Teratoma-associated and so-called pure Wilms tumour of the ovary represent two separate tumour types with distinct molecular features.

AIMS: Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma-associated and pure ovarian WT may represent different tumour types with diverging molecular backgrounds. To test this hypothesis, we comprehensively characterized a series of five tumours originally diagnosed as ovarian WT. METHODS AND RESULTS: The five cases comprised three teratoma-associated (two mature and one immature) and two pure WTs. Two of the teratoma-associated WTs consisted of small nodular arrangements of "glandular"/epithelial structures, while the third consisted of both an epithelial and a diffuse spindle cell/blastemal component. The pure WTs consisted of "glandular" structures, which were positive for sex cord markers (including inhibin and SF1) together with a rhabdomyosarcomatous component. The two pure WTs harboured DICER1 pathogenic variants (PVs), while the three associated with teratomas were DICER1 wildtype. Panel-based DNA sequencing of four of the cases did not identify PVs in the other genes investigated. Analysis of the HA19/IGF2 imprinting region showed retention of imprinting in the pure WTs but loss of heterozygosity with hypomethylation of the ICR1 region in two of three teratoma-associated WTs. Furthermore, copy number variation and clustering-based whole-genome DNA methylation analyses identified divergent molecular profiles for pure and teratoma-associated WTs. CONCLUSION: Based on the morphological features, immunophenotype, and molecular findings (DICER1 PVs, copy number, and DNA methylation profiles), we suggest that the two cases diagnosed as pure primary ovarian WT represent moderately to poorly differentiated Sertoli Leydig cell tumours (SLCTs), while the tumours arising in teratomas represent true WTs. It is possible that at least some prior cases reported as pure primary ovarian WT represent SLCTs.

Multi-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry.

The HercepTest was approved 20+ years ago as the companion diagnostic test for trastuzumab in human epidermal growth factor 2 (HER2) or ERBB2 gene-amplified/overexpressing breast cancers. Subsequent HER2 immunohistochemistry (IHC) assays followed, including the now most common Ventana 4B5 assay. Although this IHC assay has become the clinical standard, its reliability, reproducibility, and accuracy have largely been approved and accepted on the basis of concordance among small numbers of pathologists without validation in a real-world setting. In this study, we evaluated the concordance and interrater reliability of scoring HER2 IHC in 170 breast cancer biopsies by 18 breast cancer-specialized pathologists from 15 institutions. We used the Observers Needed to Evaluate Subjective Tests method to determine the plateau of concordance and the minimum number of pathologists needed to estimate interrater agreement values for large numbers of raters, as seen in the real-world setting. We report substantial discordance within the intermediate categories (<1% agreement for 1+ and 3.6% agreement for 2+) in the 4-category HER2 IHC scoring system. The discordance within the IHC 0 cases is also substantial with an overall percent agreement (OPA) of only 25% and poor interrater reliability metrics (0.49 Fleiss' kappa, 0.55 intraclass correlation coefficient). This discordance can be partially reduced by using a 3-category system (28.8% vs 46.5% OPA for 4-category and 3-category scoring systems, respectively). Observers Needed to Evaluate Subjective Tests plots suggest that the OPA for the task of determining a HER2 IHC score 0 from not 0 plateaus statistically around 59.4% at 10 raters. Conversely, at the task of scoring HER2 IHC as 3+ or not 3+ pathologists' concordance was much higher with an OPA that plateaus at 87.1% with 6 raters. This suggests that legacy HER2 IHC remains valuable for finding the patients in whom the ERBB2 gene is amplified but unacceptably discordant in assigning HER2-low or HER2-negative status for the emerging HER2-low therapies.

High-Grade Endometrial Stromal Sarcomas With YWHAE::NUTM2 Gene Fusion Exhibit Recurrent CDKN2A Alterations and Absence of p16 Staining is a Poor Prognostic Marker.

High-grade endometrial stromal sarcomas (HGESSs) are aggressive uterine tumors harboring oncogenic fusion proteins. We performed a molecular study of 36 HGESSs with YWHAE::NUTM2 gene fusion, assessing co-occurring genetic events, and showed that these tumors frequently harbor recurrent events involving the CDKN2A locus on chromosome 9p. Using array-based copy number profiling and CDKN2A fluorescence in situ hybridization, we identified homozygous and hemizygous deletions of CDKN2A in 18% and 14% of tumors (n = 22 analyzed), respectively. While all YWHAE-rearranged HGESSs with retained disomy for CDKN2A were immunohistochemically positive for p16INK4 (p16), all tumors with homozygous deletion of CDKN2A showed complete absence of p16 staining. Of the 2 tumors with a hemizygous deletion of CDKN2A, 1 showed diffuse and strong p16 positivity, whereas the other showed complete absence of staining. In the p16-negative case, we did not find intragenic mutations or DNA promoter methylation to explain the p16 protein loss, implicating other mechanisms in the regulation of protein expression. In our cohort, subclonal or complete absence of p16 staining was associated with worse overall survival compared with positive p16 staining (1-year overall survival: 28.6% vs 90.7%, respectively; n = 32; P < .001), with all 7 patients in the p16-negative group having succumbed to their disease within 2 years of diagnosis. Our results suggested CDKN2A alterations as a cooperative driver of tumorigenesis in a subset of HGESSs with the YWHAE::NUTM2 gene fusion and showed p16 to be a potential prognostic marker.

Folate Receptor Alpha Is Preferentially Expressed in the Carcinoma Component of Endometrial Carcinosarcomas: A Potential Target for Adjuvant Therapy.

Carcinosarcomas (CSs) of the endometrium are biphasic malignancies, composed of high-grade carcinomatous and sarcomatous components. Surgical stage and pathologic characteristics are the most important prognostic findings, with a 5-yr survival of 15% to 30% in advance stage disease. Folate receptor alpha (FRA) overexpression has been observed in endometrial carcinomas and not yet studied in CSs. This study evaluates semiquantitative expression of FRA in both carcinomatous and sarcomatous components of CSs on whole tissue sections. Immunohistochemistry for FRA expression was performed and extent and intensity of staining were recorded for each case for both histologic components. A total of 46 cases were stained for FRA. The majority of these (40/46, 87%) showed FRA staining at variable intensity in the carcinomatous component, stronger in serous carcinomas and high-grade endometrioid, while only a small subset of tumors demonstrated weak staining in the sarcomatous component (2/46, 4.35%). CS is known to be associated with poor prognosis and adjuvant therapy is recommended even in low stage disease. Serous and high-grade endometrioid carcinomas are the most common carcinomatous components of CSs and are known to show consistently high FRA expression. Folate plays a role in tumor cell migration and loss of cellular adhesion, which are key steps in epithelial-mesenchymal transition, the process by which CS develops from carcinoma cells. Our study shows expression of FRA in the carcinomatous component of almost all CS cases (87%), further favoring FRA as a target for adjuvant treatment. While expression of FRA in the sarcomatous component was rarely observed, the carcinomatous component being associated with metastatic potential underscores the importance of anti-FRA therapy for systemic disease control.

Management of Lobular Neoplasia Found on Core Needle Biopsy Performed for Calcifications Using Precise Radiologic-Pathologic Correlation.

OBJECTIVE. The purpose of our study was to evaluate the upgrade rate of calcified lobular neoplasia (LN) versus incidental noncalcified classic LN found on core needle biopsy performed for the evaluation of suspicious calcifications. MATERIALS AND METHODS. This retrospective study included 390 consecutive image-guided breast core needle biopsies with microcalcifications as the target that were performed between December 2009 and July 2017. In 81 of the 390 core biopsies, the highest-risk lesion was LN that then underwent either excision or imaging follow-up. Core biopsy results were compared with excision and imaging follow-up findings. An upgrade of LN was defined as ductal carcinoma in situ or invasive ductal or lobular carcinoma. RESULTS. Of 81 LN diagnosed on core biopsy performed for calcifications, 16 had calcifications within the LN. Fifteen of these 16 cases underwent surgical excision, and three (3/15, 20.0%) were upgraded on excision. Of the 64 core biopsies showing incidental noncalcified LN with benign concordant entities containing calcifications, 42 underwent surgical excision, and one LN (1/42, 2.4%) was upgraded. Twenty-three total lesions (one calcified LN and 22 noncalcified LN) were followed with imaging rather than excision. No cancers were detected among the follow-up group. One case was deemed to have discordant findings on radiologic-pathologic review and was sent for excision, which showed invasive cancer with tubulolobular and lobular features. CONCLUSION. Women undergoing stereotactic core needle biopsy for calcifications revealing noncalcified incidental classic LN and a benign concordant entity that could explain the presence of the target calcifications have a low risk of upgrade and may be followed with imaging. Surgical excision should be offered to women who have LN with calcifications.

Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer.

The US Food and Drug Administration (FDA) approved the PD-L1 immunohistochemical assay, SP142, as a companion test to determine eligibility for atezolizumab therapy in patients with advanced triple negative breast cancer (TNBC) but data in lung cancer studies suggest the assay suffers from poor reproducibility. We sought to evaluate reproducibility and concordance in PD-L1 scoring across multiple pathologists. Full TNBC sections were stained with SP142 and SP263 assays and interpreted for percentage (%) immune cell (IC) staining by 19 pathologists from 14 academic institutions. Proportion of PD-L1 positive cases (defined as ≥1% IC) was determined for each assay as well as concordance across observers. We utilized a new method we call Observers Needed to Evaluate Subjective Tests (ONEST) to determine the minimum number of evaluators needed to estimate concordance between large numbers of readers, as occurs in the real-world setting. PD-L1 was interpreted as positive with the SP142 assay in an average 58% of cases compared with 78% with SP263 (p < 0.0001). IC positive continuous scores ranged from 1 to 95% (mean = 20%) and 1 to 90% (mean = 10%) for SP263 and SP142, respectively. With SP142, 26 cases (38%) showed complete two category (<1% vs. ≥1%) concordance; with SP263, 38 cases (50%) showed complete agreement. The intraclass correlation coefficient (ICC) for two category scoring of SP263 and SP142 was 0.513 and 0.560. ONEST plots showed decreasing overall percent agreement (OPA) as observer number increased, reaching a low plateau of 0.46 at ten observers for SP263 and 0.41 at eight observers for SP142. IC scoring with both assays showed poor reproducibility across multiple pathologists with ONEST analysis suggesting more than half of pathologists will disagree about IC scores. This could lead to many patients either receiving atezolizumab when they are unlikely to benefit, or not receiving atezolizumab when they may benefit.

Diagnosing Anal Squamous Intraepithelial Lesions With and Without p16: An Interobserver Variability Study.

OBJECTIVE: Morphologic diagnosis and grading of anal squamous intraepithelial lesions (ASILs) are challenging. In this study, we investigated interobserver variability and p16 utility in accurately grading anal SIL. MATERIALS AND METHODS: Six pathologists evaluated the degree of SIL on hematoxylin and eosin slides from 146 anal biopsies, followed by the review of both p16 and hematoxylin and eosin slides in cases where p16 was previously performed. κ was calculated in the following 4 ways: (A) 4-tiered diagnosis (negative for SIL [NSIL], anal intraepithelial neoplasia [AIN 1, AIN 2, AIN 3]); (B) 3-tiered diagnosis (NSIL and AIN 1 [pooled], AIN 2, AIN 3); (A) 3-tiered diagnosis (NSIL, low-grade SIL, high-grade SIL [HSIL]); and (D) 2-tiered diagnosis (no HSIL, HSIL). RESULTS: There is only moderate agreement with a 4-tiered diagnosis with or without p16 (κ = 0.48-0.57). There is substantial agreement when AIN 2 and AIN 3 are pooled as HSIL in cases with or without p16 review (κ = 0.71-0.78). There is almost perfect agreement with a 2-tiered diagnosis of negative for HSIL and HSIL both in cases where p16 was used and where p16 was not required, with the best agreement for a 2-tiered diagnosis with concurrent p16 review. CONCLUSIONS: This study highlights the importance of a judicious use of p16 for diagnosis. When there is no need for p16 by the Lower Anogenital Squamous Terminology guidelines, interobserver agreement was substantial to almost perfect with a 2-tiered diagnosis. However, when its use is indicated but it is not performed or reviewed, the agreement is much lower even with a 2-tiered diagnosis. Rational use of p16 will ensure diagnostic accuracy and the best possible patient care.

Endometrial tumors with yolk sac tumor-like morphologic patterns or immunophenotypes: an expanded appraisal.

Uterine yolk sac tumors have gained increased recognition in recent years. The current study is a multi-faceted examination of yolk sac tumor-like phenotypes in endometrial tumors, based on an analysis of 3 groups of uterine tumors: Group 1: 9 endometrial tumors that had been classified as yolk sac tumor, or as having a yolk sac tumor component, were assessed with a 35-marker immunohistochemical panel, with the goal of defining their immunophenotypic spectrum; Group 2, comprised of 70 endometrial carcinomas of various histotypes, were analyzed for their expression of SALL4, Glypican-3, and AFP, to assess the specificity of these markers for yolk sac tumors relative to endometrial carcinomas; Group 3, comprised of 626 archived cases of endometrial carcinoma/carcinosarcoma, reviewed to define the frequency of yolk sac tumor-like morphology therein. Yolk sac tumor areas in the Group 1 cases were consistently immunoreactive for SALL4 and Glypican-3; variably positive for AFP (89%), Villin (89%), PLAP (78%), 34ßE12 (67%), CAM 5.2 (62.5%), EMA (56%), CD117 (50%), p16 (50%), CDX2 (44%), p53 (44% aberrant), MOC31 (37.5%), CK7 (33%), GATA3 (33%), CK5 (25%), and PAX8 (11%); and were negative for CD30, Napsin A, OCT4, estrogen, androgen, and progesterone receptors. 29 (41%) of the 70 group-2 cases expressed at least one of the 3 markers, and 96% of the positive cases was a high-grade histotype. Glypican-3, SALL4, and AFP were positive in 30, 20, and 2.8% of group-2 cases respectively; however, co-expression of any 2, or all 3 markers was uncommon (<9 and 1.4% of cases respectively). Potential yolk sac tumor-like morphology was identified in 5 (0.8%) of 626 group-3 cases, and three were ultimately deemed to be true yolk sac tumor phenotypes based on their morphologic and immunophenotypic similarity to the group 1 cases. These findings highlight the broad immunophenotypic spectrum of uterine yolk sac tumors, the potential pitfalls associated with using immunophenotypes alone to define yolk sac tumor differentiation in endometrial carcinoma, and the utility and limitations of morphologic assessment to identify yolk sac tumors at this site.

GATA3 Expression in Common Gynecologic Carcinomas: A Potential Pitfall.

GATA binding protein 3 (GATA3) immunohistochemistry is primarily used as a marker of breast and urothelial differentiation, particularly in metastatic settings. In the gynecologic tract it also serves a robust marker for mesonephric and trophoblastic tumors. However, expression has also been described in more common malignancies of gynecologic tract including ovarian, endometrial, and cervical carcinomas. Data on the distribution of GATA3 expression in gynecologic malignancies is somewhat limited, particularly across different histologic subtypes of ovarian, endometrial, and cervical carcinomas. To assess the rates of GATA3 expression among common gynecologic cancers of various histologic types, 100 ovarian carcinomas, 64 endometrial carcinomas/atypical hyperplasias, 16 cervical squamous cell carcinomas (SCCs), and 14 endocervical adenocarcinomas were evaluated by immunohistochemistry for GATA3 positivity. Eight percent of endometrial carcinomas expressed GATA3, including 2 serous carcinomas, 1 carcinosarcoma, and 1 case of atypical hyperplasia. Six percent of ovarian carcinomas were GATA3-positive including 2 clear cell carcinomas, 2 mucinous adenocarcinomas, and 2 high-grade serous carcinomas. Thirty-eight percent of cervical SCCs showed weak to moderate staining in up to 50% of tumor cells. All endocervical adenocarcinomas were entirely negative for GATA3. In summary, GATA3 shows focal weak to moderate expression in a subset of endometrial and ovarian carcinomas. In contrast, usual-type endocervical adenocarcinomas are typically negative for GATA3, which can be helpful in differentiating them from mesonephric proliferations or carcinomas. A larger proportion of cervical SCCs express GATA3, therefore caution should be exercised when using this stain in the setting of a lower genitourinary carcinomas.

Developmental disorders and malformations of the breast.

Developmental abnormalities and malformations of the breast are rare and encompass a variety of genetic, syndromic, acquired and sporadic conditions. Abnormalities in development may include irregularities in the nipple areolar complex and/or the underlying glandular tissue, resulting in under or overdevelopment of breasts. Age of presentation and clinical severity is dependent on the underlying biologic cause. Abnormalities may involve the entirety of unilateral or bilateral breasts, particularly in association with syndromic conditions or endocrine abnormalities. Disordered development may also be focal, resulting in tumor-like lesions such as hamartomas, pseudoangiomatous stromal hyperplasia and gynecomastia. In this review, we discuss the disorders of breast development including etiologies, clinical presentations and corresponding histopathologic features.

Clear Cell Renal Cell Carcinoma Metastatic to the Gynecologic Tract: A Clinicopathologic Analysis of 17 Cases.

Clear cell renal cell carcinomas (CCRCC) rarely metastasizes to the gynecologic tract. In this study, we analyzed a multi-institutional data set to provide insights into the clinical, morphologic, and immunophenotypic features of this phenomenon. Seventeen metastatic CCRCC involving the gynecologic tract [ovary/fallopian tube (n=9), vulva (n=2), uterine corpus (n=3), cervix (n=2), uterine serosa (n=1)] were analyzed. Mean patient age was 62 yr (range: 45-79 yr). Most cases (15/17) presented as a recurrence 6 to 72 mo postnephrectomy, 1 case was concurrently diagnosed, and 1 case (a cervical metastasis) was diagnosed prenephrectomy. In 10 cases, metastases to other locations were identified within 6 wk of the gynecologic tract lesion. The adnexa were the most common site of metastases and the mean tumor size of adnexal metastases was 3.7 cm; in only 2 of 9 cases were metastases bilateral and only 1 had external surface nodules. The morphologic and immunohistochemical features of metastatic CCRCC were compared with those of 102 müllerian clear cell carcinomas (müllerian CCC: 49 endometrial, 53 ovarian). Although CCRCC and müllerian CCC displayed extensive morphologic overlap, a higher mitotic index and a higher frequency of an alveolar pattern were seen in CCRCC, whereas diffuse hobnail cells, hyaline globules, tubulocystic pattern, or any papillary pattern were more frequently seen in müllerian CCC. CA-IX, CD10, and renal cell carcinoma antigen were more frequently expressed in CCRCC than müllerian CCC, whereas Napsin-A, CK7, and p504S showed the reverse. PAX8 and HNF1ß did not significantly distinguish between the 2 groups. In summary, gynecologic tract metastases most often occur as a relapse of a previously resected CCRCC, and these relapses may occur many years postnephrectomy. Gynecologic tract metastases are often accompanied by concurrent metastases to other organs. The gross pathology of metastatic CCRCC in the ovary may potentially overlap with primary neoplasia. However, the expected morphology and immunophenotype of CCRCC are maintained in most gynecologic tract metastases. As such, although metastatic CCRCC and müllerian CCC may display significant overlap in pathologic features, several morphologic and immunophenotypic features are useful in their distinction.

Cytologic predictors of malignancy in bile duct brushings: a multi-reviewer analysis of 60 cases.

Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly.

Interobserver Reproducibility Among Gynecologic Pathologists in Diagnosing Heterologous Osteosarcomatous Component in Gynecologic Tract Carcinosarcomas.

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.

Clinical Significance of Positive Pelvic Washings in Uterine Papillary Serous Carcinoma Confined to an Endometrial Polyp.

Uterine papillary serous carcinoma (UPSC) represents 10% of endometrial carcinomas. Significant number of patients initially present with extrauterine disease. The role of adjuvant treatment in low stage, especially polyp-confined UPSC is controversial. This multi-institutional study evaluated the significance of positive pelvic washing (PW) and adjuvant treatment on disease recurrence in a setting of endometrial polyp-confined UPSC. Surgical pathology files from 3 institutions were searched for cases of endometrial polyp-confined UPSC. Following histologic review, cases were clinically staged as Stage I, without myoinvasion or lymphovascular invasion. Clinicopathologic characteristics, results of PW, and type of adjuvant therapy were recorded. Statistical analysis using the Kaplan-Meier method for survival and Fisher exact test were performed. Thirty-three patients were included in the study. All patients were diagnosed with polyp-confined UPSC. The size of the polyp ranged from 0.3 to 4.3 cm. PW was positive for tumor cells in 8/33 (24%) patients. Twenty-two patients (66.6%) received some type of adjuvant treatment. Six patients (18%) developed recurrent disease. There was no significant difference in disease-free survival in the patients receiving adjuvant treatment versus not (P=0.375). However, there was significant association (P=0.0013) between positive PW and disease recurrence. Data are conflicting whether positive PW affects prognosis in low-stage endometrial carcinomas. Our study showed that in UPSC, malignant cells can be present in PW without lymphovascular invasion or myoinvasion and may have negative prognostic implication. Our data also reflect the controversies in the role of adjuvant treatment in endometrium-confined UPSC.

Case report: MR imaging features of disseminated uterine leiomyosarcoma presenting after hysterectomy with morcellation.

A 53-year-old woman underwent elective hysterectomy for symptomatic anemia secondary to abnormal uterine bleeding. She presented 15 months later with complaints of abdominal fullness. Abdominopelvic magnetic resonance imaging demonstrated multiple confluent enhancing solid masses centered in the pelvis and extending cranially to the level of the umbilicus. Additional separate nodules also were visible along the peritoneum. Biopsy demonstrated leiomyosarcoma. Additional clinical information was obtained, which revealed that the patient's prior hysterectomy was performed with morcellation. In November 2014, the United States Food and Drug Administration issued a warning discouraging the use of morcellation during hysterectomy and myomectomy because of the risk of seeding unsuspected malignancy. Radiologists should be aware of this potential complication of morcellation and its imaging appearance so that the correct diagnosis can be suggested in the imaging report.

Magnetic resonance imaging of rectal cancer: staging and restaging evaluation.

Magnetic resonance imaging is used to non-invasively stage and restage rectal adenocarcinomas. Accurate staging is important as the depth of tumor extension and the presence or absence of lymph node metastases determines if an individual will undergo preoperative neoadjuvant chemoradiation. Accurate description of tumor location is important for presurgical planning. The relationship of the tumor to the anal sphincter in addition to the depth of local invasion determines the surgical approach used for resection. High-resolution T2-weighted imaging is the primary sequence used for initial staging. The addition of diffusion-weighted imaging improves accuracy in the assessment of treatment response on restaging scans. Approximately 10%-30% of individuals will experience a complete pathologic response following chemoradiation with no residual viable tumor found in the resected specimen at histopathologic assessment. In some centers, individuals with no residual tumor visible on restaging MR who are thought to be at high operative risk are monitored with serial imaging and a "watch and wait" approach in lieu of resection. Normal rectal anatomy, MR technique utilized for staging and restaging scans, and TMN staging are reviewed. An overview of surgical techniques used for resection including newer, minimally invasive endoluminal techniques is included.

Mesenteric masses: approach to differential diagnosis at MRI with histopathologic correlation.

Magnetic resonance imaging (MRI) is an outstanding tool for the identification and characterization of mesenteric masses. Mesenteric masses may be solid or cystic. Most solid mesenteric masses are neoplastic, with sclerosing mesenteritis a notable exception. Entirely cystic mesenteric masses are typically benign. The excellent soft-tissue contrast afforded by MRI aids in narrowing the differential diagnosis of mesenteric masses. Accurately characterizing both solid and cystic mesenteric masses is important, as management ranges from active surveillance to medical management to surgical resection, depending on the tissue composition of the mass. An MRI-based approach to the differential diagnosis of mesenteric masses is presented.

Practical Updates and Diagnostic Challenges in Endometrial Carcinoma.

CONTEXT.­: Clinical management of endometrial carcinoma largely depends on the morphologic parameters ascertained based on the pathologic evaluation of surgical resection specimens. However, there are numerous controversial and nonstandardized aspects of both the macroscopic and microscopic assessment of surgical specimens, including grossing, adequate sampling, diagnosis, staging, reporting, and ancillary testing. OBJECTIVE.­: To provide a comprehensive practical review of standardized grossing, key morphologic findings for reporting and staging, and diagnostic and prognostic use of ancillary testing in endometrial carcinomas. DATA SOURCES.­: The existing literature, recommendations of the International Society of Gynecological Pathologists, and specialty consensus guidelines. CONCLUSIONS.­: This review article summarizes important aspects of the grossing and sampling of surgical resection specimens for microscopic examination, key morphologic parameters that are required for reporting and staging, and morphologic features and immunoprofiles helpful in the differential diagnosis of low-grade and high-grade endometrial carcinomas, as well as the current status of the molecular classification of endometrial carcinoma and human epidermal growth factor receptor 2 testing in serous carcinoma. The information presented herein can be helpful in overcoming diagnostic challenges and issues related to the pathology reporting of endometrial carcinoma to practicing anatomic pathologists.

The Malignant Potential of Ovarian Steroid Cell Tumors Revisited: A Multi-institutional Clinicopathologic Analysis of 115 Cases.

Steroid cell tumors (SCTs) of the ovary are rare and understudied, and as such, uncertainties remain about their malignant potential, as well as clinicopathologic predictors of patient outcome. Based on a multi-institutional cohort of cases, we present findings from the largest study of SCT reported to date. Clinicopathologic data were documented on 115 cases of SCT that were assembled from 17 institutions. The median patient age was 55 years (range: 9 to 84). When measured, preoperative androgen levels were elevated in 84.2% (48/57) of patients. A total of 111 (96.5%) cases were classified as stage I (103 stage IA; 2 stage IB; 6 stage IC). The stage distribution for the remaining 4 patients was as follows: stage II (n = 1), III (n = 3; 1 IIIA, 1 IIIB, 1 IIIC). The median tumor size was 3 cm (range: 0.2 to 22). Cytologic atypia, microscopic tumor necrosis, microscopic tumor hemorrhage, and a mitotic index of >1 mitotic figure/10 high-power fields were present in 52% (60/115), 9.6% (11/115), 37% (43/115), and 19% (22/115) of cases, respectively. Of 115 patients, 7 (6.1%) recurred postexcision, 4 (3.5%) ultimately died of disease, and 10 (8.7%) either recurred, died of disease, or were advanced stage at presentation. The median duration to recurrence postresection was 33 months (range: 23 to 180). Four of the 7 recurrences were stage IA at baseline. Tumor size >4 cm, International Federation of Gynecology and Obstetrics (FIGO) stage ≥IB, tumor necrosis, and tumor hemorrhage were each significantly associated with reduced recurrence-free survival in log-rank tests and univariable Cox models, with age older than 65 years being of marginal significance (hazard ratio [HR]: 5.4, 95% CI: 1.0-30.0, P = 0.05). Multivariable analyses suggested that FIGO stage ≥IB (HR: 27.5, 95% CI: 2.6-290.5), and age older than >65 years (HR: 21.8, 95% CI: 1.6-303.9) were the only parameters that were independently associated with recurrence. Cross-section analyses showed that tumor necrosis, tumor hemorrhage, and larger tumor size were significantly associated with a FIGO stage ≥IB status, which bolstered the conclusion that they are not independent predictors of recurrence. In summary, <10% of SCTs are clinically malignant, a substantially lower frequency than has previously been reported in the literature. Clinicopathologic predictors of patient outcomes that are prospectively applicable in practice could not be definitively established. Recurrences may occur many years (up to 15 y in this study) after primary resection, even in stage IA cases.