Small Cell Research Articles

Perihippocampal failure after hippocampal-avoidance brain radiotherapy in small cell lung cancer patients: Cases report and literature review.

Brain metastasis is a major concern, and may occur in roughly 50% of patients during the clinical course of small cell lung cancer (SCLC). Because prophylactic cranial irradiation reduces the incidence of brain metastases and improves overall survival, prophylactic cranial irradiation is recommended for SCLC patients without distant metastases or an extensive stage and have responded well to systemic therapy. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) is preferred to preserve hippocampal function while minimizing negative cognitive effects. Reducing the dose delivered to the hippocampus below the therapeutic brain dose may increase the risk of hippocampal progression; thus, HA-WBRT may be associated with a risk of perihippocampal recurrence. Three patients with SCLC received HA-WBRT and developed intracranial failure during clinical follow-up; 3 relapsed with intracranial failure in the perihippocampal region after 12, 13, and 7 months, respectively. Compared to the therapeutic brain dose of cases and the underdose region around the HA region, we matched MRI scans of intracranial failure and previous planning scans of simulation and found a deviation of the underdosed region within the perihippocampal failure of approximately 55% to 63%. Perihippocampal failure is a rare clinical outcome in SCLC patients following HA-WBRT. Perihippocampal failure could be caused by an underdose of radiation or by the aggressiveness of the cancer itself. More research into this topic is encouraged.

Unexpected rare uterine carcinosarcoma with neuroendocrine differentiation: Reflections on clinical diagnosis and treatment of a case report.

Uterine carcinosarcoma (UCS) is a rare and highly invasive malignant tumor.It exhibits an ectopic growth pattern of the uterus,and its histological features are biphasic differentiation of malignant epithelial components (cancer) and malignant mesenchymal components (sarcoma). The pathological pattern of high-component neuroendocrine differentiation is extremely rare. Due to the inherent heterogeneity of tumors, it increases the difficulty of accurate identification and diagnosis. The author introduces a rare case of primary endometrial carcinosarcoma (heterologous) with small cell neuroendocrine carcinoma (SCNEC) components. There is limited literature on this rare pathological differentiation pattern and a lack of guidelines for the best treatment methods, which prompts reflection on the diagnosis, optimal treatment strategies, and how preoperative diagnosis can affect patient prognosis for endometrial carcinosarcoma with neuroendocrine differentiation. The patient is an elderly woman who presents with abnormal vaginal bleeding after menopause. Transvaginal ultrasound examination shows that the uterus is slightly enlarged, and there is a lack of homogeneous echogenicity in the uterine cavity. Subsequently, a hysteroscopic curettage was performed, and a space-occupying lesion was observed on the anterior wall of the uterine cavity. Preoperative endometrial biopsy revealed SCNEC of the endometrium. The patient underwent radical hysterectomy, and the postoperative pathological results showed that UCS (heterologous) was accompanied by SCNEC components (about 80%). The patient received radical hysterectomy, followed by adjuvant chemotherapy. After 7 months of follow-up, no tumor recurrence or metastasis was found at the time of writing this article. The histological type of UCS (heterologous) with cell neuroendocrine carcinoma components is rare and highly invasive, with a high misdiagnosis rate in preoperative biopsy. There are currently no effective treatment guidelines for this type of case. The unusual appearance of SCNEC components in this case poses a challenge for both pathologists and surgeon. The rare differentiation pattern of this case exposes the complexity of its management and the necessity of prospective trials to determine the optimal treatment plan.

Population based study on the progress in survival of primarily metastatic lung cancer patients in Germany

Lung cancer is known for its high mortality; many patients already present with metastases at the time of diagnosis. The aim of this study is to assess the impact of new treatment strategies on the survival of primarily metastatic lung cancer patients and to analyze the differences in outcomes between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. Population-based data, provided by the Robert-Koch Institute in Germany, was used and patients diagnosed between 2007 and 2018 were included in the study. We differentiated between NSCLC and SCLC patients and analyzed the survival over time for both sexes separately, using the Kaplan–Meier method. To evaluate survival advantages, we calculated multivariable hazard ratios. In total, 127,723 patients were considered for the study. We observed a moderate increase in survival over time. All patients showed an increased survival rate when undergoing chemotherapy. Minimal to no increase in survival was shown in NSCLC patients when receiving radiotherapy, whereas SCLC patients’ survival time did benefit from it. NSCLC patients receiving immunotherapy showed an increase in survival as well. It can be concluded that advancements in radiotherapy, the application of chemotherapy, and the introduction of immunotherapies lead to an increased survival time of both NSCLC and SCLC primarily metastatic lung cancer patients.

Trends and comparative outcomes between operative approaches for segmentectomy in lung cancer

BackgroundSegmentectomy is increasingly performed for non–small cell lung cancer. However, comparative outcomes data among open, robotic-assisted, and video-assisted thoracoscopic approaches are limited. MethodsA retrospective cohort study of non–small cell lung cancer segmentectomy cases (2013-2021) from the Society of Thoracic Surgeons General Thoracic Surgery Database was performed. Baseline characteristics were balanced using inverse probability of treatment weighting and compared by operative approach. Volume trends, outcomes, and nodal upstaging were assessed. ResultsOf 9927 patients who underwent segmentectomy, 84.8% underwent minimally invasive surgery, with robotic-assisted thoracoscopic surgery becoming the most common approach in 2019. Open segmentectomy is more likely to be performed at low-volume centers (P < .0001), whereas robotic-assisted thoracoscopic surgery is more likely to be performed at high-volume centers (P < .0001). Video-assisted thoracoscopic surgery had a higher open conversion rate than robotic-assisted thoracoscopic surgery (odds ratio, 11.8; CI, 7.01-21.6; P < .001). Minimally invasive surgery had less 30-day morbidity compared with open segmentectomy (video-assisted thoracoscopic surgery odds ratio, 0.71; 95% CI, 0.55-0.94; P = .013; robotic-assisted thoracoscopic surgery odds ratio, 0.59; CI, 0.43-0.81; P = .001). The number of nodes and stations harvested were highest for robotic-assisted thoracoscopic surgery; however, N1 upstaging was more likely in open compared with robotic-assisted thoracoscopic surgery (odds ratio, 0.63; CI, 0.45-0.89; P < .007) and video-assisted thoracoscopic surgery (odds ratio, 0.61; CI, 0.46-0.83; P = .001). ConclusionsSegmentectomy volume has increased considerably, with robotic-assisted thoracoscopic surgery becoming the most common approach. Minimally invasive surgery has less major morbidity compared with open segmentectomy, with no difference between video-assisted thoracoscopic surgery and robotic-assisted thoracoscopic surgery. However, risk of open conversion is higher with video-assisted thoracoscopic surgery. Robotic-assisted thoracoscopic surgery had increased nodal harvest, whereas hilar nodal upstaging was highest with thoracotomy. This study reveals significant differences in outcomes exist between segmentectomy operative approach; the impact of approach on survival merits further investigation.

The transcriptional co-repressor Runx1t1 is essential for MYCN-driven neuroblastoma tumorigenesis

MYCN oncogene amplification is frequently observed in aggressive childhood neuroblastoma. Using an unbiased large-scale mutagenesis screen in neuroblastoma-prone transgenic mice, we identify a single germline point mutation in the transcriptional corepressor Runx1t1, which abolishes MYCN-driven tumorigenesis. This loss-of-function mutation disrupts a highly conserved zinc finger domain within Runx1t1. Deletion of one Runx1t1 allele in an independent Runx1t1 knockout mouse model is also sufficient to prevent MYCN-driven neuroblastoma development, and reverse ganglia hyperplasia, a known pre-requisite for tumorigenesis. Silencing RUNX1T1 in human neuroblastoma cells decreases colony formation in vitro, and inhibits tumor growth in vivo. Moreover, RUNX1T1 knockdown inhibits the viability of PAX3-FOXO1 fusion-driven rhabdomyosarcoma and MYC-driven small cell lung cancer cells. Despite the role of Runx1t1 in MYCN-driven tumorigenesis neither gene directly regulates the other. We show RUNX1T1 forms part of a transcriptional LSD1-CoREST3-HDAC repressive complex recruited by HAND2 to enhancer regions to regulate chromatin accessibility and cell-fate pathway genes.

Cytomorphological characteristics of low-grade papillary urothelial carcinoma in voided urine samples: Distinction from benign and high-grade papillary urothelial carcinoma.

Given its frequent recurrence and the potential for high-grade transformation, accurate diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology is clinically important. We attempted to identify cytomorphologic features in urine samples, which could be helpful for the identification of LGPUC. We conducted a retrospective review of voided urine specimens collected from patients with histopathologic diagnoses of LGPUC. Their cytomorphological features were compared with those from patients with benign conditions and high-grade papillary urothelial carcinoma (HGPUC). A total of 115 voided urine specimens were evaluated, including 30 benign, 41 LGPUC, and 44 HGPUC cases. In LGPUC, 18 cases (44%) were diagnosed as atypical, a proportion significantly higher than that observed in benign cases (4 cases, 13%), while the remaining 23 cases (56%) were diagnosed as negative. LGPUC urine samples tended to have higher cellularity than benign cases, but the difference was not statistically significant. Three cytological features, namely nuclear enlargement, higher nuclear-to-cytoplasmic (N/C) ratio, and presence of small cell clusters, were statistically more prevalent in LGPUC compared to benign cases, although the changes were relatively subtle. In contrast, cytomorphological distinction between LGPUC and HGPUC was evident, as high cellularity, nuclear enlargement, hyperchromasia, high N/C ratio, irregular nuclear membrane, and apoptosis were significantly more prevalent in HGPUC cases. Several cytomorphologic features in voided urine samples were more prevalent in cases with LGPUC, albeit not observed in all instances. Since these alterations were relatively subtle, meticulous attention to these cytomorphologic details is crucial to suggest the possibility of LGPUC.

Surgical treatment of small cell lung cancer

Surgical treatment of small cell lung cancer

Small cell cancer of the esophagus, treatment outcomes of a rare histological type

Purpose: To demonstrate treatment outcomes in two patients with small cell esophageal cancer. Cases reports. Patient M. was assigned to receive polychemotherapy (PC H) composed of etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days, followed by chemoradiotherapy (CRT). The patient received 1 cycle of PCT , which was well tolerated. Then, the patient received a cycle of 3D-conformal radiation therapy concurrently with 2 cycles of chemotherapy: etoposide 120 mg/m2 + cisplatin 80 mg/m2. Chemoradiotherapy was well tolerated. Dysphagia regression to grade I was observed. Currently, the patient continues to receive treatment (etoposide 100 mg/ m2 intravenously on days 1–3 + cisplatin 80 mg/m2 on day 1, every 21 days for 6 cycles and lanreotide 120 mg subcutaneously, every 28 days) and tolerates it well. Patient A. was assigned to receive PCT with etoposide 120 mg/m2 + cisplatin 80 mg/m2. After 4 cycles of PCT , the follow-up CT images revealed disease progression (enlarged retroperitoneal lymph nodes). The patient underwent external bean radiation therapy to the primary tumor. Radiotherapy was relatively well tolerated. The patient underwent the course of radiation therapy relatively satisfactorily. Due to the progression of the disease, symptomatic treatment was assigned. The patient died 9 months after diagnosis. Conclusion. Small cell carcinoma of the esophagus is a rare histological type with poor prognosis. Concurrent platinum-based chemoradiotherapy allows achievement of stable disease and disease control.

Camrelizumab combined with anlotinib as second-line therapy for metastatic or recurrent small cell lung cancer: a retrospective cohort study.

This retrospective study evaluates the efficacy of camrelizumab combined with anlotinib versus chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC) undergoing second-line treatment. Data were sourced from medical records at a Chinese medical facility, involving 34 patients diagnosed with ES-SCLC after failing first-line treatment. Patients were divided into two groups: one received camrelizumab (200 mg every 3 weeks) with anlotinib (12 mg daily for 14 days followed by a 7-day rest), while the other group received physician-chosen chemotherapy administered every 3 weeks. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), and disease control rate (DCR). The combination therapy group showed a significant improvement in PFS compared to the chemotherapy group (median PFS: 7 months vs. 3 months; hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.15-0.77; p<0.001). However, there was no statistically significant difference in OS between the groups (16.3 months vs. 17.3 months; p=0.82). The ORR was 52.9% in the combination therapy group versus 23.5% in the chemotherapy group (p=0.08), and the DCR was 82.4% compared to 58.8% (p=0.26). Grade 3 or higher adverse events were observed in 17.6% of the combination therapy group and 29.4% of the chemotherapy group. The findings suggest that the combination of camrelizumab and anlotinib offers a superior anti-tumor response with a manageable safety profile in a second-line setting for ES-SCLC patients. This combination regimen may be a viable option for second-line ES-SCLC treatment.

Global Burden of Lung Cancer: Prognosis, Symptom Management, And Challenges with Pulmonary Fibrosis

Lung cancer represents a significant global health burden, accounting for the highest number of cancer-related deaths worldwide. Despite advancements in treatment modalities, the prognosis remains poor, with a low 5-year survival rate post-diagnosis and substantial mortality within the first year. Patients often experience debilitating symptoms such as fatigue, pain, dyspnea, and coughing, which severely impact their physical and psychological well-being. Pain management is particularly challenging and critical due to its potential leading to depression and anxiety. Lung cancer encompasses histological classifications such as adenocarcinoma, squamous cell carcinoma, large cell carcinoma and small cell lung cancer (SCLC), each with distinctive subtypes. Patients with idiopathic pulmonary fibrosis (IPF) face exacerbated challenges when they also develop lung cancer, impacting their prognosis significantly compared to those with lung cancer alone. The management of pulmonary fibrosis (PF) in lung cancer necessitates a multifaceted approach, incorporating supportive care, pharmacological interventions, and emerging therapies like molecular targeted therapies, gene therapy, and stem cell therapy. This comprehensive management requires collaboration among various healthcare professionals to optimize outcomes and enhance quality of life for affected patients. Despite considerable progress, managing fibrosis in lung cancer remains complex due to its heterogeneous nature and varied progression. Ongoing future research aims to identify biomarkers for early detection, refine treatment strategies, and explore novel therapies through clinical trials. This review highlights lung cancer's global burden, poor prognosis, and severe symptoms impacting patient well-being. It discusses histological types, compounded challenges with IPF, and the need for a multifaceted treatment approach. Emphasis is placed on ongoing research for early detection, refined treatments, and novel therapies to improve outcomes.

Second-line treatment outcomes after first-line chemotherapy plus immunotherapy in Extensive-Stage small cell lung cancer (ES-SCLC) patients: A large French multicenter study

IntroductionChemotherapy combined with immunotherapy (CT-IO) is the standard treatment for patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC). This study evaluates the effectiveness of second-line (2L) following CT-IO. Patients and MethodsAll patients from 10 centers who received a 2L after a first-line CT-IO were included. They were divided into 3 groups: platinum-based, lurbinectedin or others (topotecan, CAV, taxanes). We assessed overall survival (OS) and 2L progression-free survival (2L-PFS) according to treatment and platinum free-interval (PFI) < or ≥ 90 days. ResultsAmong 82 patients included, median age was 67.0 years, 29.3 % had a Performans Status ≥ 2, 36.6 % had brain progression, 69.5 % were considered “platine-sensitive” and 30.5 % “platine-resistant” (PFI ≥ or < 90 days, respectively). As 2L, 37/82 patients (45.1 %) received platinum-doublet, 21/82 (25.6 %) lurbinectedin and 24/82 (29.3 %) others. Patients with a PFI ≥ 90 days received mainly platinum-based rechallenge (34/57, 59.6 %). With a median follow-up of 18.5 months, the median OS was 5.0 months (95 %CI, 1.5–7.9) / 6.8 months (95 %CI, 5.5–8.7) for platinum-resistant / sensitive, respectively (log rank p = 0.017). The median 2L-PFS was 1.9 months (95 %CI, 1.2–4.7) / 3.9 months (95 %CI, 2.9–6.0) for platinum-resistant / sensitive, respectively. Median OS was 8.1 (95 %CI, 6.3–12.9) / 4.9 (95 %CI, 3.7–6.8) / 5.1 months (95 %CI, 2.5–7.8) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.017). Median 2L-PFS was 4.6 (95 %CI, 3.9–7.2) / 2.7 (95 %CI, 1.6–3.9) / 2.2 months (95 %CI, 1.5–4.1) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.025). DiscussionPlatinum-based rechallenge after a first-line CT-IO showed promising results despite particularly unfavorable characteristics within our real-word population. Lurbinectedin when used after IO demonstrated as low efficacy as other platinum-free regimens.

Real world results of locally advanced and metastatic lung cancer patients treated with platinum doublet chemotherapy in first line: Moroccan cohort

BackgroundDoublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown. MethodsIn this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint. ResultsOverall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167–208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405–559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142–238; hazard ratio for progression: 1.21, 95 % CI, 0.29–5.02; p = 0.27), while the median OS was 428 (95 % CI, 324–940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193–277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41–7.27; p = 0.69, while the median OS was 273 (95 % CI, 241–459) days (hazard ratio for death: 2.95; 95 % CI, 0.4–21.7; p = 0.51). Grade 3–4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients. ConclusionMoving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.

Experimental investigation of porous gyroid structure: Effect of cell size and porosity on performance

This paper presents an experimental investigation of three triply periodic minimal surface based gyroid sheet samples with varying cell size and porosity. The thermal and hydraulic performances of the samples were analyzed and compared under different design parameters (cell size and porosity). The experimental results revealed that the gyroid structures achieved uniform temperature distribution, allowing for the disruption of the thermal boundary layer and enhancing heat transfer. The gyroid structure characterised by small cell size and low porosity (Gyroid-A: 15 mm/0.75) dissipates more heat from its surface compared to the structure with large cell size and high porosity (Gyroid-C: 32 mm/0.9). Gyroid-A also exhibits higher Nusselt number and convection heat transfer coefficient with 51.5 % increase as compared to Gyroid-C. In addition, Gyroid-A has the lowest thermal resistance (with maximum of 45.4 % reduction) and the highest specific pressure drop as compared to the other gyroid structures. Moreover, Gyroid-A exhibits lower total entropy generation (75.9 % reduction) and higher overall performance evaluation criteria, PEC (more efficient heat transfer in relation to flow resistance) as compared to Gyroid-C. The experimental results of this work is important for the design and optimization of heat transfer applications utilizing gyroid sheet structures for effective heat dissipation.

Osimertinib in a patient with end-stage kidney disease not on hemodialysis.

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) effective in non- small cell lung cancer (NSCLC) with EGFR mutations. Since the drug is primally eliminated by the fecal route no dose adjustment is needed in patient with chronic-kidney disease (CKD); despite this there is limited data about its safety in cancer patients with end-stage renal disease (ESRD). Herein, we reported a case report of a 77-year-old woman, diagnosed in 2018 with lung adenocarcinoma EGFR mutated with lymph nodal and cerebral metastasis, who started Osimertinib 80 mg/day. She under- went 41 cycles of therapy with no Osimertinib interruptions, no severe toxicities and obtaining complete radiological response. We conclude that Osimertinib has an acceptable safety profile also in cancer patients with ESRD not undergoing hemodialysis (HD).

Undifferentiated Round Cell Sarcoma With CRTC1::SS18 Fusion: Expanding Clinicopathologic Features of a Rare Translocation Sarcoma With Prominent Desmoplastic Stroma

Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS–non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range, 12-42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round-to-epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor. Immunohistochemical results were nonspecific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exons 1 to 2 of CRTC1 (the 5′ partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3′ partner gene) on chromosome 18. The clinical course was variable. Although 1 previously reported case demonstrated aggressive behavior with a fatal outcome, 2 others had a relatively indolent course with gradual growth for 6 to 7 years prior to resection. Two cases developed metastatic disease, including 1 case with bilateral lung metastasis and 1 with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aimed to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.

Diagnostic efficiency of intravoxel incoherent motion-based virtual magnetic resonance elastography in pulmonary neoplasms

BackgroundThe aim of the study were as below. (1) To investigate the feasibility of intravoxel incoherent motion (IVIM)-based virtual magnetic resonance elastography (vMRE) to provide quantitative estimates of tissue stiffness in pulmonary neoplasms. (2) To verify the diagnostic performance of shifted apparent diffusion coefficient (sADC) and reconstructed virtual stiffness values in distinguishing neoplasm nature.MethodsThis study enrolled 59 patients (37 males, 22 females) with one pulmonary neoplasm who underwent computed tomography-guided percutaneous transthoracic needle biopsy (PTNB) with pathological diagnosis (26 adenocarcinoma, 10 squamous cell carcinoma, 3 small cell carcinoma, 4 tuberculosis and 16 non-specific benign; mean age, 60.81 ± 9.80 years). IVIM was performed on a 3 T magnetic resonance imaging scanner before biopsy. sADC and virtual shear stiffness maps reflecting lesion stiffness were reconstructed. sADC and virtual stiffness values of neoplasm were extracted, and the diagnostic performance of vMRE in distinguishing benign and malignant and detailed pathological type were explored.ResultsCompared to benign neoplasms, malignant ones had a significantly lower sADC and a higher virtual stiffness value (P < 0.001). Subsequent subtype analyses showed that the sADC values of adenocarcinoma and squamous cell carcinoma groups were significantly lower than non-specific benign group (P = 0.013 and 0.001, respectively). Additionally, virtual stiffness values of the adenocarcinoma and squamous cell carcinoma subtypes were significantly higher than non-specific benign group (P = 0.008 and 0.001, respectively). However, no significant correlation was found among other subtype groups.ConclusionsNon-invasive vMRE demonstrated diagnostic efficiency in differentiating the nature of pulmonary neoplasm. vMRE is promising as a new method for clinical diagnosis.

MUC5AC immunoreactivity in scattered tumor cells is useful for diagnosing CIC-rearranged sarcoma.

CIC-rearranged sarcoma is an aggressive round cell sarcoma, and an alternative ATXN1/ATXN1L fusion has been reported. Diagnosis may be difficult, and molecular assays may suffer from imperfect sensitivity. Characteristic histology and ETV4 immunohistochemical positivity are diagnostically helpful. However, ETV4 staining is unavailable in most laboratories. Here, we explored the diagnostic utility of MUC5AC immunohistochemistry in CIC-rearranged sarcomas. All 30 cases, except one, of CIC-rearranged sarcomas and 2 ATXN1-rearranged sarcomas were positive for MUC5AC, although the number of immunopositive cells was generally low (< 5%) in most samples, representing a characteristic scattered pattern. The only MUC5AC-negative case had the lowest tumor volume. Among the 110 mimicking round cell malignancies, 12 tumors showed MUC5AC positivity, including occasional cases of synovial sarcoma and small cell carcinoma, whereas the remaining 98 samples were negative. Despite its lower specificity than that of ETV4 and sparse reactivity that requires careful interpretation, MUC5AC may serve as a useful marker for CIC/ATXN1-rearranged sarcoma because of its wider accessibility.

Exploring the causal association between uric acid and lung cancer in east Asian and European populations: a mendelian randomization study

BackgroundLung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer.MethodsMendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association.ResultsA significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer.ConclusionsThe results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice.

TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern

A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors’ database. Among the 16 TPPP-BRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a “syringoid” appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.

Single-cell analysis of treatment-resistant prostate cancer: Implications of cell state changes for cell surface antigen–targeted therapies

Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)-a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival. To understand how lineage markers vary across the evolution of lineage plasticity in prostate cancer, we applied single-cell analyses to 21 human prostate tumor biopsies and two genetically engineered mouse models, together with tissue microarray analysis on 131 tumor samples. Not only did we observe a higher degree of phenotypic heterogeneity in castrate-resistant PRAD and NEPC than previously anticipated but also found that the expression of molecules targeted therapeutically, namely PSMA, STEAP1, STEAP2, TROP2, CEACAM5, and DLL3, varied within a subset of gene-regulatory networks (GRNs). We also noted that NEPC and small cell lung cancer subtypes shared a set of GRNs, indicative of conserved biologic pathways that may be exploited therapeutically across tumor types. While this extreme level of transcriptional heterogeneity, particularly in cell surface marker expression, may mitigate the durability of clinical responses to current and future antigen-directed therapies, its delineation may yield signatures for patient selection in clinical trials, potentially across distinct cancer types.