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1.
Hum Pathol ; 2024 Jun 21.
Article En | MEDLINE | ID: mdl-38909709

OBJECTIVES: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. METHODS: Patients with pSCC (n=121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P=.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1). CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.

2.
J Cutan Pathol ; 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38837468

An 11-year-old female was referred from an outside institution after a diagnostic biopsy and subsequent excision of a progressively enlarging reddish-brown nodule demonstrated features concerning for a balloon cell nevus with severe atypia versus a high-grade melanocytoma. Upon review of the initial biopsy specimen and molecular data, we favored the diagnosis to be consistent with a high-grade melanocytoma with balloon cell changes while considering the possibility of balloon cell melanoma due to concerning histopathologic and genetic abnormalities. In this case study, we discuss critical diagnostic considerations in this rare pediatric case and highlight important pathologic and clinical features of melanocytomas and balloon cell melanoma.

3.
Plant Cell Environ ; 2024 Jun 19.
Article En | MEDLINE | ID: mdl-38894696

Verticillium wilt, caused by the soilborne fungus Verticillium dahliae, poses a serious threat to the health of more than 200 plant species worldwide. Although plant rhizosphere-associated microbiota can influence plant resistance to V. dahliae, empirical evidence underlying Verticillium wilt resistance of perennial trees is scarce. In this study, we systemically investigated the effect of the soil microbiota on the resistance of smoke trees (Cotinus coggygria) to Verticillium wilt using field, greenhouse and laboratory experiments. Comparative analysis of the soil microbiota in the two stands of smoke trees suggested that Bacillus represented the most abundant and key microbial genus related to potential disease suppression. Smoke tree seedlings were inoculated with isolated Bacillus strains, which exhibited disease suppressiveness and plant growth-promoting properties. Furthermore, repletion of Bacillus agents to disease conducive soil significantly resulted in reduced incidence of smoke tree wilt and increased resistance of the soil microbiota to V. dahliae. Finally, we explored a more effective combination of Bacillus agents with the fungicide propiconazole to combat Verticillium wilt. The results establish a foundation for the development of an effective control for this disease. Overall, this work provides a direct link between Bacillus enrichment and disease resistance of smoke trees, facilitating the development of green control strategies and measurements of soil-borne diseases.

4.
Comput Biol Med ; 178: 108709, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38878398

With the significant advancements of Large Language Models (LLMs) in the field of Natural Language Processing (NLP), the development of image-text multimodal models has garnered widespread attention. Current surveys on image-text multimodal models mainly focus on representative models or application domains, but lack a review on how general technical models influence the development of domain-specific models, which is crucial for domain researchers. Based on this, this paper first reviews the technological evolution of image-text multimodal models, from early explorations of feature space to visual language encoding structures, and then to the latest large model architectures. Next, from the perspective of technological evolution, we explain how the development of general image-text multimodal technologies promotes the progress of multimodal technologies in the biomedical field, as well as the importance and complexity of specific datasets in the biomedical domain. Then, centered on the tasks of image-text multimodal models, we analyze their common components and challenges. After that, we summarize the architecture, components, and data of general image-text multimodal models, and introduce the applications and improvements of image-text multimodal models in the biomedical field. Finally, we categorize the challenges faced in the development and application of general models into external factors and intrinsic factors, further refining them into 2 external factors and 5 intrinsic factors, and propose targeted solutions, providing guidance for future research directions. For more details and data, please visit our GitHub page: https://github.com/i2vec/A-survey-on-image-text-multimodal-models.

5.
Article En | MEDLINE | ID: mdl-38881402

Sinonasal mucosal melanoma (SNMM) is a rare malignancy with poor prognosis and high recurrence rate. In those with recurrence, survival is dismal. Immunotherapy is an emerging area of investigation; however, there is a scarcity of data on immunotherapy outcomes in SNMM patients with recurrence. We report outcomes of immunotherapy in recurrent SNMM patients with distant versus nondistant recurrence. Fifty-four patients with recurrent SNMM were identified, and 31 (57.4%) had distant recurrence. One-year overall survival (OS) following recurrence was 47.5% (95% confidence interval [CI]: 34.0%-60.9%), with a median survival of 2.8 years (95% CI: 2.0-5.3). In those with distant recurrence, receipt of immunotherapy was associated with better OS compared to those without immunotherapy (hazard ratio [HR] = 0.29 [95% CI: 0.12-0.68], P = .004). While patients with nondistant recurrence (n = 23), who received immunotherapy (n = 6) had worse OS compared to those who did not receive immunotherapy (HR = 4.76 [95% CI: 1.36, 15.89], P = .02). LEVEL OF EVIDENCE: Level IV.

6.
Hellenic J Cardiol ; 2024 Jun 11.
Article En | MEDLINE | ID: mdl-38871180

BACKGROUND: A couple of cardiac magnetic resonance (CMR) attributes strongly predict adverse remodeling after ST-segment-elevation myocardial infarction, but the value of incorporating high-risk CMR attributes, particularly in patients with non-reduced ejection fraction, remains undetermined. This study sought to evaluate the independent and incremental predictive value of a multiparametric CMR approach for adverse remodeling after STEMI across left ventricular ejection fraction (LVEF) categories. METHODS: A total of 157 STEMI patients undergoing primary percutaneous coronary intervention were prospectively enrolled. Adverse remodeling was defined as ≥20% enlargement in left ventricular end-diastolic volume from index admission to 3 months follow-up. RESULTS: Adverse remodeling occurred in 23.6% of patients. After adjustment for clinical risk factors, a stroke volume index <29.6 mL/m2, a global longitudinal strain >-7.5%, an infarct size >39.2%, a microvascular obstruction >4.9%, and a myocardial salvage index <36.4 were independently associated with adverse remodeling. The incidence of adverse remodeling increased with the increasing number of high-risk CMR attributes, regardless of LVEF (LVEF ≤40%: P=0.026; 40%

7.
Hum Pathol ; 150: 1-8, 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38876201

Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored YAP1::NUTM1 fusion gene by RNA sequencing. MAML2 fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.

9.
Hum Pathol ; 148: 81-86, 2024 Jun.
Article En | MEDLINE | ID: mdl-38782101

The staging for pT2/pT3 penile squamous cell carcinoma (pSCC) has undergone major changes. Some authors proposed criteria wherein the distinction between pT2/pT3 was made using the same histopathological variables that are currently utilized to differentiate pT1a/pT1b. In this single-institution, North American study, we focused on (HPV-negative) pT2/3 pSCCs (i.e., tumors invading corpus spongiosum/corpus cavernosum), and compared the prognostic ability of the following systems: (i) AJCC (8th edition) criteria; (ii) modified staging criteria proposed by Sali et al. (Am J Surg Pathol. 2020; 44:1112-7). In the proposed system, pT2 tumors were defined as those devoid of lymphovascular invasion (LVI) or perineural invasion (PNI), and were not poorly differentiated; whereas pT3 showed one or more of the following: LVI, PNI, and/or grade 3. 48 pT2/pT3 cases were included (AJCC, pT2: 27 and pT3: 21; Proposed, pT2: 22 and pT3: 26). The disease-free survival (DFS) and progression-free survival (PFS) did not differ between pT2 and pT3, following the current AJCC definitions (p = 0.19 and p = 0.10, respectively). When the pT2/3 stages were reconstructed using the modified criteria, however, a statistically significant difference was present in both DFS and PFS between pT2 and pT3 (p = 0.004 and p = 0.003, respectively). The proposed staging system has the potential to improve the prognostication of pT2/pT3 tumors in pSCC. Each of these histopathologic variables has been shown to have a significant association with outcomes in pSCC, which is an advantage. Further studies are needed to demonstrate the utility of this modified staging system in patient populations from other geographic regions.


Carcinoma, Squamous Cell , Neoplasm Staging , Penile Neoplasms , Humans , Penile Neoplasms/pathology , Penile Neoplasms/virology , Male , Neoplasm Staging/methods , Neoplasm Staging/standards , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Middle Aged , Aged , Adult , Prognosis , North America , Aged, 80 and over
11.
iScience ; 27(4): 109513, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38600975

Early detection of left ventricular remodeling (LVR) is crucial. While cardiac magnetic resonance (CMR) provides valuable information, it has limitations. Coronary angiography-derived fractional flow reserve (caFFR) and index of microcirculatory resistance (caIMR) offer viable alternatives. 157 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention were prospectively included. 23.6% of patients showed LVR. Machine learning algorithms constructed three LVR prediction models: Model 1 incorporated clinical and procedural parameters, Model 2 added CMR parameters, and Model 3 included echocardiographic and functional parameters (caFFR and caIMR) with Model 1. The random forest algorithm showed robust performance, achieving AUC of 0.77, 0.84, and 0.85 for Models 1, 2, and 3. SHAP analysis identified top features in Model 2 (infarct size, microvascular obstruction, admission hemoglobin) and Model 3 (current smoking, caFFR, admission hemoglobin). Findings indicate coronary physiology and echocardiographic parameters effectively predict LVR in patients with STEMI, suggesting their potential to replace CMR.

12.
Front Public Health ; 12: 1333077, 2024.
Article En | MEDLINE | ID: mdl-38584928

Background: Most existing studies have only investigated the direct effects of the built environment on respiratory diseases. However, there is mounting evidence that the built environment of cities has an indirect influence on public health via influencing air pollution. Exploring the "urban built environment-air pollution-respiratory diseases" cascade mechanism is important for creating a healthy respiratory environment, which is the aim of this study. Methods: The study gathered clinical data from 2015 to 2017 on patients with respiratory diseases from Tongji Hospital in Wuhan. Additionally, daily air pollution levels (sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter (PM2.5, PM10), and ozone (O3)), meteorological data (average temperature and relative humidity), and data on urban built environment were gathered. We used Spearman correlation to investigate the connection between air pollution and meteorological variables; distributed lag non-linear model (DLNM) was used to investigate the short-term relationships between respiratory diseases, air pollutants, and meteorological factors; the impacts of spatial heterogeneity in the built environment on air pollution were examined using the multiscale geographically weighted regression model (MGWR). Results: During the study period, the mean level of respiratory diseases (average age 54) was 15.97 persons per day, of which 9.519 for males (average age 57) and 6.451 for females (average age 48); the 24 h mean levels of PM10, PM2.5, NO2, SO2 and O3 were 78.056 µg/m3, 71.962 µg/m3, 54.468 µg/m3, 12.898 µg/m3, and 46.904 µg/m3, respectively; highest association was investigated between PM10 and SO2 (r = 0.762, p < 0.01), followed by NO2 and PM2.5 (r = 0.73, p < 0.01), and PM10 and PM2.5 (r = 0.704, p < 0.01). We observed a significant lag effect of NO2 on respiratory diseases, for lag 0 day and lag 1 day, a 10 µg/m3 increase in NO2 concentration corresponded to 1.009% (95% CI: 1.001, 1.017%) and 1.005% (95% CI: 1.001, 1.011%) increase of respiratory diseases. The spatial distribution of NO2 was significantly influenced by high-density urban development (population density, building density, number of shopping service facilities, and construction land, the bandwidth of these four factors are 43), while green space and parks can effectively reduce air pollution (R2 = 0.649). Conclusion: Previous studies have focused on the effects of air pollution on respiratory diseases and the effects of built environment on air pollution, while this study combines these three aspects and explores the relationship between them. Furthermore, the theory of the "built environment-air pollution-respiratory diseases" cascading mechanism is practically investigated and broken down into specific experimental steps, which has not been found in previous studies. Additionally, we observed a lag effect of NO2 on respiratory diseases and spatial heterogeneity of built environment in the distribution of NO2.


Air Pollution , Respiratory Tract Diseases , Male , Female , Humans , Middle Aged , Cities , Nitrogen Dioxide/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Respiratory Tract Diseases/epidemiology , Respiratory Tract Diseases/etiology , Particulate Matter/analysis
13.
J Cutan Pathol ; 51(7): 538-548, 2024 Jul.
Article En | MEDLINE | ID: mdl-38556256

BACKGROUND: While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histopathology that are difficult to classify based on morphology. AIMS: Our goal was to investigate the benefits of next-generation sequencing in diagnosing complex cutaneous neoplasms. MATERIALS & METHODS: Departmental archives were searched for fusion-driven cutaneous neoplasms. Slides were retrieved and clinical information including follow-up was obtained. RESULTS: Fifteen cases occurred in eight female and seven male patients, with a median age of 26 years (range: 1-83) at diagnosis. Tumors involved the extremities (9), scalp (5), and head and neck (1). Predominant features included myoepithelial (5), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (3), and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (4) with LIFR (2), TRPS1 (1) and CHCHD7. Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 (2), and a novel fusion: ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), soft tissue myoepithelioma (4), cutaneous syncytial myoepithelioma (1), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (2), clear cell sarcoma (2), and angiomatoid fibrous histiocytoma (1). DISCUSSION AND CONCLUSION: Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.


Skin Neoplasms , Humans , Female , Male , Adult , Skin Neoplasms/pathology , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Middle Aged , Aged , Child , Adolescent , Aged, 80 and over , Child, Preschool , Infant , Oncogene Proteins, Fusion/genetics , High-Throughput Nucleotide Sequencing/methods , Transcription Factors/genetics , Neoplasms, Adnexal and Skin Appendage/pathology , Neoplasms, Adnexal and Skin Appendage/genetics , Neoplasms, Adnexal and Skin Appendage/diagnosis , Young Adult , Gene Rearrangement
14.
Am J Dermatopathol ; 46(4): 212-217, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38354373

BACKGROUND: Cutaneous malignant mixed tumor (MMT) is a rare sweat gland-derived tumor characterized by admixed malignant epithelial cells and chondromyxoid stroma. Approximately 50 cases have been described in the literature. Metastasis, which may occur in more than one-third of cases, is most common in the lung. METHODS: We summarized the clinicopathologic features of a patient with cutaneous MMT metastatic to the lungs. A literature review of similar cases was completed using Web of Science, Scopus, and PubMed databases. RESULTS: A woman in her 70s presented with an enlarging mass on her left eyebrow; histopathologic examination showed large islands of atypical cells with increased mitotic activity, admixed with necrosis on a background of fibrotic and chondromyxoid stroma. Multiple lung nodules were identified during follow-up. Examination of a pulmonary core needle biopsy specimen was consistent with metastatic cutaneous MMT. Literature review identified 10 cases published between 1980 and 2017. Most primary tumors were large (≥4 cm). Local recurrence was uncommon, and the lung was the only metastatic site in 5 cases. Histopathologically, metastatic tumors were described as more cellular, with diminished stromal tissue compared with the primary lesion. CONCLUSION: This is 1 of the 11 reports of cutaneous MMT with metastasis to the lungs found in the English-language literature published after 1980. Of note, most reports were published before 1990, making this case study one of the few contemporary descriptions of cutaneous MMT with pulmonary metastases. We think that the present case report will increase the awareness of this rare tumor.


Lung Neoplasms , Mixed Tumor, Malignant , Neoplasms, Connective Tissue , Skin Neoplasms , Sweat Gland Neoplasms , Female , Humans , Lung Neoplasms/secondary , Skin Neoplasms/pathology , Sweat Gland Neoplasms/pathology , Aged
15.
Pathol Res Pract ; 253: 155058, 2024 Jan.
Article En | MEDLINE | ID: mdl-38181578

Primary melanoma of the nipple (PMN) is exceedingly rare, with only single cases reported to date. We identified 10 patients with PMN: 5 females, 5 males, median age 55.5 years (range 29-66) at diagnosis of melanoma in situ (4 cases) or invasive melanoma (6 cases, Breslow depth 0.2 mm to 3.5 mm). Follow-up was available for all 10 patients (median 19 months, range 1-183). Nine patients had no evidence of disease; one patient died of disease (13.5 months) after presenting with a nodal metastasis. One case was exceptional, because the patient presented with a pigmented lesion that histopathologically exhibited co-existence of melanoma in situ and Paget disease, a challenging differential diagnosis due to immunohistochemical pitfalls in distinction between melanoma in situ and the pigmented variant of mammary Paget disease. Here we report the second largest series of PMN including a case of PMN colliding with mammary Paget disease, to raise awareness of these rare malignancies.


Adenocarcinoma , Breast Neoplasms , Melanoma , Paget's Disease, Mammary , Skin Neoplasms , Male , Female , Humans , Adult , Middle Aged , Aged , Melanoma/complications , Melanoma/diagnosis , Melanoma/pathology , Paget's Disease, Mammary/diagnosis , Nipples/pathology , Skin Neoplasms/pathology , Adenocarcinoma/pathology , Breast Neoplasms/complications , Breast Neoplasms/pathology
16.
J Magn Reson Imaging ; 59(2): 548-560, 2024 Feb.
Article En | MEDLINE | ID: mdl-37222658

BACKGROUND: It is uncertain how various degree of glycemic status affect left ventricular (LV) myocardial strain in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). PURPOSE: To investigate the relationship of glycemic status and myocardial strain in STEMI patients. STUDY TYPE: Prospective cohort study. POPULATION: 282 STEMI patients with cardiac magnetic resonance imaging 5 ± 2 days post-PPCI. Patients were divided into three groups based on the level of glycated hemoglobin A1c (HbA1c) (group 1: HbA1c < 5.7%; group 2: 5.7% ≤ HbA1c < 6.5%; group 3: HbA1c ≥ 6.5%). FIELD STRENGTH/SEQUENCE: 3.0-T; late gadolinium enhancement, balanced steady-state free precession cine sequence, black blood fat-suppressed T2-weighted. ASSESSMENT: LV function, myocardial strain, and infarct characteristics (infarct size, microvascular obstruction, and intramyocardial hemorrhage) were compared among the three groups by one-way analysis of variance (ANOVA) or Wilcoxon rank sum test. Intraobserver and interobserver reproducibility of LV myocardial strain was evaluated. STATISTICAL TESTS: ANOVA or Wilcoxon rank sum test, Pearson chi-square or Fisher's exact test, Spearman's correlation analyses and multivariable linear regression analysis. A two-tailed P value <0.05 was considered statistically significant. RESULTS: Infarct characteristics were similar among the three groups (P = 0.934, P = 0.097, P = 0.533, respectively). Patients with HbA1c ≥ 6.5% had decreased LV myocardial strain compared with HbA1c 5.7%-6.4%, as evidenced by global radial (GRS), global circumferential (GCS), and global longitudinal (GLS) strain. However, no significant differences in myocardial strain were observed between patients with HbA1c 5.7%-6.4% and HbA1c < 5.7% (P = 0.716; P = 0.294; P = 0.883, respectively). After adjustment for confounders, HbA1c as a continuous variable (beta coefficient [ß] = -0.676; ß = 0.172; ß = 0.205, respectively) and HbA1c ≥ 6.5% (ß = -3.682; ß = 0.552; ß = 0.681, respectively) were both independently associated with decreased GRS, GCS, and GLS. DATA CONCLUSION: Patients with uncontrolled blood glucose (categorized in group HbA1c ≥ 6.5%) had worse myocardial strain. The level of HbA1c appeared to be independently associated with decreased myocardial strain in STEMI patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.


Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnostic imaging , Contrast Media , Treatment Outcome , Prospective Studies , Reproducibility of Results , Glycated Hemoglobin , Magnetic Resonance Imaging, Cine , Gadolinium , Magnetic Resonance Imaging , Ventricular Function, Left , Stroke Volume
18.
Hum Pathol ; 142: 42-50, 2023 Dec.
Article En | MEDLINE | ID: mdl-37977513

OBJECTIVES: There is an unmet need for therapeutically relevant biomarkers for advanced penile squamous cell carcinoma (pSCC). Proposed immunohistochemistry (IHC)-based biomarkers include programmed death-ligand 1 (PD-L1), trophoblast cell-surface antigen 2 (TROP2), and nectin-4; however, there is a paucity of data pertaining to these biomarkers. Herein, we investigated the expression of PD-L1, TROP2, and nectin-4 in a well-annotated cohort of pSCCs. METHODS: A single-institution pathology archive was queried for patients who had a partial or total penectomy for pSCC between January 2000 and December 2022. Whole-slide sections were stained with antibodies against PD-L1 (22C3), TROP2, and nectin-4. Expression in tumor cells was quantified using H-scores (0-300). Associations between IHC expression, human papilloma virus (HPV) status, clinicopathologic findings, and outcome parameters were evaluated. RESULTS: This study included 121 patients. For PD-L1, the median combined positive and H-scores were 1 and 0, respectively; 32.7 % of the cases had an H-score>0. Compared to PD-L1-negative tumors, PD-L1-positive tumors had higher pT stage and grade. The median TROP2 and nectin-4 H-scores were 230 and 140, respectively, with high TROP2 and nectin-4, defined by an H-score>200, noted in 80.7 % and 10.9 % of cases, respectively. High-risk HPV-positive cases had higher TROP2 and nectin-4 scores compared to HPV-negative cases. Patients with high TROP2 expression had significantly more disease progression, and patients with high nectin-4 expression had significantly fewer deaths due to disease. CONCLUSIONS: High expression of TROP2 and nectin-4 in pSCC support evaluation of these markers as therapeutic targets pending validation of our findings.


Carcinoma, Squamous Cell , Papillomavirus Infections , Penile Neoplasms , Male , Humans , B7-H1 Antigen/metabolism , Nectins , Papillomavirus Infections/complications , Carcinoma, Squamous Cell/metabolism , Biomarkers , Penile Neoplasms/surgery , Penile Neoplasms/pathology , Biomarkers, Tumor/metabolism
19.
Case Rep Pathol ; 2023: 9979532, 2023.
Article En | MEDLINE | ID: mdl-37942426

Introduction. Assessment of axillary lymph nodes in breast carcinoma is an important part of staging to guide appropriate clinical management. Lymph node inclusions of different types, including nevoid, squamous, and glandular, are rare but have been reported in multiple different anatomic locations including the axilla. These can result in diagnostic challenges and pose risks of misdiagnoses. Rarely, malignancies may arise intrinsic to otherwise incidental benign nodal inclusions. Case Presentation. We report a case of ductal carcinoma diagnosed within a squamous epithelial inclusion cyst within an axillary lymph node in a patient with pure ductal carcinoma in situ (DCIS) of the ipsilateral right breast. To our knowledge, this is the fifth report in the literature of breast carcinoma confirmed within an axillary inclusion in a patient with pure DCIS. Evaluation of the primary DCIS and lymph node inclusions, by routine and immunohistochemical stains, was performed for assessment. Discussion. The presence of lymph node inclusions can pose a challenge in assessment of benignity and malignancy, on frozen and permanent histologic sections. Pathologists should carefully evaluate lymph node inclusions to ensure that intrinsic malignancies are not missed within rare otherwise benign appearing incidental epithelial rests.

20.
Circ J ; 87(10): 1369-1379, 2023 09 25.
Article En | MEDLINE | ID: mdl-37612051

BACKGROUND: The effects of obstructive sleep apnea (OSA) on the prognosis of acute coronary syndrome (ACS) without revascularization remain unclear, so the aim of the present study was to elucidate the association of OSA with subsequent cardiovascular events in ACS patients with and without revascularization.Methods and Results: We prospectively recruited hospitalized ACS patients undergoing sleep monitoring between June 2015 and January 2020. OSA was defined as an apnea-hypopnea index ≥15 events/h. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Among 1,927 patients, 52.6% had OSA and 69.4% underwent revascularization. During a 2.9-year follow-up (1.5-3.6 years), the risk of MACCE was similar in patients with or without revascularization. OSA was an independent predictor of MACCE in the non-revascularization group (22.6% vs. 14.6%; hazard ratio (HR) 1.861; 95% confidence interval (CI) 1.239-2.796; P=0.003) but not in revascularization group (22.3% vs. 19.3%; HR 1.135; 95% CI 0.882-1.460; P=0.324). The incremental risk in the non-revascularization group was attributable to more hospitalizations for unstable angina (14.2% vs. 8.6%; HR 1.896; 95% CI 1.124-3.199; P=0.016). CONCLUSIONS: For patients with ACS, OSA was independently associated with higher risk of recurrent cardiovascular events among patients without revascularization but not among patients undergoing revascularization. The benefits of suitable OSA treatment for patients without revascularization need further investigation.


Acute Coronary Syndrome , Sleep Apnea, Obstructive , Humans , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/surgery , Prospective Studies , Sleep , Angina, Unstable/epidemiology , Risk Factors
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