Diagn Pathol [JOURNAL]
Sun
200 papers
Usefulness of BRG1 immunostaining in detecting SMARCA4 deficiency in "so-called" cancers of unknown primary in daily pathology practice.
Hasegawa C, Washimi K, Hiroshima Y … +5 more , Takahashi H, Sato S, Yoshioka E, Okubo Y, Miyagi Y
Diagn Pathol · 2025 Dec · PMID 41327322 · Full text
BACKGROUND: SMARCA4 encodes BRG1, loss of which is associated with aggressive tumor biology. Although SMARCA4 deficiency has been described in various malignancies, its role in “so-called” cancers of unknown primary (“so...
BACKGROUND: SMARCA4 encodes BRG1, loss of which is associated with aggressive tumor biology. Although SMARCA4 deficiency has been described in various malignancies, its role in “so-called” cancers of unknown primary (“so-called” CUP), that is, metastatic tumors encountered in pathology practice without a clear primary site, remains unclear. METHODS: We retrospectively studied 108 cases submitted as so-called “CUP” between 2017 and 2023, in which the primary site could not be determined at the time of diagnosis. Histological features and BRG1 immunohistochemistry were reviewed. BRG1 loss was defined as complete absence of nuclear staining in tumor cells. Comprehensive genomic profiling (CGP) was performed in selected cases with sufficient residual tissue. Tumor mutation burden (TMB) ≥ 10 mutations/Mb was defined as TMB-high. RESULTS: BRG1 loss was observed in 13 tumors (12%). BRG1-loss tumors were significantly more likely to involve the thoracic cavity (85% vs. 36%; p < 0.001) and exhibited prominent necrosis, higher mitotic counts, and nuclear inclusions compared with BRG1-preserved tumors. All nine BRG1-loss tumors tested by CGP harbored pathogenic SMARCA4 mutations, and 78% (7/9 cases) were TMB-high compared with 14% (1/7 cases) of BRG1-preserved tumors. PD-L1 positivity was detected in one of 11 BRG1-loss cases tested. Other mutations observed in BRG-1 loss tumors were not distinctive enough to indicate the primary site. CONCLUSIONS: BRG1 immunostaining is a sensitive surrogate of SMARCA4 deficiency in “so-called” CUP. Although BRG1 status does not reliably identify the site of origin, it highlights tumors enriched for thoracic involvement and TMB-high status. These findings support the use of BRG1 as a practical screening tool to select cases for further genomic testing and therapeutic stratification, including potential consideration of immune checkpoint inhibitors.
Aberrant TTF-1 expression in metastatic colorectal adenocarcinoma mimicking primary lung cancer: a case report and review of diagnostic pitfalls.
Tran NT, Van Thai N, Khuyen NT … +2 more , Le LT, Khoa LTA
Diagn Pathol · 2025 Nov · PMID 41310725 · Full text
A 43-year-old man with sigmoid colon adenocarcinoma (low-grade, moderately) developed multiple pulmonary metastases, presenting an unusual immunohistochemical profile. Histologically, resected lung nodules showed metasta...
A 43-year-old man with sigmoid colon adenocarcinoma (low-grade, moderately) developed multiple pulmonary metastases, presenting an unusual immunohistochemical profile. Histologically, resected lung nodules showed metastatic adenocarcinoma consistent with colorectal origin, yet the tumor cells paradoxically expressed thyroid transcription factor-1 (TTF-1) - a marker typically specific to primary lung adenocarcinoma. Immunophenotyping demonstrated TTF-1 nuclear positivity in the metastatic tumor alongside a classic colorectal profile: cytokeratin 7 (CK7) negativity, cytokeratin 20 (CK20) positivity, strong caudal-type homeobox transcription factor 2 (CDX2) and special AT-rich sequence-binding protein 2 (SATB2) nuclear expression, and absence of Napsin A. The patient underwent surgical resection of the primary sigmoid colon tumor and received 16 cycles of capecitabine plus bevacizumab chemotherapy. Molecular testing revealed a KRAS c.35G > T (p.G12V) mutation in the tumor. This case highlights a potential diagnostic pitfall in metastatic colorectal cancer: aberrant TTF-1 expression can mimic a primary lung tumor. We discuss how the comprehensive immunohistochemical panel and genetic findings confirmed the colorectal origin of the lung lesions, emphasizing that combined marker profiles (TTF-1 +/CK7 -/CK20 +/CDX2 +/SATB2 +/Napsin A -) are more consistent with metastatic colorectal adenocarcinoma rather than an enteric-type adenocarcinoma of the lung, primary. The report reviews relevant literature and underscores the importance of correlating clinical history with pathology to avoid misdiagnosis.
SMARCB1 (INI-1) deficient vulvar neoplasms: report of 4 cases with review of literature.
Kamboj M, Chadha P, Sharma A … +7 more , Gupta S, Jain V, Bansal D, Pasricha S, Gupta G, Durga G, Mehta A
Diagn Pathol · 2025 Nov · PMID 41291778 · Full text
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 tum...
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.
ANGPTL4 overexpression is associated with progression and poor prognoses of olfactory neuroblastoma.
Yunyun Y, Yahui L, Yingshi P
Diagn Pathol · 2025 Nov · PMID 41286937 · Full text
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 formali...
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.
Utility of optimal proportion of tumor-infiltrating lymphocytes as a prognostic prediction of clinical outcome in intrahepatic cholangiocarcinoma: a single institution retrospective analysis.
Kunprom W, Poonsiri N, Intarawichian P … +14 more , Sa-Ngiamwibool P, Sangkhamanon S, Thanee M, Loilome W, Titapun A, Jareanrat A, Thanasukarn V, Srisuk T, Luvira V, Eurboonyanun K, Promsorn J, Koonmee S, Prajumwongs P, Aphivatanasiri C
Diagn Pathol · 2025 Nov · PMID 41286924 · Full text
BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA), prevalent in Northeastern Thailand, presents challenges due to late diagnosis and metastasis. Prognostic factors are crucial. Tumor-infiltrating lymphocytes (TILs) hold...
BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA), prevalent in Northeastern Thailand, presents challenges due to late diagnosis and metastasis. Prognostic factors are crucial. Tumor-infiltrating lymphocytes (TILs) hold promise as prognostic indicators and for immunotherapy, but their optimal proportion in iCCA prognosis is yet to be determined. We propose to evaluate the optimal proportion of TILs for predicting the outcomes of iCCA. METHODS: We analyzed TIL levels in 190 iCCA cases across four models with varying TIL cut-offs. Correlations with clinicopathological features were examined, followed by univariate and multivariate survival analyses. Subgroup analysis differentiated early and late-stage disease to assess TILs predictive potential. RESULTS: Results showed that at least 20% of TILs were significantly associated with smaller tumor size and growth patterns of intraductal (ID) and ID mixed types. Multivariate analysis revealed that 20%-40% of TILs were an independent factor for predicting good survival of patients. In addition, the 20% cut-off value was an independent factor for predicting the survival outcome of patients with early-stage disease. CONCLUSION: In this study, we identified the optimal proportion of stromal TILs for prognostic prediction in early-stage iCCA patients. Further research is warranted to validate the role of TILs as a prognostic biomarker and to explore their potential utility in guiding patient monitoring and risk stratification in early-stage disease.
Prognostic value of manual and digital PD-L1 expression in pT3 and pT4 colon cancer.
Jepsen DNM, Jensen MB, Bennedsen ALB … +6 more , Grantzau TL, Eriksen TT, Eriksen JO, Bzorek M, Gögenur I, Fiehn AK
Diagn Pathol · 2025 Nov · PMID 41272706 · Full text
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...
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.
Prognostic utility of macrophage polarization (CD68/CD163 ratio) in Egyptian JAK2 positive myeloproliferative neoplasm patients: a single center study.
Mahgoub SMA, Yehia MSM, Arafat AMA
Diagn Pathol · 2025 Nov · PMID 41239536 · Full text
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...
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.
Molecular abnormalities and clinical features in adult patients with acute myeloid leukemia in Thailand.
Chantrathammachart P, Jinawath A, Puavilai T … +9 more , Arsa L, Police P, Noikongdee P, Phojanasenee T, Sae-Lim P, Piyajaroenkij T, Choksomnuk P, Chuncharunee S, Niparuck P
Diagn Pathol · 2025 Nov · PMID 41225577 · Full text
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,...
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 × 10/L), and mutations of FLT3-ITD and NPM1 were associated with high WBC count (> 100 × 10/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.
Histopathological profile of endometrium among peri and post-menopausal women with abnormal uterine bleeding and its correlation with endometrial thickness by transvaginal sonography: a retrospective study.
S V, Kudva R
Diagn Pathol · 2025 Nov · PMID 41214795 · Full text
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 transf...
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.
Clinical significance of quantification of perineural cancer invasion on MRI-targeted prostate biopsy.
Ramineni M, Wang Y, Miyamoto H
Diagn Pathol · 2025 Nov · PMID 41214685 · Full text
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 d...
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.
High-grade uterine endometrial stromal sarcoma harboring GLI1 and MDM2/CDK4 co-amplifications.
Zhang L, Luan L, Zhang L … +9 more , Huang Y, Gu W, Yu S, Shen L, Huang J, Shao Y, Su J, Hou Y, Xu C
Diagn Pathol · 2025 Nov · PMID 41199293 · Full text
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 tumo...
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.
Integrated in-silico and in-vitro analysis of lncRNA H19/miRNA-675/p53 in OSCC: Structural characterization and molecular docking insights.
Sekar R, Jayaraman S, Veeraraghavan V … +4 more , Varadarajan S, Alagumuthu M, Rajendran P, Venkatesalu B
Diagn Pathol · 2025 Nov · PMID 41199286 · Full text
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-miR6...
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.
Diagnostic value of AHNAK2 immunohistochemical expression in papillary thyroid carcinoma: an immunohistochemical study.
Zhang X, Chen L, Deng M … +11 more , Liang H, Jiang D, Wang H, Liu Y, Zhang R, Xu L, Liu J, Sujie A, Xu C, Liu Y, Hou Y
Diagn Pathol · 2025 Nov · PMID 41188896 · Full text
Multiple immunohistochemical markers including galectin-3 and BRAF V600E have been used to identify benign and malignant thyroid tumors. AHNAK nucleoprotein 2 (AHNAK2) is a novel oncogene that belongs to the AHNAK protei...
Multiple immunohistochemical markers including galectin-3 and BRAF V600E have been used to identify benign and malignant thyroid tumors. AHNAK nucleoprotein 2 (AHNAK2) is a novel oncogene that belongs to the AHNAK protein family and is upregulated in many malignant tumors, including thyroid cancers. However, its actual value in pathological diagnosis remains unknown. Therefore, we utilized a set of well-studied markers to further confirm the diagnostic role of AHNAK2 in differentiating thyroid tumors. Two hundred ninety-six papillary thyroid carcinomas (PTCs), 167 follicular adenomas (FAs), 36 follicular thyroid carcinomas (FTCs), and 11 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were collected. Markers including AHNAK2, galectin-3, BRAF V600E, HBME-1, Thyroid Peroxidase (TPO), CD56, and cyclin-D1 were used simultaneously for immunohistochemistry (IHC). The positivity rates of the PTC markers were as follows: AHNAK2 (95%), galectin-3 (89.5%), BRAF V600E (82.4%), HBME-1 (84.1%) CK19 (99.7%), cyclin-D1 (98.0%), TPO (61.1%), and CD56 (47.3%). AHNAK2 (4.2%), galectin-3 (6.0%), BRAF V600E (0.0%), HBME-1 (16.8%); CK19 (88.6%), cyclin-D1 (78.4%), TPO (94.0%), and CD56 (94.6%) were identified in FA. The areas under the receiver operating characteristic (ROC) curves for each marker in distinguishing PTCs from FAs were AHNAK2 (0.964), galectin-3 (0.935), BRAF V600E (0.907), HBME-1 (0.882), cyclin-D1 (0.776), CK19 (0.752), CD56 (0.053), TPO (0.004), and AHNAK2 in combination with galectin-3 and BRAF V600E (0.992). We firstly found that AHNAK2 was highly expressed in PTC and could be a new promising diagnostic marker for distinguishing thyroid tumors. The combination of AHNAK2 with galectin-3 and BRAF V600E can serve as an efficient diagnostic IHC panel for thyroid cancer, with great clinical potential.
Two unusual cases of tongue schwannoma with self-injurious factors: case reports and systemic literature review.
Du G, Zhang J, Chen X … +4 more , Lu R, Zhang J, Schmidt E, Zhou G
Diagn Pathol · 2025 Oct · PMID 41131578 · Full text
We present two cases of tongue schwannoma in two young males. The unusual, exogenetic clinical manifestation might be a big challenge for most dentists in making a correct diagnosis. The two patients had no special genet...
We present two cases of tongue schwannoma in two young males. The unusual, exogenetic clinical manifestation might be a big challenge for most dentists in making a correct diagnosis. The two patients had no special genetic or environmental background. Both patients denied cigarette smoking or alcohol abuse. Physical examination of the cervical lymph nodes yielded negative results. Their astonishing medical histories revealed that both had self-injurious practices using sharp instruments. The diagnosis of tongue schwannoma was confirmed by histopathology, revealing typical Antoni type A and B areas, and reactivity with S-100 by immunohistochemistry. The lesions were excised transorally under local anesthesia with no signs of recurrence for more than two years.
Inflammatory fibroid polyps of the colon: a study on the morphological spectrum, immunoexpression characteristics, and outcomes.
Changfei Q, Tingzhen Z, Xiangling L … +2 more , Dingzhun L, Zhang W
Diagn Pathol · 2025 Oct · PMID 41131517 · Full text
BACKGROUND: Colonic inflammatory fibroid polyps (IFPs) have not been extensively studied. METHODS: In this study, we collected nine cases of colonic IFPs and provide a comprehensive description of the clinicopathological...
BACKGROUND: Colonic inflammatory fibroid polyps (IFPs) have not been extensively studied. METHODS: In this study, we collected nine cases of colonic IFPs and provide a comprehensive description of the clinicopathological features and developmental outcomes of these lesions. RESULTS: These nine cases of colonic IFPs can be classified into four types on the basis of their pathological characteristics: early-stage, classic, inflammatory, and sclerotic. The early-stage type of IFP is characterized by the deposition of fibrosis around blood vessels and between glands. The classic type of IFP is easily identifiable by its “onion-skin-like” structure; however, immunohistochemical (IHC) staining for CD34 may demonstrate focal positivity or even negativity. The inflammatory type of IFP is large and characterized by significant infiltration of plasma cells. IHC staining revealed variable positivity for both CD34 and PDGFRα across different regions of the lesions. The sclerotic type of IFP is characterized by substantial deposition of collagen. Furthermore, our findings suggest that early-stage IFPs have the potential to either develop into classic-type IFPs or degenerate into sclerotic-type IFPs. Additionally, classic-type IFPs may acquire PDGFRα mutations and ultimately transform into inflammatory-type IFPs. CONCLUSIONS: Colonic IFPs exhibit a distinct morphological spectrum and unique immunoexpression characteristics as they progress. Only inflammatory-type and classic-type IFPs with PDGFRα mutations or immunoexpression should be regarded as genuine neoplastic lesions.
Fine-needle aspiration cytology for the diagnosis of ewing's sarcoma in bone: a case report.
Cai Y, Gu J, Wei X … +6 more , Wang J, Fang J, Zhang H, Lv K, Meng Z, Liang Z
Diagn Pathol · 2025 Oct · PMID 41107967 · Full text
Ewing's sarcoma (ES) is an aggressive small round cell tumor traditionally diagnosed through open biopsy. We present a systematically evaluated case suggesting that standardized ultrasound-guided fine-needle aspiration c...
Ewing's sarcoma (ES) is an aggressive small round cell tumor traditionally diagnosed through open biopsy. We present a systematically evaluated case suggesting that standardized ultrasound-guided fine-needle aspiration cytology (FNAC), when combined with immunohistochemical (IHC) and molecular analysis, may provide diagnostic reliability approaching that of open biopsy. A 26-year-old female presented with an insidiously developing left popliteal fossa mass. Ultrasound-guided FNAC demonstrated characteristic small round blue cells, with IHC showing diffuse positivity for CD99, FLI-1, and Bcl-2. Subsequent fluorescence in situ hybridization (FISH) analysis identified the EWSR1 gene rearrangement. The patient exhibited significant radiographic response to neoadjuvant chemotherapy after two cycles, as evidenced by MRI. Definitive surgical resection specimens similarly demonstrated EWSR1 rearrangement by FISH, corroborating the initial diagnosis. Following four adjuvant chemotherapy cycles, the patient achieved disease-free status at the last follow-up. This case highlights the potential utility of optimized FNAC specimen triage (incorporating smears, liquid-based cytology, and cell blocks) for rare tumors, enabling comprehensive ancillary testing while maintaining diagnostic accuracy and supporting timely therapeutic decision-making.
Invasive breast carcinoma in a patient with PHTS: a case report.
Zhan H, Fischbach N, Lynch M … +3 more , Liang Y, Krishnamurti U, Cohen P
Diagn Pathol · 2025 Oct · PMID 41107919 · Full text
BACKGROUND: PTEN hamartoma tumor syndrome (PHTS) is a rare, multisystem disorder caused by germline pathogenic variants in the PTEN gene, predisposing individuals to various malignancies, including breast cancer. CASE PR...
BACKGROUND: PTEN hamartoma tumor syndrome (PHTS) is a rare, multisystem disorder caused by germline pathogenic variants in the PTEN gene, predisposing individuals to various malignancies, including breast cancer. CASE PRESENTATION: We describe a 26-year-old woman with longstanding bilateral palpable breast masses and spontaneous bloody nipple discharge. Imaging revealed numerous cysts and masses, predominantly in the right breast. Multiple biopsies showed benign papilloma with focal atypical ductal hyperplasia (ADH), while total mastectomy specimens revealed multifocal, poorly differentiated, triple-negative invasive carcinoma. An axillary lymph node contained ectopic breast tissue with associated papillary proliferation. Genetic testing identified a pathogenic germline PTEN variant (c.209 + 4_209 + 7delAGTA), confirming PTEN hamartoma tumor syndrome (PHTS). CONCLUSION: This case underscores the importance of considering PHTS in young patients presenting with extensive papillomatosis and other unusual breast pathologic findings, even in the absence of a family history of cancer. Early recognition enables timely genetic counseling, confirmatory testing, and implementation of appropriate surveillance and management strategies.
Clinical significance and expression of ALDH1 in triple-negative breast cancer.
Yang Y, Li Z, Zhu Y … +3 more , Guo C, Yang L, Zhang J
Diagn Pathol · 2025 Oct · PMID 41102839 · Full text
BACKGROUND: Triple-negative breast cancer (TNBC) is aggressive and has limited therapeutic options due to the absence of targeted therapies, highlighting the urgent need for prognostic biomarkers linked to cancer stemnes...
BACKGROUND: Triple-negative breast cancer (TNBC) is aggressive and has limited therapeutic options due to the absence of targeted therapies, highlighting the urgent need for prognostic biomarkers linked to cancer stemness and chemoresistance. Aldehyde dehydrogenase 1 (ALDH1), a key regulator of stem cell properties, remains incompletely characterized in TNBC clinical cohorts. METHODS: ALDH1 mRNA expression levels were analyzed using the GEO2R online database, and its prognostic significance was assessed via the Kaplan‒Meier plotter tool. Immunohistochemical (IHC) staining was performed on a tissue microarray comprising 96 TNBC samples and paired adjacent normal tissues from patients treated at Binzhou People's Hospital between 2016 and 2022. The associations between ALDH1 expression and clinicopathological parameters were evaluated using the chi-square test. RESULTS: Bioinformatics analysis revealed significantly higher ALDH1 mRNA expression in TNBC tissues compared to adjacent benign tissues. Kaplan‒Meier survival analysis demonstrated that elevated ALDH1 mRNA expression was associated with poor prognosis in TNBC patients. IHC staining further confirmed elevated ALDH1 protein expression in TNBC tissues compared with normal adjacent tissues. However, there was no significant correlation between ALDH1 expression and conventional clinicopathological parameters, including age, menopausal status, tumor size, TNM stage, histological grade, histological subtype, axillary lymph node metastasis and the Ki-67 index (p > 0.05). High ALDH1 expression was significantly associated with poorer overall survival ( χ = 16.836, p < 0.001). CONCLUSION: Our data demonstrate that ALDH1 expression is not significantly associated with conventional clinicopathological parameters (such as age, TNM stage, or histological grade). Instead, it is associated with poorer survival on univariate analysis in TNBC patients. Its lack of association with clinicopathological factors suggests its potential utility as a supplementary prognostic indicator.
Metastatic endometrial stromal sarcoma with sex cord and neuroendocrine differentiation harboring a complex gene fusion.
Sibira R, Cooke K, Shah A … +4 more , Li X, Sen S, Varghese L, Klein M
Diagn Pathol · 2025 Oct · PMID 41102766 · Full text
BACKGROUND: Low-grade endometrial stromal sarcoma (LGESS) is a malignant stromal tumor characterized by an indolent clinical course, often with late recurrence or distant metastasis after a prolonged period of remission....
BACKGROUND: Low-grade endometrial stromal sarcoma (LGESS) is a malignant stromal tumor characterized by an indolent clinical course, often with late recurrence or distant metastasis after a prolonged period of remission. These tumors can exhibit various lineage differentiations, making diagnosis challenging, especially in cases of remote recurrence. Most of these tumors are driven by fusions involving the JAZF1, SUZ12, and/or PHF1 genes. MATERIALS AND METHODS: A case of metastatic endometrial stromal sarcoma was collected. Clinicopathologic and molecular features were documented. RESULTS: A senior lady with a remote history of an unknown uterine neoplasm. Imaging of the chest revealed bilateral, enlarging pulmonary nodules, which were histologically and immunohistochemically characterized as mesenchymal-like neoplastic cells with sex cord and neuroendocrine differentiation. RNA-based next-generation sequencing identified a complex JAZF1::DLG5::PHF1 fusion, confirming a diagnosis of metastatic endometrial stromal sarcoma with sex cord and neuroendocrine differentiation. CONCLUSION: This report underscores the propensity of low-grade endometrial stromal sarcoma to metastasize after a prolonged period of remission, in which the tumor exhibited sex cord and unique neuroendocrine differentiation. We also present a complex fusion in which the DLG5 gene acts as a 'filler' to maintain the in-frame configuration.
EWSR1::BEND2 fusion sarcoma of the urinary bladder - a case report and review of literature.
Halava V, Tuominen J, Lindholm P … +3 more , Kyyrönen T, Kallajoki M, Orte K
Diagn Pathol · 2025 Oct · PMID 41102727 · Full text
In this case report we describe a Ewing-like high grade small round cell sarcoma of the urinary bladder in which an extremely rare EWSR1::BEND2 fusion was found. A 28-year-old male patient presented with hematuria and in...
In this case report we describe a Ewing-like high grade small round cell sarcoma of the urinary bladder in which an extremely rare EWSR1::BEND2 fusion was found. A 28-year-old male patient presented with hematuria and in the following examinations a large necrotic bladder tumor with spreading to adjacent prostatic tissue and multiple lung metastases were found. Histology showed a poorly differentiated small round cell tumor with perivascular rosettes and moderate membranous positivity for CD99. The methylation profile of the tumor did not match with any of the tumor entities grouped by the sarcoma classifier. With tumor agnostic methods, mainly next generation sequencing, novel fusions are being found at an accelerating rate. Our case adds to the expanding group of EWSR1 fusion neoplasms, and describes the effects of a Ewing sarcoma treatment protocol on this type of sarcoma. The relevance of traditional methods for detecting Ewing sarcoma with fluorescence in situ hybridization is decreasing as EWSR1 rearrangements are detected in tumors that show different clinical behavior and morphology. The classification of these tumors into WHO defined entities to guide treatment is a challenge.
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