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BACKGROUND: The great obstetrical syndromes of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether 1 or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. OBJECTIVE: This study aimed to determine how the quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent or reversed umbilical artery Doppler indices and hypertensive disorders of pregnancy or the 2 conditions combined among subjects with disease severity that warrant early preterm delivery. We hypothesized that the trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulated that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction with no additional effect when hypertension is concomitantly present. STUDY DESIGN: In this retrospective cohort study, paraffin-embedded placental tissue was obtained from 4 groups, namely (1) patients with severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, (2) patients with severe fetal growth restriction with absent or reversed umbilical artery Doppler indices and no hypertension, (3) gestational age-matched, appropriately grown pregnancies with hypertensive disease, and (4) gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed, followed by artificial intelligence-driven morphometric analyses. The number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled using linear regression. RESULTS: Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi; 95% confidence interval, -467 to -98; P<.01), a smaller stem villous area (-4.3 mm2; 95% confidence interval, -7.3 to -1.2; P<.01), and fewer stem villous vessels (-4967 stem villous vessels; 95% confidence interval, -8501 to -1433; P<.01) with no difference in the total vascular area. In contrast, placental abnormalities in cases with severe growth restriction were limited to terminal villi with global decreases in the number of villi (-873 terminal villi; 95% confidence interval, -1501 to -246; P<.01), the villous area (-1.5 mm2; 95% confidence interval, -2.7 to -0.4; P<.01), the number of blood vessels (-5165 terminal villous vessels; 95% confidence interval, -8201 to -2128; P<.01), and the vascular area (-0.6 mm2; 95% confidence interval, -1.1 to -0.1; P=.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. CONCLUSION: Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent or reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions in the combination of growth restriction and hypertension, suggesting that distinct pathophysiological pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to lead to more severe pathologic consequences. Delineating mechanisms that underly the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.
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While conventional autopsy is the gold-standard for determining cause of demise in the fetal and neonatal population, molecular analysis is increasingly used as an ancillary tool. Testing methods and tissue selection should be optimized to provide informative genetic results. This institutional review compares testing modalities and postmortem tissue type in 53 demises occurring between 20 weeks of gestation and 28 days of life. Testing success, defined as completion of analysis, varies by technique and may require viable cells for culture or extractable nucleic acid. Success was achieved by microarray in 29/30 tests (96.7%), karyotype in 40/54 tests (74.1%), fluorescent in situ hybridization in 5/9 tests (55.6%), and focused gene panels in 2/2 tests (100%). With respect to tissue type, postmortem prepartum amniotic fluid was analyzed to completion in 100% of tests performed; compared to 84.0%, 54.5%, and 80.8% of tests using placenta, fetal only, and mixed fetal-placental tissue collection, respectively. Sampling skin (83.3%, in cases with minimal maceration) and kidney (75.0%) were often successful, compared to lower efficacy of umbilical cord (57.1%) and liver (25.0%). Addition of genetic testing into cases with anomalous clinical and gross findings can increase the utility of the final report for family counseling and future pregnancy planning.
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Morte Fetal , Natimorto , Recém-Nascido , Gravidez , Feminino , Humanos , Natimorto/epidemiologia , Morte Fetal/etiologia , Placenta/patologia , Hibridização in Situ Fluorescente , Autopsia/métodosRESUMO
Follicular dendritic cell sarcoma is a rare dendritic/histiocytic tumor of intermediate malignant potential, which often involves extranodal sites, most commonly the gastrointestinal tract and mediastinum with only 5 cases reported in the female genital tract. We present the clinical and pathologic features of 2 such examples arising in the uterine corpus. Both patients (63 and 72-yr old) presented with postmenopausal bleeding and underwent an endometrial biopsy diagnostic of follicular dendritic cell sarcoma that was followed by hysterectomy. The tumors were polypoid, 3.5 and 5.0 cm, and were confined to the endometrium. Microscopically, ovoid to round to spindled tumor cells with pale eosinophilic cytoplasm and vesicular nuclei were arranged predominantly in sheets with an accompanying lymphocyte-rich inflammatory infiltrate. The tumor cells were positive for CD35, CD23, D2-40 in both tumors and additionally positive for CD21 in 1 tumor, all highlighting cell bodies and processes. Patients were alive without evidence of disease at 1 and 4 years with no adjuvant treatment. These cases highlight the importance of entertaining a broad differential diagnosis in lesions with epithelioid and/or spindled morphology involving the uterus.
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Sarcoma de Células Dendríticas Foliculares , Humanos , Feminino , Sarcoma de Células Dendríticas Foliculares/diagnóstico , Sarcoma de Células Dendríticas Foliculares/cirurgia , Sarcoma de Células Dendríticas Foliculares/patologia , Útero/patologia , Histerectomia , Biópsia , Endométrio/patologia , Biomarcadores Tumorais/análiseRESUMO
Ovarian germ cell tumors (GCT) account for 2% to 3% of malignant ovarian neoplasms in Western countries and typically occur within the first 2 decades. When presenting later in life, GCTs may be associated with epithelial malignancies. In these circumstances, it has been theorized that these tumors may originate from a somatic, rather than germ cell origin, especially in the postmenopausal setting; however, the true derivation is not fully understood. Our database was searched for primary ovarian GCTs associated with a malignant epithelial component in patients above 35 yr of age, from 2006 to 2021. Two cases were identified and in each case, slides were reviewed and targeted next-generation sequencing was utilized to identify and compare gene mutation variants in morphologically distinct components. Patient A is a 58-yr-old, with choriocarcinoma and minor component of mucinous adenocarcinoma, and patient B is a 43-yr-old, with yolk sac tumor and minor component of endometrioid adenocarcinoma. The morphologically distinct areas in each case showed disparate staining patterns; however, next-generation sequencing demonstrated identical mutation variants within both the germ cell and epithelial components. Variants in CDKN2A , PIK3CA , PIK3R1 , and TP53 were present in patient A's tumor, while patient B's tumor showed CTNNB1 , PIK3R1 , and 2 PTEN variants. These mutational patterns are similar to those seen in pure epithelial counterparts, suggesting somatic derivation of the germ cell component. These rare tumors portend a poor prognosis and understanding their origin has clinical and therapeutic implications.
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Adenocarcinoma Mucinoso , Coriocarcinoma , Tumor do Seio Endodérmico , Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/genética , Carcinoma Endometrioide , Coriocarcinoma/diagnóstico , Coriocarcinoma/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/genéticaRESUMO
Based on findings from The Cancer Genome Atlas and the Proactive Molecular Risk Classifier for Endometrial Cancer algorithm, endometrial carcinoma can now be stratified into 4 prognostically distinct subgroups based on molecular alterations and immunohistochemical (IHC) aberrations. In this study, we describe the de novo adoption and clinical reporting of prognostic subgroup classification based on next-generation sequencing (NGS) and IHC analyses of all endometrial carcinoma resections at a single institution, framed by the Exploration, Preparation, Implementation, and Sustainment model. Results from the first 13 months show 188 tumors underwent analysis by a combination of IHC and a medium-sized (56 analyzed genes) NGS-based assay. All cases were assigned as either POLE (POLE-mutated) (5.3%), mismatch repair deficient (27.7%), no specific molecular profile (45.7%), or p53 abnormal (21.3%) inclusive of multiple-classifier cases. NGS-based analysis revealed additional distinctions among the subgroups, including reduced levels of PI3K pathway activation in the p53 abnormal subgroup, an increased rate of CTNNB1 activating mutation in the no specific molecular profile subgroup, and lower TP53 mutation variant allele frequencies in POLE and mismatch repair deficient subgroups compared with the p53 abnormal subgroup. Overall, we describe the testing protocol, reporting, and results of a combination of NGS and IHC to prospectively prognosticate endometrial carcinomas at a single tertiary care center.
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OBJECTIVE: To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets. METHODS: The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC. RESULTS: In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (p < 0.001) and demonstrated inferior survival (p < 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient. CONCLUSIONS: The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.
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Carcinoma Adenoescamoso , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Colo do Útero/patologia , Feminino , Humanos , Neoplasias do Colo do Útero/patologiaRESUMO
Pregnancies complicated by severe, early-onset fetal growth restriction with abnormal Doppler velocimetry (FGRadv) have a sparse villous vascular tree secondary to impaired angiogenesis. As endothelial cell (EC) and stromal matrix interactions are key regulators of angiogenesis, we investigated the role of placental stromal villous matrix on fetoplacental EC angiogenesis. We have developed a novel model of generating placental fibroblast (FB) cell-derived matrices (CDMs), allowing us to interrogate placenta-specific human EC and stromal matrix interactions and their effects on fetoplacental angiogenesis. We found that as compared with control ECs plated on control matrix, FGRadv ECs plated on FGRadv matrix exhibited severe migrational defects, as measured by velocity, directionality, accumulated distance, and Euclidean distance in conjunction with less proliferation. However, control ECs, when interacting with FGRadv CDM, also demonstrated significant impairment in proliferation and migratory properties. Conversely several angiogenic attributes were rescued in FGRadv ECs subjected to control matrix, demonstrating the importance of placental villous stromal matrix and EC-stromal matrix interactions in regulation of fetoplacental angiogenesis.
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Células Endoteliais/fisiologia , Matriz Extracelular/fisiologia , Retardo do Crescimento Fetal/etiologia , Neovascularização Fisiológica , Placenta/fisiopatologia , Adulto , Estudos de Casos e Controles , Movimento Celular , Microambiente Celular , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Humanos , GravidezRESUMO
OBJECTIVES: Stage I, grade 1 endometrial cancers have low recurrence rates and often do not receive adjuvant therapy. We compared recurrent cases to matched non-recurrent controls to evaluate for molecular markers associated with higher risk of recurrence. METHODS: A case-control study including all cases of recurrent stage I, grade 1 endometrioid endometrial cancer at one institution in a ten-year period. Cases were matched to controls by age, BMI, weight and stage. Molecular testing and immunohistochemistry were performed on archival tumor specimens: microsatellite instability (MSI-H), mismatch repair status, POLE mutational status, and next-generation sequencing. RESULTS: 15 stage I, grade 1 endometrial cancer cases with recurrent disease and available tumor specimens were identified. CTNNB1 and MSI-H were present at significantly higher rates in cases than controls (CTNNB1 60% vs. 28%, OR 3.9, 95%CI 1.1-14.7, pâ¯=â¯0.04 and MSI-H 53% vs. 21%, OR 4.4, 95%CI 1.1-17.0, pâ¯=â¯0.03). POLE mutations were found in 0% of cases vs. 7% of controls (pâ¯=â¯0.54). Among specimens demonstrating microsatellite stability (MSS), 100% of cases vs. 26% of controls had CTNNB1 mutations (pâ¯<â¯0.001). CTNNB1 wild type tumors were MSI-H in 100% of cases vs. 19% of controls (pâ¯<â¯0.001). CONCLUSIONS: Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors. MSI-H is also present at significantly higher rates in recurrent cases. These markers may be useful for prognostic risk stratification and adjuvant therapy decision-making in this otherwise low-risk population.
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Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Recidiva Local de Neoplasia/genética , beta Catenina/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/patologia , Estudos de Casos e Controles , Classe I de Fosfatidilinositol 3-Quinases/genética , DNA Polimerase II/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Proteínas de Membrana/genética , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Leiomyosarcomas are rare, aggressive tumors, which exhibit a poor prognosis regardless of stage. Pre-operative diagnosis can be difficult as leiomyosarcoma can mimic features of the more common, benign uterine leiomyoma. The goal of this study was to identify specific molecular markers to discriminate between uterine leiomyosarcomas and leiomyomas to facilitate timely, accurate diagnosis and treatment. Gene expression profiles of three leiomyosarcomas, leiomyomas, and normal myometrial tissue samples were analyzed using the Affymetrix Human Gene 1.0 ST Array. GC-robust multiarray average calculation and ANOVA statistical testing were used to identify differentially expressed genes. Sixty genes, with functional roles in tumor progression or suppression, exhibited divergent expression profiles in leiomyosarcomas and leiomyomas, compared to normal myometrium. Differential RNA and protein levels of seven genes, with the most discriminatory expression patterns, were confirmed by RTPCR and immunohistochemistry in an additional 10 leiomyosarcoma and 20 leiomyoma independent samples. CHI3L1, MELK, PRC1, TOP2A, and TPX2 were overexpressed in leiomyosarcomas, while HPGD and TES were overexpressed in leiomyomas. Distinguishing leiomyosarcomas from leiomyomas represents a diagnostic challenge, particularly in the context of minimally invasive surgery. The unique gene expression signatures identified in this study may accurately differentiate between these tumor types at the earliest stage and provides potential prognostic factors and novel therapeutic targets for the treatment of leiomyosarcoma.
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Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Leiomioma/genética , Leiomiossarcoma/genética , Neoplasias Uterinas/genética , Idoso , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteína 1 Semelhante à Quitinase-3/genética , Proteína 1 Semelhante à Quitinase-3/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Oxirredutases Intramoleculares , Leiomioma/diagnóstico , Leiomioma/metabolismo , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Sensibilidade e Especificidade , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/metabolismoRESUMO
PURPOSE: To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. METHODS: This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization. RESULTS: Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01). CONCLUSION: Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.
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Carcinossarcoma/secundário , Neoplasias Uterinas/patologia , Carcinossarcoma/mortalidade , Carcinossarcoma/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Projetos Piloto , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/cirurgiaRESUMO
OBJECTIVE: The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS). METHODS: This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I-IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome. RESULTS: Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36-2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39-2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08). CONCLUSION: In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.
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Vasos Sanguíneos/patologia , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Vasos Linfáticos/patologia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Quimioterapia Adjuvante , Progressão da Doença , Feminino , Humanos , Histerectomia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Intervalo Livre de Progressão , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND OBJECTIVES: To examine association of lympho-vascular space invasion (LVSI) with clinico-pathological factors and to evaluate survival of women with low-grade serous ovarian carcinoma containing areas of LVSI. METHODS: This is a multicenter retrospective study examining consecutive cases of surgically treated stage I-IV low-grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico-pathological findings and survival outcome. RESULTS: LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1-51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression-free survival (5-year rates 21.0% vs 35.7%, adjusted-hazard ratio 1.57, 95%CI 1.06-2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08-6.35, P = 0.047). CONCLUSION: LVSI in the ovarian tumor is associated with adverse clinico-pathological characteristics and decreased progression-free survival in women with low-grade serous ovarian carcinoma.
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Cistadenocarcinoma Seroso/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Linfonodos/patologia , Vasos Linfáticos/patologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Adulto , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Vasos Linfáticos/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVES: Intraoperative frozen section has greater than 90% accuracy for ovarian tumors; however, mucinous histology has been shown to be associated with increased frozen section inaccuracy. Recent data demonstrate that primary ovarian mucinous carcinomas have no lymph node involvement, even when extraovarian disease is present, and therefore may not require lymph node dissection. Our primary objective is to evaluate the accuracy of identifying mucinous histology on frozen section. METHODS/MATERIALS: A cross-sectional review of mucinous ovarian tumors in surgical patients at one institution from 2006 to 2016 was performed. Cases reporting a mucinous ovarian tumor on frozen section or final pathology were identified. Frozen section results were compared with final diagnosis to calculate concordance rates. Analyses with χ and t tests were performed to identify variables associated with pathology discordance. RESULTS: A total of 126 mucinous ovarian tumors were identified. Of these, 106 were reported as mucinous on frozen section and 103 (97.2%) were concordant on final pathology. Discordant cases included 2 serous and 1 clear cell tumor. Among the 103 mucinous tumors, classification as malignant, borderline, or benign was concordant in 74 (71.8%) of 103 cases, whereas 22 (21.4%) of 103 were discordant and 7 (6.8%) were deferred to final pathology. Lymph node dissection was performed in 33 cases; the only case with lymph node metastasis was a gastrointestinal mucinous adenocarcinoma. Discordance between frozen section and final pathology was associated with larger tumor size and diagnosis other than benign: discordant cases had a mean tumor size of 21.7 cm compared with 14.4 cm for concordant cases (P < 0.001), and 93.5% of discordant cases were borderline or malignant, compared with 30.5% of concordant cases (P < 0.001). CONCLUSIONS: Intraoperative identification of mucinous histology by frozen section is reliable with a concordance rate to final pathology of 97.2%. No lymph node metastases were present in any malignant or borderline primary ovarian cases.
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Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Estudos Transversais , Feminino , Secções Congeladas , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The discovery of a uterine diverticulum is a rare event. Diverticula can lead to outcomes including pelvic pain, ectopic pregnancy, and diverticula rupture and should be considered in cases of uterine cystic masses. We report a case of a 32-year-old G3P0030 with a complicated pregnancy and surgical history who presented to us following an abnormal laparoscopy for severe pelvic pain four years after salpingectomy for a tubal pregnancy. This laparoscopy reported a cornual uterine cystic structure. Saline infusion sonohysterography was performed with fluid filling a uterine cornual cystic mass. On hysteroscopy, no outpouching was identified. With chromopertubation on laparoscopy, methylene blue filled the diverticulum. The diverticulum was laparoscopically removed. Pathology examination was consistent with a diverticulum containing a placental implantation site and necrotic chorionic villi.
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Divertículo/diagnóstico , Doenças Uterinas/diagnóstico , Útero , Aborto Induzido , Aborto Espontâneo , Adulto , Divertículo/patologia , Divertículo/cirurgia , Feminino , Humanos , Laparoscopia , Cistos Ovarianos/complicações , Cistos Ovarianos/cirurgia , Dor Pélvica , Gravidez , Gravidez Tubária/cirurgia , Salpingectomia , Ultrassonografia , Doenças Uterinas/patologia , Doenças Uterinas/cirurgia , Útero/patologia , Útero/cirurgiaRESUMO
OBJECTIVE: The mechanisms underlying the histogenesis and aggressiveness of uterine carcinosarcoma (UCS) are poorly understood; however, previous studies implicate epithelial-mesenchymal transition (EMT). Fascin is a proinvasive, actin-bundling protein and an important component of EMT. It is associated with poor outcomes in human carcinoma, especially in estrogen receptor (ER)-negative tumors arising in organs normally expressing ER. We sought to evaluate fascin expression in UCS and its relationship to ER status, clinicopathologic indicators of tumor aggressiveness, and survival outcomes. METHOD: Forty-four surgically staged cases of UCS were immunohistochemically evaluated for fascin and estrogen receptor-α expression and correlated with clinicopathologic parameters derived from electronic medical records and pathology reports. RESULTS: Fascin was only expressed in malignant epithelium and mesenchyma and was uniformly absent in background benign counterparts. Increased expression was associated with extrapelvic disease (P = 0.028), higher stage (P = 0.021), larger tumor size (P = 0.032), shorter progression-free interval (P = 0.035), and reduced estrogen receptor-α expression (P = 0.04). CONCLUSION: Fascin is aberrantly expressed in both elements of UCS and is associated with aggressive behavior and worse outcome. As a component of EMT and mediator of invasion, fascin may serve as a target in future therapies.
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Carcinossarcoma/metabolismo , Carcinossarcoma/patologia , Proteínas de Transporte/biossíntese , Proteínas dos Microfilamentos/biossíntese , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptores de Estrogênio/biossíntese , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
OBJECTIVES: Endometrial cancer is a hormonally responsive malignancy. Response to progestins is associated with estrogen receptor (ER) and progesterone receptor (PR) status. CD133 is a marker of endometrial cancer stem cells. We postulated that CD133+ cells express ER and PR and that progestin therapy differentially regulates CD133+ cells. METHODS: The Ishikawa (ER/PR positive) and KLE (ER/PR negative) cell lines were examined for the presence of CD133 populations. Cell lines were treated with 30.4µM medroxyprogesterone 17-acetate (MPA) for 6days. After treatment, cell counts, apoptosis assays and CD133+ populations were examined. In a clinical project, we identified 12 endometrial cancer patients who were treated with progestin drugs at our institution. Using immunohistochemistry, CD133, ER, PR, and androgen receptor (AR) expression was scored and evaluated for change over time on serial biopsies. RESULTS: CD133+ populations were identified in Ishikawa and KLE cell lines. MPA treatment resulted in a significant reduction in the percentage of live cells (Ishikawa, P=0.036; KLE, P=0.0002), significant increase in apoptosis (Ishikawa, P=0.01; KLE, P=0.0006) and significant decrease in CD133+ populations (Ishikawa, P<0.0001; KLE, P=0.0001). ER, PR, AR and CD133 were present in 96.4%, 96.4%, 89.3% and 100% of patient samples respectively. Paralleling the in vitro results, CD133 expression decreased in patients who had histologic response to progestin treatment. CONCLUSION: CD133+ populations decreased after treatment with MPA in an in vitro model and in patients responding to treatment with progestins. Progestin treatment differentially decreases CD133+ cells.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Antígenos CD , Antineoplásicos Hormonais/farmacologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Glicoproteínas , Acetato de Medroxiprogesterona/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Peptídeos , Antígeno AC133 , Adulto , Idoso , Antígenos CD/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Apoptose/efeitos dos fármacos , Contagem de Células , Linhagem Celular Tumoral , Feminino , Glicoproteínas/metabolismo , Humanos , Acetato de Medroxiprogesterona/uso terapêutico , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Peptídeos/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
OBJECTIVE: The maternal-fetal inflammatory response contributes to both preterm premature rupture of membranes (PPROM) and adverse neurological outcomes. Additionally, cytokines associated with fetal placental inflammation can be detrimental to brain development regardless of inciting infection. We investigated whether differential patterns of cytokine markers in maternal and fetal plasma samples reflect subtypes of placental inflammation and neurological outcomes at 6 months in infants born to mothers with PPROM. STUDY DESIGN: Within a prospective cohort study of 25 women with PPROM, plasma cytokines (interleukin [IL]-1ß, IL-6, IL-8, and tumor necrosis factor-α) were measured by enzyme-linked immunosorbent assay from maternal blood samples at rupture and delivery, and from fetal umbilical cord blood samples. Patterns of cytokine expression were correlated with specific placenta pathologies. Infants underwent cranial ultrasound after birth and standardized neurological examinations at 6 months' corrected gestational age. Predictors of inflammation and adverse neurological outcome were assessed by logistic regression, adjusting for gestational age at birth. RESULTS: Inflammation of the fetal side of the placenta was associated with elevated maternal IL-6 and IL-8 at delivery and fetal IL-1ß, IL-6, IL-8, and tumor necrosis factor-α. Worse neurological outcome at 6 months was associated with inflammation of the fetal side of the placenta and shorter duration from rupture of membrane to delivery, independent of gestational age at birth or cranial ultrasound results. CONCLUSION: Our findings support the connection between fetal inflammation with adverse neurological outcome with PPROM, regardless of cranial ultrasound results. Further longitudinal studies are needed to adequately examine these patterns, and will aid in risk assessment and intervention strategies.
Assuntos
Corioamnionite/imunologia , Sangue Fetal/imunologia , Ruptura Prematura de Membranas Fetais/imunologia , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Doenças do Sistema Nervoso/imunologia , Placenta/patologia , Fator de Necrose Tumoral alfa/imunologia , Adulto , Corioamnionite/patologia , Estudos de Coortes , Citocinas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Ruptura Prematura de Membranas Fetais/patologia , Idade Gestacional , Humanos , Recém-Nascido , Inflamação/imunologia , Masculino , Doenças do Sistema Nervoso/fisiopatologia , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: Cytokeratin 5 (CK5) is an epithelial cell marker implicated in stem and progenitor cell activity in glandular reproductive tissues and endocrine and chemotherapy resistance in estrogen receptor (ER)(+) breast cancer. The goal of this study was to determine the prevalence of CK5 expression in ovarian cancer and the response of CK5(+) cell populations to cisplatin therapy. MATERIALS AND METHODS: Cytokeratin 5 expression was evaluated in 2 ovarian tissue microarrays, representing 137 neoplasms, and 6 ovarian cancer cell lines. Cell lines were treated with IC(50) (half-maximal inhibitory concentration) cisplatin, and the prevalence of CK5(+) cells pretreatment and posttreatment was determined. Proliferation of CK5(+) versus CK5(-) cell populations was determined using 5-bromo-2'-deoxyuridine incorporation. Chemotherapy-induced apoptosis in CK5(+) versus CK5(-) cells was measured using immunohistochemical staining for cleaved caspase-3. RESULTS: Cytokeratin 5 was expressed in 39.3% (42 of 107) of epithelial ovarian cancers with a range of 1% to 80% positive cells. Serous and endometrioid histologic subtypes had the highest percentage of CK5(+) specimens. Cytokeratin 5 expression correlated with ER positivity (38 of 42 CK5(+) tumors were also ER(+)). Cytokeratin 5 was expressed in 5 of 6 overall and 4 of 4 ER(+) epithelial ovarian cancer cell lines ranging from 2.4% to 52.7% positive cells. Cytokeratin 5(+) compared with CK5(-) cells were slower proliferating. The prevalence of CK5(+) cells increased after 48-hour cisplatin treatment in 4 of 5 cell lines tested. Cytokeratin 5(+) ovarian cancer cells compared with CK5(-) ovarian cancer cells were more resistant to cisplatin-induced apoptosis. CONCLUSIONS: Cytokeratin 5 is expressed in a significant proportion of epithelial ovarian cancers and represents a slower proliferating chemoresistant subpopulation that may warrant cotargeting in combination therapy.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Queratina-5/análise , Neoplasias Epiteliais e Glandulares/química , Neoplasias Ovarianas/química , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Receptores de Estrogênio/análise , Análise Serial de TecidosRESUMO
Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor. Surgery is the only effective treatment for BMPM, and affected tissues occasionally must be sacrificed to achieve adequate debulking. A 25-year-old female was diagnosed with BMPM. She was counseled on fertility preservation and had oocyte cryopreservation prior to her debulking. Fertility preservation through embryo or oocyte cryopreservation is a valuable option for patients at risk of losing reproductive tissues during extensive surgery and chemotherapy.
Assuntos
Preservação da Fertilidade , Mesotelioma Cístico/cirurgia , Neoplasias Peritoneais/cirurgia , Adulto , Criopreservação , Feminino , Humanos , Mesotelioma Cístico/patologia , Oócitos/fisiologia , Neoplasias Peritoneais/patologiaRESUMO
OBJECTIVE: This study aims to examine the prognostic importance of preoperative cervical cytologic diagnosis with atypical glandular cells (AGC) or malignant cells (MC) as a predictor of poor outcomes in endometrial cancer. MATERIALS AND METHODS: A total of 563 patients were surgically staged for endometrial adenocarcinoma from 2002 to 2012 at our institution. Of these patients, 106 were included to perform a case-control study (39 patients with AGC or MC and 67 controls). Included patients were not significantly different from excluded patients and were matched for age, race, and body mass index. Outcome variables included presence of extrauterine disease (International Federation of Gynecology and Obstetrics stage ≥II) and high intermediate risk (HIR) disease. Further analysis sought to improve the prediction combining AGC or MC with other factors, such as grade and CA-125 levels. Standard statistical analyses were used. RESULTS: Among the patients with AGC or MC, 53.8% had HIR disease compared with 30.3% with normal cervical cytologic diagnosis (odds ratio [OR], 2.68; 95% confidence interval [CI], 1.18-6.09; P = 0.02). Extrauterine disease was found in 43.6% of patients with AGC or MC compared with that of 15.2% in patients with normal cervical cytologic diagnosis (OR, 4.33; 95% CI, 1.72-10.90; P < 0.01). Multivariate analysis confirmed that AGC or MC was an independent predictor of HIR disease (OR, 8.41; 95% CI, 1.34-52.78; P = 0.02) and extrauterine disease (OR, 4.78; 95% CI, 1.26-18.1; P = 0.02). The combination of elevated CA-125 levels with AGC or MC cervical cytologic diagnosis increased the statistical prediction of extrauterine disease (OR, 13.3; 95% CI, 3.1-56.8; P < 0.01) and HIR disease (OR, 5.83; 95% CI, 1.44-23.71; P = 0.02). CONCLUSIONS: Patients with AGC or MC on preoperative cervical cytology are at risk for extrauterine and HIR disease. These preoperative findings should warn surgeons of the potential of extrauterine or occult metastatic disease.