OBJECTIVE: Chromosome conformation-based karyotype analysis (C-MoKa) technology was used to test a couple who had experienced multiple adverse pregnancies in order to provide them with genetic counseling and reproductive guidance. METHODS: A couple presented at the Reproductive Medicine Center of the First Hospital of Lanzhou University in 2023 was selected as the study subject. Through C-MoKa testing, copy number variation sequencing (CNV-seq), and preimplantation genetic testing for aneuploidy (PGT-A), it was found that the couple's repeatedly miscarried fetuses and abnormal embryos exhibited highly similar chromosomal structural abnormalities. Using C-MoKa, the potential genetic abnormalities in both partners were traced, and reproductive guidance was provided based on the result. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-09). RESULTS: CNV-seq analysis of the couple's miscarriage fetal chorionic villi showed del(18)(q21.2q23)(28.90 Mb) and dup(13)(q31.2q34)(26.26 Mb). Chromosomal karyotyping analysis of both partners showed no abnormality. From 2024 to 2025, the couple underwent three rounds of PGT-A assisted reproduction. The first embryo test showed del(13)(q31.2q34)(26.77 Mb) and dup(18)(q21.2q23)(29.08 Mb). The second embryo test showed dup(13)(q31.2q34)(26.26 Mb) and del(18)(q21.2q23)(28.90 Mb). And the third embryo test results showed complex chromosomal abnormalities. In 2025, after genetic counseling, the couple had opted C-MoKa test, which has detected no abnormality in the wife, but a balanced 46,XY,t(13;18)(q31.2;q21.2) translocation in the husband. CONCLUSION As a high-throughput sequencing method based on the three-dimensional conformation of chromatin, C-MoKa has the advantages of high resolution and high accuracy, and can accurately detect balanced translocations with similar banding patterns. It has therefore offered a powerful new tool for chromosomal analysis.
Female ; Humans ; Male ; Pregnancy ; Abortion, Habitual/genetics* ; DNA Copy Number Variations ; Karyotyping/methods* ; Preimplantation Diagnosis ; Translocation, Genetic

OBJECTIVE: To investigate the genetic mechanism for adverse pregnancies due to submicroscopic chromosomal structural variants in two cases, and to provide a precise guidance for preimplantation genetic testing. METHODS: Two families who had visited Chengdu Women's and Children's Central Hospital for reproduction guidance due to recurrent miscarriages, adverse pregnancy history and abnormal genetic testing of the offspring in June and December 2023 were selected as the study subjects. Chromosomal karyotyping and optical genome mapping (OGM) were carried out on peripheral blood samples from the two couples, and preimplantation genetic testing for structural rearrangement (PGT-SR) were performed on the blastocyst trophoblasts. This study was approved by the Medical Ethics Committee of the Hospital (Ethic No.: 2023-23). RESULTS: No abnormality was found on the G-banded karyotyping analysis for both couples. The OGM results revealed that the female partner of couple 1 had a translocation between 4pter-p16.3 (3.99 Mb) and 11pter-p15.4 (2.66 Mb), whilst no abnormality was found in the male partner. Similarly, the male partner of couple 2 had a translocation between 19q13.43-qter (1.90 Mb) and 22q13.31-qter (3.34 Mb). No abnormality was found in the female partner of couple 2. Neither breakpoints nor the adjacent region had involved an OMIM gene, except the formation of a fusion gene ZIM2-AS1-Z82186.1 (Both genes are non-coding, and the fusion gene was deemed as variant of unknown significance). PGT-SR of 11 blastocysts derived from couple 1 revealed that one embryo was suitable for priority transfer, three embryos were suitable for transfer, one embryo was recommended for genetic counselling, and six embryos were unsuitable for the transfer. For couple 2, six blastocysts were tested, of which only one embryo was deemed suitable for transfer. CONCLUSION When genetic testing of offspring indicates copy number variations such as deletions, duplications or mosaicism, the high-resolution OGM technique can be selected to screen parents for submicroscopic chromosomal structural variations. The result can facilitate accurate assessment for the risk of recurrence in offspring, selection of suitable method for reproduction, and identifying targets for PGT.
Humans ; Female ; Pregnancy ; Adult ; Male ; Karyotyping ; Chromosome Aberrations ; Abortion, Habitual/genetics* ; Preimplantation Diagnosis ; Genetic Testing

OBJECTIVE: To explore the application value of artificial intelligence (AI)-assisted chromosomal karyotype analysis in the diagnosis of prenatal chromosomal mosaicism. METHODS: A retrospective analysis was conducted on 172 pregnant women who underwent amniocentesis at the Department of Medical Genetics and Prenatal Diagnosis, the Third Affiliated Hospital of Zhengzhou University between January 2019 and December 2024. All cases whose fetuses were diagnosed with chromosomal mosaicism via karyotype analysis and stratified into two groups based on the analytical software employed: the conventional analysis group (n = 70), which utilized Leica analysis software for karyotype image recognition and cell counting; and the AI-assisted analysis group (n = 102), which utilized AI-assisted software for the same procedures. The clinical performance of AI-assisted karyotype analysis in diagnosing chromosomal mosaicism was comprehensively evaluated by comparing the types of mosaic karyotypes, distribution of mosaic ratios, and verification outcomes of different detection modalities between the two groups. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-406-01). RESULTS: No statistically significant difference was observed in baseline characteristics (maternal age, gestational week, and indications for prenatal diagnosis) between the two groups. Regarding the detection efficacy for numerical and structural mosaicisms, no significant difference was found in the detection of numerical mosaicism. However, the conventional analysis group exhibited a significantly higher detection rate of autosomal structural mosaicism compared to the AI-assisted group (11.43% vs. 0.98%, P < 0.05). Numerical mosaicism cases were further verified using copy number variation sequencing (CNV-seq) and/or fluorescence in situ hybridization (FISH). The AI-assisted group demonstrated a significantly lower inconsistency rate (5.56% vs. 20.41%, P < 0.05) compared to the conventional group. For low-proportion (< 10%) chromosomal mosaicism, the AI-assisted group had a significantly lower detection rate (13.25% vs. 29.69%, P < 0.05). Subsequent validation of low-proportion mosaicism by CNV-seq and/or FISH showed a higher consistency rate in the AI-assisted group (81.82% vs. 54.55%), though the difference did not reach statistical significance (P = 0.360). CONCLUSION For the karyotyping analysis of prenatal chromosomal mosaicism, AI-assisted karyotype analysis shows high accuracy and consistency in identifying numerical chromosomal mosaicism, particularly in reducing the detection of low-proportion (< 10%) mosaicism while improving verification accuracy. AI-assisted analysis can significantly improve the detection accuracy of numerical mosaicism and mitigate the risk of misclassification for low-proportion (< 10%) mosaicism, thereby providing more precise clinical evidence for the prenatal diagnosis of chromosomal mosaicisms.
Humans ; Female ; Mosaicism ; Pregnancy ; Karyotyping/methods* ; Artificial Intelligence ; Prenatal Diagnosis/methods* ; Adult ; Retrospective Studies ; Chromosome Disorders/genetics* ; Amniocentesis

OBJECTIVE: To investigate the detection patterns, clinical phenotypic characteristics, and differences in diagnostic timeliness of Klinefelter syndrome (KS) across prenatal and postnatal stages, with an aim to provide a basis for optimizing strategies for early screening, diagnosis, and intervention. METHODS: A retrospective study was conducted to analyze data from two phases. The prenatal diagnosis group included 33,302 pregnant women who underwent amniocytic karyotyping due to advanced maternal age, abnormal ultrasound findings, or high-risk non-invasive prenatal testing (NIPT). The postnatal diagnosis group included 52,101 patients who underwent peripheral blood karyotyping due to primary infertility, abnormal external genitalia, or growth and developmental abnormalities. Additionally, medical histories of adult diagnosed patients were reviewed retrospectively to identify early occult symptoms. This study was approved by the Medical Ethics Committee of Chengdu Women's and Children's Central Hospital (Ethics No.: LCYJ-2025-030). RESULTS: In the prenatal group, 96 cases of KS were detected (detection rate 0.29%). The primary indications for referral were NIPT indicating sex chromosome abnormalities (45.83%), advanced maternal age (16.66%), and ultrasound abnormalities (17.70%). In the postnatal group, 128 cases of KS were detected (detection rate 0.25%). Clinical presentations were primarily primary infertility/azoospermia (77.34%), and the patients were predominantly adults (84.40%). Retrospective analysis revealed that adult patients presented with specific physical signs that had been overlooked during childhood. CONCLUSION As KS lacks typical early clinical manifestations, diagnosis is often delayed until adulthood when reproductive needs arise, showing a pattern of "passive detection" and resulting in missed opportunities for optimal intervention. By conducting a comparative analysis of prenatal diagnostic data and postnatal retrospective data, a risk association model linking prenatal screening indications with childhood-specific signs was developed. This study has provided empirical evidence for establishing a multidisciplinary, full life-cycle management system of "screening ~ diagnosis ~ monitoring ~ intervention" helping to shift from "passive detection in adulthood" to "proactive management across the entire life course," and laid a foundation for improving early diagnosis rate and long-term quality of life for patients.
Humans ; Klinefelter Syndrome/genetics* ; Female ; Adult ; Pregnancy ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Male ; Phenotype ; Karyotyping ; Young Adult ; Adolescent ; Middle Aged

Abstract An 18-year-old female with Systemic Lupus Erythematosus (SLE) presented with bilateral thigh pain, fever, and diarrhea three days before admission. Diagnosed with SLE one month earlier, she reported prior symptoms, including joint pain, malar rash, hair loss, and hyperpigmented lesions. Initial investigations revealed elevated transaminase levels (AST 355, ALT 132), positive ANA, decreased complement levels (C3 68, C4 16.8), and raised creatine kinase (619). A muscle biopsy confirmed myositis. The patient was treated with immunosuppressant (a combination of steroids and hydroxychloroquine) and supportive therapy. By the eighth day of hospitalization, her symptoms, especially thigh pain, resolved. Electromyocardiography was done, and the results were normal, indicating therapeutic success. This case highlights the importance of prompt diagnosis and management of myositis as a rare SLE manifestation to achieve favorable outcomes.
Systemic Lupus Erythematosus (SLE) ; Myositis ; Muscle Biopsy ; Electromyocardiography

Background: Frozen section biopsy (FSB) is a critical intraoperative diagnostic procedure that supports real-time surgical decision-making. Its accuracy and clinical value depend not only on technical laboratory processes but also on physicians’ knowledge, attitudes, practices, and adherence to institutional clinical guidelines. In tertiary hospitals with high surgical volume, variations in guideline compliance may affect diagnostic reliability and patient safety. Objective: This study examined the knowledge, attitudes, and practices of medical doctors regarding FSB and assessed their adherence to institutional clinical guidelines and standards. Methodology: A descriptive-correlational research design was conducted among 105 surgical residents and fellows at a tertiary hospital in the Philippines. Data were collected using a validated, researcher-developed questionnaire that measured knowledge, attitudes, practices, and adherence to FSB clinical guidelines. Descriptive statistics were used to summarize levels of knowledge, attitude, practice, and adherence. Correlation analysis was performed to determine the relationships among these variables. Results: The respondents demonstrated a generally knowledgeable level of FSB knowledge (mean = 2.51), a neutral attitude toward FSB implementation (mean = 3.17), and a high level of procedural practice compliance (mean = 4.03). Adherence to institutional clinical guidelines was rated as sometimes observed across key domains, particularly in referral processes and endorsement protocols. Significant associations were identified between components of knowledge, attitudes, and practices and adherence to FSB standards. Conclusion While medical doctors showed adequate procedural practice and foundational knowledge of FSB, inconsistencies in adherence to institutional clinical guidelines remain. Strengthening policy dissemination, clarifying professional roles in FSB decision-making, and reinforcing interdisciplinary communication are necessary to enhance compliance, improve diagnostic reliability, and promote patient safety.
Frozen Sections ; Biopsy

Introduction: Metaplastic thymoma is an exceptionally rare thymic epithelial neoplasm, with fewer than 40 cases reported in the literature. It is defined by a distinctive biphasic proliferation of epithelioid epithelial nests and bland spindle cell fascicles, accompanied by a characteristic immunohistochemical profile. In limited cytology specimens, the lack of architectural context and potentially incomplete sampling can obscure the biphasic nature, leading to diagnostic difficulty. We describe a case initially interpreted as an epithelioid neoplasm on fine needle aspiration (FNA), with subsequent resection confirming metaplastic thymoma. Case Description: A 66-year-old male presented with an anterior mediastinal mass. FNA revealed a highly cellular specimen composed predominantly of polygonal tumor cells arranged in cohesive sheets. The cells displayed round to ovoid, hyperchromatic nuclei with moderate to marked pleomorphism, irregular nuclear membranes, conspicuous nucleoli, and abundant eosinophilic cytoplasm. Dystrophic calcifications were noted within a hemorrhagic background. An epithelioid tumor was favored on cytologic evaluation. The patient subsequently underwent video-assisted thoracoscopic surgery with excision of the mass. The specimen was well-encapsulated, lobulated, and traversed by fibrous septations. Microscopically, the tumor demonstrated a biphasic architecture: cohesive nests of epithelioid cells closely admixed with intersecting fascicles of bland spindle cells. Immature T-lymphocytes were not identified. Immunohistochemical staining showed diffuse cytokeratin and p40 positivity in the epithelioid component. In contrast, the spindle cell component lacked cytokeratin expression but exhibited strong vimentin positivity and patchy EMA reactivity. Both components were negative for CD5 and CD117. The Ki-67 proliferation index was low (1–2%). Discussion: Diagnosing metaplastic thymoma on cytology is challenging due to the tumor’s inherently biphasic architecture, which may not be adequately represented in limited FNA samples. In this case, the cytologic material disproportionately sampled the epithelioid component, masking the spindle cell element critical for diagnosis. Additionally, the lymphocyte-poor background mimicked type A or AB thymoma, further contributing to potential misclassification. Accurate diagnosis relies on careful integration of cytologic features with histologic, immunohistochemical, radiologic, and clinical data. Recognition of this rare entity is important, as its behavior differs substantially from other anterior mediastinal tumors, including thymic carcinoma and more aggressive thymoma subtypes. Conclusion Metaplastic thymoma can present as a purely epithelioid lesion on limited biopsy material, obscuring its hallmark biphasic nature. Awareness of this rare thymic neoplasm and correlation with resection findings are essential to avoid misdiagnosis. When accurately identified and completely excised, metaplastic thymoma carries an excellent prognosis.
Biopsy, Fine-Needle ; Thymoma

Cerebrovascular disease is uncommon in patients with HIV, occurring in up to 1.9% of patients, 0.2% were presenting with transient ischemic attacks. The central nervous system is the first part of the body to be affected by the human immunodeficiency virus. This case report is a unique presentation of a 33-year-old male who presented with focal neurologic deficits that lasted for one hour with a background of promiscuous history. The patient was positive for HIV screening test and CD4 count and was started on a combination of antiretroviral therapy. This is the first documented case report in the Philippines. This case report demonstrates the need for a high index of suspicion for early detection of the cause in HIV-positive patients with recurrent transient ischemic attacks, given the high morbidity and mortality that is associated with this condition if delayed or undiagnosed.

BACKGROUND

Thyroid fine-needle aspiration biopsy (FNAB) is widely used for thyroid nodule characterization, with approximately 2.7% of samples classified as "inadequate." Non-diagnostic samples pose limitations, resulting in repeated procedures, and unnecessary diagnostic thyroidectomies. Conventional smear (CS) is commonly the method of choice for cytologic preparation of thyroid FNAB. The cell block technique is an alternative that concentrates cells providing additional material for better evaluation and ancillary testing. While conventional smears are commonly used, introducing routine complementary cell blocks could potentially lower costs associated with repeat procedures and improve patient management.

The study aimed to investigate the diagnostic value of incorporating the cell block technique as adjunct to conventional smear technique in reducing nondiagnostic rates (Bethesda Category I) in thyroid-fine needle aspiration biopsies (FNAB) conducted in 2 private hospitals.

This is a multi-center, retrospective cross-sectional study with 701 samples from 528 adult patients, who underwent thyroid FNAB between January 2020 - September 2022. The primary outcome of interest is the reduction in non-diagnostic rates with the combined use of conventional smears and cell block.

The non-diagnostic rates were significantly higher with cell block technique (28.10%) as compared to conventional smears (16.26%), p-value < .01. The results show that conventional smears have lower non-diagnostic rates. With smear cytology alone, 114 (16.3%) of all samples were nondiagnostic. With the addition of cell block technique, 15 of these samples were reclassified as benign (n = 13), Bethesda III (n = 1) or Bethesda IV (n = 1). The rest of the non-diagnostic samples (n = 99) remained Bethesda I. Overall, the equivalent decrease in non-diagnostic rate was 2.1%.

The combined use of cell block and conventional smears did not significantly decrease nondiagnostic rates in thyroid FNAB. In general, conventional smears demonstrated superior diagnostic efficacy across all Bethesda categories, establishing it as the preferred sampling preparation method for thyroid FNAB. Cell blocks should be considered a supplementary technique, particularly in cases where ancillary methods like immunohistochemistry or molecular testing are needed.

OBJECTIVE

The aim of this study was to determine the upgrade rate in diagnosis of biopsy-proven papillary breast lesions on core needle biopsy and their respective surgical excisions, and to assess for predictive factors associated with an upgrade at St. Luke’s Medical Center – Global City.

A retrospective review of our institution’s database identified 184 papillary breast lesions diagnosed by core needle biopsy. The study population consisted of 71 samples that met the inclusion criteria. The overall upgrade and concordance rates were determined and analyzed if there was any significant association with clinical demographics, radiologic findings, and core diameter on gross examination. Continuous variables were presented as mean and median, and Shapiro-Wilk test was used to assess normality of data. Categorical variables were expressed as frequencies and percentages. Simple logistic regression analysis with Firth’s bias correction was performed to determine the variables associated with a diagnostic upgrade. P values ≤0.05 were considered statistically significant.

A total 71 patients, all female, were included in the study. The overall upgrade rate was 8.45% (95% CI: 3.16-17.49%) in comparison with the diagnosis of the initial CNB and SE alone. This translated to 6/71 samples in this study. The overall concordance was 91.55% based on clinical significance, and an individual diagnosis concordance rate of 78.87%. None of the predictive factors (i.e., age, history of breast cancer, BI-RADS score, and gross core diameter) assessed showed an association with a diagnostic upgrade.

The computed overall upgrade rate is within range of currently published literature. The concordance rates for both clinical significance and individual diagnosis were quite high, suggesting good reproducibility of histopathologic diagnosis within our institution. This was also found to be consistent with other studies. Of the predictive factors, none showed an association to a diagnostic upgrade. Despite the latter, our findings may be of value within the medical center in further exploring and expanding the data set at hand, such that it may hopefully contribute to local guidelines in managing PBLs in the future.