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Aims Atypical polypoid adenomyoma (APAM) is an uncommon uterine lesion composed of complex endometrioid glands with frequent squamous morular metaplasia and fibromuscular stroma. On endometrial curettage, biopsy or polypectomy specimens, the admixture of endometrioid glands and smooth muscle raises the differential diagnosis of myoinvasive endometrioid carcinoma. Reproductive-age APAM patients may opt for fertility preservation, whereas myoinvasive carcinoma is treated surgically. One previous study reported an incidental finding that the stroma of APAM, in contrast to that of other polypoid lesions, was SATB2-positive. APAM has also been reported to show increased stromal p16 staining. We aimed to assess whether SATB2 and p16 are useful stains for the distinction of APAM from myoinvasive carcinoma and benign adenomyomatous polyps. Methods and results Cases of 'atypical polypoid adenomyoma' (n = 32), 'adenomyomatous polyp' (n = 39) and 'myoinvasive endometrioid carcinoma' (n = 30) were identified. Morphological features were assessed, along with the intensity and extent of SATB2 and p16 staining in the stromal component of each lesion. SATB2 expression was seen in the stromal components of 30 of 32 (94%) APAMs, versus none of 39 (0%) benign adenomyomatous polyps and five of 30 (17%) myoinvasive endometrioid carcinomas. Stromal p16 expression was seen in 31 of 31 (100%) APAMs, versus 20 of 39 (51%) benign adenomyomatous polyps and 12 of 30 (40%) myoinvasive endometrioid carcinomas. Conclusions Patchy to diffuse SATB2 and block-type p16 staining of fibromuscular stroma separating atypical endometrioid glands is more consistent with APAM than with myoinvasive endometrioid carcinoma. These stains are potentially useful adjuncts to careful morphological evaluation of endometrial biopsies/curettings.

Ovarian germ cell tumors, including yolk sac tumors, are most commonly diagnosed in children and young women. Most so-called yolk sac tumors reported in women35 years old have been associated with an epithelial proliferation (endometriosis or carcinoma). Here, we describe eight cases clinically diagnosed as uterine or ovarian germ cell tumors in women35 years old. In addition to routine morphologic examination and immunohistochemical evaluation, we present data from targeted next-generation sequencing (NGS) and isochromosome (12p) fluorescence in situ hybridization (FISH). We identified two groups of tumors with mixed germ cell and epithelial features: (1) tumors with background endometriosis and endometrioid carcinoma-like mutations (PTEN, PIK3CA, FGFR2, and CTNNB1), and (2) high-grade morphology, presumptive presence of isochromosome (12p) by FISH, and TP53 or PIK3CA mutations. These findings support the notion that the "germ cell tumor" component of these tumors is often somatically derived. Two tumors in our cohort were from premenopausal women; one showed no detectable mutations by NGS (suggestive of germ cell derivation), whereas the other showed PIK3CA, PTEN, and CTNNB1 mutations (suggestive of somatic derivation). Accurate classification of these tumors is likely important for selection of appropriate chemotherapy.

PURPOSE: To examine radiologic-histopathologic correlation and the diagnostic performance of transvaginal US prior to risk-reducing salpingo-oophorectomy (RRSO) in women at high risk for tubo-ovarian carcinoma (TOC). MATERIALS AND METHODS: This retrospective study included 147 women (mean age, 49 years; age range, 28–75 years) at high risk for TOC who underwent transvaginal US within 6 months of planned RRSO between May 1, 2007, and March 14, 2018. Histopathologic results were reviewed. Fellowship-trained abdominal radiologists reinterpreted transvaginal US findings by using standardized descriptors. Descriptive statistical analysis and multiple logistic regression were performed. RESULTS: Of the 147 women, 136 had mutations in BRCA1, BRCA2, Lynch syndrome, BRIP1, and RAD51D genes, and 11 had a family history of TOC. Histopathologic reports showed 130 (88.4%) benign nonneoplastic results, 10 (6.8%) benign neoplasms, five (3.4%) malignant neoplasms, and two (1.4%) isolated p53 signature lesions. Transvaginal US results showed benign findings in 95 (64.6%) women and abnormal findings in 11 (7.5%) women; one or both ovaries were not visualized in 41 (27.9%) women. Hydrosalpinx was absent in all TOC and p53 signature lesions at transvaginal US. Transvaginal US had 20% sensitivity (one of five), 93% specificity (132 of 142), 9% positive predictive value (one of 11), and 97% negative predictive value (132 of 136) for TOC. Cancer was detected in one of five women at transvaginal US, and three of five false-negative lesions were microscopic or very small. CONCLUSION: Preoperative transvaginal US had low sensitivity for detecting TOC in women at high risk for TOC. Clinically relevant precursors and early cancers were too small to be detected. Keywords: Genital/Reproductive, Ultrasound Supplemental material is available for this article. © RSNA, 2020

The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high-grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as currently defined and lends credence to the effort of subclassifying some tumors as truly "high-grade endometrial stromal sarcomas." Our study also shows that, in the context of undifferentiated endometrial sarcomas, recognition of cytomorphologic features on routine hematoxylin and eosin-stained sections may be used to select tumors with specific molecular genetic changes-that is, translocations involving YWHAE. Our conclusions will help further efforts towards proper sub-classification of these tumors which will aid in diagnosis and potentially affect clinical management.

Rationale and Objectives This study aimed to determine whether uterine leiomyoma can be distinguished from uterine leiomyosarcoma on ultrasound (US), computed tomography (CT), and/or magnetic resonance imaging (MRI) without diffusion-weighted imaging. Materials and Methods Institutional review board approval was obtained and informed consent was waived for this Health Insurance Portability and Accountability Act–compliant retrospective case-control diagnostic accuracy study. All subjects with resected uterine leiomyosarcoma diagnosed over a 17-year period (1998–2014) at a single institution for whom pre-resection US ( n = 10), CT ( n = 11), or MRI ( n = 7) was available were matched by tumor size and imaging modality with 28 subjects with resected uterine leiomyoma. Six blinded radiologists (three attendings, three residents) assigned 5-point Likert scores for the following features: (1) margins, (2) necrosis, (3) hemorrhage, (4) vascularity, (5) calcifications, (6) heterogeneity, and (7) likelihood of malignancy (primary end point). Mean suspicion scores were calculated and receiver operating characteristic curves were generated. The ability of individual morphologic features to predict malignancy was assessed with logistic regression. Results Mean suspicion scores were 2.5 ± 1.2 (attendings) and 2.4 ± 1.3 (residents) for leiomyoma, and 2.7 ± 1.3 (attendings) and 2.7 ± 1.4 (residents) for leiomyosarcoma. The areas under the receiver operating characteristic curves (range: 0.330–0.685) were not significantly different from chance, either overall ( P = .36–.88) or by any modality ( P = .28–.96), for any reader. Reader experience had no effect on diagnostic accuracy. No morphologic parameter was significantly predictive of malignancy ( P = .10–.97). Conclusions Uterine leiomyoma cannot be differentiated accurately from leiomyosarcoma on US, CT, or MRI without diffusion-weighted imaging.

Fat necrosis of the breast is a relatively common reactive/reparative process that may be either primary, often after trauma, or secondary to prior surgery or therapeutic irradiation. Mammary fat necrosis may closely mimic breast neoplasia, both clinically and radiographically, and is thus frequently biopsied. In the majority of cases fat necrosis in the breast shows classic morphologic features and is a straightforward diagnosis. However, over the past several years we have seen a number of more challenging cases of mammary fat necrosis complicated by a distinctive cellular, spindled proliferation of macrophages, mimicking various spindle cell neoplasms of the breast. Herein we report our experience with such lesions. A total of 118 cases of fat necrosis involving the breast were retrieved from our institutional and consultation archives for the period 1994 to 2011. The final study group of 20 cases included only (1) consultation cases submitted specifically with concern for a spindle cell neoplasm and (2) institutional cases presenting as a mass lesion and showing an identical spindle cell proliferation. The tumors occurred in 20 women (mean age 58 y; range, 24 to 70 y), involved both breasts (left, 11 cases; right, 9 cases), and ranged in size from 0.8 to 2.5 cm (mean 1.5 cm). Additional clinical information was available for 18 (90%) patients; a history of ipsilateral breast carcinoma and prior therapeutic irradiation were documented in 7 of 18 (39%) and 6 of 18 (33%) patients, respectively. Radiographic reports and/or imaging was available for 17 (85%) patients; radiographic impressions were "suspicious for malignancy" (10 cases, 59%), "indeterminate" (2 cases, 12%), or "benign" (5 cases, 29%). The patients underwent core needle (14 cases, 70%) and excisional (6 cases, 30%) biopsies. The morphologic features of all cases were similar, showing a moderately cellular, fascicular proliferation of mitotically active, normochromatic, lightly eosinophilic spindled cells with mild nuclear variability, folded or grooved nuclei, and indistinct nucleoli. Chronic inflammatory cells and multinucleated giant cells were often admixed with the spindled cells, with more typical features of fat necrosis frequently present at the periphery. Immunohistochemical analysis performed at Mayo Clinic showed the lesional cells to express the histiocyte-associated markers CD163 (8 of 8, 100%), CD11c (8 of 8, 100%), and CD31 (4 of 8, 50%) and to be negative for keratins using the OSCAR monoclonal antibody (0 of 8, 0%). Studies conducted at outside institutions showed absent expression of various keratins, S100 protein, p63, and β-catenin protein. Histochemical staining for mycobacterial and fungal organisms was negative. Follow-up (18 patients, 1 to 120 mo, mean 37 mo) showed all patients to be alive without disease. Additional surgical procedures (6 patients) showed only fat necrosis. We believe that these lesions represent an exaggerated histiocytic reaction to fat necrosis in the breast. Awareness of this distinctive pseudotumor should help to prevent its misdiagnosis as various other mammary spindle cell neoplasms.

ObjectiveThis study aimed to determine the progression-free interval (PFI) for patients with platinum-resistant ovarian cancer on antiestrogen therapy (AET), and to correlate PFI with tumor estrogen receptor (ER) expression status.Materials and MethodsThis single-institution retrospective cohort study investigated platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancers treated with tamoxifen or an aromatase inhibitor from January 1999 to January 2012. Median PFI was calculated and a 95% confidence interval was constructed by bootstrapping. Relationships of PFI with disease characteristics were examined using 1-way analysis of variance or Pearson correlation. Estrogen receptor status of tumor specimens was assessed by immunohistochemistry. Progression-free interval was compared between ER groups with the Mann-Whitney test. Kaplan-Meier estimate was used to determine overall survival.ResultsNinety-nine patients met inclusion criteria: 77 (78%) received tamoxifen and 22 (22%) an aromatase inhibitor. Patients had a mean of 4 prior chemotherapy regimens (range, 1–14). Median PFI for any AET was 4.0 months (range, 1–49; 95% confidence interval, 3.0–5.0). Progression-free interval was independent of the number of prior treatments and type of AET, but longer with earlier stage at diagnosis. Estrogen receptor status was obtained for 63 patients, 44 were positive and 19 were negative. Progression-free interval was not statistically significant between ER-positive (median, 4.0 months) and ER-negative (median, 2.0 months) tumor status (P= 0.36).ConclusionsThis is the largest study to date investigating AET in heavily pretreated, platinum-resistant ovarian cancer patients. The median PFI of 4.0 months is comparable to standard cytotoxic therapies, and some patients with PFI greater than this median interval had ER-negative tumors. Given the limited adverse effects of AET, as well as low cost including oral administration, this treatment should be considered in all patients with platinum-resistant ovarian cancer.

Transthoracic fine needle aspiration (TFNA)/core needle biopsy (CNB) under computed tomography (CT) guidance has proved useful in the assessment of pulmonary nodules. We sought to determine the TFNA false-negative (FN) rate at our institution and identify potential causes of FN diagnoses. Medical records were reviewed from 1,043 consecutive patients who underwent CT-guided TFNA with or without CNB of lung nodules over a 5-year time period (2003-2007). Thirty-seven FN cases of "negative" TFNA/CNB with malignant outcome were identified with 36 cases available for review, of which 35 had a corresponding CNB. Cases were reviewed independently (blinded to original diagnosis) by three pathologists with 15 age- and sex-matched positive and negative controls. Diagnosis (i.e., nondiagnostic, negative or positive for malignancy, atypical or suspicious) and qualitative assessments were recorded. Consensus diagnosis was suspicious or positive in 10 (28%) of 36 TFNA cases and suspicious in 1 (3%) of 35 CNB cases, indicating potential interpretive errors. Of the 11 interpretive errors (including both suspicious and positive cases), 8 were adenocarcinomas, 1 squamous cell carcinoma, 1 metastatic renal cell carcinoma, and 1 lymphoma. The remaining 25 FN cases (69.4%) were considered sampling errors and consisted of 7 adenocarcinomas, 3 nonsmall cell carcinomas, 3 lymphomas, 2 squamous cell carcinomas, and 2 renal cell carcinomas. Interpretive and sampling error cases were more likely to abut the pleura, while histopathologically, they tended to be necrotic and air-dried. The overall FN rate in this patient cohort is 3.5% (1.1% interpretive and 2.4% sampling errors).