Diagnostic Pathology最新文献

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.

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.

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.

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.