Diagnostic Pathology最新文献

SMARCB1 (INI-1) deficient vulvar neoplasms are rare tumors with scarce available literature. These tumors can be comprised of proximal type epithelioid sarcoma (ES), myoepithelial carcinoma (MEC), myoepithelioma-like tumor of the vulvar region (MELTVR), and myxoepithelioid tumor with chordoid features (METC). A subset of vulvar yolk sac tumors (VYSTs) also exhibit INI-1 deficiency. Unlike other vulvar germ cell tumors, some researchers speculate these to be of non-germ cell origin. Herein, we report a spectrum of INI-1 deficient vulvar tumors comprising VYST (1 case), ES (1 case) and MELTVR (2 cases) which showed variable histomorphological features and concomitant lack of INI-1 expression on immunohistochemistry. The clinical course ranges from indolent to aggressive and all tumors warrant close clinical follow up. Management includes surgical excision with or without adjuvant therapy. Recognition of these unique neoplasms can aid in refining the classification scheme for such uncommon vulvar tumors.

Objective: To analyze expression levels of angiopoietin‑like 4 (ANGPTL4) in olfactory neuroblastoma (ONB) to investigate the association between ANGPTL4 and ONB.

Methods: Immunohistochemistry was performed on 109 formalin‑fixed, paraffin‑embedded ONB tissue samples to detected the expression of ANGPTL4. Immunofluorescence co-localization was performed to detected the expression sites of ANGPTL4. Western blotting was used to measure the protein levels of ANGPTL4, Hypoxia-inducible factor (HIF-1α), and CD31 in tumor and Para tumoral tissues. The non‑parametric Kruskal-Wallis test was used to evaluate differential expression of ANGPTL4 and clinicopathological parameters of ONB. Cox regression analysis was used to evaluate the association between ANGPTL4 expression levels and ONB prognosis.

Results: Immunohistochemistry revealed that ANGPTL4 expression (moderately positive + strongly positive) was higher in high grade (Ⅲ+Ⅳ) ONB (98.2%; 55/56) compared with low grade (Ⅰ+Ⅱ) ONB (56.6%; 30/53). Immunofluorescence co-localization revealed that ANGPTL4 both focus on microvessel and macrophage, in addition, ANGPTL4 is co-located with HIF-1a. Western blotting showed that ANGPTL4, HIF-1α and CD31 expression was significantly increased in the tumor area compared with the paratumor area. The clinical significance of ANGPTL4 expression was analyzed in 109 ONB tissues, and high expression levels of ANGPTL4 were positively associated with the pathological grade (P < 0.001) and local recurrence (P < 0.001). Kaplan-Meier analysis revealed that patients with high ANGPTL4 expression had shorter disease‑free survival (DFS; P = 0.021, mean survival time: 93 ± 10.042 vs. 153 ± 13.835), but no difference in overall survival (P = 0.121). Multivariate Cox regression analysis revealed that ANGPTL4 was an independent prognostic factor for DFS (P = 0.028).

Conclusions: These results demonstrated that ANGPTL4 might associated with a poor prognosis of ONB. ANGPTL4 expression were focus on CD34, macrophage and HIF-1α, suggesting that ANGPTL4 might associated with hypoxia and might play important role in angiogenesis and inflammatory. ANGPTL4 is a novel therapeutic target for ONB.

Background: Programmed death ligand 1 (PD-L1) is a prognostic marker in several malignancies, but the prognostic value of PD-L1 expression in colorectal cancer (CRC) is inconclusive. Lack of standardized scoring systems for PD-L1 evaluation in CRC has led to inconsistent findings. This exploratory study aimed to evaluate PD-L1 expression using manual and digital methods and correlate the results to overall survival (OS) in a cohort of patients with pT3 and pT4 colon cancer (CC).

Methods: From a previously published study, 162 patients with pT3 and pT4 CC were included. One tumor slide representing the invasive margin was selected and stained for PD-L1 (22C3). PD-L1 was evaluated according to the tumor proportion score (TPS), the immune cell score (ICS), and the combined positive score (CPS). Additionally, a digital algorithm for detecting PD-L1 positive cells was developed. The manual and digital PD-L1 expression scores were correlated to OS in the entire cohort, and in subgroups according to mismatch repair (MMR) status.

Results: Only 1 case was classified with a TPS of ≥ 1%. The ICS was classified as < 1%, 1-9%, and ≥ 10% in 66%, 30.2% and 3.7% of the tumors, respectively. The CPS was classified as < 1, 1-9, and ≥ 10 in 82.7%, 15.4%, and 1.9% of the tumors, respectively. A high digital PD-L1 expression score was an independent prognostic factor for longer OS, adjusted for age, pT-category and adjuvant chemotherapy (aHR = 0.40, 95% CI = 0.19-0.86, p = 0.018). In the pMMR subgroup, both a CPS ≥ 1 and a high digital score were significantly associated with longer OS in the multivariate analyses (aHR = 0.24, 95% CI = 0.06-0.99, p = 0.049, and aHR = 0.34, 95% CI = 0.12-0.97, p = 0.043, respectively).

Conclusions: Our results suggest that high PD-L1 expression is associated with longer OS. In future studies examining PD-L1 expression as a prognostic biomarker in CC, assessing PD-L1 expression using a digital approach or the CPS can be recommended.

Background: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders with variable clinical outcomes influenced by the bone marrow microenvironment. Tumor-associated macrophages (TAMs), particularly the M1 (CD68⁺) and M2 (CD163⁺) subtypes, play critical roles in inflammation, fibrosis, and immune modulation. This study evaluates CD68- and CD163-positive macrophage frequencies across MPN subtypes and their clinical/prognostic significance.

Methods: In this retrospective cohort study, 121 patients with histopathologically confirmed BCR::ABL1-negative, JAK2V617F-positive MPNs were assessed for CD68 and CD163 expression. The CD68/CD163 ratio was analyzed for associations with thrombosis, leukemic/fibrotic transformation, and survival outcomes using receiver operating characteristic (ROC) curves and Kaplan-Meier analyses.

Results: A CD68/CD163 ratio > 1.63 correlated with shorter thrombosis-free survival (41.4 vs. 68.2 months; p = 0.001; hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.45-4.14) and secondary myelofibrosis progression-free survival (48.3 vs. 79.0 months; p = 0.001; HR 2.67, 95% CI 1.55-4.60). The ratio predicted thrombosis (area under the curve [AUC] = 0.677, 95% CI 0.58-0.77; p = 0.001) and secondary myelofibrosis (AUC = 0.779, 95% CI 0.69-0.87; p < 0.001). CD68 alone showed excellent diagnostic accuracy for the prediction of secondary myelofibrosis (AUC = 0.851, 95% CI 0.78-0.92; specificity = 100%).

Conclusions: TAM polarization, reflected by the CD68/CD163 ratio, is a prognostic marker in MPNs, particularly for thrombosis and fibrotic progression. These findings support integrating TAM profiling into routine histopathology and suggest macrophage-targeted therapies as potential strategies for MPN management.

Background: The genetic heterogeneity observed in acute myeloid leukemia (AML) contributes to a wide range of clinical presentations and prognoses. We conducted a retrospective study to investigate genetic abnormalities, clinical characteristics, and survival of AML patients.

Methods: Targeted exome analysis of 25 genes using a QIAact Myeloid DNA UMI Panel with the GeneReader NGS was performed.

Results: De novo AML (dAML) and secondary AML (sAML) were observed in 163 and 56 patients, respectively. ASXL1, SRSF2, and RUNX1 mutations were significantly observed in sAML patients. Among dAML patients, mutant IDH1, ASXL1, TP53, and TET2 were associated with low WBC count (< 4 × 10⁹/L), and mutations of FLT3-ITD and NPM1 were associated with high WBC count (> 100 × 10⁹/L). In dAML group, KIT and FLT3-TKD mutations were commonly found in favorable cytogenetic risk, RAS and SF3B1 mutations were significantly observed in the abnormal chromosome 3 group, whereas IDH1, IDH2, RUNX1, and SRSF2 mutations were significantly observed in trisomy group. Mutant TP53 was seen significantly in AML patients with complex and monosomy karyotypes. ASXL1, IDH1, IDH2, TP53, and SRSF2 mutations were independent factors associated with poor OS through univariate analysis. Nevertheless, multivariate analysis showed IDH1 (HR = 2.699; 95% CI: 1.331-5.473), TP53 (HR = 2.200; 95% CI: 1.409-3.435) and ASXL1 (HR = 1.592; 95% CI: 1.040-2.436) mutations were significantly associated with short OS in AML patients. In contrast, RUNX1 (HR = 3.667; 95% CI: 1.213-11.084) and DNMT3A (HR = 2.094; 95% CI: 1.080-4.081) mutations were significantly associated with poor DFS on multivariate analysis.

Conclusions: The complexity of AML was influenced by various cytogenetic and molecular abnormalities, which contributed to patients' heterogeneous presentation and survival outcomes. In addition to the previous data, IDH1, IDH2, and DNMT3A mutations might have affected survival outcomes in AML patients in our retrospective cohort. However, further studies with larger sample sizes are needed to validate these observations.

Background: Abnormal uterine bleeding (AUB) is a prevalent clinical concern, particularly in women approaching or beyond menopause. With a myriad of possible etiologies ranging from benign hyperplasia to malignant transformations, accurate diagnosis becomes crucial. This study aims to examine the histopathological patterns of the endometrium in peri- and postmenopausal women presenting with abnormal uterine bleeding and correlate these findings with endometrial thickness (ET) measured by transvaginal sonography (TVS).

Methods: A retrospective cohort of 307 women aged 40 and above presenting with abnormal uterine bleeding was evaluated over a year period. Clinical history and transvaginal sonography findings were meticulously recorded. Endometrial samples obtained through biopsy or curettage were studied. The correlation between endometrial thickness and histological diagnosis was statistically analyzed using Mann-Whitney U Test and Chi square test, with a focus on distinguishing functional, benign, pre-malignant, and malignant endometrial pathologies.

Results: Endometrial polyp is the most frequent pattern in both perimenopausal and postmenopausal women. An ET > 11 mm in peri menopausal and postmenopausal women showed a strong association with hyperplasia and malignancy. This suggests that transvaginal sonography, as a non-invasive tool, can significantly guide diagnostic and management strategies when interpreted alongside clinical and histopathological parameters.

Conclusion: Endometrial thickness serves as a valuable adjunct in the evaluation of abnormal uterine bleeding. However, the gold standard for a conclusive diagnosis is endometrial tissue biopsy. Integrating histopathology with imaging findings enhances diagnostic precision, allowing early identification of precancerous and cancerous lesions, especially in the postmenopausal cohort. Our study concludes that endometrial sample is recommended when ET > 11 mm in perimenopausal and ET > 5 mm in postmenopausal women, particularly when bleeding is persistent.

Background: MRI-targeted biopsy (T-Bx) has considerably improved the detection of clinically significant prostate cancer, while the clinical impact of perineural invasion (PNI) seen on T-Bx remains unclear. We aimed to determine the prognostic significance of PNI quantification on T-Bx.

Methods: We assessed 169 consecutive patients undergoing T-Bx, along with systematic biopsy, and subsequent radical prostatectomy by quantifying actual PNI foci on T-Bx and comparing their postoperative oncologic outcomes.

Results: No PNI was detected on T-Bx in 136 (80.5%) cases, whereas 1 (n = 18; 10.7%), 2 (n = 7; 4.1%), 3 (n = 5; 3.0%), and 4 (n = 3; 1.8%) foci of PNI were present on T-Bx of the remaining cases. Compared to cases with no PNI, those exhibiting single PNI had significantly higher pT stage and significantly higher incidence of lymph node metastasis. However, there were no significant differences in any of the clinicopathologic features examined, including tumor grade, stage, and volume, between cases with single vs. multifocal PNI. Univariate survival analysis revealed a significantly higher risk of biochemical recurrence following prostatectomy in patients with PNI (vs. no PNI; P < 0.001) or multifocal PNI (vs. single PNI; P = 0.043) on T-Bx. Differences in recurrence-free survival between 0 vs. 1 PNI (P = 0.176), 1 vs. 2 PNI (P = 0.187), and 2 vs. 3-4 PNI (P = 0.939) were not statistically significant. In multivariable analyses, multifocal PNI (vs. single PNI) on T-Bx showed significance for the risk of postoperative recurrence (hazard ratio 4.922 or 6.173, P < 0.05).

Conclusions: Multifocal PNI on T-Bx was found to be associated with significantly poorer oncologic outcomes, as an independent predictor, in men with prostate cancer undergoing radical prostatectomy. PNI quantification on T-Bx may thus provide useful information for the more accurate risk stratification of prostate cancer.

Background: Long non-coding RNAs (lncRNA) H19 has drawn special attention because of its varied role in several malignancies, including OSCC. Therefore, this study was conducted to assess the association between H19-miR675-p53 by in-silico analysis, quantify the expression levels of H19, miRNA-675, and target oncogene p53 in cancerous versus normal individuals, and Correlate the Clinicopathological findings with their expression pattern.

Methods: The secondary structure of lncRNA H19 was predicted using the RNAfold web server ( http://rna.tbi.univie.ac.at/cgi-bin/RNAWebSuite/RNAfold.cgi ). The FASTA sequence of H19 was retrieved from the NCBI database ( https://www.ncbi.nlm.nih.gov/ ). We performed molecular docking studies to analyze the interaction between miRNA-675 and p53 using the MDockPP ( https://zougrouptoolkit.missouri.edu/MDockPP/ ) web server. Real-time PCR was used to measure the amounts of H19 and miR-675, and Immunohistochemistry was used to analyse the pattern of p53 expression.

Result: The study successfully associated miR-675 from the first exon of H19 modulating p53 via in silico analysis. It was found that H19 and miR-675 levels were higher in OSCC patients (3.12 ± 1.16) compared to healthy patients (1.0 ± 0.0), and was statistically significant (p-value < 0.001).

Conclusion: The specificity of H19 expression in OSCC compared to normal presents an attractive target for cancer-specific therapies, minimizing the risk of off-target effects.

GLI1 gene alterations including fusions and amplifications compromise a subset of malignant mesenchymal tumors exhibiting characteristic monomorphic nested morphology and frequent S100 positivity, which mimic glomus tumors or well differentiated neuroendocrine tumors. We report four high-grade uterine endometrial stromal sarcomas (ESS) harboring GLI1 and MDM2/CDK4 co-amplifications with a median age of 51.5 years (range 43 ~ 72 years). Histologically, tumors showed a heterogenous morphology, including ovoid to spindle cells, showing nested/nodular arrangement (4/4). Myxoid background was observed at least partially in 4 tumors with prominent capillary networks. Mitoses index was 2 to 20/10 HPF (median 9.5/10 HPF). Immunochemically, tumors showed diffuse staining of CD10 (3/4) with frequently positive CyclinD1(2/4 tested) and mostly negative S100 protein (3/4). Next-generationsequencing (NGS) studies revealed GLI1 and MDM2/CDK4 co-amplification in all cases (4/4) and GLI1 fusion in 1 case (1/4), which were validated by fluorescence in situ hybridization (FISH) analysis. BCOR fusions were firstly identified with GLI1 and MDM2/CDK4 co-amplification in 2 cases (2/4). Copy number (CN) segmentation data showed GLI1 co-amplified cases present generally a single peak at the 12q13.3-15 locus. Follow-up (range:3 to 112 months; median 37.5 months) showed recurrence and/or metastasis in all cases (4/4), in which 1 patient developed lungs and liver metastasis. Relapse-free survival (RFS) analysis showed similar median RFS between GLI1 co-amplified HGESS and GLI1 non-amplified HGESS groups, which were shorter than LGESS group. Unusual clinicopathologic features of these HGESS with GLI1 and MDM2/CDK4 co-amplification mimicked other neoplasms, which caused significant diagnostic challenge and pitfalls. However, identification of GLI1 alterations in these tumors is beneficial for diagnosis and potential use of targeted GLI1 inhibitors.