Pulmonary Tumors Research Articles

(1041) - Fatal Right Heart Failure Due to Pulmonary Tumor Emboli Syndrome in a Patient with Undiagnosed Colon Cancer

(1041) - Fatal Right Heart Failure Due to Pulmonary Tumor Emboli Syndrome in a Patient with Undiagnosed Colon Cancer

Abstract 3970: Impairment of tumor reactive CD8 T cells in liver cancer

Abstract Tumor reactive (TR) CD8 T cells in the liver have been studied in the setting of both immunotherapy and cellular therapy with the predominant dogma that these cells have equivalent functionality in the liver as compared to other organ sites. Herein, we detail that TR+ CD8 T cells are functionally impaired in the liver immune microenvironment in mice with liver tumors.TR+ CD8 T cells were studied in BALB/c and C57BL/6 mice injected intrahepatic, intravenous, and subcutaneously with either a colon (CT26) or a melanoma (B16F10) cancer cell line to create intrahepatic, pulmonary and subcutaneous tumors, respectively. Additionally, an ⍺CD8 antibody with IgG control was used to conduct functional studies. Samples were analyzed using flow cytometry and liver weights were measured. A high frequency of TR+ CD8 T cells were found in the liver in mice with intrahepatic tumors. Despite ~70% of CD8 T cells being tumor reactive in intrahepatic tumors, liver tumor growth kinetics were faster than subcutaneous tumors. Higher proportion of the TR+ CD8 T cells were found to be exhausted in the liver tumor by flow cytometry. Functional depletion of the CD8 T cells caused a fivefold higher tumor growth in the subcutaneous model but in contrast had no effect on intrahepatic tumors. In conclusion, despite the high frequency of “killer” tumor reactive T cells in the liver, the growth kinetics of the liver tumors, flow cytometry as well as functional studies demonstrate the impairment of TR+ CD8 T cells in the liver. We aim to dissect the mechanisms mediating intrahepatic TR CD8+ T cell exhaustion in primary liver tumors as well as metastatic models. Additionally, we aim to determine significant costimulatory molecules specific to intrahepatic exhaustion which could lead to better therapeutic models. Citation Format: Rajiv S. Trehan, Marlaine Soliman, Xin Wang, Patrick Huang, Noemi Kedei, Xiao Bin Zhu, Matthias Seifert, Mohamed-Reda Benmebarek, Amran Nur, Firouzeh Korangy, Chi Ma, Tim F. Greten. Impairment of tumor reactive CD8 T cells in liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3970.

Abstract 6925: Integrative single-cell tracking of genome evolution and tumor cell plasticity in small cell lung cancer (SCLC)

Abstract SCLC is the deadliest type of lung cancer, which is mostly diagnosed at late stages and accounts for 15% of pulmonary tumors. Even though chemotherapy is initially effective, patients with SCLC relapse quickly and develop resistant tumors. Genome studies revealed a universal loss of TP53 and RB1; recent transcriptional studies categorized SCLC based on the expression of 4 lineage transcription factors (TFs). We aimed to dissect how genomic cues impact transcriptional phenotypes, tumor cell plasticity and the dynamics of tumor and immune cell interactions, to thus decipher molecular mechanisms of phenotypic divergence and therapy resistance in SCLC. We performed genome sequencing and single cell transcriptome profiling of 55 tumors from patients with SCLC, including primary tumors, local and distant metastases and of paired relapsing tumors acquired after chemotherapy. Single cell sequencing was performed with the 10x Genomics platform and yielded > 200.000 cells. Transcriptome profiles at single cell levels revealed co-expression of at least two of the lineage TFs ASCL1, NEUROD1 or POU2F3 in each tumor. Copy number (cn) estimation for transcriptome data pointed to genomic events impacting transcriptional heterogeneity within the tumor. Furthermore, our data pointed to a marked intra- and interpatient, as well as to inter-metastatic heterogeneity. To specifically investigate how underlying genetic alterations affect molecular phenotypes, integrative studies across all patients were performed. This revealed shared transcriptional programs in tumors with amplifications of MYC family members; trajectory inference for cases with low and high-level copy gains of MYCN pointed to distinct transcriptional states. We performed multi-regional and longitudinal studies of matched patient cases to reconstruct the genomic patterns of clonal evolution, and projected genomic subsets to transcriptional profiles at single cell level, thus analyzing the effect of genome diversity on the transcriptional landscape. Additionally, tumor intrinsic profiles of heterogeneity were mapped to single cell data of patient tumors to elucidate the effects on tumor-immune cell interactions. All together our data points to a concerted regulation of a multitude of lineage factors and transcriptional programs in each SCLC tumor and provides a first comprehensive framework for the study of underlying genetic alterations that shape the transcriptional landscape and phenotypic plasticity in SCLC. Citation Format: Marcel Schmiel, Laura Kaiser, Maria Cartolano, Martin Peifer, Roman K. Thomas, Julie George. Integrative single-cell tracking of genome evolution and tumor cell plasticity in small cell lung cancer (SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6925.

Uncommon Tumors of the Lung: Recently Described and Rediscovered Tumors.

The great majority of primary pulmonary neoplasms are represented by non-small cell carcinomas-adenocarcinoma and squamous cell carcinoma. In addition, there is another group of neoplasms such as those of neuroendocrine origin that also represent a meaningful subset of primary lung neoplasms. Basically, any other tumor that is not in these groups of tumors may represent an unusual lung neoplasm. To highlight more recently described unusual tumoral entities that may represent a challenge in diagnosis and that require awareness of their existence. This is a review of 3 different entities: bronchiolar adenoma, adenofibroma, and hemangioblastoma-like clear cell stromal tumor. These tumoral conditions are rare, and a review of the literature is presented. The most relevant morphologic, immunohistochemical, and molecular aspects of bronchiolar adenoma, adenofibroma, and hemangioblastoma-like clear cell stromal tumor are presented. The difficulty of arriving at an unequivocal diagnosis in small biopsies is highlighted. The 3 entities represent uncommon tumors occurring primarily in the lung and a diagnostic challenge not only in biopsy specimens but also often in surgically resected specimens. The use of immunohistochemical stains and in some cases of molecular diagnostics is of aid in arriving at final interpretation.

Thoracic manifestations of tularaemia: a case series.

Tularaemia is a zoonotic disease caused by Francisella tularensis, a highly virulent bacterium that affects humans and small wild animals. It is transmitted through direct contact with infected animals or indirectly through contaminated soil, water or arthropod bites (e.g. ticks). Primary thoracic manifestations of tularaemia are infrequent and, therefore, a diagnostic challenge for clinicians. We report six tularaemia cases with exclusively thoracic involvement diagnosed in a clinic for pulmonary diseases in Bavaria between 10/2020 and 02/2022. All patients lived or were active in rural areas, four reported a recent tick bite. All patients presented with thoracic lymphadenopathy and pulmonary tumours or consolidations; all underwent bronchoscopy with EBUS-TBNA of lymph nodes, three lung biopsies as well. Five patients showed inflammatory changes in the endobronchial mucosa. The main histological findings were necrotic epithelioid granulomas with remarkable granulocyte infiltration. All cases were identified by positive serology, five by PCR (here identification of F.t. ssp. Holarctica) from biopsy as well. As first-line therapy, oral ciprofloxacin was given (5/6); in 2/6 cases, a combination of quinolone-rifampicin was given. Pulmonary tularaemia may occur after tick bites and without extrathoracic manifestations. In patients who present with thoracic lymphadenopathy and pulmonary consolidations and who are exposed to increased outdoor activities, tularaemia should be included in the diagnostic pathway. Histologically, the presence of neutrophil-granulocyte infiltrations might help to distinguish tularaemia from other granulomatous infections, e.g. tuberculosis. The combination of quinolone-rifampicin rather than i.v. gentamicin reduced length of hospital stay in two patients.

Protein-assisted synthesis of chitosan-coated minicells enhance dendritic cell recruitment for therapeutic immunomodulation within pulmonary tumors

The efficacy of cancer therapies is significantly compromised by the immunosuppressive tumor milieu. Herein, we introduce a previously unidentified therapeutic strategy that harnesses the synergistic potential of chitosan-coated bacterial vesicles and a targeted chemotherapeutic agent to activate dendritic cells, thereby reshaping the immunosuppressive milieu for enhanced cancer therapy. Our study focuses on the protein-mediated modification of bacterium-derived minicells with chitosan molecules, facilitating the precise delivery of Doxorubicin to tumor sites guided by folate-mediated homing cues. These engineered minicells demonstrate remarkable specificity in targeting lung carcinomas, triggering immunogenic cell death and releasing tumor antigens and damage-associated molecular patterns, including calreticulin and high mobility group box 1. Additionally, the chitosan coating, coupled with bacterial DNA from the minicells, initiates the generation of reactive oxygen species and mitochondrial DNA release. These orchestrated events culminate in dendritic cell maturation via activation of the stimulator of interferon genes signaling pathway, resulting in the recruitment of CD4+ and CD8+ cytotoxic T cells and the secretion of interferon-β, interferon-γ, and interleukin-12. Consequently, this integrated approach disrupts the immunosuppressive tumor microenvironment, impeding tumor progression. By leveraging bacterial vesicles as potent dendritic cell activators, our strategy presents a promising paradigm for synergistic cancer treatment, seamlessly integrating chemotherapy and immunotherapy.

Operative treatment of pulmonary primitive neuroectodermal tumor: a case report and literature review

BackgroundPulmonary primitive neuroectodermal tumor (PNET), a member of the Ewing sarcoma family of tumors, is a rare malignancy that is associated with a grim prognosis. To date, fewer than 30 cases of pulmonary PNET have been reported. In this case report, we present the clinical details of a 12-year-old girl with pulmonary PNET who underwent surgical treatment. We also conducted an analysis and summary of other relevant studies and the surgical outcomes.Case presentationIn May 2018, a 12-year-old girl was admitted with symptoms of cough and blood-tinged phlegm. A computed tomography scan revealed a large mass, measuring 12.9 cm × 8.1 cm, in the right middle and lower lungs. A percutaneous lung biopsy confirmed poorly differentiated tumor cells with a nested growth pattern. Immunohistochemical staining demonstrated positive expression of CD99, CD56, Vimentin, and Synaptophysin. The patient was diagnosed with pulmonary PNET. Following three cycles of neoadjuvant chemotherapy, a substantial reduction in tumor volume was observed. Subsequently, the patient underwent a surgical procedure involving pneumonectomy and partial resection of the left atrium with the assistance of cardiopulmonary bypass. The patient was discharged 37 days after surgery. During a three-year follow-up period, she exhibited no signs of tumor recurrence and has successfully returned to school.ConclusionsThis case highlights the successful management of an advanced PNET with neoadjuvant chemotherapy, pneumonectomy, and partial resection of the left atrium employing cardiopulmonary bypass. The patient remained disease-free after three years. Our analysis of surgically treated cases indicates that neoadjuvant chemotherapy can contribute to improved prognoses for PNET patients. It is crucial to emphasize that complete surgical excision remains the cornerstone of treatment, underscoring the importance of surgeons considering radical surgical approaches whenever feasible for patients with pulmonary PNETs.

Lung Function Evaluated By Structured Light Plethysmography in Children After Lung Surgery: A Preliminary Analysis.

Background: Structured light plethysmography (SLP) is a novel light-based method that captures chest wall movements to evaluate tidal breathing. Methods: Thirty-two children who underwent lung surgery were enrolled. Their clinical history was collected along with spirometry and SLP. Results: Median age of surgery was 9 months (interquartile range 4-30). Most frequent diagnosis was congenital pulmonary airway malformation (14/32), then pulmonary sequestration (9/32), tumor (5/32), and bronchogenic cyst (4/32). The most frequent surgical approach was lobectomy (59%), segmentectomy (38%), and complete resection (3%). More than 80% had surgery when younger than 3 years of age. Eight patients had short-term complications (pleural effusion was the most frequent), while long-term effects were reported in 15 patients (19% recurrent cough, 13% thoracic deformities, 13% airway infections, 9% wheezing, 6% reduced exercise tolerance, and 3% columnar deformities). Spirometry was normal in 9/22 patients. Nine patients had a restrictive pattern, while 4 showed a mild bronco-reactivity. Ten patients did not perform spirometry because of young age. SLP revealed the presence of obstructive pattern in 10% of patients (IE50 > 1.88) and showed a significant difference between the two hemithorax in 29% of patients. Discussion: SLP may be a new method to evaluate lung function, without collaboration and radiation exposure, in children who underwent lung resection, also in preschool age.

Pulmonary Involvement in Recurrent Respiratory Papillomatosis: A Systematic Review.

Recurrent respiratory papillomatosis (RRP) is a non-malignant disease, characterized by the production of wart-like growths in the respiratory tract, affecting both young people and adults (juvenile-onset recurrent respiratory papillomatosis, JORRP, and adult-onset recurrent respiratory papillomatosis, AORRP, respectively). Infection caused by human papillomavirus (HPV) is known as the main factor involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review aimed to evaluate the prevalence of severe complications, such as lung involvement and lung tumor in JORRP and AORRP patients, and assess the role of HPV genotypes in the progression of disease severity following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). A total of 378 studies were found on PubMed and Scopus using the following MESH terms: "recurrent respiratory papillomatosis and lung tumor" and "pulmonary tumor and recurrent respiratory papillomatosis". Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI: 4-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7-18%; I2: 85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1-7%; I2: 67.1%) and a pooled prevalence mortality for this group of 4% (95% CI:2-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV-11 was 21% (95% CI: 5-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11-positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Completely portal robotic lobectomy in lung cancer: is subcostal specimen removal necessary?

Background The best place for specimen extraction is a relevant question since either after robotic or video-thoracoscopic lobectomy, both intercostal and subcostal routes can be potential extraction routes. In this study, we studied completely portal robotic lobectomies (CPRL-4) for pulmonary neoplasms to investigate the efficacy and feasibility of subcostal specimen removal by comparing the two techniques. Material and Methods Between January 2014 and July 2021, data from 90 patients who underwent robotic thoracic surgery with a Da Vinci Surgical System SI (Intuitive Surgical Inc., Mountain View, California, USA) were collected and retrospectively analyzed. Out of 90 patients, we analyzed 36 CPRL-4 cases. We removed specimens traditionally via intercostal utility thoracotomy in the first 22 patients (group A) and via subcostal incision in the next consecutive 14 patients (group B). Operative parameters, postoperative parameters, the visual analog scale (VAS) and SF36 life quality scoring were comparatively analyzed. Results The mean docking time was significantly higher in group B than in group A (26.2 ± 5.3 vs 17.8 ± 4.1) (p = .001). In terms of early-stage postoperative pain, group B had significantly lower pain scores compared to group A (p < .05). There was no significant difference between the groups in terms of SF36 life quality scoring. Conclusion We can conclude that performing a subcostal incision is not a sophisticated process, though it significantly prolongs the docking time. Although our study is based on a small group, we noticed that removing the specimen through the subcostal incision after CPRL-4 is potentially useful, has several advantages and it is a practical, feasible, and safe method. Clinical Registration Number 2018/57

SALTT study: A retrospective analysis of 111 SAlivary gland tumors of Lung and Tracheobronchial Tree

IntroductionPrimary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway. Methods and resultsWe retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6–78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067). ConclusionIt is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.

Endobronchial chondrosarcoma presenting as recurrent pneumonia: a rare pulmonary tumour

BackgroundChondrosarcoma is a group of bone tumours made up of cells responsible for cartilage production. It usually affects the axial skeleton, including the pelvis, scapula and base of the skull with frequent metastasis to the lungs. Primary pulmonary involvement with chondrosarcoma is rarely seen.Case presentationIn this case report, we will discuss a case of endobronchial chondrosarcoma presenting as recurrent pneumonia.ConclusionsOnly a few cases of primary pulmonary chondrosarcoma are reported with endobronchial involvement, therefore being quite rare.

Analysis of screening outcomes and factors influencing compliance among community-based lung cancer high-risk population in Nanchang, China, 2018-2020.

To investigate the screening results and compliance of low-dose computed tomography (LDCT) screening among the high-risk lung cancer populations in Jiangxi Province from 2018 to 2020, and to explore the related influencing factors of compliance. From November 2018 to October 2020, permanent residents in Nanchang City were selected and their demographic data and lung cancer risk factor data were collected to screen high-risk groups, and LDCT screening was performed on high-risk groups with diagnostic reports by 2 chief physicians. Descriptive analysis method was used to analyze the basic information of screening, screening results and screening compliance. χ2 and logistic regression test were used to conduct single and multi-factor analysis of screening compliance. A total of 26,588 people participated in this screening, of which 34.4% (n=9,139) were at high risk of lung cancer, 3,773 participants were completed LDCT screening, and the screening compliance rate was 41.3%. Screening results showed that 389 participants were positive for suspected pulmonary tumor or lung nodules, the screening positive rate of 10.3%. The logistic multivariable results of screening compliance showed that the compliance was better in males, those who quit smoking, those with chronic respiratory diseases and family history of cancer, and those who have primary education, those with a history of occupational harmful exposure had a poor compliance. Compliance with lung cancer screening in Jiangxi Province, China still needs to be improved, and gender, education level, harmful occupational exposure, smoking, chronic respiratory diseases, and family history of tumors cancer play an important role on screening compliance.

Ciliated Muconodular Papillary Tumors of the Lung Harboring STRN::ALK Fusion: Case Report and Review of the Literature.

Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor, typically occurring in middle-aged and elderly individuals. The molecular mutation spectrum of CMPT remains insufficiently explored. Commonly known driver gene alterations include KRAS, BRAF, EGFR, and ALK rearrangement. This report details the clinicopathological features of 2 patients presenting with CMPT as pulmonary nodules during clinical examinations. Microscopic analysis revealed tumors with glandular or papillary structures, consisting of mucinous cells, ciliated columnar cells, and basal cells. Notably, both patients exhibited STRN::ALK fusion, a finding not previously associated with CMPT. STRN::ALK fusion serves as a target for therapy in various tumors, including non-small cell lung cancer, thyroid cancer, and colon cancer. Consequently, we conducted a review of relevant literature, summarizing the clinicopathological and molecular characteristics of CMPT to facilitate further research. Our insights enhance the understanding of this uncommon tumor and contribute to the expansion of its molecular alteration spectrum.

Pulmonary neoplasm with features favouring glomus tumour

Pulmonary neoplasm with features favouring glomus tumour

Folliculin gene-negative Birt-Hogg-Dube syndrome: a case report

Introduction and importance: Birt-Hogg-Dube (BHD) is a rare genetic disorder that results from a mutation in the folliculin (FLCN) gene. Manifestations include pulmonary cysts, fibrofolliculomas, renal tumors, and pneumothoraces. Genetic testing can be used to confirm the diagnosis when suspected. BHD syndrome is diagnosed in patients with negative FLCN gene results using diagnostic criteria. Case presentation: A male in his 20s presented with recurrent pneumothoraces. A physical examination revealed bumps on his face and upper body. A chest computed tomography scan revealed cystic lesions. Blood tests, ESR, and CRP levels were unremarkable. Punch skin biopsy revealed fibrofolliculomas. Genetic testing for the FLCN mutation returned negative. His history, physical exam, imaging, and histopathology suggested BHD syndrome despite having a negative family history and genetic analysis. Eventually, the patient was diagnosed with FLCN gene-negative BHD syndrome. Clinical discussion: More than a hundred families have been identified to have BHD worldwide. There are a few cases in the literature describing patients phenotypically presenting with BHD despite having a negative genetic analysis. One study in Japan found 16 out of 157 individuals having a clinical presentation of BHD with no mutations. Also, decreased expression of the FLCN mRNA may lead to BHD. Conclusion: BHD syndrome can present with a negative FLCN gene mutation; however, patients must meet the known diagnostic criteria such as criteria made by Menko et al., Gupta et al., and Schmidt et al. in order to have a diagnosis of BHD syndrome. Also, a qualitative decrease of FLCN with the absence of mutations may also lead to BHD.

Abstract B066: PDGFR upregulation functions as a bypass mechanism contributing to FGFR inhibitor resistance in metastatic breast cancer

Abstract Breast cancer (BC) is the most diagnosed cancer in females in the United States and the second leading cause of cancer related deaths among women. The fibroblast growth factor receptor (FGFR) signaling pathway is frequently activated in BC, making it an attractive therapeutic target, especially in metastatic disease. However, clinical trials using FGFR inhibitors in BC have been disappointing in comparison to other cancer types treated with these therapies. As a result, BC patients with activated FGFR do not have a targeted therapeutic option. Failure of FGFR inhibitors is indicative of intrinsic or acquired resistance mechanisms in metastatic BC. Herein we demonstrate significant efficacy of the FGFR inhibitor, pemigatinib, in the 4T07 murine model of BC utilizing a tail vein model to induce pulmonary tumors. Despite this initial response, pemigatinib fails to eliminate minimal residual disease (MRD) and allows for accelerated tumor return after pemigatinib cessation. Characterizing the MRD by IHC following pemigatinib treatment shows that expression of platelet-derived growth factor receptor (PDGFR) is significantly increased on tumor cells. This rise in PDGFR expression following pemigatinib treatment increases the responsiveness of 4T07 cells to platelet-derived growth factor ligand indicating PDGFR may act as an alternate signaling pathway bypassing FGFR signaling. Mechanistically, previous studies indicate that PDGFR protein expression is transcriptionally repressed by restriction of enhancer positioning by the CTCF insulator. DNA methylation surrounding CTCF causes its dissociation enhancing protein expression of PDGFR. Along these lines cotreatment with a DNA methyl transferase inhibitor prevents the increase of PDGFR protein expression induced by pemigatinib. Overall, our study determined that a highly potent FGFR inhibitor can inhibit tumor growth in a metastatic site, but it fails to eliminate MRD giving rise to tumor recurrence. Upregulation of PDGFR may act as a bypass mechanism of resistance allowing for tumor cell survival during pemigatinib treatment. Finally, our findings suggest that dual inhibition of DNA methylation and FGFR could improve patient response in metastatic BC. Citation Format: Mitchell Ayers, Michael Wendt. PDGFR upregulation functions as a bypass mechanism contributing to FGFR inhibitor resistance in metastatic breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B066.

CASE REPORT: RARE CASE OF PNEUMOCYTOMA

Pulmonary sclerosing (Pneumocytoma) is a rare benign pulmonary tumor of primitive epithelial origin. Because of the unspecific radiological features mimicking malignancies and their histological heterogeneity, the differential diagnosis with adenocarcinoma and carcinoid tumors is still challenging. We report a case of sclerosing pneumocytoma, as well as a review of the literature. Immunohistochemical findings showed intense staining of the cuboidal epithelial cells for cytokeratin-pool and TTF-1, with focal positivity for progesterone receptors. Round and spindle cells expressed positivity for vimentin, TTF-1, and focally for the progesterone receptor. Since the pre- and intraoperative diagnosis should guide surgical decision-making, obtaining a sufficient specimen size to find representative material in the cell block is of paramount importance. This overview highlights what physicians need to know regarding clinical manifestations, radiological and histological features as well as recent advances in immunohistochemistry in the diagnosis of this disease.

Multi-omic dataset of patient-derived tumor organoids of neuroendocrine neoplasms.

Organoids are 3-dimensional experimental models that summarize the anatomical and functional structure of an organ. Although a promising experimental model for precision medicine, patient-derived tumor organoids (PDTOs) have currently been developed only for a fraction of tumor types. We have generated the first multi-omic dataset (whole-genome sequencing [WGS] and RNA-sequencing [RNA-seq]) of PDTOs from the rare and understudied pulmonary neuroendocrine tumors (n = 12; 6 grade 1, 6 grade 2) and provide data from other rare neuroendocrine neoplasms: small intestine (ileal) neuroendocrine tumors (n = 6; 2 grade 1 and 4 grade 2) and large-cell neuroendocrine carcinoma (n = 5; 1 pancreatic and 4 pulmonary). This dataset includes a matched sample from the parental sample (primary tumor or metastasis) for a majority of samples (21/23) and longitudinal sampling of the PDTOs (1 to 2 time points), for a total of n = 47 RNA-seq and n = 33 WGS. We here provide quality control for each technique and the raw and processed data as well as all scripts for genomic analyses to ensure an optimal reuse of the data. In addition, we report gene expression data and somatic small variant calls and describe how they were generated, in particular how we used WGS somatic calls to train a random forest classifier to detect variants in tumor-only RNA-seq. We also report all histopathological images used for medical diagnosis: hematoxylin and eosin-stained slides, brightfield images, and immunohistochemistry images of protein markers of clinical relevance. This dataset will be critical to future studies relying on this PDTO biobank, such as drug screens for novel therapies and experiments investigating the mechanisms of carcinogenesis in these understudied diseases.

Self-evolving persistent luminescence nanoprobes for autofluorescence-free ratiometric imaging and on-demand enhanced chemodynamic therapy of pulmonary metastatic tumors.

Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.