderline tumor (SBT), presence/absence of micropapillary/cribriform pattern (MP/CP), architectural pattern in the invasive component, and presence/absence of desmoplasia or fibrosis. The incidence of ovarian LGSC was 4.7%. LGSC patients ranged in age from 19 to 79 years (mean, 52 y), with 21.2% younger than 40 years. HGSC patients ranged in age from 38 to 90 years (mean, 62 y), with 1.6% younger than 40 years. LGSCs were staged as follows: stage I (2), stage III (23), and stage IV (8). Twenty-eight of 33 LGSC cases had concurrent SBT, with this component accounting for >50% of the neoplasm in 15 cases. In addition, MP/CP was noted in 19 cases. Invasion patterns included micropapillae (93%), cribriform nests (74%), elongated papillae (26%), glandular (44.4%), medium-sized papillae (33.3%), solid nests (22.2%), macropapillae (19%), and single cells (19%). In addition, desmoplasia (44.4%) and fibrosis (37%) were noted. Follow-up data ranging from 13 to 195 months (median 61.2 mo) were available on 30/33 LGSC patients: 18 (60%) were dead of disease; 1 (3.3%) was dead of other cause; 5 (16.7%) were alive with disease; and 6 (20%) had no evidence of disease. Follow-up data from 1 to 169 months (median 48 mo) were available on 185 HGSC patients: 132 (71.4%) were dead of disease; 3 (1.6%) were dead of other cause; 21 (11.4%) were alive with disease; and 29 (15.7%) had no evidence of disease. Ovarian LGSC is rare with a predilection for younger patients relative to HGSC. Most LGSC cases are associated with SBT with an MP/CP, and their invasive component usually contains a micropapillary pattern. Most patients with ovarian LGSC present with advanced-stage disease and have a short-term survival advantage over patients with HGSC (estimated 5 y survival: 62.3% vs. 43.9%). However, over a prolonged period of time, this survival advantage decreases (estimated 10 y survival: 21.2% vs. 22.7%).

Objective: Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with a poor prognosis. SCCOHT has recently been shown to be associated with SMARCA4 gene mutations as well as molecular and genetic similarities to malignant rhabdoid tumors (MRT). The objective of our study is to describe the clinical characteristics, treatment modalities and outcomes of 47 patients with SCCOHT., Methods: We performed a retrospective analysis of 47 patients with SCCOHT evaluated at MD Anderson Cancer Center between 1990 and 2014. Medical records were reviewed for demographic information, pathologic findings, treatment regimens and outcomes., Results: Median age at diagnosis was 30 years (range 5-46). All patients underwent surgery with unilateral salpingo-oophorectomy (USO) performed in 26 patients (55%), and hysterectomy with bilateral salpingooophorectomy (BSO) in 21 patients (45%). Sixteen patients (34.0%) had stage I disease, six (12.8%) stage II, 23 (48.9%) stage III, and two patients (4.3%) had stage IV disease. Information on adjuvant treatment was available for 43 patients: 83.3% received chemotherapy alone, 9.5% chemotherapy followed by radiotherapy, 2.4% chemoradiation, and 4.8% did not receive any adjuvant therapy. Median follow-up was 13.2 months (range, 0.1 to 210.7) with a median overall survival of 14.9 months. Multi-agent chemotherapy and radiotherapy were associated with a better prognosis., Conclusion: Our findings suggest that aggressive therapy including multi-agent chemotherapy and possibly radiotherapy may extend survival. Further study is needed to improve outcomes in these patients including the adoption of systemic therapies used in MRT as well as the development of novel agents targeting specific mutations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Gliomatosis peritonei, a rare condition often associated with immature ovarian teratoma, is characterized by the presence of mature glial tissue in the peritoneum. We retrospectively evaluated 21 patients with gliomatosis peritonei and studied their clinicopathologic features and immunophenotype. The patients' ages ranged from 5 to 42 years (median, 19 years). Their primary ovarian tumors consisted of immature teratoma (n=14), mixed germ cell tumors (n=6), and mature teratoma with a carcinoid tumor (n=1). Gliomatosis peritonei was diagnosed at the same time as primary ovarian neoplasm in 16 patients and secondary surgery in 5 patients. Also, 11 of 21 patients had metastatic immature teratoma (n=4), metastatic mature teratoma (n=2), or both (n=5). One patient developed glioma arising from gliomatosis peritonei. Seventeen patients had follow-up information and were alive with no evidence of disease (n=13), alive with disease (n=3), or alive with an unknown disease status (n=1). The follow-up durations ranged from 1 to 229 months (mean, 49 months; median, 23 months). Immunohistochemistry results demonstrated that SOX2 was expressed in all cases of gliomatosis peritonei and glioma with tissue available (nine of nine cases), whereas OCT4 and NANOG were negative in all cases with available tissue (eight of eight cases). In conclusion, both gliomatosis peritonei and glioma arising from it show a SOX2+/OCT4-/NANOG- immunophenotype. These findings demonstrated that gliomatosis peritonei is associated with favorable prognosis, although it is important to rule out potentially associated immature teratoma and malignant transformation. SOX2 may have an important role in the development of gliomatosis peritonei.

Gastric-type mucinous adenocarcinoma, an uncommon subtype of cervical carcinoma, is characterized by a distinct morphology and immunophenotype. Herein, we report a case of a 71-year-old woman who received neoadjuvant radiotherapy and chemotherapy after cervical biopsy revealed moderately differentiated invasive endocervical adenocarcinoma. Subsequently, the outside patient underwent radical hysterectomy with bilateral salpingo-oophorectomy. The post-neoadjuvant therapy hysterectomy specimen showed tumor cells with clear cytoplasm, hyperchromatic nuclei with irregular contours, which mimicked clear cell carcinoma. However, immunohistochemical staining showed that these tumor cells were positive for carcinoembryonic antigen, cytokeratin 7 (diffuse), and cytokeratin 20 (patchy), After review of the pretreatment cervical biopsy specimen, the tumor was favored to represent a gastric-type mucinous adenocarcinoma of the cervix. Pathologists should be aware of this rare tumor and its post-neoadjuvant therapy morphologic changes, which can make diagnosis more challenging.

Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.

Endometrioid stromal sarcoma (also known as extrauterine endometrial stromal sarcoma [EESS]) is an uncommon tumor that occurs in women over a wide age range. The extrauterine location, non-gynecologic symptoms and signs at presentation, and confounding histologic features can pose a diagnostic challenge. In this study, we present the clinicopathologic features of 63 cases of EESS seen during a period of 21 years at our institution. Clinical information and pathology material were reviewed. Ages ranged from 27 to 87 years (median: 50 years). The most common symptoms and signs were an abdominal or pelvic mass, pain, vaginal bleeding, and gastrointestinal symptoms. The tumor size ranged from 1.2 to 24.5 cm. The most common sites of involvement were the ovaries (25), bowel wall (28), abdomen/peritoneum (37), pelvis (20), and vagina (6). Multiple sites were involved in 40 cases. Forty-six of 49 tumors had a classic microscopic appearance, and 3 had dedifferentiation; in 20 cases, there was vascular invasion. Fibroma-like stroma was seen in 30, hyaline plaques in 23, sex cord elements in 11, smooth muscle differentiation in 4, and myxoid change in 4 cases. Endometriosis was noted in 30 cases. Immunohistochemical results included: CD10 positivity in 31, desmin positivity in 9 (focal), estrogen receptor positivity in 28, and progesterone receptor positivity in 33 cases. In 25% of cases, an initial diagnosis other than EESS was made: sex cord-stromal tumors (4), gastrointestinal stromal tumor (3), leiomyosarcoma (3), liposarcoma (1), müllerian adenosarcoma (1), synovial sarcoma (1), malignant peripheral nerve sheath tumor (1), small round blue cell tumor (1), and atypical stromal endometriosis (1). Primary treatment was cytoreductive surgery for 61 patients and hormonal therapy for 2 patients. Adjuvant treatment included hormonal therapy, chemotherapy, and radiation therapy. Follow-up (5 to 336 months) information was available for 53 patients: alive with no evidence of disease, 29; alive with disease, 15; and dead of disease, 9 (median period of 70 months from diagnosis to death). Thirty-three patients had recurrent disease, and 10 patients were lost to follow-up. EESS is commonly associated with endometriosis and tends to be indolent with a propensity for recurrence. Seven of 9 patients who died of the disease had bowel involvement, and 3 had tumors with dedifferentiation. Besides the latter, no other histologic finding correlated with the clinical behavior of these tumors.

Objectives: Lymphatic mapping studies in women with cervical cancer typically identify sentinel nodes (SLNs) in the pelvis and not the parametrium. We added India ink as a mapping agent to determine whether this would allow us to pathologically identify sentinel parametrial nodes and to test our hypothesis that the parametrial nodes are the true SLNs in women with cervical cancer., Methods: We performed lymphatic mapping and SLN biopsy in 20 women with early-stage cervical cancer undergoing radical hysterectomy or trachelectomy using a "triple injection" technique with blue dye, radiocolloid, and India ink. Pathologic processing of parametrium and nodal tissue was then performed to identify India ink in specimens., Results: On pathology review, 15 (75%) patients had a parametrial node identified, and 9 patients (45%) had bilateral parametrial nodes identified; the median number of parametrial nodes identified was 2 (range, 0-7). India ink was seen in at least 1 parametrial node in 13 (87%) of the 15 patients with a parametrial node identified pathologically. Of the 9 patients with bilateral parametrial nodes identified pathologically, only 5 (54%) had bilateral parametrial nodes containing India ink. India ink was found in 26 (44%) of 59 SLNs and only 1 (0.3%) of 289 non-SLNs. In 5 patients, India ink was seen in a SLN on the same side of the pelvis where a parametrial node was identified but not microscopically black., Conclusions: There appears to be direct drainage of cervical lesions to pelvic nodal basins bypassing small parametrial nodes. Parametrial nodes, therefore, may not always be the SLNs in women with cervical cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To review our experience with conization with intraoperative frozen section analysis and to compare results from our tertiary cancer center with those from 2 community hospitals., Methods: The records of all women who underwent conization with intraoperative frozen section analysis from January 1, 1997, through April 30, 2011, at The University of Texas MD Anderson Cancer Center and 2 community hospitals-The Woman's Hospital of Texas and St. Luke's Episcopal Hospital-were reviewed. Findings on pathologic analysis of frozen sections, permanent loop electrosurgical excisional procedure/conization specimens, and hysterectomy specimens were compared for each patient, and the results from the cancer center were compared to those from the community hospitals., Results: One hundred fifty-three patients met the inclusion criteria. Rates of accuracy of conization with frozen section analysis in predicting definitive pathologic findings were as follows: cervix with no residual disease after prior extirpative procedure, 96.5% (95% CI 86.9-100%); cervical squamous carcinoma in situ, 95.4% (95% CI 84.5-100%); cervical adenocarcinoma in situ, 98.7% (95% CI 92.7-100%); microinvasive carcinoma, 97.4% (95% CI 90.1-100%); and invasive carcinoma≥3 mm, 100%. Most importantly, conization with frozen section analysis was 100% accurate for triaging patients to simple or radical hysterectomy. Finally, this approach performed equally well in the cancer center with subspecialized pathologists and the 2 community hospitals with general pathologists., Conclusion: Conization with frozen section analysis is an effective technique for intraoperative triage of patients to immediate simple or radical hysterectomy and can be accurately performed in both academic and community hospitals., (Copyright © 2012 Elsevier Inc. All rights reserved.)

► Vaginal melanoma in situ is a rare neoplasm with a paucity of data regarding the optimal management. ► More conservative approaches are needed to avoid the disfigurement, pain and postoperative complications associated with repeated surgical interventions. ► Imiquimod may prove to be a useful treatment modality for patients with vulvar or vaginal melanoma in situ.

► Ovarian small-cell carcinoma of the hypercalcemic type is a rare neoplasm with no standard treatment. ► The chemotherapy regimen including vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin and etoposide (VPCBAE) has limited toxicities and was effective in the 3 patients described in this case report.

The findings of positron emission tomography combined with computed tomography (PET/CT) in a patient with FIGO stage IIA adenoma malignum of the uterine cervix are described in this article. PET/CT showed that the cervical tumor was intensely hypermetabolic with no evidence of disease spread. However, lymphadenectomy revealed metastatic spread to paraaortic lymph nodes. PET/CT may be useful in identifying primary site of disease in patients with adenoma malignum; however, the utility in detecting metastatic nodal disease remains to be determined.

It has been proposed that an adequate lymph node (LN) dissection in cases of endometrial carcinoma (CA) should contain a determined number of pelvic (P) and/or para-aortic (PA) LNs. As a result, our surgeons have certain expectations regarding the number of PLNs and PALNs reported per case. Failure to meet these expectations has become a challenge in our practice. In an attempt to solve this problem, we wanted to ascertain whether a pathology factor such as disregarding small LNs not detected on gross examination was responsible for any discrepancy between expected and reported LN counts. To achieve this goal, we evaluated the impact of the microscopic examination of residual adipose tissue (AT) after the routine processing of LN dissections performed as part of the staging procedure for patients with endometrial CA (endometrioid, serous, and clear cell CA) on the LN counts and status for hysterectomies performed from 2006 to the present. In addition, we assessed whether other factors such as surgical procedure type, operating surgeon, histologic subtype of CA, depth of myometrial invasion, or body mass index had an impact on the number of LNs obtained. The number of PLNs and PALNs were recorded. All LN specimens were processed by dissecting LNs from the surrounding AT. The number of LNs submitted per cassette was recorded in the section code. In cases in which residual AT was submitted, hematoxylin and eosin-stained slides of the additional tissue were reviewed to determine the number and size of any additional LNs and their status. Two hundred fifty-eight patients had a median of 11 PLNs (range, 1 to 38) and 6 PALNs (range, 1 to 25). Fifty of 78 cases (64%) in which residual AT was submitted had additional LNs (median size, 4.0 mm): median 2 PLNs and 3 PALNs. There was no significant association between the number of LNs obtained and whether the residual AT was submitted (PLN, P=0.2; PALN, P=0.78). There were no cases in which metastatic endometrial CA was present exclusively in the additional LNs. Compared with open hysterectomy, laparoscopically and robotically obtained lymphadenectomy specimens had an average of 3 and 0.8 more PALNs, respectively (P=0.002). No similar association was found for PLNs or total LNs. Evidence for some difference in LN counts between surgeons was observed. No evidence of an association between body mass index, histologic subtype of endometrial CA or depth of myometrial invasion and LN count was identified. In our experience, the standard processing of lymphadenectomy specimens adequately reflects the actual numbers of LNs obtained in cases of endometrial CA. Submitting the residual AT does not increase the number of reported LNs or the detection of positive LNs. Additional studies are required to determine the actual numbers of PLNs and PALNs present and to determine whether a revision of the number of LNs required to consider a lymphadenectomy as adequate is necessary.

Sciatic (catamenial) radiculopathy, waxing and waning with the menstrual cycle, is an uncommon condition typically caused by pelvic endometriosis affecting the lumbosacral plexus or proximal sciatic nerve. The authors describe a woman with catamenial sciatica caused by endometriosis affecting the sciatic nerve trunk in the upper thigh. Symptomatic with leg pain for 5 years, this patient developed gluteal atrophy and sensory loss and decreased strength in the L-5 dermatomyotome, a distribution confirmed by electromyography. Magnetic resonance imaging suggested thickening of the sciatic nerve at and distal to the sciatic notch. At operation the nerve showed extrinsic and intrinsic abnormality, proven to be endometriosis. Her symptoms improved, and she began gonadotropin-releasing hormone agonist therapy for further suppression. This very unusual case shows that endometriosis can affect the sciatic nerve over a range of territory inside and outside the pelvis, and that surgery must be appropriately directed to avoid negative exploration. Surgical decompression achieves good relief of symptoms, and medical therapy also allows sustained suppression of this disease.

Objective: Patients with micrometastasis to para-aortic lymph nodes may benefit from extended field chemoradiation. To determine the rate of para-aortic node micrometastasis in patients with locally advanced cervical cancer undergoing laparoscopic extraperitoneal para-aortic lymphadenectomy., Methods: We prospectively identified consecutive patients diagnosed with stage IB2-IVA biopsy-proven cervical cancer. Eligible patients included those who were candidates for treatment with radiotherapy and concurrent chemotherapy and had no evidence of para-aortic lymphadenopathy (all lymph nodes< 2 cm in diameter) by preoperative computed tomography or magnetic resonance imaging. All patients underwent preoperative positron emission tomography/computed tomography and laparoscopic extraperitoneal para-aortic lymphadenectomy. All lymph nodes were assessed for metastasis by routine hematoxylin-eosin (H&E) staining. Ultrastaging (serial sectioning) and immunohistochemical analysis were performed in H&E-negative specimens., Results: Thirteen (22%) of 60 consecutive patients had para-aortic lymph node metastases detected on routine H&E staining. Of the remaining 47 patients, one (2.1%) had evidence of micrometastasis, which was detected by ultrastaging. This patient completed whole pelvic radiotherapy and chemotherapy but had a recurrence 27 months after completion of therapy., Conclusions: The rate of para-aortic node micrometastasis in patients with locally advanced cervical cancer is low. The role of routine ultrastaging and immunohistochemical analysis in such patients remains uncertain. Future studies are needed to determine the clinical impact of para-aortic node micrometastasis in patients with locally advanced cervical cancer., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The technique of sentinel lymph node (SLN) detection is increasingly being applied in patients with uterine cervix carcinoma. This study presents the pathologic findings of SLNs in 48 such patients. The institutional pathology files were searched for all patients with a diagnosis of cervical squamous cell carcinoma who had SLNs reported. Patient age, follow-up, tumor size, presence/absence of lymphatic invasion, number and status of SLNs and non-SLNs, location of SLNs, and size of metastases in SLNs were recorded. All SLNs were sectioned in 2-mm slices perpendicular to the long axis and submitted entirely for microscopic examination. For all SLNs negative on the initial hematoxylin and eosin (H&E) stained slides, an ultrastaging protocol was performed consisting of 5 sets of slides at 40-mum intervals (1 H&E slide+2 unstained slides), representing an additional 5 intervals. Lymph nodes negative by the additional H&E intervals had immunohistochemistry for cytokeratin performed on 1 unstained slide. Forty-eight patients ranging from 25 to 62 years of age had a total of 208 SLNs removed. Fifteen (31%) patients had positive SLNs with 1 to 5 positive SLNs per case. The metastasis size ranged from a single cell to 27 mm. Twelve patients had metastasis detected by routine processing in 23 SLNs, whereas ultrastaging detected metastases in 3 SLNs of 3 additional patients. In 2 patients with metastasis detected by ultrastaging, the metastasis was detected by wide H&E intervals (level 2 for 1 patient; level 3 for 1 patient); in 1 patient, the metastasis was detected only by immunohistochemistry and consisted of a single cell. Of the 15 patients with positive SLNs, 3 patients had a total of 6 positive non-SLNs. All of the patients with a positive SLN are currently living. Thirty-three (69%) patients had negative SLNs. Of these, 1 patient had a single positive non-SLN for a false negative rate of 6.25%. Negative SLN predicts negative non-SLN. For most patients with a positive SLN, the SLN will be the only metastasis detected; a minority of patients with a positive SLN may have a positive non-SLN.

Thyroid transcription factor-1 (TTF-1) protein expression is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or the thyroid, the expression of this marker has been studied in only a limited number of ovarian neoplasms. Our study examines the incidence of TTF-1 expression in a variety of ovarian epithelial neoplasms. Tissue microarrays of 138 ovarian serous carcinomas, 65 endometrioid adenocarcinomas, 35 mucinous adenocarcinomas, 30 mucinous neoplasms of low malignant potential, and 10 clear cell carcinomas were stained with anti-TTF1-antibody. In addition, whole tissue sections of 19 serous carcinomas, 5 endometrioid adenocarcinomas, 7 mucinous adenocarcinomas, and 3 clear cell carcinomas were stained. In the tissue microarrays, TTF-1 nuclear expression was demonstrated in 2 of 65 (3%) of the endometrioid adenocarcinomas; no nuclear immunoreactivity was identified in the remaining ovarian neoplasms. In the whole tissue sections, TTF-1 nuclear staining was present in 7 of 19 (37%) serous carcinomas, 1 of 5 (20%) endometrioid adenocarcinomas, and 1 of 3 (33%) clear cell carcinomas. In most of the positive cases, staining was focal, but in one endometrioid adenocarcinoma in the tissue microarray and in one serous and one clear cell carcinoma in the whole tissue sections, there was diffuse positivity. Overall, there was nuclear staining in 0.7% of tumors in the tissue microarray and 26% in the whole tissue sections. Although TTF-1 nuclear expression is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional immunoreactivity of ovarian carcinomas should be considered in the evaluation of neoplasms of unknown primary origin. It should also be taken into consideration when evaluating adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy.

Objective: To determine the patterns of lymphatic drainage from primary vaginal cancers utilizing lymphoscintigraphy and to determine if this clinical information would affect treatment planning., Methods: For women with newly diagnosed vaginal cancer, pretreatment lymphatic mapping and sentinel lymph node identification were performed using lymphoscintigraphy. In patients who underwent surgery, sentinel lymph nodes were identified intraoperatively using radiocolloid and patent blue dye. The impact of pretreatment lymphoscintigraphy findings on radiation planning in women who received radiation as initial treatment was noted., Results: Fourteen women were enrolled during the study period. At least 1 sentinel lymph node was identified on pretreatment lymphoscintigraphy in 11 patients (79%). The median number of sentinel nodes found per patient was 2, and bilateral sentinel nodes were found in 6 (55%) of the 11 patients with sentinel nodes identified. Among these 11 patients, 5 (45%) had sentinel nodes identified in the groin only, 4 (36%) had sentinel nodes identified in the pelvis only, and 2 (18%) had sentinel nodes identified in both the groin and the pelvis. No relationship was observed between sentinel lymph node location and primary tumor histologic subtype or location. Three (33%) of the 9 women treated initially with radiation therapy had their radiation field altered as a result of the lymphoscintigraphy findings., Conclusion: In women with vaginal cancer, lymphatic drainage from the primary lesion does not always follow the lymphatic channels that would have been predicted anatomically. The addition of lymphoscintigraphy to the pretreatment evaluation for women with vaginal cancer may significantly improve comprehensive treatment planning.

Uterine tumors with neuroectodermal differentiation, frequently referred to as primitive neuroectodermal tumors (PNETs), are uncommon. The clinicopathologic features of 17 such cases reviewed at the M.D. Anderson Cancer Center (MDACC) are presented along with a review of the literature. All of the pathology material was reviewed at MDACC, and in all cases, immunohistochemistry contributed to the diagnosis. In 12 cases, in situ hybridization techniques were used to determine whether a rearrangement of the EWSR1 gene, required for a diagnosis of peripheral PNET, was present. Clinical information was obtained from a patient chart review. Ages ranged from 31 to 81 years (median 58). Clinical presentations included vaginal bleeding (9), back pain (1), presumed fibroids (2), pelvic mass (1), incidental finding at hysterectomy (1), and unknown (3). Twelve patients had surgery or imaging to determine stage: I (2), II (0), III (6), and IV (4). Five patients had biopsy only. Ten tumors had only neuroectodermal components. In 7 tumors, the neuroectodermal component was admixed with an additional component including unclassified sarcoma (2 cases), rhabdomyosarcoma, endometrioid carcinoma, adenosarcoma and malignant mixed Mullerian tumor (2 cases). Follow-up, available for 13 patients, ranged from 2 to 41 months with 7 patients dead of disease 2 to 26 months after diagnosis. Six patients are alive with no evidence of disease after follow-up ranging from 6 to 41 months. Four patients were lost to follow-up. Results for the most commonly used immunohistochemistry studies include cytokeratin, 13/15 tumors negative (2 focally positive); synaptophysin, 15/16 tumors positive; neurofilament, 10/11 tumors positive; and CD99, 7/9 tumors positive (2 tumors had nonspecific cytoplasmic staining). None of the 12 tumors tested had a detectable rearrangement in the EWSR1 gene. Uterine tumors with neuroectodermal differentiation, similar to more common endometrial malignancies, tend to occur in postmenopausal women and frequently present with vaginal bleeding. An immunohistochemistry panel including cytokeratin, neurofilament, synaptophysin, and CD99 can highlight neuroectodermal differentiation and identify tumors for which molecular testing should be considered. Tumors without a rearrangement of the EWSR1 gene should be descriptively characterized as uterine tumors with neuroectodermal differentiation or alternatively central type PNETs rather than PNET, not otherwise specified to avoid confusion with peripheral PNET.

We report the first case of a secondary tumor arising from a peritoneal nodule of mature teratoma in a patient with growing teratoma syndrome (GTS) of the ovary. The patient originally presented 19 years ago with an immature teratoma of the ovary and positive retroperitoneal lymph nodes. After surgery and chemotherapy, mature teratomas recurred as abdominal and pelvic masses after 1, 6, and 19 years. Upon the last recurrence, a trabecular carcinoid tumor developed in a mature teratoma associated with the liver. This case illustrates the importance of long-term follow-up for patients with GTS of the ovary, where the recurrent masses can appear many years after the primary tumor, compress the abdominal and pelvic structures and give rise to secondary neoplasms. In addition, we present a literature review of GTS of the ovary and some novel observations about this entity. On the basis of our review of ovarian GTS cases in the literature, we have found that ovarian GTS nodules tend to appear for the first time within 2 years of the initial primary. They remain confined almost exclusively to the pelvis, abdomen, and the retroperitoneum and do not venture to distant systemic sites. This new information may help identify and screen women with germ cell tumors of the ovary at risk for GTS.

Thyroid transcription factor-1 (TTF-1) is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or thyroid, endocervical and endometrial adenocarcinomas have not been studied in large numbers. Our study provides data regarding the incidence and distribution of TTF-1 expression in these tumors. Twenty-eight endocervical (9 well, 12 moderately, and 7 poorly differentiated), 32 endometrioid endometrial adenocarcinomas (11 grade I, 8 grade II, and 13 grade III), and 13 uterine serous carcinomas were retrieved and stained with TTF-1. None of the tumors had a neuroendocrine component. The hematoxylin and eosin and anti-TTF-1 antibody stained sections were reviewed, and the presence and distribution of TTF-1 nuclear positivity was recorded. A semiquantitative grading system used to evaluate the distribution of TTF-1 staining (0 = negative, 1+ = <5%, 2+ = 5% to 25%, 3+ = 26% to 50%, 4+ = 51% to 75%, and 5+ = >75%). TTF-1 expression was seen in 1 of 28 (4%) of the endocervical adenocarcinomas and this was 4+ in distribution. The positive endocervical carcinoma was poorly differentiated. TTF-1 expression was present in 6 of 32 (19%) of the endometrioid adenocarcinomas (1 grade I, 2 grade II, and 3 grade III) and varied from 1+ to 4+ in distribution. Only 2 of 32 (6%) of the endometrioid adenocarcinomas stained diffusely (4+). There was no apparent correlation between the degree of differentiation and TTF-1 positivity in the adenocarcinomas. Three of 13 (23%) serous carcinomas were also positive (1 case 5+ and 2 cases 1+). Although TTF-1 is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional expression of endometrial and endocervical carcinomas should be kept in mind when evaluating neoplasms of uncertain origin. It should also be taken into consideration in the evaluation of adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy.

Many patients with pancreatic carcinoma have stent placement for biliary obstruction before resection. Stent-associated atypia, found in common bile duct (CBD) margins at the time of resection, may be confused with malignancy. We evaluated histologic and immunohistochemical changes in CBD margins from resection specimens for pancreatic carcinoma. Histologic findings in CBDs, including ulcer and inflammation; epithelial metaplasia, atypia, and gland complexity; and increased wall thickness, nerve entrapment, and smooth muscle content, were compared in 30 stented and 31 nonstented CBD margins from pancreaticoduodenectomies for carcinoma and 13 normal CBDs from autopsy material. The proliferation index was calculated for stented and nonstented CBDs after Ki-67 immunohistochemical staining. Immunostaining for Ki-67, p53, and c-erbB-2 was performed in stented CBDs and corresponding carcinomas. All the histologic changes occurred more frequently in stented and nonstented CBD margins from carcinoma patients than in normal CBDs. Stented CBDs had significantly increased epithelial changes and Ki-67 proliferation rate as compared with nonstented CBDs. The stented CBDs had significantly less p53 and c-erbB-2 expression as compared with corresponding pancreatic carcinomas. Caution should be applied when interpreting atypia in CBD margins from patients with a history of CBD stenting. Changes found in stented CBDs are characteristic, and in most cases can be distinguished from malignancy. In difficult cases, immunohistochemistry may be useful.

Objectives: Elevated serum levels of CA125 are observed not only in association with primary ovarian epithelial neoplasms but also in a variety of other clinical settings, including ovarian involvement by metastatic disease. There is considerable overlap in gross and histologic features between primary ovarian tumors and metastatic colorectal adenocarcinoma, which can make diagnosis particularly challenging in the setting of an increased CA125 level. The aims of this study were to determine how frequently serum CA125 is elevated in women with ovarian involvement by metastatic colorectal adenocarcinoma and to compare the features of cases with and without associated elevations of serum CA125., Methods: Eighty-nine cases of histologically confirmed ovarian involvement by metastatic colorectal adenocarcinoma were identified by retrospective review. Clinicopathologic data were analyzed, including preoperative serum CA125 level (available in 42 cases). Features of cases with an associated increase in serum CA125 were compared with those of cases with no such elevation., Results: Twenty-nine patients had an elevated serum CA125 level (>35 U/mL) preoperatively (range 39.0-556.3, median 143.0, mean 199.1). Thirteen patients had a serum CA125 level within the reference range, while forty-seven patients had no preoperative testing for serum CA125. Clinical, gross, and histologic features of cases with an associated increase in serum CA125 were generally similar to those of cases with a non-elevated serum CA125 concentration. In three cases, the tumor was initially diagnosed as an ovarian primary., Conclusions: At least 32.6% of women with ovarian involvement by metastatic colorectal adenocarcinoma have an elevated serum CA125 level prior to oophorectomy. Such cases do not differ significantly from cases lacking such an association with respect to a variety of clinicopathologic features. The possibility of metastasis from a colorectal carcinoma merits consideration in the formation of the differential diagnosis for a woman with an adnexal mass and elevated serum CA125, even in the absence of an established history of gastrointestinal malignancy.

Although differential WT-1 expression between ovarian and uterine serous carcinoma has been discussed in the literature, there have been no studies of WT-1 expression in serous carcinomas in the peritoneum with or without concurrent serous carcinoma in an endometrial polyp. This study addresses this issue and includes a small series of uterine and ovarian serous carcinomas for comparison. Nine peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp, 10 peritoneal serous carcinomas without serous carcinoma in an endometrial polyp, 9 uterine serous carcinomas, and 12 ovarian serous carcinomas were stained with antibody to WT-1. Ninety-two percent of ovarian serous carcinomas and 80% of peritoneal serous carcinomas without serous carcinoma involving an endometrial polyp expressed WT-1. In contrast, 12% of peritoneal serous carcinomas with serous carcinoma in an endometrial polyp expressed WT-1 with the serous carcinoma in the endometrial polyp staining concordantly. For uterine serous carcinoma without an endometrial polyp, only 11% expressed WT-1. Peritoneal serous carcinomas without coexistent serous carcinoma in an endometrial polyp have a WT-1 expression pattern similar to ovarian serous carcinoma while peritoneal serous carcinomas with coexistent serous carcinoma in an endometrial polyp have a staining pattern similar to uterine serous carcinoma. The difference in WT-1 expression among serous carcinomas suggests a difference in biology based on the site of origin. Additionally, the difference in WT-1 expression between peritoneal serous carcinomas with and without coexistent serous carcinoma in endometrial polyps suggests that peritoneal serous carcinoma may have different pathogenetic pathways.

The clinicopathologic features of 35 cases of serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as lymphadenopathy are described. The cases were retrieved from the files of the Department of Pathology at the University of Texas M. D. Anderson Cancer Center from a 20-year period (1982-2002). The following parameters were evaluated: patient age at diagnosis, lymph node involved, primary tumor site, tumor histology, peritoneal disease status, and survival. The patients ranged in age from 30 to 85 years (mean, 59 years). The lymph nodes involved were inguinal, 20 cases; supraclavicular, 11 cases; axillary, 2 cases; cervical, 1 case; and retroperitoneal, 1 case. Primary tumor sites included 20 ovarian, 10 peritoneal, and 2 fallopian tube. In 2 patients, total abdominal hysterectomy/bilateral salpingo-oophorectomy and complete staging showed no additional tumor, and in 1 patient with a previous history of total abdominal hysterectomy/bilateral salpingo-oophorectomy for a benign condition, imaging studies did not identify a primary site. The carcinoma was high grade in 30 cases and low grade in 4 cases. In one case, the diagnosis was made on cytology material and the tumor could not be graded. Peritoneal disease status was known in 33 patients and was as follows: omentum with gross disease, 16 cases; and omentum without gross disease, 17 cases. Follow-up was available in 33 patients and ranged from 4 to 204 months, with a median survival of 36 months for stage III patients and 29 months for stage IV patients. Patients with adenopathy and minimal peritoneal disease (grossly negative omentum) had a median survival of 120 months compared with 24 months for those with bulky peritoneal disease (grossly positive omentum). Serous carcinoma of the ovary, fallopian tube, or peritoneum presenting as a lymph node metastasis is uncommon. In rare cases, a primary site may not be found. The median survival of the patients for stage is not appreciably different from those patients presenting in the usual fashion, suggesting that this atypical presentation does not adversely affect survival. Patients with minimal peritoneal disease and extra-abdominal lymph node metastases survive longer than those with bulky peritoneal disease

Adenomatous polyps are common neoplastic lesions of the large intestine. The risk of carcinoma increases with polyp size. Small polyps are typically totally embedded for histologic examination, but no standard method for sampling large, grossly benign polyps has been established. We reviewed grossly noninvasive adenomas 2.5 cm or larger to determine the percentage that contained high-grade dysplasia (HGD) and invasive cancer (IC). Based on these findings, we suggest an approach to evaluating large adenomas. Forty-three colon resections met the inclusion criteria (no previous diagnosis of cancer, no gross evidence of invasion, and totally embedded polyp). Twelve (28%) had HGD with 3% (1 of 33 slides) to 100% (4 of 4 slides) containing HGD. Five (12%) had IC with 4% (3 of 72 slides) to 42% (5 of 12 slides) containing IC. All cases with IC had HGD in other slides. Probability studies showed that in the majority of cases, polyps would need to be entirely embedded to have an estimated probability of 95% or more of detecting either HGD or IC. Therefore, grossly noninvasive adenomas should be routinely entirely embedded.