Lung cancer remains the leading cause of cancer-related deaths worldwide, with brain metastasis being one of the most common complications in advanced-stage disease. The development of noninvasive and efficient early diagnostic methods is therefore of critical clinical importance. In this study, untargeted liquid chromatography-mass spectrometry (LC-MS) was employed to perform metabolomic profiling of 66 serum samples from patients with lung cancer brain metastasis, early-stage lung cancer, and healthy controls. A total of 719 metabolites were identified with high data reliability. Comparative analysis revealed 20 significantly upregulated and 12 significantly downregulated metabolites in the lung cancer brain metastasis group. These differentially expressed metabolites were primarily enriched in amino acid and energy metabolism pathways. This specific metabolic signature was highly associated with the brain metastatic state. Although not yet validated for clinical application, this profile demonstrated robust discriminatory power within the current cohort and serves as a potential set of risk-stratification biomarkers. These findings identify a distinct metabolic phenotype associated with brain metastasis, laying the critical groundwork for future research into noninvasive diagnostic strategies. Nevertheless, further validation within independent, longitudinal cohorts is required.

Primary tumors of the pulmonary artery are rare and often mimic thromboembolic disease, leading to delayed diagnosis with potentially serious consequences.

A middle-aged woman with reduced exercise tolerance was found to have a progressive left hilar mass causing near-complete obstruction of the left pulmonary artery. Given high procedural risk, an intracardiac echocardiography (ICE)-guided endovascular biopsy was performed. Tissue sampling was successful and complication free. Histopathology and molecular analysis demonstrated a malignant pleomorphic neoplasm with MDM2 amplification, consistent with pulmonary artery intimal sarcoma.

ICE-guided biopsy enables safe, real-time tissue acquisition from central pulmonary artery lesions. This technique enables timely histological and molecular diagnosis, especially when conventional biopsy approaches are deemed too risky.

Pulmonary artery intimal sarcoma should be differentiated from thromboembolic disease using imaging and clinical progression. ICE-guided biopsy represents a safe diagnostic option in high-risk cases and supports multidisciplinary decision-making.

Adenomatoid tumor is a rare benign neoplasm of mesothelial origin occurring in various anatomical locations, including the uterus. In this article, we describe an adenomatoid tumor of the uterus exhibiting severe nuclear atypia in the clinical context of long-term hormone therapy. The patient was a 51-year-old woman who underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy for uterine leiomyomas. Gross evaluation of the uterus revealed multiple intramural and subserosal unencapsulated nodules that were both well and poorly circumscribed and measured from 4 to 25 mm. Microscopically, one of the nodules consisted of hyperplastic leiomyocytes intermixed with irregular vascular-like and tubular spaces lined by flattened cells that occasionally showed moderate to severe nuclear atypia (enlargement, hyperchromasia, and multinucleation). Bizarre pleomorphic cells were also present. Mitotic activity was minimal. The tumor cells showed diffuse positivity for calretinin, keratin AE1/AE3, L1 cell adhesion molecule, and podoplanin, while CD31, CD34, epithelial membrane antigen, HMB45, MDM2, and S100 protein stains were negative. Expression of BRCA1-associated deubiquitinase 1 and methylthioadenosine phosphorylase was retained. This immunophenotype supported a mesothelial origin of the neoplastic cells, leading to the final diagnosis of adenomatoid tumor with marked nuclear atypia. Unusual histopathological findings in adenomatoid tumors, such as marked nuclear atypia and pleomorphism, may pose significant diagnostic challenges and result in misdiagnosis. Despite these unusual features, the tumor in our study showed no evidence of aggressive behavior or malignant transformation. Although we hypothesize that these changes may be related to prolonged hormone therapy, their pathogenesis and clinical significance remain unclear, underscoring the need for further investigation.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoma with a poor prognosis. The human T-lymphotropic virus 1 (HTLV-1) is associated with immunodeficiency and increased extranodal involvement in patients with diffuse large B-cell lymphoma (DLBCL). We report on a 47-year-old woman with spastic paraparesis and hepatitis B who was diagnosed with the acute form of ATLL. The clinical picture reveals peripheral generalized lymphadenopathy and splenomegaly. Findings on a hematologic exam indicated leukocytosis with lymphocytosis. A bone marrow biopsy/aspiration confirmed 50% T-cell lymphoid infiltration. Biochemistry results revealed hypercalcemia and a high lactate dehydrogenase value. Results of a CT scan indicated abdominal and thoracic adenopathy as well as moderate splenomegaly. A supraclavicular lymph node biopsy established a DLBCL diagnosis. The final diagnosis was composite lymphoma, DLBCL, and ATLL. The CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], and prednisone) regimen was chosen due to the patient's ECOG performance status. Multiple infectious complications were diagnosed during chemotherapy-induced secondary aplasia. A complete remission, confirmed via PET-CT imaging, was obtained. After 1 month, a skin tumor on the upper right thigh was discovered and biopsied, and the histopathological exam and immunochemistry findings indicated Epstein-Barr virus-DLBCL lymphoma. The association of 2 aggressive lymphomas in a single HTLV-1 carrier is a rare report, and the evolution was severe, complicated by opportunistic infections, and unfavorable.

Synovial sarcoma (SS) is a genetically defined soft tissue sarcoma driven by the pathognomonic SS18::SSX fusion and is generally characterized by a low burden of secondary genomic alterations. We report a 42-year-old man with metastatic SS harboring both the SS18::SSX1 rearrangement and the BRAF V600E mutation. The patient developed metastatic disease following standard multimodal therapy. Comprehensive genomic profiling using DNA and RNA based next-generation sequencing identified the SS18::SSX1 fusion and the activating BRAF V600E mutation. The SS18 rearrangement was further confirmed by fluorescence in situ hybridization (FISH), and immunohistochemistry supported the histologic diagnosis. Treatment with combined BRAF and MEK inhibition (dabrafenib and trametinib) resulted in a clinical response. In addition to this index case, a literature review identified multiple additional SS harboring BRAF V600E, supporting its role as a recurrent, potentially targetable alteration in a small subset of SS. These findings highlight the value of comprehensive genomic profiling in SS, particularly in advanced or refractory cases, to identify rare but actionable molecular events that may expand therapeutic options.

Prostate cancer (PCa) is a heterogeneous and prevalent neoplasm, traditionally stratified by PSA and Gleason Score. However, these biomarkers have prognostic limitations, driving the search for new molecular markers. Alterations in DNA mismatch repair (MMR) system proteins are associated with genomic instability, therapeutic resistance, and poorer clinical outcomes. Their relevance in PCa remains poorly understood, highlighting MMR status as a potential prognostic biomarker. This systematic review, following PRISMA 2020 guidelines, evaluated the relationship between MMR protein (MSH2, MSH6, MLH1, PMS2) expression and clinical-pathological outcomes in PCa. Ten studies assessing MMR protein expression in prostate adenocarcinoma samples were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Studies revealed heterogeneous MMR protein expression. Loss of MSH2 consistently correlated with poorer clinical outcomes, including biochemical recurrence, higher Gleason Scores, and perineural invasion. MSH6 was more prevalent in high-grade tumors, without clear prognostic association. Cytoplasmic MLH1 expression was linked to aggressive histological patterns; PMS2 results were conflicting. Two studies assessed Microsatellite Instability (MSI), correlating with MSH2 and PMS2. Overall, MMR protein alterations, particularly MSH2 loss, may indicate worse PCa prognosis. However, methodological heterogeneity and lack of standardization hinder definitive conclusions. Further studies, integrating MSI analyses are crucial to confirm their prognostic.

Complex karyotype (CK) in chronic lymphocytic leukemia (CLL), defined by ≥ 3 or ≥ 5 (high-CK) chromosomal aberrations, is an established adverse prognostic marker. However, different methods for counting aberrations are used in the literature and clinical trials, potentially affecting CK classification and risk stratification. We systematically compared two established counting methods: the approach by Jondreville et al., which counts one aberration per item separated by commas, and the International System for Human Cytogenomic Nomenclature (ISCN) method, which counts unbalanced aberrations involving multiple chromosomes as two aberrations. Chromosome banding analyses from 1605 CLL patients were evaluated using both counting methods. This revealed that CK classification by the two methods disagreed in 7.5% of all cases. However, both methods performed similarly in prognostic stratification of these ambiguous cases. This suggests that the method proposed by Jondreville et al. should be adopted, as it is simpler to perform and less ambiguous. Furthermore, we compared how cases were stratified if aberrations are counted across all (sub)clones (as suggested both by Jondreville et al. and the ISCN) or only in the clone with the most aberrations. In total, 3.5% of all cases were differentially classified depending on whether aberrations were counted across all clones or only in the most complex clone. Importantly, these ambiguous cases were better stratified by counting aberrations in the most complex clone only. We therefore suggest the method proposed by Jondreville et al. to determine CK status in CLL and to count aberrations only in the clone with the most aberrations.

The SMARCA4 gene encodes a key ATPase subunit of the SWI/SNF (BAF) chromatin-remodeling complex, which plays an essential role in regulating transcription and cellular differentiation. Loss-of-function alterations of SMARCA4 are common in various human cancers, including sarcomas; however, rare SMARCA4 fusion events, presumably resulting in gain of function, have also been reported. We present two pediatric soft-tissue sarcomas harboring a novel, recurrent in-frame fusion between SMARCA4 and VEZF1 (Vascular Endothelial Zinc Finger 1), a transcription factor important for vascular development and angiogenesis. The predicted fusion protein contains the N-terminal QLQ protein interaction domain of SMARCA4 and preserves most of VEZF1's C2H2 zinc-finger DNA-binding domains. Interestingly, another component of the BAF complex, SS18, has also been reported to be fused to VEZF1 in uterine sarcoma. We propose that fusion of BAF complex components to VEZF1 leads to aberrant recruitment of chromatin-remodeling activity to VEZF1 target loci, resulting in altered chromatin architecture, dysregulated VEZF1-dependent transcription, and tumorigenesis.

The clinical features and outcomes of rhabdomyosarcoma (RMS) occurring as a secondary neoplasm are unknown. We aimed to determine the prevalence of secondary RMS (sRMS) and compare patient characteristics, treatment, and overall survival (OS) between primary RMS (pRMS) and sRMS in children, adolescents, and young adults.

We queried Surveillance, Epidemiology, and End Results data for patients 0-39 years old diagnosed with RMS from 2000 to 2021. Prevalence of sRMS was reported with 95% confidence intervals (CIs). Comparisons between pRMS and sRMS were evaluated using Chi-square or Fisher's exact test for categorical variables and Mann-Whitney U tests for continuous variables. Five-year OS from time of RMS diagnosis was calculated using Kaplan-Meier analysis.

We identified 2676 patients with pRMS and 71 patients with sRMS (prevalence: 2.6%; 95% CI: 2.0%-3.3%). Patients with sRMS were older (p < 0.001) and more likely to have non-alveolar, non-embryonal histology (p < 0.001). Radiotherapy (63.6% vs. 32.4%, p < 0.001) and chemotherapy (93% vs. 77.5%, p < 0.001) were less frequently administered to patients with sRMS. Primary malignancies preceding sRMS included germ cell tumors (28.2%) and leukemia/lymphoma (23.1%). The 5-year OS in sRMS was inferior to pRMS (37% vs. 60%, p < 0.001). OS in sRMS was associated with age (p = 0.028) and site (p = 0.004).

sRMS is rare and has distinct clinical features compared to pRMS. Treatment characteristics differed, including decreased use of chemotherapy or radiotherapy, and patients with sRMS had inferior 5-year OS. While this inferior OS is likely multifactorial, decreased use of chemotherapy and radiotherapy may be contributory.

Squamous cell carcinoma is a malignant tumor that affects the skin and mucous membranes. It may present as painless superficial lesions, or as rapidly growing, exophytic masses, sometimes ulcerated, which can invade and damage surrounding tissues. It is the second most common malignant neoplasm of the skin, characterized by high clinical variability, which makes early diagnosis and timely treatment essential to improve prognosis. The aim of this case report is to evaluate the clinical efficacy, tolerability, and durability of response of electrochemotherapy in the treatment of cutaneous squamous cell carcinoma of the lip in patient with compromised general health.

We report the case of a 79-year-old male with multiple comorbidities, including chronic kidney disease, diabetes, and ischemic heart disease, who presented with a rapidly growing lesion on the lower lip. The surgical approach would entail a functional deficit of the lips and an aesthetic impairment. Due to the patient's systemic condition, a more conservative treatment was chosen, namely treating the neoplasm with electrochemotherapy.

The treatment led to controlled necrosis of the lesion and complete healing by secondary intention within three months. The patient experienced no functional impairment or recurrence during a four-year follow-up.

This case highlights the potential of electrochemotherapy as a safe and effective alternative for managing lip squamous cell carcinoma, particularly in patients who are not candidates for surgery or radiotherapy. The favorable clinical and aesthetic outcomes support its consideration in selected cases.