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Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer-HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus-associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution's dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus-associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.
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Neoplasias del Ano , Infecciones por Papillomavirus , Prueba de Estudio Conceptual , Femenino , Humanos , Masculino , Persona de Mediana Edad , Canal Anal/virología , Canal Anal/patología , Canal Anal/diagnóstico por imagen , Neoplasias del Ano/virología , Neoplasias del Ano/patología , Neoplasias del Ano/diagnóstico por imagen , Biopsia , Virus del Papiloma Humano , Microscopía/métodos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , Lesiones Intraepiteliales Escamosas/virología , Lesiones Intraepiteliales Escamosas/patologíaRESUMEN
AIMS: The 2023 FIGO staging criteria for endometrial cancer (EC) introduced marked changes from the 2009 version. The full implication of these changes for patient diagnosis and treatment is unknown. We evaluate the differences in staging and prognostication between the two systems, with and without inclusion of molecular classification. METHODS AND RESULTS: We assigned (1) FIGO 2009, (2) 2023 molecular-agnostic and (3) 2023 molecular-informed stages to 404 fully staged and molecularly classified patients with EC. Disease-specific and progression/relapse-free survival were analysed via the Kaplan-Meier method and compared with log-rank testing; 118 of 252 (47%) FIGO 2009 stage I patients were upstaged based on histopathological findings alone. Stage I/II subgroup survival distribution analysis showed a worse prognosis in FIGO 2023 IIB and IIC patients. In the molecular-informed FIGO 2023 system, three of 15 (20%) POLE-mutated stage I/II cases were downstaged from FIGO 2009 and eight (53%) were downstaged from molecular-agnostic FIGO 2023. Fifty-one of 60 (85%) p53-abnormal tumours were upstaged from the FIGO 2009, whereas 13 of 60 (22%) were upstaged from the 2023 molecular-agnostic stage. Molecular classification improved prognostic stratification for both 2009 and 2023 FIGO systems. CONCLUSIONS: Downstaging based on POLE mutation more accurately represents patient outcomes. However, in the absence of known POLE status, applying molecular-agnostic FIGO 2023 criteria for stage I/II disease should be conducted with caution. For aggressive histotypes, additionally reporting FIGO 2009 stage should be considered. Upstaging based on substantial lymphovascular space invasion, aggressive histotype with any myometrial invasion and abnormal p53 improves prognostic discernment. Further subdivisions within stage I/II provide minimal additional prognostic information.
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AIMS: Molecular classification according to The Cancer Genome Atlas (TCGA) improves endometrial endometrioid carcinoma (EEC) prognostication and has specific treatment implications; however, original data were skewed towards low-grade and low-stage tumours. Herein, we molecularly classify EECs metastatic at the time of diagnosis or with subsequently documented recurrent/metastatic disease to examine correlation with clinical outcomes. METHODS: TCGA categories include POLE-mutated, microsatellite instability (MSI), p53 abnormal (p53 abnl) and no specific molecular profile (NSMP). POLE targeted sequencing at exons 9, 11, 13 and 14 and immunohistochemistry (IHC) for PMS2, MSH6 and p53 were performed to establish molecular classification. RESULTS: The distribution in our cohort of 141 EECs was similar to that generally reported in EEC, with nine POLE-mutated (6%), 45 MSI (32%), 16 p53 abnl (11%) and 71 NSMP (50%), with similar distributions between low- and high-stage cohorts. We demonstrate that when stratified by molecular subtype, disease-specific survival from the time of high-stage (stages III-IV) presentation or time of recurrence in low-stage (stages I-II) disease among metastatic and/or recurrent EEC is strongly associated with TCGA classification (high-stage P = 0.02, low-stage P = 0.017). Discordant molecular classification between primary and metastatic/recurrent tumours occurred in four of 105 (3.8%) patients, two related to PMS2/MSH6 IHC and two related to p53 IHC. CONCLUSIONS: We demonstrate that molecular classification is prognostically relevant not only at the time of diagnosis, but also at the time of recurrence and in the metastatic setting. Rare subclonal alterations occur and suggest a role for confirming TCGA classification in recurrent/metastatic tumours.
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Carcinoma Endometrioide , Neoplasias Endometriales , Inestabilidad de Microsatélites , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/clasificación , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Adulto , Anciano de 80 o más Años , Proteínas de Unión a Poli-ADP-Ribosa/genética , Mutación , Inmunohistoquímica , Estadificación de NeoplasiasRESUMEN
SUMMARY: We reviewed the clinicopathologic findings of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-exposed placentas at our institution. We identified patients diagnosed with SARS-CoV-2 during pregnancy (March-October 2020). Clinical data included gestational age at diagnosis and delivery and maternal symptoms. Hematoxylin and eosin slides were reviewed for maternal vascular malperfusion, fetal vascular malperfusion, chronic villitis, amniotic fluid infection, intervillous thrombi, fibrin deposition, and infarction. Immunohistochemistry (IHC) for coronavirus spike protein and RNA in situ hybridization (ISH) for SARS-CoV-2 was performed on a subset of blocks. A review of placentas from age-matched patients received March-October 2019 was conducted as a comparison cohort. A total of 151 patients were identified. Placentas in the 2 groups were similar in weight for gestational age and had similar rates of maternal vascular malperfusion, fetal vascular malperfusion, amniotic fluid infection, intervillous thrombi, fibrin deposition, and infarction. Chronic villitis was the only significantly different pathologic finding between cases and controls (29% of cases showed chronic villitis vs. 8% of controls, P <0.001). Overall, 146/151 (96.7%) cases were negative for IHC and 129/133 (97%) cases were negative for RNA ISH. There were 4 cases that stained positively for IHC/ISH, 2 of which showed massive perivillous fibrin deposition, inflammation, and decidual arteriopathy. Coronavirus disease 2019 (COVID-19)-positive patients were more likely to self-identify as Hispanic and more likely to have public health insurance. Our data suggests SARS-CoV-2 exposed placentas that stain positively for SARS-CoV-2 show abnormal fibrin deposition, inflammatory changes, and decidual arteriopathy. The group of patients with clinical COVID-19 are more likely to show chronic villitis. IHC and ISH evidence of viral infection is rare.
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COVID-19 , Placenta , Embarazo , Humanos , Femenino , Placenta/patología , COVID-19/patología , SARS-CoV-2 , ARN , Infarto/patología , FibrinaRESUMEN
Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and infant, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. Although it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathologic examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetrical and neonatal provider based on publications and expert opinion of 16 placental pathologists and a pathologists' assistant, formulated using a modified Delphi approach. These criteria include indications in which placental pathology has clinical relevance, such as pregnancy loss, maternal infection, suspected abruption, fetal growth restriction, preterm birth, nonreassuring fetal heart testing requiring urgent delivery, preeclampsia with severe features, or neonates with early evidence of multiorgan system failure including neurologic compromise. We encourage a focused gross examination by the provider or an attendant at delivery for all placentas and provide guidance for this examination. We recommend that any placenta that is abnormal on gross examination undergo a complete pathology examination. In addition, we suggest practice criteria for placental pathology services, including a list of critical values to be used by the relevant provider. We hope that these sets of triage indications, criteria, and practice suggestions will facilitate appropriate submission of placentas for pathologic examination and improve its relevance to clinical care.
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Obstetricia , Complicaciones del Embarazo , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Placenta/patología , Retardo del Crecimiento Fetal/patologíaRESUMEN
The comprehensive genomic analysis of endometrial carcinoma (EC) by The Cancer Genome Atlas (TCGA) led to the discovery of four distinct and prognostically significant molecular subgroups. Molecular classification has the potential to improve risk-stratification when integrated with clinicopathologic features and has recently been included in national and international patient management EC guidelines. Thus, the adoption of molecular classification into routine pathologic and clinical practice is likely to grow significantly in the upcoming years. Establishing an efficient and standardized workflow for performing molecular classification on ECs, and reporting both the molecular and histologic findings in an integrative manner, is imperative. Here we describe our effort to implement rapid and routine molecular classification on all ECs diagnosed at our institution. To this effect, we performed immunohistochemistry as a surrogate marker for identifying genetic and/or epigenetic alterations in DNA mismatch repair (e.g., MLH1, PMS2, MSH6, MSH2), and TP53 genes. In addition, we have developed and employed a single-gene POLE SNaPshot assay, which is a rapid and analytically sensitive method for detecting select POLE exonuclease domain mutations (EDMs). We report our molecular testing workflow and integrative reporting system as well as the clinicopathologic and molecular features of 310 ECs that underwent routine molecular classification at our institution. The 310 ECs were molecularly classified as follows: 15 (5%) POLE mutant (POLEmut), 79 (25%) mismatch repair-deficient (MMRd), 135 (44%) no specific molecular profile (NSMP), and 81 (26%) p53 abnormal (p53abnl). This work provides an initial framework for implementing routine molecular classification of ECs.
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Neoplasias Endometriales , Biomarcadores de Tumor/genética , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/patología , Femenino , Genes p53 , Humanos , Inmunohistoquímica , Mutación , Estudios ProspectivosRESUMEN
DICER1 syndrome is a tumor predisposition syndrome in which patients are at an increased risk of developing a wide variety of benign and malignant neoplasms with a hallmark constellation of pediatric pleuropulmonary blastoma, cystic nephroma, and thyroid lesions. DICER1 encodes an RNA endoribonuclease that is crucial to the processing of microRNA and may play a role in the maturation of Müllerian tissue. Within the gynecologic tract, germline mutations in DICER1 are associated with an array of rare tumors, including Sertoli-Leydig cell tumor, embryonal rhabdomyosarcoma of the cervix, gynandroblastoma, and juvenile granulosa cell tumor, which typically present in childhood, adolescence, or early adulthood. In addition, somatic DICER1 mutations have been described in rare gynecologic tumors such as adenosarcoma, Sertoli cell tumor, ovarian fibrosarcoma, cervical primitive neuroectodermal tumor, carcinosarcoma, and germ cell tumors. In light of the significant association with multiple neoplasms, genetic counseling should be considered for patients who present with a personal or family history of these rare DICER1-associated gynecologic tumors. This review highlights the most current understanding of DICER1 genetic alterations and describes the clinical, histopathologic, and immunohistochemical features and differential diagnoses for gynecologic tumors associated with DICER1 mutation.
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ARN Helicasas DEAD-box/genética , Neoplasias de los Genitales Femeninos/genética , Ribonucleasa III/genética , Adolescente , Adulto , Diagnóstico Diferencial , Femenino , Fibrosarcoma/genética , Neoplasias de los Genitales Femeninos/patología , Genitales Femeninos/patología , Mutación de Línea Germinal , Humanos , Mutación , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patologíaRESUMEN
Fumarate hydratase-deficient leiomyomas (dFH leiomyomas) often display atypical pathologic features yet exhibit a benign clinical course. Recent data suggest that dFH leiomyomas may be misclassified as smooth muscle tumors of uncertain malignant potential, a category that encompasses a heterogenous subgroup of uterine neoplasms with smooth muscle differentiation and atypical features that impart ambiguity regarding their expected clinical behavior. dFH leiomyomas can be seen in the context of hereditary leiomyomatosis and renal cell carcinoma syndrome or in the sporadic setting. In this retrospective study, we sought to examine the prevalence and clinicopathologic characteristics of dFH leiomyomas in 48 tumors previously diagnosed as smooth muscle tumors of uncertain malignant potential from 38 patients. Of these 48 tumors, 3 (6.3%) occurring in 2 patients were found to be deficient for FH by immunohistochemistry, including 1 uterine and 2 extrauterine (abdominopelvic) tumors. The 3 tumors showed histologic features typical of dFH leiomyomas, including hemangiopericytoma-like vessels, edema, macronucleoli, and atypia. Neither patient developed recurrent leiomyomas or renal cell carcinoma, and both were alive without disease at last follow-up. Our data suggest that dFH leiomyomas should be considered in the differential diagnosis of smooth muscle tumors of uncertain malignant potential, even in the context of extrauterine disease. Identification of FH deficiency in these tumors supports their classification as dFH leiomyomas despite their atypical morphologic features and/or clinical presentation. Importantly, detection of dFH in these cases may identify women at increased risk for hereditary leiomyomatosis and renal cell carcinoma who would benefit from genetic counseling and consideration for FH germline testing.
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Carcinoma de Células Renales , Neoplasias Renales , Leiomiomatosis , Neoplasias Cutáneas , Tumor de Músculo Liso , Neoplasias Uterinas , Carcinoma de Células Renales/diagnóstico , Diagnóstico Diferencial , Femenino , Fumarato Hidratasa/deficiencia , Fumarato Hidratasa/genética , Humanos , Neoplasias Renales/diagnóstico , Leiomiomatosis/diagnóstico , Leiomiomatosis/genética , Leiomiomatosis/patología , Masculino , Errores Innatos del Metabolismo , Hipotonía Muscular , Trastornos Psicomotores , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Tumor de Músculo Liso/diagnóstico , Neoplasias Uterinas/patologíaRESUMEN
The obstetrical conditions placenta accreta spectrum (PAS) and placenta previa are a significant source of pregnancy-associated morbidity and mortality, yet the specific molecular and cellular underpinnings of these conditions are not known. In this study, we identified misregulated gene expression patterns in tissues from placenta previa and percreta (the most extreme form of PAS) compared with control cases. By comparing this gene set with existing placental single-cell and bulk RNA-Seq datasets, we show that the upregulated genes predominantly mark extravillous trophoblasts. We performed immunofluorescence on several candidate molecules and found that PRG2 and AQPEP protein levels are upregulated in both the fetal membranes and the placental disk in both conditions. While this increased AQPEP expression remains restricted to trophoblasts, PRG2 is mislocalized and is found throughout the fetal membranes. Using a larger patient cohort with a diverse set of gestationally aged-matched controls, we validated PRG2 as a marker for both previa and PAS and AQPEP as a marker for only previa in the fetal membranes. Our findings suggest that the extraembryonic tissues surrounding the conceptus, including both the fetal membranes and the placental disk, harbor a signature of previa and PAS that is characteristic of EVTs and that may reflect increased trophoblast invasiveness.
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Proteína Mayor Básica del Eosinófilo/genética , Membranas Extraembrionarias/metabolismo , Regulación de la Expresión Génica , Metaloproteasas/genética , Placenta Accreta/metabolismo , Placenta Previa/metabolismo , Proteoglicanos/genética , Proteína Mayor Básica del Eosinófilo/metabolismo , Femenino , Humanos , Metaloproteasas/metabolismo , Embarazo , Proteoglicanos/metabolismoRESUMEN
Low-grade serous carcinomas only rarely coexist with or progress to high-grade tumors. We present a case of low-grade serous carcinoma with transformation to carcinosarcoma on recurrence in the lymph node. Identical BRAF V600E and telomerase reverse transcriptase promoter mutations were identified in both the original and recurrent tumor. Given that telomerase reverse transcriptase promotor mutations are thought to play a role in progression of other tumor types, the function of telomerase reverse transcriptase mutations in BRAF mutated low-grade serous carcinoma deserves investigation.
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Carcinosarcoma/diagnóstico , Neoplasias Ováricas/diagnóstico , Regiones Promotoras Genéticas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Telomerasa/genética , Anciano , Carcinosarcoma/genética , Carcinosarcoma/patología , Progresión de la Enfermedad , Femenino , Humanos , Ganglios Linfáticos/patología , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Ovario/patologíaRESUMEN
To evaluate the correlation between p16 expression and clinical outcomes in patients with primary vaginal cancer treated with definitive radiotherapy. P16 immunohistochemical was performed on 25 patient samples and recorded from pathology reports in 7 patients. P53 immunohistochemical was performed on 3 p16-negative samples. Baseline characteristics were compared using the Fisher exact test. Outcomes were compared using log-rank tests, and cox proportional hazards models. Survival and recurrence analysis was performed with the Kaplan-Meier method and cumulative incidence estimates. P16 expression was positive in 29 patients and negative in 3 patients. Two of the p16-negative tumors showed positive expression of p53. The median overall survival, progression-free survival and 2-yr cumulative incidence of recurrence were 66 mo [95% confidence interval (CI), 31-96], 34 mo (95% CI, 21-86), and 19% (95% CI, 7%-34%), respectively. P16-positive tumors had higher median overall survival and progression-free survival compared with p16-negative tumors (82 vs. 31 mo, P=0.02 and 35 vs 16 mo, P=0.04, respectively). The 2-yr cumulative incidence of recurrence was 14% for p16-positive tumors compared with 67% for p16-negative tumors (P=0.07). On univariable analysis, p16-negative status, age older than 65, and advanced stage were associated with inferior overall survival. P16 negativity is an independent predictor of inferior overall survival. P16-positive vaginal cancers have a better prognosis and decreased incidence of recurrence compared with p16-negative tumors. These prognostic findings associated with p16-negative vaginal cancers will need to be confirmed in larger patient cohorts.
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Biomarcadores de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias Vaginales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Vaginales/metabolismo , Neoplasias Vaginales/patología , Neoplasias Vaginales/radioterapiaRESUMEN
OBJECTIVES: Emerging evidence suggests that extent of lymphovascular space invasion (LVSI) predicts for risk of lymph node metastasis in endometrioid uterine cancers. However, this correlation remains unknown in the setting of uterine serous carcinoma (USC). We sought to examine the association between extent of LVSI and other histopathologic characteristics with risk of nodal metastasis for women with USC. MATERIALS/METHODS: Pathological data from all cases of uterine serous carcinoma between July 1998 to July 2015 at our institution were reviewed. Descriptive, univariate, and multivariate logistic regression analysis of selected pathologic features were performed. RESULTS: 88 patients with USC underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy. Surgical staging revealed the following FIGO stage distributions: I (41%), II (8%), III (32%), IV (19%). LVSI was present in 44 (50%) patients. 36 patients (41%) had LN metastases with median number of total nodes removed of 17 (range, 1-49). On univariate analysis, depth of myometrial invasion, LVSI, tumor size, and cervical stromal involvement were significantly associated with nodal involvement. In a multivariate model, LVSI (OR 6.25, 95% CI 2.2-18.0, p<0.01) and cervical stromal involvement (OR 3.33, 95% CI 1.10-10.0, p=0.03) were the only factors that remained significant. Among patients with LVSI-positive disease, extensive LVSI was associated with increased risk of nodal involvement compared to focal LVSI (90% vs 29%, p=0.04). CONCLUSIONS: Presence and extent of LVSI, and cervical stromal invasion are important predictors for lymph node metastasis in uterine serous carcinoma.
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Cistadenocarcinoma Seroso/secundario , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Distinguishing hyalinized stroma from osteoid production by a heterologous osteosarcomatous component can be challenging in gynecologic tract carcinosarcomas. As heterologous components in a carcinosarcoma may have prognostic and therapeutic implications, it is important that these are recognized. This study examines interobserver reproducibility among gynecologic pathologists in the diagnosis of osteosarcomatous components, and its correlation with expression of the novel antibody SATB2 (marker of osteoblastic differentiation) in these osteosarcomatous foci. Digital H&E images from 20 gynecologic tract carcinosarcomas were reviewed by 22 gynecologic pathologists with a request to determine the presence or absence of an osteosarcomatous component. The 20 preselected cases included areas of classic heterologous osteosarcoma (malignant cells producing osteoid; n=10) and osteosarcoma mimics (malignant cells with admixed nonosteoid matrix; n=10). Interobserver agreement was evaluated and SATB2 scored on all 20 cases and compared with the original diagnoses. Moderate agreement (Fleiss' κ=0.483) was identified for the 22 raters scoring the 20 cases with a median sensitivity of 7/10 and a median specificity of 9/10 for the diagnosis of osteosarcoma. SATB2 showed 100% sensitivity (10/10) and 60% (6/10) specificity in discriminating classic osteosarcoma from osteosarcoma mimics. Utilizing negative SATB2 as a surrogate marker to exclude osteosarcoma, 73% (16/22) of the reviewers would have downgraded at least 1 case to not contain an osteosarcomatous component (range, 1-6 cases, median 1 case). Gynecologic pathologists demonstrate only a moderate level of agreement in the diagnosis of heterologous osteosarcoma based on morphologic grounds. In such instances, a negative SATB2 staining may assist in increasing accuracy in the diagnosis of an osteosarcomatous component.
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Carcinosarcoma/patología , Neoplasias de los Genitales Femeninos/patología , Variaciones Dependientes del Observador , Osteosarcoma/patología , Patólogos , Biomarcadores de Tumor/análisis , Femenino , Neoplasias de los Genitales Femeninos/terapia , Humanos , Proteínas de Unión a la Región de Fijación a la Matriz/análisis , Tumor Mulleriano Mixto/patología , Osteosarcoma/química , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Factores de Transcripción/análisisRESUMEN
Pelvic lymphadenectomy in early-stage endometrial cancer is controversial, but the findings influence prognosis and treatment decisions. Noninvasive tools to identify women at high risk of lymph node metastasis can assist in determining the need for lymph node dissection and adjuvant treatment for patients who do not have a lymph node dissection performed initially. A retrospective review of surgical pathology was conducted for endometrioid endometrial adenocarcinoma at our institution. Univariate and multivariate logistic regression analysis of selected pathologic features were performed. A nomogram to predict for lymph node metastasis was constructed. From August 1996 to October 2013, 296 patients underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy for endometrioid endometrial adenocarcinoma. Median age at surgery was 62.7 yr (range, 24.9-93.6 yr). Median number of lymph nodes removed was 13 (range, 1-72). Of all patients, 38 (12.8%) had lymph node metastases. On univariate analysis, tumor size ≥4 cm, grade, lymphovascular space involvement, cervical stromal involvement, adnexal or serosal or parametrial involvement, positive pelvic washings, and deep (more than one half) myometrial invasion were all significantly associated with lymph node involvement. In a multivariate model, lymphovascular space involvement, deep myometrial invasion, and cervical stromal involvement remained significant predictors of nodal involvement, whereas tumor size of ≥4 cm was borderline significant. A lymph node predictive nomogram was constructed using these factors. Our nomogram can help estimate risk of nodal disease and aid in directing the need for additional surgery or adjuvant therapy in patients without lymph node surgery. Lymphovascular space involvement is the most important predictor for lymph node metastases, regardless of grade, and should be consistently assessed.
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Carcinoma Endometrioide/diagnóstico , Neoplasias Endometriales/diagnóstico , Nomogramas , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/secundario , Carcinoma Endometrioide/cirugía , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Endometrio/patología , Endometrio/cirugía , Femenino , Humanos , Histerectomía , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico , Persona de Mediana Edad , Pelvis/patología , Pelvis/cirugía , Pronóstico , Estudios Retrospectivos , Riesgo , Adulto JovenRESUMEN
OBJECT OF STUDY: Retained products of conception (RPOC) displays variable vascularity, ranging from avascular to markedly vascular on color Doppler sonography. We hypothesize that variability in sonographic vascularity may be due to histopathologic variation in the placental tissue. MATERIALS, METHODS, AND PROCEDURES: After institutional review board approval, sonographic images and pathologic specimens were retrospectively reviewed in 26 patients with pathologically proven RPOC. Ultrasound (US) images were scored 0-3 for the degree of vascularity by two radiologists blinded to the diagnosis. Corresponding pathologic specimens were evaluated for vascularization of chorionic villi, degree of inflammation, morphology of maternal arteries, chorionic villous preservation, and percentage of clot, membranes, chorionic villi, and decidua/myometrium. Statistical analysis, including multiple linear regression, was performed. RESULTS: RPOC with histologically avascular chorionic villi or those with markedly reduced vascularization had significantly lower US vascularity scores (p = 0.030) than those with chorionic villi showing normal or decreased vascularization. Sonographically avascular RPOC had a significantly lower percentage villi (p = 0.028) and higher percentage of decidua (p = 0.004) than specimens where US showed any Doppler vascularity. Histologic vascularity of villi (p = 0.049) and non-observation of maternal arteries (p = 0.001) were significant predictors of US vascularity scores in multivariate linear regression analysis, while inflammation of villi (p = 0.053) was a marginally significant predictor. SIGNIFICANCE OF THE CONCLUSIONS: Histologic vascularity of villi appears to contribute to the observed variation in sonographic vascularity. This finding may underlie known differences in clinical outcomes between sonographic vascularity groups.
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Placenta/diagnóstico por imagen , Ultrasonografía Doppler en Color , Adolescente , Adulto , Vellosidades Coriónicas/diagnóstico por imagen , Vellosidades Coriónicas/patología , Femenino , Fertilización , Humanos , Persona de Mediana Edad , Placenta/patología , Embarazo , Radiografía , Estudios Retrospectivos , Adulto JovenRESUMEN
Stanford Health Care, which provides about 7% of overall healthcare to approximately 9 million people in the San Francisco Bay Area, has undergone significant changes due to the opening of a second hospital in late 2019 and, more importantly, the COVID-19 pandemic. We examine the impact of these events on anatomic pathology (AP) cases, aiming to enhance operational efficiency in response to evolving healthcare demands. We extracted historical census, admission, lab tests, operation, and AP data since 2015. An approximately 45% increase in the volume of laboratory tests (P < 0.0001) and a 17% increase in AP cases (P < 0.0001) occurred post-pandemic. These increases were associated with progressively increasing (P < 0.0001) hospital census. Census increase stemmed from higher admission through the emergency department (ED), and longer lengths of stay mostly for transfer patients, likely due to the greater capability of the new ED and changes in regional and local practice patterns post-pandemic. Higher census led to overcapacity, which has an inverted U relationship that peaked at 103% capacity for AP cases and 114% capacity for laboratory tests. Overcapacity led to a lower capability to perform clinical activities, particularly those related to surgical procedures. We conclude by suggesting parameters for optimal operations in the post-pandemic era.
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In pathology, the deployment of artificial intelligence (AI) in clinical settings is constrained by limitations in data collection and in model transparency and interpretability. Here we describe a digital pathology framework, nuclei.io, that incorporates active learning and human-in-the-loop real-time feedback for the rapid creation of diverse datasets and models. We validate the effectiveness of the framework via two crossover user studies that leveraged collaboration between the AI and the pathologist, including the identification of plasma cells in endometrial biopsies and the detection of colorectal cancer metastasis in lymph nodes. In both studies, nuclei.io yielded considerable diagnostic performance improvements. Collaboration between clinicians and AI will aid digital pathology by enhancing accuracies and efficiencies.
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In the last two decades there have been significant advances in our understanding of female genital tract tumours. The discovery of BRCA1 and BRCA2 genes in ovarian cancer and the mismatch repair genes in endometrial carcinoma has revolutionized our approach to the diagnosis and screening of women for ovarian and uterine cancers. This review discusses the pathogenesis of these two hereditary syndromes in depth and explains how the molecular genetics is tailoring the manner in which these diseases are diagnosed and potentially treated. Other, less common hereditary conditions associated with gynaecological tract manifestations, such as Cowden syndrome, Peutz-Jeghers syndrome, Gorlin syndrome and hereditary leiomyomatosis and renal cell carcinoma, are also summarized briefly.
Asunto(s)
Reparación de la Incompatibilidad de ADN/genética , Neoplasias Endometriales/genética , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , Neoplasias Ováricas/genética , Terapia Combinada , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/terapia , Femenino , Humanos , Tamizaje Masivo/métodos , Tamizaje Masivo/tendencias , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/terapiaRESUMEN
Ovarian cancer is the fifth leading cause of cancer-related deaths in women and the most lethal gynecologic cancer. It is curable when discovered at an early stage, but usually remains asymptomatic until advanced stages. It is crucial to diagnose the disease before it metastasizes to distant organs for optimal patient management. Conventional transvaginal ultrasound imaging offers limited sensitivity and specificity in the ovarian cancer detection. With molecularly targeted ligands addressing targets, such as kinase insert domain receptor (KDR), attached to contrast microbubbles, ultrasound molecular imaging (USMI) can be used to detect, characterize and monitor ovarian cancer at a molecular level. In this article, the authors propose a standardized protocol is proposed for the accurate correlation between in- vivo transvaginal KDR-targeted USMI and ex vivo histology and immunohistochemistry in clinical translational studies. The detailed procedures of in vivo USMI and ex vivo immunohistochemistry are described for four molecular markers, CD31 and KDR with a focus on how to enable the accurate correlation between in vivo imaging findings and ex vivo expression of the molecular markers, even if not the entire tumor could can be imaged by USMI, which is not an uncommon scenario in clinical translational studies. This work aims to enhance the workflow and the accuracy of characterization of ovarian masses on transvaginal USMI using histology and immunohistochemistry as reference standards, which involves sonographers, radiologists, surgeons, and pathologists in a highly collaborative research effort of USMI in cancer.