Improving Malignancy Detection Rates in Body Fluids Submitted to the Hematology Laboratory for Nucleated Cell Count and Differential: A Quality Improvement Study.

CONTEXT.­: Body fluid specimens are regularly submitted to the hematology laboratory for cell count and differential. Unless there is high clinical suspicion for malignancy, most cases lack concurrent cytology review and may not benefit from more focused examination for malignancy. OBJECTIVE.­: To compare rates of malignancy detection before and after fluid-focused training for hematology technologists as part of a quality improvement initiative. DESIGN.­: During an 8-week pretraining period, body fluids submitted to the cytology laboratory were correlated with concurrent hematology specimens. After slide review and training sessions for the hematology technologists, the same data were collected for a 4-week period. Discrepant cases were reviewed by hematology laboratory supervisors and pathologists. RESULTS.­: We collected 465 pretraining and 249 posttraining body fluids with concurrent cytology and hematology evaluation. In the pretraining cohort, 48 cases (10.3%) were diagnosed as malignant by cytology; of those, 33 were detected by hematology. In the posttraining cohort, 30 cases (12.0%) were diagnosed as malignant by cytology of which 27 were detected by hematology. Of the 18 discrepant cases (all carcinomas), hematology slide review showed definite features of malignancy in 15 and no tumor cells in 3. The malignancy detection rate by the hematology laboratory significantly improved after training (68.8% versus 90.0%, P = .01). CONCLUSIONS.­: We demonstrate the comparatively lower malignancy detection rate for body fluid specimens processed in our hematology laboratory, particularly for carcinomas. Hematology technologist education/training improved the malignancy detection rate, an important quality improvement given the large proportion of body fluids undergoing hematology evaluation without concurrent cytology reviews.

Smears are important for adequate cytologic diagnosis of kidney lesions.

INTRODUCTION: Traditionally at our institution, smears with or without liquid-based cytology (LBC) and core biopsies (CBs) have been obtained by radiologists performing image-guided fine-needle aspiration biopsies (FNABs) of deep organs. Since 2015, however, there has been a shift to providing cytology with samples for LBC only when obtaining CBs. The impression among our institution's cytologists is that LBC alone is less often adequate for diagnosis compared with smears and LBC together. We examined a series of kidney FNABs pre- and post-"LBC only" to evaluate this impression. MATERIALS AND METHODS: With institutional review board approval, we compared all kidney FNABs from 2012 to those from 2015. We recorded the type(s) of cytology preparation(s), the number of cytology slides, the cytology diagnosis, the concurrent CB diagnosis, and whether there was a subsequent excision and the excision diagnosis. We examined cytology and CB slides as needed. RESULTS: In 2012, 105 patients underwent 111 kidney biopsies, 109 with smears made. In 2015, 58 patients underwent 62 kidney biopsies, 7 with smears made. In 2012, there were 13 (12%) nondiagnostic (ND) cytology cases and 19 (17%) cases where the cytology and CB diagnoses were discrepant. By comparison, in 2015, there were 20 (32%) ND cytology cases and 21 (33%) discrepant cases. CONCLUSIONS: There were more cytology slides per case and fewer ND diagnoses in 2012 compared with 2015 (12% versus 32%, respectively, P = 0.001). Concordance was also better in 2012 (83% versus 67%, P = 0.015). We believe that our metrics would improve if we returned to the procedures followed in 2012.

Touch Preps of Products of Conception for Rule-Out Ectopic Pregnancy: A Viable Alternative to Frozen Section.

OBJECTIVES: Tissue confirmation of the intrauterine location of a pregnancy can be difficult grossly, necessitating a frozen section diagnosis. First-trimester tissue is often scant and can be exhausted by frozen section. We examined 39 endometrial curettings performed for rule-out ectopic pregnancy by touch prep to examine the utility of cytopathology in documenting trophoblast or chorionic villi (products of conception [POC]). METHODS: First-trimester curettage specimens sent to the Massachusetts General Hospital Pathology Departmentreceived a gross examination followed by a touch prep of the area most suspicious for villi. Touch preps were reviewed blinded to the final diagnosis and then compared. RESULTS: Thirty-three of the 39 touch preps and histology specimens were concordant, including all 11 negative histology specimens and 22 of the 28 positive histology specimens. CONCLUSIONS: POC can be diagnosed by touch prep and may offer confirmation of grossly identified villi. Positive predictive value is 100%. Negative touch preps should receive further evaluation.

Trends in Cervical Cytology Screening and Reporting Practices: Results From the College of American Pathologists 2011 PAP Education Supplemental Questionnaire.

CONTEXT: The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2011 gynecologic cytology survey. OBJECTIVE: To provide a cross-sectional survey of gynecologic cytology practices in 2010. DESIGN: In 2011, a survey was sent to 1604 laboratories participating in the College of American Pathologists gynecologic cytology interlaboratory comparison education program and proficiency testing programs requesting data from 2010 on the following topics: terminology/reporting, cytotechnologist workload, quality assurance, reagents, and ancillary testing. RESULTS: Six hundred and twenty-five laboratories (39%) replied to the survey. The nonstandard use of "low-grade squamous intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion" is used by most laboratories to report the presence of low-grade squamous intraepithelial lesion with possibility of high-grade squamous intraepithelial lesion. Most laboratories also report the presence or absence of cells from the transformation zone. Most respondents do not limit cytotechnologist screening workload during the work shift. Only about one-third of laboratories (188 of 582; 32%) use image-assisted screening devices. Rapid prescreening as a quality assurance measure is used by only 3.5% (21 of 594) of the laboratories. When used for screening, most laboratories use the imager for retrospective review of slides to detect human locator and interpretive errors. Most laboratories receive both liquid-based cytology samples (mainly ThinPrep, Hologic, Marlborough, Massachusetts) and conventional Papanicolaou tests. Expiration dates of liquid-based cytology test vials are not usually recorded. CONCLUSIONS: The field of gynecologic cytology is evolving rapidly. These survey results offer a snapshot of national gynecologic cytology practices in 2010.

Young investigator challenge: The accuracy of the nuclear-to-cytoplasmic ratio estimation among trained morphologists.

BACKGROUND: The estimation of the nuclear-to-cytoplasmic ratio (N:C ratio) is an important factor in diagnosing atypia and malignancy in pathological specimens, particularly in cytology. Many algorithms for determining malignant potential make reference to specific, decimal N:C ratios without specifying how the ratio should be measured, with the implication that the observer is intended to estimate this ratio by eye. The authors wanted to determine how accurate trained morphologists (including attending pathologists, pathology residents, and cytotechnologists) are at estimating the N:C ratio without a measuring device. METHODS: Two surveys were prepared containing ideal and real cell images of various N:C ratios. Participants were instructed to select their best estimate from a list of decimal ratios. The data were tabulated and analyzed to determine how accurate the estimates were and whether there was any performance difference between ideal and real images. RESULTS: The absolute and percentage deviation from the actual N:C ratio decreased steadily with increasing N:C ratio. Aggregate performance was found to be closely correlated between real and ideal images, although interobserver variation was not significantly different among participants in the real images quiz, but was significantly different on the ideal images quiz. CONCLUSIONS: Trained morphologists make relatively accurate estimations of the N:C ratio and become increasingly more accurate as the depicted N:C ratio increases. This suggests that including N:C ratio decimals as a criteria for the diagnosis of atypia is valid for high N:C ratios.

Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone.

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts.

Human papillomavirus testing and reporting rates in 2012: results of a College of American Pathologists national survey.

CONTEXT: College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratory parameters. OBJECTIVE: To evaluate changes in laboratory human papillomavirus (HPV) testing patterns in laboratories incorporating HPV testing with Papanicolaou tests in 2012. DESIGN: Data were analyzed from the CAP HPV Supplemental Questionnaire distributed to 1771 laboratories participating in either CAP HPV or CAP Papanicolaou proficiency testing in 2013. RESULTS: A total of 1022 laboratories (58%) responded. There were more high-risk (HR) HPV tests performed per institution as compared to previous surveys. There were more HPV tests performed within an institution as compared to previous surveys. Hybrid Capture 2 (HC2) remains the most common method (42.4%, 239 of 564); Cervista and cobas methods are used in 37.2% (210 of 564) and 14.9% (84 of 564) of laboratories, respectively. Human papillomavirus testing is offered as a reflex test after a Papanicolaou test result of atypical squamous cells of undetermined significance (ASC-US) in 89.6% of laboratories (476 of 531); as a cotest for women aged 30 years and older in 60.3% (404 of 531); as reflex testing after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) in 42.7% (320 of 531); and as reflex testing after atypical glandular cells (AGC) in 27.3% (145 of 531). The HPV-positive rates for ASC-US and ASC-H were similar in 2012 and 2006. Cervista (49.2%, 88 of 179) and Roche cobas (27.4%, 49 of 179) are the most common methods used for genotyping. Most laboratories use the CAP Human Papillomavirus for Cytology Program for proficiency testing. CONCLUSIONS: There was an increase in annual volume of HR-HPV testing with a shift toward in-house HR-HPV testing. Genotyping volumes also increased. HC2 and Cervista are most commonly used, with an increasing volume of Roche cobas testing. The most common indication for HPV testing among all laboratories was ASC-US reflex testing, but an increase in HPV cotesting was observed. The data provide an update into persisting and newer trends in HPV testing practices.

Interinstitutional whole slide imaging teleconsultation service development: assessment using internal training and clinical consultation cases.

CONTEXT: Assessment of accuracy and feasibility of whole slide imaging (WSI) for interinstitutional consultation in surgical pathology. OBJECTIVES: To train technical and pathologist staff in WSI technology, establish and evaluate a WSI workflow using training cases and second-opinion consultations, and assess diagnostic accuracy. DESIGN: First, WSI training and evaluation using selected subspecialty service cases were performed and compared with the clinical glass slide (GS) diagnosis. Second, WSI and GS diagnoses of consecutive, second-opinion consultation cases were compared. Discrepancies underwent adjudication to determine a reference diagnosis. Participant observations on WSI initiation to practice were gathered. RESULTS: There were 130 cases evaluated, with 123 correlations (94.6%) and 6 minor (4.6%) and 1 major (0.8%) discrepancies. The 74 consultation cases interpreted had 52 correlations (70.3%), and 18 minor (24.3%) and 4 major (5.4%) discrepancies. The WSI and GS adjusted major discrepancy rates in second-opinion consultations were 2.7% (2 of 74) and 4.1% (3 of 74), respectively. Statistical analysis showed that WSI was not inferior to GS interpretation. Pathologists agreed the software was easy to use and the images were adequate, but more time was spent rendering WSI interpretations. CONCLUSIONS: A significant learning curve was observed in the transition from the training set to clinical consultation cases associated both with WSI interpretation and adjustments to the digital analogs of routine GS workflow. Results from second-opinion consultations indicated that WSI interpretation was as accurate as GS interpretation among properly trained and experienced users. Overall, WSI-based practice appears feasible for second-opinion consultations.

Non-16/non-18 high-risk human papillomavirus types predominate in anal cytology categories of negative for intraepithelial lesion and atypical cells of undetermined significance.

INTRODUCTION: Screening for anal carcinoma continues to grow despite controversy regarding its efficacy. High-risk human papillomavirus (HR-HPV) has been adopted as a cotest with anal Papanicolaou tests. We sought to identify the prevalence of HR-HPV types in the most common anal cytology specimens: negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cell of undetermined significance (ASC-US). MATERIALS AND METHODS: Anal cytology specimens were identified and tested for HR-HPV using Roche cobas 4800 HR-HPV analysis (Roche Molecular Systems, Inc., Indianapolis, Ind) and, if positive, typed further for: HPV-16, -18, and/or non-16/non-18 "other" HR-HPV type. RESULTS: There were 642 specimens from 538 patients. The most common interpretation was NILM (48.6%) and ASC-US (25.7%). Of NILM cases, 47% were HR-HPV+ (53% in men, 33% in women, P = 0.03, χ2). In ASC-US cases, 73% were HR-HPV+ (74% in male patients, 70% in female patients). The most common HPV subtype was non-16/non-18 HR-HPV "other" types in 89% of cases. HPV-16 and HPV-18 were positive in 35% and 18% of cases, respectively. In patients with non-16/non-18 HR-HPV+ anal cytology, 16 of 79 had biopsies histologically diagnosed as at least high-grade squamous intraepithelial lesion (HSIL+). However, the relative risk of having HSIL+ was 2.3-times higher for anal cytology positive for HPV-16, -18, with/without coinfection with non-16/non-18 HR-HPV than those positive for non-16/non-18 "other" HR-HPV types alone. CONCLUSIONS: Non-16/non-18 "other" HR-HPV types are most prevalent in anal cytology interpretations of NILM and ASC-US. Patients with HR-HPV+ NILM or ASC-US, negative for HPV-16/-18, are at lower relative risk of having subsequent histologic HSIL+, but a percentage of these patients still harbor HSIL+ on biopsy.

Clear vision through the haze: a practical approach to ground-glass opacity.

Ground-glass opacity (GGO) is a common, nonspecific imaging finding on chest computed tomography that may occur in a variety of pulmonary diseases. GGO may be the result of partial filling of alveolar spaces, thickening of the alveolar walls or septal interstitium, or a combination of partial filling of alveolar spaces and thickening of the alveolar walls and septal interstitium at the histopathologic level. Diseases that commonly manifest on chest computed tomography as GGO include pulmonary edema, alveolar hemorrhage, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, and pulmonary alveolar proteinosis. Generating an extensive list of possible causes of GGO in radiologic reports would not be helpful to referring physicians. Preferably, a more concise and focused list of differential diagnostic possibilities may be constructed using a systematic approach to further classify GGO based on morphology, distribution, and ancillary imaging findings, such as the presence of cysts, traction bronchiectasis, and air trapping. Correlation with clinical history, such as the chronicity of symptoms, the patient's immune status, and preexisting medical conditions is vital. By thorough analysis of imaging patterns and consideration of relevant clinical information, the radiologist can generate a succinct and useful imaging differential diagnosis when confronted with the nonspecific finding of GGO.

Transitional cell carcinoma of the ovary: a case-control study.

OBJECTIVES: The aim of this study is to compare response to chemotherapy and survival between patients with transitional call carcinoma of the ovary (TCCO) and papillary serous ovarian cancer (PSOC). METHODS: We identified women with both pure and mixed TCCO who were treated between 2000 and 2010. Each case was matched to two women with PSOC by age, grade, stage, and year of diagnosis. Correlation between categorical variables was assessed with chi square test. The Kaplan-Meier survival analysis was used to generate overall survival data (OS). Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model. RESULTS: Eighty-one women diagnosed with TCCO were selected as cases and compared to 162 controls. Women with TCCO had a lower rate of platinum resistance compared to controls (9% vs. 25%; p=0.01). When multivariate logistic regression was used to control for other factors independently associated with platinum resistance, patients with TCCO had a significantly lower risk of platinum resistance compared to PSOC. Median progression-free survival was not significantly different (27 months vs. 22 months; p=0.15) for women with TCCO and PSOC, respectively. Median OS, however, was significantly different at 83 months vs. 52 months for the TCCO and PSOC groups, respectively (p=0.01). A Cox proportional hazards model identified optimal cytoreduction, transitional cell histology, age, stage, and platinum and paclitaxel chemotherapy as independent predictors of OS. CONCLUSIONS: Patients with TCCO are less likely to demonstrate resistance to platinum chemotherapy and have improved overall survival when compared to patients with PSOC.

Using the ASC:SIL ratio, human papillomavirus, and interobserver variability to assess and monitor cytopathology fellow training performance.

BACKGROUND: The goal of this study was to assess objective measurements of cytopathology fellow performance during their training. METHODS: The authors examined cytopathology performance characteristics (the ratio of atypical squamous cells to squamous intraepithelial lesions [ASC:SIL], interobserver variability [IOV], high-risk human papillomavirus [hr-HPV]-positive atypical squamous cells of undetermined significance [ASC-US]) of cytopathology fellows and assessed whether they could be used as tools to further their education. RESULTS: The ASC:SIL ratio, the proportion of hr-HPV-positive ASC-US, and IOV were calculated for 5 consecutive cytopathology fellows. The average ASC:SIL ratio for the fellows was 1.15. The overall average Cohen κ-coefficient (κ-value) between fellow and cytopathologist interpretation was 0.75 (substantial agreement). The conditional κ-value for ASC-US only was higher for cases the fellows called ASC-US (0.70) than for cases the cytopathologist called ASC-US (0.60). Of the cases that were diagnosed as "negative for intraepithelial lesion or malignancy" (NILM) by the fellow and ASC-US by the pathologist, 33.2% were positive for hr-HPV. This was higher than the expected frequency of hr-HPV-positive results in the NILM population, suggesting that the fellows were over-interpreting NILM in hr-HPV-positive cases that had cytologic features sufficient for an ASC-US interpretation. CONCLUSIONS: In this study, agreement was compared between trainee and cytopathologist to determine where a fellow's interpretation differed. With the use of IOV, the ASC:SIL ratio, and the percentage of hr-HPV-positive results in the NILM, ASC-US, and low-grade SIL categories, the authors attempted to outline objective assessments and areas of improvement for fellows before they enter independent practice.

Fine-needle aspiration cytology in Ethiopia.

CONTEXT: Most of the population in Ethiopia lives below the poverty line with severely limited access to health care. The burden of infectious diseases is high, but benign and malignant neoplasms are also encountered frequently. For diagnosis of palpable lesions in this setting, fine-needle aspiration biopsy is the method of choice. OBJECTIVE: To present findings from several patients from 3 major hospitals in Ethiopia who underwent fine-needle aspiration biopsy. DATA SOURCES: Representative cytopathology cases of routinely encountered problems are shown. Often patients present with clinically advanced lesions. Staffing, technique, and equipment used for fine-needle aspiration biopsy are described at Black Lion Hospital (Addis Ababa), the University of Gonder Hospital (Gonder), and Ayder Referral Hospital of Mekelle University in the Tigray region of northern Ethiopia. CONCLUSIONS: Fine-needle aspiration biopsy is a highly effective method for diagnosis of mass lesions, especially in an environment with sparse health care resources, such as Ethiopia. This article illustrates the work of Ethiopian cytopathologists and emphasizes the constraints under which they perform their work.

The evolution of the Papanicolaou smear.

The Papanicolaou smear or cervicovaginal cytology has been the mainstay of screening for cervical cancer in women of over 60 years. In this article, the origins of the Pap smear as a screening method and the many changes associated with the use of the Pap smear are detailed.

Low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion: a category with an increased outcome of high-grade lesions: use as a quality assurance measure.

"Low-grade squamous intraepithelial lesion (LSIL), cannot exclude high-grade squamous intraepithelial lesion" (LSIL-H) is an increasingly used, equivocal interpretive category in gynecologic cytology. In an effort to evaluate its potential usefulness as a measure of quality assurance, we studied patterns of use of the LSIL-H diagnosis compared with "LSIL" and "high-grade squamous intraepithelial lesion" (HSIL) with corresponding histologic outcomes for 10 cytopathologists in our practice. In our laboratory, while the overall rate of associated cervical intraepithelial neoplasia 2 or greater on histologic follow-up for LSIL-H was intermediate between that of LSIL and HSIL, the outcomes for individual cytopathologists varied widely. Monitoring this particular utilization-outcome data with periodic confidential feedback to individual cytopathologists offers an opportunity for practice improvement within a laboratory and serves as an additional measure of quality assurance. These data may be useful for establishing and/or realigning the diagnostic criteria for this equivocal cytologic interpretation endorsed by a pathology practice.

Prevalence of abnormalities influences cytologists' error rates in screening for cervical cancer.

CONTEXT: Medical screening tasks are often difficult, visual searches with low target prevalence (low rates of disease). Under laboratory conditions, when targets are rare, nonexpert searchers show decreases in false-positive results and increases in false-negative results compared with results when targets are common. This prevalence effect is not due to vigilance failures or target unfamiliarity. OBJECTIVE: To determine whether prevalence effects could be a source of elevated false-negative errors in medical experts. DESIGN: We studied 2 groups of cytologists involved in cervical cancer screening (Boston, Massachusetts, and South Wales, UK). Cytologists evaluated photomicrographs of cells at low (2% or 5%) or higher (50%) rates of abnormality prevalence. Two versions of the experiment were performed. The Boston, Massachusetts, group made decisions of normal or abnormal findings using a 4-point rating scale. Additionally, the group from South Wales localized apparent abnormalities. RESULTS: In both groups, there is evidence for prevalence effects. False-negative errors were 17% (higher prevalence), rising to 30% (low prevalence) in the Boston, Massachusetts, group. The error rate was 27% (higher prevalence), rising to 42% (low prevalence) in the South Wales group. (Comparisons between the 2 groups are not meaningful because the stimulus sets were different.) CONCLUSIONS: These results provide the first evidence, to our knowledge, that experts are not immune to the effects of prevalence even with stimuli from their domain of expertise. Prevalence is a factor to consider in screening for disease by human observers and has significant implications for cytology-based cervical cancer screening in the post-human papillomavirus vaccine era, when prevalence rates of high-grade lesions in the population are expected to decline.

Testing for human papillomavirus in cervical cancer screening: a review of indications and methodology.

High-risk human papillomavirus (hrHPV) testing has become an integral component of cervical cancer screening, given that persistent infection with hrHPV was recognized as a significant risk factor for most precancers and cancers of the cervix. Particularly, testing for hrHPV types (in conjunction with cervical cytology) has been approved for primary screening in women over 30 years of age and for cost-effective triaging of equivocal cervical cytology results. HPV was a small double-stranded DNA virus that cannot be cultured in vitro; so, different types of tests have been developed to detect its presence. Various molecular techniques were available for detecting the presence and/or quantity of hrHPV. In this review, the testing options for hrHPV and its surrogates, with an emphasis on those approved by the US Food and Drug Administration (FDA), were detailed. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.

Tissue-specific signatures of activating PIK3CA and RAS mutations in carcinosarcomas of gynecologic origin.

OBJECTIVES: Gynecologic carcinosarcoma is an aggressive malignancy that requires more effective treatment approaches. However, therapeutic implications regarding the specific gynecologic site of origin and the admixture of carcinomatous and sarcomatous elements that define this tumor remain uncertain. Therefore, broad genotyping was performed to identify tissue-specific somatic mutational profiles that may help direct targeted therapies in this complex neoplasia. METHODS: Genotyping was conducted on primary gynecologic carcinosarcomas arising from various disease sites (uterus, ovary, fallopian tube, vagina) and within isolated histological subcomponents. Nucleic acids extracted from diagnostic tissue were used in a genotyping platform that simultaneously queried >120 common mutations across 14 cancer genes. Mutational status was correlated with clinical variables using logistic regression and Kaplan-Meier survival estimates. RESULTS: Cancer gene mutations were identified in 46% of the 52 patient cohort and include TP53 (23%), PIK3CA (19%), KRAS (15%), CTNNB1 (4%) and NRAS (2%). Mutation in a single gene was observed in 31% of patient samples, while synchronous mutations involving 2 and 3 genes were noted in 13% and 2% of samples, respectively. Comparative evaluation of the carcinomatous and sarcomatous elements within a tumor demonstrated a similar mutation signature. Mutations in PIK3CA, KRAS and NRAS were exclusive to tumors of uterine origin and age-adjusted Cox proportional hazards modeling associated advanced age, stage and TP53 mutations with decreased survival in the uterine subset. CONCLUSION: While carcinosarcomas across gynecologic disease sites are histologically similar, therapeutically relevant mutations in the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways predominated in carcinosarcomas arising in the uterus.