Clinicopathological Features Research Articles

Prognostic factors of cutaneous soft tissue sarcomas in children: a SEER population-based study.

This study aims to analyze the clinicopathological characteristics and survival outcomes of cutaneous soft tissue sarcomas (CSTS) in children. We selected pediatric cases of CSTS diagnosed between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were calculated using Kaplan-Meier methods. We performed univariate analyses with the log-rank test and multivariate survival analyses using Cox proportional-hazards models to determine factors affecting overall survival (OS). Additionally, we constructed a predictive nomogram based on the outcomes of the Cox regression. A total of 148 pediatric patients with CSTS were reviewed. The median age at diagnosis was 13 years (range: 0-18 years). Prognostically, tumors located on the extremities showed better outcomes compared to those on the head, neck, or trunk. Among the histological types, angiosarcoma had the lowest five-year survival rate at 51.3%, which was substantially lower compared to fibrous histiocytoma and leiomyosarcoma. Cox regression analysis highlighted surgical intervention as the only significant independent prognostic factor for OS, with an increased risk of mortality observed in patients not undergoing surgery. Additionally, patients with distant-stage disease exhibited significantly lower survival rates than those with localized conditions. Pediatric CSTS represents a diverse and infrequent group of tumors, predominantly fibrous histiocytoma and leiomyosarcoma. Surgery was identified as the crucial determinant of survival, underscoring its role in effectively managing these patients.

Germline mutations of TP53 gene can be a key factor in prostate cancer genesis

Aim: The aim of this study is to investigate whether germline alterations of exon 5 of TP53 gene could be detected in the blood of known men with prostate cancer and to assess the potential association between the genomic alteration affecting this gene and clinicopathological characteristics of the patients. Methods: Forty-eight blood samples from men diagnosed with prostate cancer were analyzed for TP53 germline mutations and confirmed by Sanger sequencing. The frequency and distribution of high-frequency mutations were analyzed according to the pathological criteria of the patients and a computational study was performed to assess the effect of new mutations. Results: The Sanger sequencing revealed that 79% of the population studied carry mutations in TP53 gene. In summary, a total of 137 mutations have been identified in this gene, out of which 115 are new mutations. Frameshift mutations were the most frequent; the mutation c.392delA was recorded in fifteen cases (31%); the mutations c.383delC and c.432delG were observed at a frequency of 12.5% and 10% respectively. The most frequent missense mutation was the variant c.502C>A (p.His168Asn) identified in eleven patients (23%). One nonsense mutation was identified in one patient and resulted in a stop codon in position 126 (tyrosine). All codons affected by these alterations are part of the DNA binding domain of the protein TP53. Conclusions: The germline mutation frequency observed in prostate cancer patients, and the new mutations recorded in TP53 gene, could be in favor of a potential association of genomic alterations in this gene and prostate cancer genesis, thereby constituting a tool, similar to other genes in the DNA repair pathway such as BRCA1 and BRCA2. This could contribute to the advancement of diagnosis and therapeutic strategies for prostate cancer.

The Prognostic Impact of Tumor Size and BRAF Mutational Status in Middle Eastern Differentiated Thyroid Cancer.

Tumor size at diagnosis has been widely used as a major mortality risk factor in risk stratification of DTC. The current study was designed to analyze whether tumor size at diagnosis is a major prognostic factor in Middle Eastern DTC. We conducted a comparative study of the relationship between tumor size at diagnosis and event free survival (EFS) with respect to BRAF status in 1709 consecutive patients treated surgically for DTC. Patients were divided into four groups according to the size of tumor and BRAF mutation status: Group 1 (≤4 cm without BRAF mutation), Group 2 (≤4 cm with BRAF mutation), Group 3 (>4 cm without BRAF mutation) and Group 4 (>4 cm with BRAF mutation). Predictors of EFS were compared using the Log-rank test and Cox proportional hazards models. Tumor size >4cm was associated with adverse clinico-pathologic characteristics, such as older age, male gender, bilateral tumors, extrathyroidal extension, lymphovascular invasion, advanced tumor stage and persistent/recurrent disease. Tumor size was also inversely associated with BRAF mutation. Both tumor size (> 4cm) and BRAF mutation were associated with EFS on univariate analysis. On subgroup analysis, larger tumor size was an independent predictor of EFS (Group 3 vs. Group 1), irrespective of BRAF mutation status. Also, within the BRAF mutant tumors, larger tumor size was still an independent predictor of EFS (Group 4 vs. Group 2). Tumor size is an independent predictor of EFS in Middle Eastern DTC patients, regardless of BRAF mutational status.

Multimodal deep learning radiomics model for predicting postoperative progression in solid stage I non-small cell lung cancer

PurposeTo explore the application value of a multimodal deep learning radiomics (MDLR) model in predicting the risk status of postoperative progression in solid stage I non-small cell lung cancer (NSCLC).Materials and MethodsA total of 459 patients with histologically confirmed solid stage I NSCLC who underwent surgical resection in our institution from January 2014 to September 2019 were reviewed retrospectively. At another medical center, 104 patients were reviewed as an external validation cohort according to the same criteria. A univariate analysis was conducted on the clinicopathological characteristics and subjective CT findings of the progression and non-progression groups. The clinicopathological characteristics and subjective CT findings that exhibited significant differences were used as input variables for the extreme learning machine (ELM) classifier to construct the clinical model. We used the transfer learning strategy to train the ResNet18 model, used the model to extract deep learning features from all CT images, and then used the ELM classifier to classify the deep learning features to obtain the deep learning signature (DLS). A MDLR model incorporating clinicopathological characteristics, subjective CT findings and DLS was constructed. The diagnostic efficiencies of the clinical model, DLS model and MDLR model were evaluated by the area under the curve (AUC).ResultsUnivariate analysis indicated that size (p = 0.004), neuron-specific enolase (NSE) (p = 0.03), carbohydrate antigen 19 − 9 (CA199) (p = 0.003), and pathological stage (p = 0.027) were significantly associated with the progression of solid stage I NSCLC after surgery. Therefore, these clinical characteristics were incorporated into the clinical model to predict the risk of progression in postoperative solid-stage NSCLC patients. A total of 294 deep learning features with nonzero coefficients were selected. The DLS in the progressive group was (0.721 ± 0.371), which was higher than that in the nonprogressive group (0.113 ± 0.350) (p < 0.001). The combination of size、NSE、CA199、pathological stage and DLS demonstrated the superior performance in differentiating postoperative progression status. The AUC of the MDLR model was 0.885 (95% confidence interval [CI]: 0.842–0.927), higher than that of the clinical model (0.675 (95% CI: 0.599–0.752)) and DLS model (0.882 (95% CI: 0.835–0.929)). The DeLong test and decision in curve analysis revealed that the MDLR model was the most predictive and clinically useful model.ConclusionMDLR model is effective in predicting the risk of postoperative progression of solid stage I NSCLC, and it is helpful for the treatment and follow-up of solid stage I NSCLC patients.

Clinical study on conversion therapy of hepatocellular carcinoma - summary and comparison of clinical data from a single center of consecutive four years

AimThe purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy.MethodsA retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed.ResultsA total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively.ConclusionsWith conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery.Trial registrationThis was a retrospective study and it did not interfere with treatment decisions.

Investigating the feasibility of 18F-flortaucipir PET imaging in the antemortem diagnosis of primary age-related tauopathy (PART): An observational imaging-pathological study.

Primary age-related tauopathy (PART) is characterized by neurofibrillary tangles and minimal β-amyloid deposition,diagnosed postmortem.This study investigates18F-flortaucipir(FTP) PET imaging for antemortem PART diagnosis. We analyzed FTP PET scans from 50 autopsy-confirmed PART and 13 control subjects. Temporal lobe uptake was assessed both qualitatively and quantitatively. Demographic and clinicopathological characteristics and voxel-level uptake using SPM12 were compared between FTP-positive and FTP-negative cases. Intra-reader reproducibility was evaluated with Krippendorff's alpha. Minimal/mild and moderate FTP uptake was seen in 32% of PART cases and 62% of controls, primarily in the left inferior temporal lobe. No demographic or clinicopathological differences were found between FTP-positive and FTP-negative cases. High intra-reader reproducibility (α=0.83) was noted. FTP PET imaging did not show a specific uptake pattern for PART diagnosis, indicating that in vivo PART identification using FTP PET is challenging. Similar uptake in controls suggests non-specific uptake in PART. 18F-flortaucipir (FTP) PET scans were analyzed for diagnosing PART antemortem. 32% of PART cases had minimal/mild FTP uptake in the left inferior temporal lobe. Similar to PART FTP uptake was found in 62% of control subjects. No specific uptake pattern was found, challenging in vivo PART diagnosis.

Low-grade Papillary Nasopharyngeal Adenocarcinoma: A Clinicopathologic Series of 35 Cases.

Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is a rare neoplasm originating from the surface mucosal epithelium in the nasopharynx. To clarify its clinicopathologic, immunohistochemical, and molecular features, we retrospectively enrolled 35 patients diagnosed with LGNPPA between May 2016 and March 2024. Our cohort consisted of 14 male and 21 female patients aged 11 to 71 years (median: 37y). The most common symptoms were rhinorrhea and nasal obstruction. Most tumors originated from the roof of the nasopharynx and were clinically staged as T1N0M0. None of the patients had a history of thyroid tumors. Microscopically, most of the LGNPPA were composed of irregular papillary structures covered with single-layer columnar or cuboidal epithelium. Eighteen cases (18/35, 51.4%) showed squamous epithelium coverage, and 9 cases (9/35, 25.7%) showed the characteristic transformation of squamous epithelium into neoplasm. Squamous differentiation and a significant spindle cell component were noted in 9 cases (9/35, 25.7%) and 26 cases (26/35, 74.3%), respectively. All cases were positive for thyroid transcription factor-1 protein, CK7, EMA, and Galectin-3 but negative for thyroglobulin, PAX8, and Napsin A. Ki-67 labeling was low and ranged from 2% to 5%. The Epstein-Barr virus or human papilloma virus infection and BRAF V600E mutation were not detected in any of the cases. All patients underwent endoscopic surgical resection, and 4 patients received radiotherapy followed by endoscopic surgery. Complete follow-up data were available for 33 patients. All patients had no recurrent or metastatic disease in the last follow-up (3 to 88mo). A definitive diagnosis depends on histopathology and immunohistochemistry studies. The optimal treatment for patients with LGNPPA is total excision. Given the extremely indolent biological behavior of LGNPPA, it may be more appropriate to classify it as a primary papillary epithelial tumor rather than an adenocarcinoma of the nasopharynx.

The Relationship Between miR-196a2 Polymorphism and Colorectal Cancer Risk

ABSTRACT Objective MicroRNAs are small endogenous, non-coding, single-stranded posttranscriptional RNA molecules. The discovery of microRNAs has made new contributions to cancer diagnosis and treatment. These microRNAs reported as a responsible for colorectal cancer development with several epigenetic changes. In this study, it was aimed to evaluate the relationship between the polymorphism of miR-196a-2 polymorphism rs11614913 and colorectal cancer in Turkish population. Methods Two hundred colorectal cancer patient (124 colon cancer and 76 rectal cancer) and 240 health control individuals were included in our study, which was planned as a hospital based retrospective cohort study. MiR-196a2 polymorphism in peripheral blood samples has been determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. Significance of the results has been evaluated by using SPSS (20.0 SPSS Inc., Chicago, IL, USA.) statistical program. Results miR-196a2 C / C + C / T genotypes was found to be associated with the risk of colorectal cancer development (p: 0.001; OR: 2.04, 95% CI: 1.293-3.236). The subgroup analysis, showed that the C / C + C / T genotype increased the risk of colon cancer development 2.11 times (p: 0.016; 95% CI: 1.136-3.918) and rectal cancer 2.86 times (p: 0.011; 95% CI:1.242-6.592). The relationship between any clinicopathological features of colorectal cancer and the frequency of the C / C + C / T genotype of miR196a2 was not statistically significant (p&gt; 0.05). Conclusion This study supports that miR-196a2's C / C + C / T genotypes is related with increased colorectal cancer development risk.

Rectal Cancer in Young Adults: A Single Center Experience.

Purpose: Individuals below the age of 40 make up only 3%-11% of colorectal cancer (CRC) cases. In this study, we aimed to review clinicopathological characteristics of rectal cancer in young adults. Methods: Rectal adenocancer patients aged ≤40 were included in this study from Antalya Training and Research Hospital. A single-arm descriptive study was designed. Results: There were 85 patients in the final analyses (n = 85). The median age was 37 (19-40). Mucinous adenocarcinoma and signet-cell carcinoma rates were 11.8% for each. Twenty patients (24.4%) had high-grade cancer. Fourteen patients (16.5%) had CRC history in a first-degree relative. None of the patients were diagnosed through a screening test. Of the 85 patients, 41 (48.2%) were stage 3 and 23 (27.1%) were stage 4 at the time of diagnosis. Thirty-four (54.8%) of the 62 nonmetastatic patients had neoadjuvant and 27 (43.5%) had adjuvant treatment because of having an upfront surgery before presentation. In the nonmetastatic population, the 5-year disease-free survival rate was 69.7 ± 6.5%. De-novo metastatic underwent chemotherapy, and biological agents were administered when feasible. KRAS mutation rate was 56.5% among metastatic patients. The median progression-free survival for the first-line treatment was 11.2 months (5.7-16.6), and the median overall survival was 22.3 months (15.4-29.1). Conclusion: We demonstrated that rectal cancer is usually diagnosed at late stages in young individuals which is compatible with the previous reports. Low cancer awareness in young patients and their caregivers and adverse histological features were advocated as the reason for the diagnostic delay. However, future studies may elucidate the reason behind the common diagnosis at advanced stages.

Impact of chromosomal aberrations detected by chromosome banding analysis in symptomatic Waldenström's macroglobulinemia.

The clinicopathologic features and prognostic impact of MYD88 L265P (MYDL265P) and CXCR4 mutations (CXCR4Mut) have been well reported, although little is known regarding the impact of chromosomal aberrations (CA) detected by chromosome banding analysis (CBA) in symptomatic Waldenström's macroglobulinemia (sWM). Thus, we investigated the clinicopathologic features and prognostic impact in sWM with CAs identified by CBA. We retrospectively analyzed the clinicopathologic results and genomic alterations by droplet digital PCR, fluorescence in situ hybridization (FISH), and CBA using the G-banding method in bone marrow samples from sWM patients collected between April 2010 and March 2024 at our institute. The relationship between CAs and clinicopathologic features was evaluated, as well as the time to next treatment (TTNT). Thirty-five patients were enrolled. The median age was 71 years, and the median hemoglobin level was 10.1g/dL. The median serum IgM and M-protein levels were 3,009mg/dL and 2.95g/dL, respectively. MYDL265P was found in 30/35 patients (85.7%), whereas CXCR4Mut was found in 3/35 patients (8.6%). Deletion 6q identified by FISH in 5/18 patients (28%), and CAs using CBA in 9/34 patients (26%), including 4/34 (12%) complex karyotypes. sWM with CAs had more anemia (p = 0.04) and hypoalbuminemia (p = 0.007), in addition to higher serum M-protein and IgM levels (p = 0.03). With a median follow-up of 73 months, the median TTNT in patients with and without CAs was 27 and 68 months, respectively. CAs with CBA may be associated with clinical aggressiveness and shorter TTNT in sWM.

TP53 mutations and survival in ovarian carcinoma patients receiving first-line chemotherapy plus bevacizumab: Results of the MITO16A/MaNGO OV-2 study.

To date, there are no biomarkers that define a patient subpopulation responsive to bevacizumab (BEV), an effective treatment option for advanced ovarian carcinoma (OC). In the context of the MITO16A/MaNGO OV-2 trial, a Phase IV study of chemotherapy combined with BEV in first-line treatment of advanced OC, we evaluated TP53 mutations by next-generation sequencing and p53 expression by immunohistochemistry (IHC) on 202 and 311 cases, respectively. We further correlated TP53 mutations in terms of type, function, and site, and IHC data with patients' clinicopathological characteristics and survival. TP53 missense mutations of unknown function (named unclassified) represented the majority of variants in our population (44.4%) and were associated with a significantly improved overall survival (OS) both in univariable (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.20-0.92, p = .03) and multivariable analysis (HR = 0.39, 95% CI = 0.18-0.86, p = .02). Concordance between TP53 mutational analysis and IHC was 91%. We observed an HR of 0.70 for OS in patients with p53 IHC overexpression compared to p53 wild-type, which however did not reach statistical significance (p = .31, 95% CI = 0.36-1.38). Our results indicate that the presence of unclassified TP53 mutations has favorable prognostic significance in patients with OC receiving upfront BEV plus chemotherapy. In particular, unclassified missense TP53 mutations characterize a subpopulation of patients with a significant survival advantage, independently of clinicopathological characteristics. Our findings warrant future investigations to confirm the prognostic impact of TP53 mutations in BEV-treated OC patients and deserve to be assessed for their potential predictive role in future randomized clinical studies.

ARAF Amplification in Small-Cell Lung Cancer-Transformed Tumors Following Resistance to Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors

Background/Objectives: Although tyrosine kinase inhibitors (TKIs) targeting EGFR-activating mutations significantly improved the outcome of EGFR-mutant NSCLC, resistance inevitably emerges. Despite the heterogeneity of these resistance mechanisms, many induce activation of MAPK signaling in the presence of EGFR-TKIs. While ARAF gene amplification is identified as a resistance mechanism that activates MAPK signaling by directly interacting with RAS, little is known about its clinicopathologic characteristics. Methods: We conducted a single-center retrospective analysis of the presence of ARAF amplification in re-biopsied samples in patients with EGFR-mutant NSCLC resistant to EGFR-TKIs. Demographic data, treatment course, and clinical molecular testing reports were extracted from electronic medical records. ARAF amplification was determined using a gene copy number assay. RNA sequence analysis was performed in patients with ARAF amplification as well as presenting histologic transformations to small-cell lung carcinoma (SCLC). Results: ARAF amplification was identified in five of ninety-seven patients resistant to erlotinib or gefitinib, and four of forty-eight patients resistant to Osimertinib. ARAF amplification was dominantly observed in female patients with EGFR exon 19 deletion. All ARAF-amplified tumors retained their founder EGFR mutation and were absent of secondary mutations. Two cases were found where ARAF amplification correlated with a histological transformation to SCLC. Conclusions: ARAF amplification was identified in 5–8% of EGFR-TKI-resistant tumors. The possible roles of ARAF in SCLC transformation warrant further investigation.

Primordial Odontogenic Tumor: A Decade Post-Description Systematic Review.

Primordial odontogenic tumor (POT) is a rare benign tumor arising from odontogenic epithelium and ectomesenchyme. It typically presents in children and young adults. POT is often found in the posterior mandible and frequently presents as asymptomatic swelling. A systematic review of the literature was conducted to comprehensively analyze the clinicopathologic features of this rare entity over the past ten years. A systematic review of POT case series and case reports following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines was performed. Data on demographics and clinical characteristics, including age, sex, clinical presentation, duration of the lesion, location, and radiographic and histological features, were extracted. A quantitative description of immunohistochemical studies reported in the literature was also performed. Treatment, a follow-up period, and recurrence were collected for analysis. This review included 26 studies involving 36 POT cases. Patients often presented with asymptomatic swelling at a median age of 12 years, with a male-to-female ratio of 1.18:1. The posterior mandible was the most commonly affected site, while three cases were noted in the anterior region exclusively in the maxilla. Most lesions appeared as unilocular radiolucencies with well-defined borders; however, five cases exhibited fine trabeculation or radiopacities. The primary histological features observed in POT included ectomesenchymal stroma lined by columnar cells with nuclear reverse polarity. Most cases were treated through enucleation and curettage (50.0%), followed by tumor excision (36.1%). Only one case demonstrated recurrence among the 29 cases with known follow-up information. This study offers comprehensive and current descriptive data on POT, enhancing the ability of clinicians and pathologists to accurately identify these rare lesions and thereby avoid misdiagnosis and inappropriate management.

Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer

ObjectiveIncreased glutamine metabolism by cancer cells via upregulation of the drug-targetable enzyme glutaminase may contribute to an immune-suppressive tumor microenvironment. Inhibiting glutamine metabolism can not only suppress tumor growth, but...

Parathyroid carcinoma: molecular pathology and correlation with clinicopathologic features, a single center experience

Abstract Introduction/Objective Parathyroid Carcinomas are rare malignant neoplasms, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single center regarding the clinic-pathologic and genetic analysis of parathyroid carcinoma cases. Methods/Case Report The study is a retrospective review of all patients with parathyroid carcinoma that were evaluated at a tertiary oncologic center from 2001 until 2023. Results (if a Case Study enter NA) A total of nine cases (6 male and 3 female) were identified, with a mean age at diagnosis of 52 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 7), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and a mean PTH of 1123 pg/ml (&amp;lt;a href=“tel:276- 2500”&amp;gt;276-2500&amp;lt;/a&amp;gt;). En bloc surgical resection was performed in 6 patients and 3 patients underwent adjuvant radiotherapy. Recurrence was observed in 4 cases (44.4%) after a median of 24 months following surgery. Negative immunohistochemical staining of parafibromin was noted in 3/4 cases of recurrence. Parathyroid carcinoma was diagnosed on the basis of finding lesions with vascular or perineural invasion, capsular penetration, and/or documented metastases. Immunohistochemical staining for parafibromin, Ki-67, and E-cadherin was performed on formalin-fixed, paraffin-embedded tissue samples. Next generation sequencing (NGS) was performed in 6/9 cases and CDC73 mutations were present in 38.5% of analyzed patients. Loss of TP53 and RB1 alleles and CCND1 amplification were other reported genetic alterations in the study cohort. Conclusion Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Inactivating CDC73 alterations which include truncating or frameshift mutations, as well as missense mutations lead to the loss of parafibromin immunoreactivity. Other molecular alterations like PTEN and PIK3CA mutations may represent potential targets for molecular therapy. An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish parathyroid carcinoma from other parathyroid neoplasms.

Establishment of the Prognostic Signature with Genes Related to G2/M Checkpoint in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality in the world. Prognostic indicators such as clinicopathological characteristics and single molecular signature are far from satisfactory in clinical practice. More and more researches have suggested that polygenic prognostic features could predict the prognosis of cancer more precisely than single genes nowadays. In this study, we performed gene set enrichment analysis (GSEA) to identify the sets of TCGA hallmark genes. Univariate Cox regression analysis was used to select preliminary genes, and then multivariate Cox regression analysis was used to identify genes associated with overall survival (OS). We also used Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis to validate the prognostic gene signature. Lastly, qRT-PCR was used to evaluate the expression of these genes in clinical samples, and immunohistochemical staining was performed to confirm the signature. A 12-gene signature was finally built and the risk score was significantly associated with the survival of the patients. Subsequent validation by qRT-PCR and immunohistochemical staining in clinical specimens confirmed the value of the risk score in predicting the prognosis. We developed a 12-gene signature that could predict the prognosis of HCC patients. This signature is of high precision and would help identifying subgroups of HCC patients with high or low risk of unfavorable survival.

Clonal Bronchopulmonary B-Cell Proliferations of Indeterminate Malignant Potential in Patients with Common Variable Immune Deficiency (CVID) associated Granulomatous Lymphocytic Interstitial Lung Disease (GLILD)

Abstract Introduction/Objective Pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is often challenging to distinguish from reactive nodular lymphoid hyperplasia, and assessing B-cell clonality in such cases is crucial in making the distinction. However, patients with common variable immune deficiency (CVID) can harbor clonal or oligoclonal lymphoid populations in their tissues, particularly in association with granulomatous lymphocytic interstitial lung disease (GLILD), making the distinction from MALT lymphoma extremely challenging. We report six cases of GLILD with clonal or oligoclonal B cell infiltrates in lung wedge resection specimens and describe their clinicopathologic characteristics, management, and outcomes. Methods/Case Report A retrospective review was performed to collect lung wedge resection specimens from patients with CVID showing atypical B-cell infiltrates associated with GLILD between 01/2015 and 08/2023. The clinicopathologic findings, management, and response to treatment were studied. Results (if a Case Study enter NA) A total of six GLILD cases were identified with variable degrees of architectural and cytologic lymphoid atypia. Clonality of the lymphoid infiltrate was assessed by kappa/lambda in situ hybridization staining in all six, flow cytometry in 3/6, and IGH gene rearrangement in 4/6 cases. The infiltrate showed frank lambda restriction in 1/6, lambda predominance in 1/6, polytypic expression in 1/6, and no significant plasmacytic component in 3/6 cases. Flow cytometry detected atypical light chain skewed B-cell populations in 3/3 of cases. IGH was positive for clonality in 3/4 and oligoclonal in 1/4 cases. Four patients received therapeutic intervention for GLILD, including one with Rituximab monotherapy, two with Rituximab+Azathioprine, and one with Rituximab+Mycophenolate leading to marked symptomatic and radiologic improvement in all four patients. The remaining two patients were observed to have stable disease. Conclusion Patients with CVID can harbor clonal B-cell populations due to their underlying immune dysfunction. Studies have shown that these can be transient and may not always progress to overt lymphoma. In the setting of GLILD, detecting these populations makes the distinction from MALT lymphoma very challenging. Given that the first- line therapy for both GLILD and MALT is anti-CD20 therapy, the malignant potential of these clones remains uncertain and can only be determined with long-term clinical follow-up.

Beyond the Surface: Uncovering the PML::RARA Fusion in Cytogenetically Cryptic and FISH-Negative Acute Promyelocytic Leukemia- A Case Report and Review of the Literature

Abstract Introduction/Objective Chromosomal t(15;17)(q22;q21), resulting in a fusion between the PML gene on chromosome 15q22 and the RARA gene on chromosome 17q21, is the cytogenetic hallmark of acute promyelocytic leukemia (APL). Conventional karyotyping, along with fluorescence in situ hybridization (FISH), can detect the PML/RARA rearrangements in up to 98% of APL cases. Reverse transcriptase-polymerase chain reaction (RT-PCR) is often used to confirm the initial diagnosis. APL with PML::RARA fusion, which is negative with FISH and conventional karyotyping approaches but positive with RT-PCR, is extremely rare. Herein, we report a de novo APL case that was positive by RT-PCR but negative by cytogenetics and FISH studies. A comprehensive review of the literature was also performed. Methods/Case Report A 23-year-old male presented to the ED for left upper extremity weakness 2 days after post- dental cleaning. Upon admission, he developed intracranial hemorrhage, necessitating urgent decompressive hemicraniectomy. Blood smear revealed promyelocytes; flow cytometric analysis showed a CD13+, CD33+, MPO+, CD117+, CD34-, and HLA-DR- abnormal cell population. STAT interphase FISH analyses for PML/RARA fusion and RARA break-apart were negative. A diagnosis of APL was made based on abnormal promyelocytes and characteristic flow cytometry findings. ATRA was immediately administrated. However, the post-operative course was complicated by significant coagulopathy, pancytopenia, and multi-organ failure, and the patient expired 7 days later. RT-PCR returned positive for PML::RARA long fusion transcript; the conventional cytogenetics study was uninformative. The clinical, pathological, and genetic features of 31 cases of FISH/Cytogenetics-negative APL harboring cryptic rearrangements of PML-RARA, detected by RT-PCR in the literature, have been reviewed. Various detection methods were also discussed. Results (if a Case Study enter NA) N/A Conclusion Conventional cytogenetics, FISH and RT-PCR analysis are complementary studies for all clinical suspected APL cases. The clinicopathological characteristics also play critical roles in APL diagnosis when genetic confirmation of the PML::RARA fusion is unavailable.

Leiomyomas of the Gastrointestinal Tract: A Clinicopathologic Review

Abstract Introduction/Objective Leiomyomas are benign smooth muscle tumors that can be found anywhere along the gastrointestinal tract (GIT). We undertook a retrospective study to investigate the incidence of GIT leiomyomas and to gain better understanding of their clinicopathologic characteristics. Methods/Case Report The surgical pathology files at our institution were searched for GIT leiomyomas encountered between 07/1994 and 12/2023. The clinical and histopathological findings were recorded. Results (if a Case Study enter NA) 74 leiomyomas were identified in various GIT locations, including esophagus (8), stomach (20), duodenum (3), colon (37) and rectum (6). There were 40 females and 34 males, with an average age of 61.5 years. Esophageal leiomyomas showed a mean size of 2.2 cm. 5/8 patients had synchronous adenocarcinomas of gastroesophageal junction and 1/8 patient had synchronous squamous cell carcinoma of esophagus. Gastric leiomyomas showed a mean size of 2.0 cm. 6/20 patients had synchronous and 4/20 patients had metachronous GIT cancers. 2/6 patients who had leiomyomas with synchronous GIT cancers also presented with gastrointestinal stromal tumors (GIST). Duodenal leiomyomas showed a mean size of 0.7 cm. 1/3 patient had synchronous pancreatic adenocarcinoma. Colonic leiomyomas showed a mean tumor size of 0.6 cm. 2/37 patients had synchronous and 6/37 patients had metachronous GIT cancers. Rectal leiomyomas showed a mean tumor size of 0.9 cm. 1/6 patient had metachronous non-GIT sarcoma. Adenomatous polyps coexisted with 10/37 colonic leiomyomas, 2/6 rectal leiomyomas and 1/20 gastric leiomyoma. Immunohistochemical stains (αSMA, Desmin, CD117, DOG-1, CD34) were consistently utilized in diagnosis to exclude GIST. Conclusion Leiomyomas were most frequently found in the colon (50.0%), followed by the stomach (27.0%). Esophageal and gastric leiomyomas showed larger sizes (averaged 2.2 and 2.0 cm respectively) than duodenal, colonic, and rectal counterparts (averaged 0.7, 0.6, and 1 cm, respectively). This suggests an association between tumor locations and clinical features. Synchronous malignancies occurred in 20.2% of cases, mainly gastroesophageal/colonic adenocarcinomas. Metachronous malignancies were noted in 14.8% of cases. Given the high incidence of synchronous/metachronous malignancies (35.1%) in the gastrointestinal tract, close clinical surveillance is warranted for these patients.

Biological Adaptations in Rhabdomyosarcoma Tumor Cells in lymph nodes: A Case Report of RMS with FUS::TFCP2 translocation

Abstract Introduction/Objective The WHO classification categorizes Rhabdomyosarcoma (RMS) into four main subtypes based on clinicopathological and molecular features. However, TFCP2-rearranged RMS, a rare tumor, does not neatly fit into any of these subtypes. Literature review identified only two reported cases of RMS with FUS::TFCP2 fusion and a round cell component. Methods/Case Report We present a rare case of RMS in lymph nodes with FUS::TFCP2 translocation in a 29-year- old female with a history of spindle cell rhabdomyosarcoma in the bilateral maxilla. The original tumor exhibited a distinctive spindle and epithelioid phenotype, coexpressing myogenic markers, epithelial markers, and ALK. FUS::TFCP2 translocation was confirmed, representing an uncommon subset of RMS. After chemotherapy, radiation, and surgery, the patient developed multiple bilateral pathologically enlarged cervical lymph nodes. Excision revealed metastatic rhabdomyosarcoma involving lymph nodes with a predominantly round cell and epithelioid morphology, with approximately 5% spindle cell growth, resembling the pattern identified in the primary resection. Results (if a Case Study enter NA) NA Conclusion Previous reports suggest that RMS with FUS::TFCP2 fusion displays a biphasic pattern, comprising solid proliferation of round cells in superficial areas and spindle cells in deeper regions. The altered cell morphology observed in our case may be attributed to the varied distribution pattern of each component with lesion depth and the cellular stress response. Previous literature reported that radiation stress potentially leads to biological adaptations of tumor cells and tumor radioresistance. Our findings underscore the distinctive phenotype of RMS with FUS::TFCP2 fusion, characterized by the coexpression of myogenic and epithelial markers, along with ALK positivity. Understanding the cellular adaptations of RMS cells could inform the development of novel clinical interventions aimed at enhancing radiosensitization and improving therapeutic efficacy, ultimately enhancing patient survival.