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Objectives: The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group-related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs)., Methods: SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs., Results: Using both whole-tissue sections and TMAs, SOX17 was positive in 94% (n = 155) of endometrial tumors and 96% (n = 242) of ovarian tumors. All breast cases (n = 241) and vulvar/cervical squamous cell carcinomas (n = 150) were negative. Among 1004 tumors from 20 sites, the only organs with positive tumors were ovary, uterus, and testis., Conclusions: SOX17 is a sensitive and specific marker for gynecologic origin in the tissues tested and may be a valuable adjunct to PAX8 and other commonly used markers to confirm endometrial or ovarian origin. SOX17 expression is lower in mucinous tumors, endocervical adenocarcinoma, high-grade neuroendocrine tumors, and undifferentiated/dedifferentiated endometrial carcinoma., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Advancements in digital imaging technology for Papanicolaou test slides, combined with artificial intelligence are driving the development and adoption of innovative computer-assisted screening methods for cervical cancer within the cytology community. Our study aimed to assess the performance of the Hologic Genius Digital Diagnostic System (HGDDS) in the interpretation of low-grade squamous intraepithelial lesions (LSIL) in ThinPrep Papanicolaou slides., Method: As part of a validation study performed with 890 ThinPrep Papanicolaou slides using the HGDDS, a subset of 146 LSIL cases were included in this study. Performance characteristics for the detection of cervical intraepithelial neoplasia (CIN) and interobserver variability among 3 cytopathologists were assessed., Results: On evaluation of the consensus results of the 3 cytopathologists, of the 146 LSIL Papanicolaou cases, 60.3% were interpreted as LSIL with the HGDDS. The remainder were interpreted as ASCUS (26%), ASC-H (10.3%), HSIL (2.7%), and NILM (0.7%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting CIN1+ lesions in the ASCUS + category with the HGDDS were 100%, 25%, 97.9%, and 100%, respectively. The sensitivity, specificity, PPV, and NPV for the detection of CIN1+ lesions in the LSIL + category with the HGDDS were 74.7%, 75%, 99.1%, and 7.7%, respectively. Kendall's W coefficient was 0.792, indicating strong agreement among participating pathologists., Conclusions: Our study demonstrated that ThinPrep Papanicolaou tests with LSIL could be interpreted with strong agreement among pathologists and with good performance indicators when utilizing the HGDDS., (Copyright © 2025 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: Artificial intelligence (AI)-based systems are transforming cytopathology practice. The aim of this study was to evaluate the sensitivity of high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) diagnosis assisted by the Hologic Genius Digital Diagnostics System (GDDS)., Methods: A validation study was performed with 890 ThinPrep Pap tests with the GDDS independently. From this set, a subset of 183 cases originally interpreted as HSIL confirmed histologically were included in this study. The sensitivity for detecting HSIL by three cytopathologists was calculated., Results: Most HSIL cases were classified as atypical glandular cell/atypical squamous cell-high grade not excluded (AGC/ASC-H) and above by all cytopathologists. Of these cases, 11.5% were classified as low-grade squamous intraepithelial lesion (LSIL) by pathologist A (P-A), 6% by pathologist B (P-B), and 5.5% by pathologist C (P-C); 3.8%, 2.7%, and 1.6% of these cases were classified as atypical squamous cell of unknown significance (ASC-US) by P-A, P-B, and P-C, respectively. The sensitivity for detection of cervical intraepithelial neoplasia 2 and above (CIN2+) lesions was 100% if ASC-US and above (ASC-US+) abnormalities were counted among all three pathologists. The sensitivity for detection of CIN2+ lesions was 84.7%, 91.3%, and 92.9% by P-A, P-B, and P-C, respectively, for ASC-H and above abnormalities. The Kendall W coefficient was 0.722, which indicated strong agreement between all pathologists., Conclusions: New-generation AI-assisted Pap test screening systems such as the GDDS have the potential to transform cytology practice. In this study, the GDDS aided in interpreting HSIL in ThinPrep Pap tests, with good sensitivity and agreement between the pathologists who interacted with this system., (© 2024 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objectives: Routine lymph node assessment in patients with endometrial intraepithelial neoplasia is institution and surgeon-dependent without clear guidelines. We sought to determine if routine sentinel lymph node (SLN) dissection at the time of laparoscopic hysterectomy for patients with a preoperative diagnosis of endometrial intraepithelial neoplasia and a preoperative ultrasound with endometrial stripe ≥20 mm is cost-effective., Methods: A decision model was created to perform two cost-effectiveness analyses: (1) hysterectomy with frozen section versus hysterectomy with SLN dissection in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia and an endometrial stripe of 20 mm or greater, and (2) the same options in all patients with a preoperative diagnosis of endometrial intraepithelial neoplasia. Costs obtained from Centers for Medicare and Medicaid Services and event probabilities and quality of life utility values were obtained through literature review., Results: In the case of preoperative endometrial stripe ≥20 mm, hysterectomy with SLN dissection cost $2469 more than hysterectomy with frozen section and gained 0.010 quality adjusted life years, or $44,997/quality-adjusted life years gained. In one-way sensitivity analyses, SLN dissection remained the favored strategy at a willingness to pay threshold of $100,000/quality-adjusted life years unless chronic lower extremity lymphedema after full lymphadenectomy had a likelihood <13.1% (base case value 18.1%); otherwise, SLN dissection was favored with individual variation of all other parameters over plausible ranges. When considering all patients with endometrial intraepithelial neoplasia, hysterectomy with frozen section was favored, with results most sensitive to variation of lymphedema risk after full lymphadenectomy., Conclusion: Hysterectomy with SLN dissection in patients with a preoperative endometrial stripe ≥20mm on ultrasound is cost-effective when compared with hysterectomy with frozen section., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Triple-negative breast cancer (TNBC) refers to an estrogen receptor-negative, progesterone receptor-negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor subtype. Immunohistochemistry (IHC) has been used as a surrogate for basal and luminal subtypes within TNBC, but prognostication of TNBC using IHC is not routinely performed. We aimed to study immunophenotypic correlations in a well-annotated cohort of consecutive TNBCs, excluding postneoadjuvant chemotherapy cases. Tissue microarrays were constructed from a total of 245 TNBC cases. IHC stains were performed and consisted of luminal (AR and INPP4B), basal (SOX10, nestin, CK5, and EGFR), and diagnostic (GCDFP15, mammaglobin, GATA3, and TRPS1) markers. Survival analysis was performed to assess the significance of clinical-pathologic variables including age, histology, grade, lymphovascular invasion, Nottingham prognostic index category, American Joint Committee on Cancer (AJCC) stage, stromal tumor-infiltrating lymphocytes at 10% increment, CD8+ T-cell count, Ki-67 index, PD-L1 status, and chemotherapy along with the results of IHC markers. Apocrine tumors show prominent reactivity for luminal markers and GCDFP15, whereas no special-type carcinomas are often positive for basal markers. TRPS1 is a sensitive marker of breast carcinoma but shows low or no expression in apocrine tumors. High AJCC stage, lack of chemotherapy, and dual SOX10/AR negativity are associated with worse outcomes on both univariable and multivariable analyses. Lymphovascular invasion and higher Nottingham prognostic index category were associated with worse outcomes on univariable but not multivariable analysis. The staining for IHC markers varies based on tumor histology, which may be considered in determining breast origin. Notably, we report that SOX10/AR dual negative status in TNBC is associated with a worse prognosis along with AJCC stage and chemotherapy status., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The primary aim of this study was to determine the upgrade rates of variant lobular carcinoma in situ (V-LCIS, ie, combined florid [F-LCIS] and pleomorphic [P-LCIS]) compared with classic LCIS (C-LCIS) when diagnosed on core needle biopsy (CNB). The secondary goal was to determine the rate of progression/development of invasive carcinoma on long-term follow-up after primary excision. After institutional review board approval, our institutional pathology database was searched for patients with "pure" LCIS diagnosed on CNB who underwent subsequent excision. Radiologic findings were reviewed, radiologic-pathologic (rad-path) correlation was performed, and follow-up patient outcome data were obtained. One hundred twenty cases of LCIS were identified on CNB (C-LCIS = 97, F-LCIS = 18, and P-LCIS = 5). Overall upgrade rates after excision for C-LCIS, F-LCIS, and P-LCIS were 14% (14/97), 44% (8/18), and 40% (2/5), respectively. Of the total cases, 79 (66%) were deemed rad-path concordant. Of these, the upgrade rate after excision for C-LCIS, F-LCIS, and P-LCIS was 7.5% (5 of 66), 40% (4 of 10), and 0% (0 of 3), respectively. The overall upgrade rate for V-LCIS was higher than for C-LCIS (P = .004), even for the cases deemed rad-path concordant (P value: .036). Most upgraded cases (23 of 24) showed pT1a disease or lower. With an average follow-up of 83 months, invasive carcinoma in the ipsilateral breast was identified in 8/120 (7%) cases. Six patients had died: 2 of (contralateral) breast cancer and 4 of other causes. Because of a high upgrade rate, V-LCIS diagnosed on CNB should always be excised. The upgrade rate for C-LCIS (even when rad-path concordant) is higher than reported in many other studies. Rad-path concordance read, surgical consultation, and individualized decision making are recommended for C-LCIS cases. The risk of developing invasive carcinoma after LCIS diagnosis is small (7% with ∼7-year follow-up), but active surveillance is required to diagnose early-stage disease., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

The clinical utility of the proliferation marker Ki67 in breast cancer treatment and prognosis is an active area of research. Studies have suggested that differences in pre-analytic and analytic factors contribute to low analytical validity of the assay, with scoring methods accounting for a large proportion of this variability. Use of standard scoring methods is limited, in part due to the time intensive nature of such reporting protocols. Therefore, use of digital image analysis tools may help to both standardize reporting and improve workflow. In this study, digital image analysis was utilized to quantify Ki67 indices in 280 breast biopsy and resection specimens during routine clinical practice. The supervised Ki67 indices were then assessed for agreement with a manual count of 500 tumor cells. Agreement was excellent, with an intraclass correlation coefficient of 0.96 for the pathologist-supervised analysis. This study illustrates an example of a rapid, accurate workflow for implementation of digital image analysis in Ki67 scoring in breast cancer., Competing Interests: R.B. reports receiving a consulting fee from Agilent technologies Inc. and ImmunoGen. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Our aim was to explore the performance of TRPS1 as an immunohistochemical diagnostic marker; find the optimal conditions for its use in breast carcinomas, especially triple-negative breast cancers (TNBCs); and compare its results in carcinomas of a select few organ sites, with an emphasis on gynecologic tumors., Methods: Tissue microarrays from breast carcinomas (n = 197), endometrial adenocarcinomas (n = 69), ovarian tumors (n = 250), vulvar squamous cell carcinomas (n = 97), pancreatic ductal adenocarcinomas (n = 20), and gastric adenocarcinomas (n = 12) were stained with TRPS1 using 2 different conditions (protocol 1: high pH; protocol 2: low pH). Breast carcinomas consisted of hormone receptor (HR)-positive/ERBB2 (formerly HER2 or HER2/neu)-negative (n = 53) samples, HR-positive/ERBB2-positive (n = 6) samples, and TNBCs (n = 138)., Results: Comparing TRPS1 results in breast carcinomas vs tumors from other organ sites, the sensitivity of TRPS1 was 91% and 87%, respectively, while the specificity was 66% and 74% for protocol 1 and 2, respectively. For TNBCs vs gynecologic tumors, the sensitivity of TRPS1 was 89% and 85%, respectively, while the specificity was 65% and 73%, respectively., Conclusions: TRPS1 stains approximately 90% of breast carcinomas but also up to 71% of endometrial carcinomas, albeit with a weaker median expression. Our data show that although TRPS1 is a highly sensitive marker for TNBCs, it is not as highly specific as previously reported., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: In the past 2 decades, cervical cancer screening guidelines in the United States have undergone numerous revisions with recent greater emphasis on primary high-risk human papillomavirus (hrHPV) testing., Materials and Methods: We examine the trends of Papanicolaou test and hrHPV testing at our large academic center across 4 years (2006, 2011, 2016, and 2021) over a 15-year period. The number of ThinPrep Papanicolaou and hrHPV tests, as well as the triggers for HPV testing, were retrospectively analyzed., Results: A total of 308,355 Papanicolaou tests and 117,477 hrHPV tests were reported across the 4 years. The number of Papanicolaou tests performed decreased nearly 3-fold over the study period, with only 43,230 Papanicolaou tests performed in 2021. The HPV test to Papanicolaou test ratio increased: 17% of Papanicolaou tests had an associated HPV test in 2006, whereas 72% of Papanicolaou tests ordered in 2021 had a companion hrHPV. The use of co-testing also increased. Overall, 73% were co-tests and 27% were reflexively ordered in the 4 one-year time periods. Co-tests constituted only 46% of HPV tests in 2006, but this increased to 93% in 2021. The percentage of positive hrHPV results decreased; in 2006, 18.3% of cases were positive, dropping to 8.6% in 2021 due to the marked increase in co-testing. Stratifying by diagnostic category, hrHPV results have remained relatively constant., Conclusion: With the numerous recent revisions of cervical screening guidelines, screening strategies at our institution reflected these changes in clinical practice. Papanicolaou and HPV co-testing became the most common screening method for women 30 to 65 years of age in our cohort., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Objectives: SOX10 expression helps identify melanocytic lesions. Over time, novel uses have been identified, such as expression in triple-negative breast cancer (TNBC). We evaluated the usefulness of SOX10 in breast pathology-specifically, identification and subtyping of TNBC and distinction from gynecologic carcinomas, use as a myoepithelial marker, and in the distinction of usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH)., Methods: Several breast and gynecologic carcinoma tissue microarrays containing a total of 492 cases were stained with SOX10. Whole sections of 34 ADH, 50 UDH, and 29 ductal carcinoma in situ (DCIS) samples were also stained with SOX10., Results: SOX10 expression was identified in 67% of consecutive TNBC cases. Expression was mostly seen in nonapocrine, androgen receptor (AR)-negative TNBCs. All gynecologic carcinomas (n = 157) were negative. All UDH cases showed mosaic SOX10 expression, while all ADH cases lacked expression. All estrogen receptor (ER)-positive DCIS (n = 19) specimens were negative for SOX10, while 2 of 10 ER-negative DCIS specimens were positive for SOX10. The latter 2 cases showed SOX10-positive invasive carcinomas., Conclusions: SOX10 identifies nonluminal AR-type TNBC and is useful in distinguishing TNBC from gynecologic carcinomas. SOX10 can distinguish UDH from ADH. SOX10 is not useful in distinguishing ADH from DCIS., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Endometrial cancer is the most common gynecologic cancer in the United States; however, reports of endometrial cancer diagnosed in the setting of intrauterine gestation are rare., Case: We describe the case of a clinical stage IA grade 1 endometrioid endometrial adenocarcinoma diagnosed at the time of D&C performed for missed abortion in a gravida 1 para 0 female with no identifiable risk factors. Fertility-sparing treatment, with combined oral megestrol acetate and levonorgestrel intrauterine system, was used to manage this incidentally-diagnosed carcinoma with endometrial sampling every 3 months., Competing Interests: The authors have no personal or financial affiliations to disclose., (© 2019 The Author(s).)

Metastatic spread of a systemic neoplasm to a central nervous system malignancy is a rare but well-documented phenomenon. Over 100 case reports of tumor-to-tumor spread involving the central nervous system have been described since the first report in 1930. Overwhelmingly, intracranial meningioma represents the most common recipient tumor, while breast and lung are the first and second most common donor malignancies, respectively. The propensity for meningiomas to harbor metastatic lesions has been attributed to cell-to-cell adhesion molecules, favorable metabolic environment as well as hormonal and mechanical factors. We distinguish the concepts of true "tumor-to-tumor metastasis" and "tumor collision" and discuss potential non-invasive diagnostic modalities that may aid in preoperatively identifying intracranial lesions harboring distal metastasis. We present the first incidence, to our knowledge, of metastatic esophageal carcinoma spread to intracranial meningioma.
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Cardiac lipomatous hypertrophy is a rare benign condition that usually involves the interatrial septum. Due to its benign nature it rarely requires intervention. Its presence outside the interatrial septum is reported infrequently. We present a case of lipomatous hypertrophy in the intraventricular septum that was complicated by a severe, symptomatic, and disabling dynamic left ventricular outflow tract obstruction. The symptoms significantly improved following the excision of the mass. In our case transthoracic echocardiogram was used to visualize the mass and measure the severity of the obstruction; Cardiac Magnetic Resonance Imaging was used to characterize the mass and histopathology confirmed the diagnosis.