OBJECTIVE: To analyze the functional impact of a rare heterozygous variant of SOS1 gene (c.283G>A, p.E95K) identified in a fetus with cervical cystic hygroma and to explore its association with the disease phenotype. METHODS: A pedigree analysis was carried out to evaluate the co-segregation of the variant with the disease phenotype. Bioinformatic tools were employed to assess the conservation, protein structure and stability. Functional validation was conducted on HEK293T cells using fluorescence quantitative reverse transcription-PCR and Western blotting to measure the expression of SOS1 and phosphorylation levels of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase. A literature review of previously reported disease-associated SOS1 variants was also carried out. This study has been approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Ethics No.: 201940). RESULTS: The variant was inherited from the husband of the woman with distinctive facial features and has co-segregated with the phenotype. Bioinformatics analysis indicated that the variant is located in a highly conserved region, and that p.E95K could disrupt key amino acid interactions and protein stability. Multiple bioinformatic predictions consistently suggested the pathogenicity of this variant. Functional assays demonstrated reduced SOS1 protein expression and decreased ERK phosphorylation. CONCLUSION This study has revealed the functional impact of the SOS1 c.283G>A (p.E95K) variant, suggesting that it may contribute to the developmental phenotypes through a haploinsufficiency mechanism.
Humans ; SOS1 Protein/chemistry* ; Female ; HEK293 Cells ; Male ; Pedigree ; Phenotype ; Adult

OBJECTIVE: To investigate the genetic etiology of a fetus diagnosed with Mandibulofacial dysostosis with microcephaly (MFDM). METHODS: A fetus that underwent prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, on May 19, 2025 was selected for analysis. Results of fetal ultrasound findings, chromosomal karyotyping, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) were collected. Sanger sequencing was performed for familial validation of the pathogenic variant. The Human Protein Atlas (HPA), STRING, and Simple ClinVar databases were queried to characterize the biological features of the candidate gene. Three-dimensional structures of the wild-type and variant proteins were modeled and analyzed, and the evolutionary conservation of the affected amino acid was assessed using UGENE. Prenatal phenotypes associated with EFTUD2 variants were summarized through a review of the literature. This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Ethics No.: 2025-KY-029-01). RESULTS: At 23⁺² weeks of gestation, ultrasound examination revealed bilateral microtia with low-set ears, mild micrognathia with a reduced mandibular-facial angle, a single umbilical artery, a slightly narrow aortic diameter, and trivial mitral regurgitation. Amniotic fluid karyotyping and CNV-seq showed no abnormalities. WES identified a de novo, previously unreported EFTUD2 variant, c.698dupA (p.V235Gfs*27), in the fetus. This frameshift variant is predicted to alter the structural integrity of the EFTUD2 protein. Literature review indicated that micrognathia and microtia or low-set ears are the most common sonographic features in fetuses with EFTUD2 variants, while secondary findings may include abnormal stomach bubble, cleft palate, single umbilical artery, gastrointestinal atresia, polyhydramnios, and reduced aortic diameter. CONCLUSION The EFTUD2: c.698dupA (p.V235Gfs*27) variant is likely the genetic cause underlying MFDM in this fetus.
Humans ; Mandibulofacial Dysostosis/diagnostic imaging* ; Microcephaly/diagnostic imaging* ; Female ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/chemistry* ; Peptide Elongation Factors/chemistry* ; Fetus ; DNA Copy Number Variations/genetics* ; Adult ; Ultrasonography, Prenatal

BACKGROUND

Early-stage endometrial cancer often presents with favorable survival rates, but high-risk factors, including TP53 mutations and high-grade serous pathology, can lead to recurrence and poor prognosis. The standard primary treatment for endometrial cancer is surgical staging, and lymph node metastases significantly impact adjuvant therapy decisions. The subgroup of p53-abnormal (p53abn) indicates the worst prognosis and potential benefits from adjuvant chemotherapy. Molecular classification, while recommended, faces practical challenges due to resource constraints.

OBJECTIVES

The study aimed to assess the incidence of p53 abnormal expression in clinical stage 1 endometrial cancer cases that underwent surgery at a government tertiary hospital, and assess its relationship with clinicopathologic factors and pelvic and paraaortic lymph node metastasis (LNM).

METHODS

A cross-sectional retrospective analysis was conducted on clinical early-stage endometrial cancer cases that underwent surgical primary treatment between January 2018 and December 2022. Patient records were reviewed to gather demographics, surgical information, and pathological evaluations. Preoperative clinical staging was determined through imaging, and surgical staging involved comprehensive lymphadenectomy. Immunohistochemistry studies for p53 were carried out on formalin-fixed paraffin-embedded tissue samples.

RESULTS

A total of 233 endometrial cancer cases were included. The mean age at diagnosis was 53.7 years. Common comorbidities included hypertension (47.2%) and dyslipidemia (20.6%). Most cases were endometrioid histology (82.8%) and low-grade tumors (85.8%). Tumor grade (p=0.010), myometrial invasion (p<0.001) and lymphovascular space invasion (p<0.001) significantly correlated with lymph node metastasis. However, tumor size and p53abn were not significantly associated with lymph node metastasis. p53abn overexpression was significantly associated with non-endometrioid histology at 33% and Grade 3 tumors at 23%. Preoperative grading demonstrated moderate reliability (0.51) with postoperative grading, with an agreement of 65.4%.

CONCLUSION

Tumor grade, myometrial invasion, and LVSI were all significantly associated with lymph node involvement. While p53 immunohistochemical stains show promise in predicting metastasis and has been associated with tumor aggressiveness, this should still be correlated with clinicopathological parameters to carry out a more accurate risk stratification of early-stage patients.

Therapeutics ; Survival Rate ; Risk Factors ; Recurrence ; Prognosis ; Pathology ; Endometrial Neoplasms ; Immunohistochemistry ; Tumor Suppressor Protein P53 ; Lymph Node Excision ; Risk Assessment

BACKGROUND AND OBJECTIVES

Orthodontic tooth movement is driven by bone remodeling influenced by systemic factors, including caffeine and ethanol. This study aimed to investigate the effects of caffeine and ethanol on the expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG), key bone remodeling biomarkers, during orthodontic tooth movement.

METHODS

A laboratory experimental study was conducted on 30 male Wistar rats divided into three groups: K1 (orthodontic force only), K2 (force + caffeine), and K3 (force + ethanol). Orthodontic force was applied using Ni-Ti coil springs. Caffeine and ethanol were administered orally daily. On days 7 and 14, maxillary tissues were collected and analyzed via immunohistochemistry for RANK and OPG expression. Data were analyzed using One-Way ANOVA and Independent Sample T-tests with significance at pRESULTS

Caffeine and ethanol administration increased RANK and OPG expression compared to controls; however, only the ethanol group showed a significant increase in RANK expression on day 14 (p = 0.044). OPG expression was significantly higher in treatment groups at both time points (pCONCLUSION

Caffeine and ethanol modulate bone remodeling marker expression during orthodontic force application, with ethanol significantly increasing RANK expression at later stages. Further studies are needed to clarify the clinical implications for orthodontic treatment.

Animals ; Tooth Movement Techniques ; Tooth Movement ; Osteoprotegerin ; Role ; Movement ; Ethanol ; Bone Remodeling ; Caffeine ; Immunohistochemistry

Abstract Embryonal rhabdomyosarcoma (ERMS) is a primitive and aggressive soft tissue tumor that arises from premature mesenchymal cells and accounts for less than 1% of prostate malignancies. We present the case of a 26-year-old Filipino male who initially sought consultation and work-up for acute urinary retention. Although his prostate-specific antigen (PSA) level was normal, a kidney-ureter-bladder (KUB) ultrasound revealed an incidental finding of an enlarged prostate gland. Subsequent imaging tests (MRI and CT) identified a large, partially exophytic mass on the prostate with intravesical extension. The patient underwent a biopsy via transurethral resection at another institution, which yielded findings of a poorly differentiated carcinoma, primarily suggesting prostatic adenocarcinoma with a Gleason score of 10 (5+5). A request for slide review was submitted to our institution, and subsequent immunohistochemistry (IHC) studies—highlighting the tumor's immunoreactivity to myogenin and desmin—confirmed the diagnosis of ERMS. In this report, we discuss the clinical features, pathogenesis, treatment, diagnosis, and prognosis of this rare prostate tumor.
Embryonal rhabdomyosarcoma ; Immunohistochemistry ; Prostate ; Young adult

Angiomyolipoma with epithelial cysts (AMLEC) is a rare subtype of angiomyolipoma that may closely mimic both malignant and benign neoplasms. We report a case of AMLEC in an 18-year-old female presenting with acute flank pain and radiologic suspicion for malignancy. This case highlights the diagnostic challenges posed by AMLEC, emphasizes its characteristic histopathologic and immunohistochemical features, and reviews current concepts regarding its pathogenesis. This case represents the first documented case of AMLEC in the Philippines.

Human ; Angiomyolipoma ; Kidney Neoplasms ; Immunohistochemistry

Background: Histopathology has been a standard in achieving and confirming a diagnosis by offering tissue-based findings as guidance in making clinical decisions. As it is reported within a standard timeframe, ancillary testing with immunohistochemistry studies can extend turnaround time (TAT), a quality indicator in surgical pathology. This study aims to benchmark the laboratory’s current practices and quantify the impact of IHCs on reporting definitive diagnoses. Objective: To compare turnaround times of surgical pathology specimens with and without additional immunohistochemistry testing. Methodology: In-house histopathology cases processed in 2024 at the Anatomic Pathology Division of NKTI were evaluated. Specimen receipt dates, report verification dates, and IHC usage are data extracted from logbooks. Cases were categorized into one of three groups depending on the need for IHCs and whether these IHCs are done after releasing an initial histopathology report or if with IHCs altogether releasing an already definitive diagnosis. Results: A total of 5,006 specimen cases were evaluated. Each category has a distinct turnaround time with 5.27 (A), 10.03 (B), and 36.01 (C) days. The medians for each category are 5, 9, and 23 days, while the most common turnaround times were 4, 6, and 15 days, respectively. A Kruskal-Wallis test indicated significant differences among the three groups (p < 0.001), while a post hoc pairwise comparison using Dunn’s test also showed significant differences (A vs B: p < 0.001; A vs C: p < 0.001; B vs C: p < 0.001). Conclusion The use of IHCs extends the TAT of cases. The interval time between sign out of routine histopathology and request for IHCs may be eliminated with precharged reflective testing. Further studies on TATs with implemented reflective testing may be performed to determine efficiency of this service.
Immunohistochemistry ; Pathology, Surgical ; Time Factors ; Medical Records

Introduction: Brenner tumors are uncommon epithelial-stromal neoplasms that usually arise in the ovary and comprise a small proportion of ovarian tumors. Extraovarian Brenner tumors are exceedingly rare, and cervical involvement is exceptional. Because of their unusual location and histologic resemblance to other cervical epithelial lesions, accurate diagnosis can be challenging on limited biopsy material. Case Description: A 43-year-old woman presented with prolonged menstrual bleeding and a clinically suspicious cervical mass. An initial cervical punch biopsy demonstrated benign inflammatory and metaplastic changes. Due to persistent symptoms, a repeat biopsy was performed. Histopathologic examination revealed well-defined nests and cords of urothelial-like epithelial cells with focal cystic change embedded in a dense fibrous stroma. The tumor cells showed elongated nuclei with dense chromatin, inconspicuous nucleoli, and clear cytoplasm with distinct cell borders. Occasional mitotic figures were present without significant cytologic atypia. Immunohistochemical studies demonstrated tumor cell positivity for GATA-3, CK7, p63, and p16, with estrogen receptor positivity in the surrounding stroma, supporting the diagnosis of a borderline extra-ovarian Brenner tumor of the cervix. Discussion: Cervical Brenner tumors are extremely rare and may closely mimic squamous cell carcinoma, transitional cell carcinoma, or benign squamous metaplasia, particularly in small biopsy specimens. Recognition of the characteristic nested urothelial-like architecture, together with a focused immunohistochemical panel, is essential for accurate classification and to prevent misdiagnosis and unnecessary aggressive management. Conclusion This case highlights a rare borderline extra-ovarian Brenner tumor arising in the cervix and emphasizes the importance of correlating histomorphologic features with immunohistochemistry in establishing the correct diagnosis of unusual cervical neoplasms.
Brenner Tumor ; Immunohistochemistry ; Urothelium ; Uterine Cervical Neoplasms

Introduction: Ovarian lymphoma is rare and often misdiagnosed, as its clinical presentation can be similar to other more frequent tumors. It accounts for <1% of all non-Hodgkin lymphomas, with high-grade B-cell lymphoma being the most frequently implicated subtype. Case Description: A 48-year-old woman presented with bilateral ovarian masses, elevated CA-125, and extensive abdominal and thoracic lymphadenopathy. She was managed as advanced ovarian cancer and underwent TAHBSO. Grossly, both ovaries were enlarged and nodular. Histology showed a round cell neoplasm composed predominantly of medium-sized, cleaved lymphocytes, admixed with scattered larger atypical cells. Initial immunohistochemistry panel demonstrated diffuse CD45 positivity and negativity for AE1/AE3, Inhibin, SALL4, Desmin, and Calretinin. Subsequently, CD20 and PAX5 showed diffuse reactivity. CD10, BCL2, and BCL6 highlighted neoplastic follicles. CD3 was negative. High-grade B-cell lymphoma was considered; however, the Ki-67 proliferative index was 38%, and c-MYC expression was low (5%). A final diagnosis of follicular lymphoma involving both ovaries was rendered. Discussion: The clinical presentation strongly suggested advanced ovarian carcinoma. However, histologic and immunophenotypic evaluation established lymphoma. Although aggressive subtypes are more common in advanced cases, indolent entities such as follicular lymphoma should also be considered, particularly in resource-limited settings where delays in diagnosis occur. Distinguishing lymphoma from carcinoma is critical, as management differs significantly and misclassification may lead to overtreatment. Conclusion Recognition of ovarian lymphoma is critical, as accurate diagnosis alters management and prevents unnecessary radical surgery.
CA-125 Antigen ; Immunohistochemistry ; Lymphoma, Follicular ; Ovarian Neoplasms

Introduction: While uterine leiomyosarcoma, an aggressive smooth muscle malignancy, has a strong propensity for hematogenous spread—most commonly to the lungs and liver—gastric metastasis remains exceedingly rare. When it occurs, it presents as a masquerading lesion that mimics primary gastric tumors, creating a significant diagnostic pitfall for both clinicians and pathologists. Case Description: A 75-year-old female presented with recurrent melena. Esophagogastroduodenoscopy revealed a friable, bell-shaped mass measuring 7 × 6 cm in the gastric fundus, suspicious for GIST. Histopathology showed spindle to epithelioid tumor cells arranged in intersecting fascicles and solid sheets with vesicular nuclei, conspicuous nucleoli, numerous mitosis, and tumor necrosis. IHCs demonstrated strong SMA positivity but negative CD117, raising consideration of undifferentiated GIST. However, subsequent DOG1 staining was negative, arguing strongly against GIST. Additional markers including S100, PanCK, CD3, CD20, CD15, and CD30 were negative. Further IHCs revealed diffuse, desmin and H-caldesmon positivity, supporting smooth muscle differentiation. Review of prior records revealed TAHBSO in 2023 for uterine leiomyosarcoma. Discussion: Metastatic involvement of the stomach is rare and most commonly arises from breast or lung primaries. Gastric metastases are rare and most commonly originate from breast or lung primaries. Metastatic uterine leiomyosarcoma presenting as a solitary gastric mass is exceedingly uncommon and may closely mimic primary gastric tumors such as GIST both endoscopically and histologically, representing an important diagnostic pitfall. Conclusion This case highlights a rare metastatic pattern of uterine leiomyosarcoma presenting as an overt gastric mass with GI bleeding. Awareness of this deceptive presentation and careful clinicopathologic correlation are essential for accurate diagnosis. To our knowledge, this represents one of the few reported cases worldwide and possibly the first documented in the Philippines.
Gastrointestinal Stromal Tumors ; Immunohistochemistry ; Leiomyosarcoma ; Gastrointestinal Hemorrhage