Diagnostic Pathology最新文献

Background: The prognostic impact of high mobility group box 1 (HMGB1) in lung adenocarcinoma may depend on its subcellular localization, while the density of tumor-infiltrating lymphocytes (TILs) reflects the host anti-tumor immune response. However, the combined prognostic value of these two factors in early-stage lung adenocarcinoma remains unclear.

Methods: This retrospective study included 112 patients with pathological stage I-II lung adenocarcinoma who underwent complete surgical resection at our institution between 2007 and 2017. None received neoadjuvant chemotherapy or radiotherapy. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tumor specimens to evaluate HMGB1 subcellular localization and stromal TILs infiltration. The latter was semi-quantitatively assessed according to the International TILs Working Group recommendations and dichotomized using the median value as the cutoff. Clinicopathological variables, including differentiation, pleural invasion, lymphovascular invasion, and pathological stage, were collected and correlated with HMGB1 localization and TIL status. Survival outcomes were analyzed using Kaplan-Meier and Cox proportional hazards models. Multivariable analyses were adjusted according to the events-per-variable (EPV) rules, and model diagnostics included proportional hazards testing and multicollinearity assessment. Interobserver agreement for HMGB1 localization was evaluated using Fleiss'κ statistics.

Results: Cytoplasmic HMGB1 expression and low TIL infiltration were significantly associated with adverse clinicopathological features, including poorer differentiation and higher rates of lymphovascular invasion. Both cytoplasmic HMGB1 and low TIL levels independently predicted a shorter DFS and OS. Patients with the combined phenotype of cytoplasmic HMGB1 and low TIL levels had the worst prognosis, with hazard ratios exceeding those of either factor alone. The integrative model based on HMGB1 localization and TIL status enhanced the prognostic discrimination beyond conventional clinicopathological parameters.

Conclusions: HMGB1 subcellular localization and TIL infiltration are independent prognostic biomarkers of early-stage lung adenocarcinoma. An integrative model combining these parameters provides enhanced risk stratification and may inform individualized postoperative management strategies.

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 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.