BACKGROUND

Carney complex (CNC) is a rare multiple endocrine neoplasia syndrome caused by PRKAR1A gene mutation and  characterized by lentigines, myxomatous tumors and various endocrine neoplasms.

CASE PRESENTATION

This is a case of a 52-year-old male patient who underwent echocardiogram for intermittent palpitations and near-syncopal attack, which revealed a left atrial myxoma. The patient also exhibited multiple lentigines and had a history of histologicallyconfirmed papillary thyroid carcinoma. Surgical excision and subsequent histopathologic examination confirmed cardiac myxoma, fulfilling three major Stratakis criteria for CNC.

DISCUSSION

This case highlights the importance of a thorough history and physical examination with a strong understanding of the syndrome’s features being key to recognizing the disease. Increasing awareness and reinforcing knowledge of CNC are crucial for preventing misdiagnosis and ensuring effective management of this rare condition. To our knowledge, this is the first published case report of CNC in the Philippines, emphasizing the need for heightened regional awareness.

CONCLUSION

CNC may present with subtle or nonspecific symptoms and atypical tumor locations. Early recognition through a high index of suspicion, targeted imaging and a multidisciplinary approach is critical to optimize outcomes and guide family screening in this rare syndrome.

Human ; Male ; Middle Aged: 45-64 Yrs Old ; Multiple Endocrine Neoplasia ; Carney Complex ; Myxoma ; Syndrome ; Neoplasms ; Mutation ; Lentigo ; Genes

Introduction: Histoplasmosis is a rare opportunistic, inhalation-acquired systemic mycosis caused by Histoplasma capsulatum, endemic to Southeast Asia, including Malaysia. Although classically seen in immunocompromised hosts, it is increasingly reported in immunocompetent individuals. Infection is associated with environmental exposures such as bat or bird droppings and soil disruption. Histoplasmosis is a progressive granulomatous disease that can closely mimic tuberculosis and malignancy, making diagnosis challenging. Case: An 87-year-old Malay male with a history of treated pulmonary tuberculosis presented with a 6-month history of intermittent fever, anorexia, weight loss, and hypotension. Initial computed tomography imaging demonstrated bilateral heterogeneous adrenal masses (right: 2.2 × 3.7 × 5.0 cm; left: 2.0 × 3.7 × 5.2 cm) with indeterminate washout characteristics. Biochemical adrenal evaluation, including a short Synacthen test, confirmed primary adrenal insufficiency. Extensive microbiological and malignancy workup, including bronchoscopy, cultures, and tumor markers, was non-diagnostic. In view of clinical deterioration and epidemiological risk, empirical antituberculous therapy was initiated; however, no clinical improvement was observed after 2 months. PET-FDG revealed intensely hypermetabolic bilateral adrenal masses (SUVmax right 16.7, left 13.2) with no other abnormal foci. Non-invasive fungal investigations were negative. Definitive diagnosis was established via computed tomography-guided adrenal biopsy, which demonstrated necrotizing granulomatous inflammation with intracellular yeasts, subsequently identified as H. capsulatum. The patient was treated with oral itraconazole and corticosteroid replacement, resulting in significant clinical improvement and planned interval radiological reassessment. Conclusion Disseminated histoplasmosis is a diagnostic challenge, particularly in frail elderly patients, where invasive procedures may be delayed. It can mimic tuberculosis and malignancy and may lack an identifiable exposure history. Non-invasive tests may be inconclusive, making tissue biopsy essential. Adrenal involvement may result in primary adrenal insufficiency, further complicating the clinical picture. Early consideration and timely confirmation are crucial for appropriate management.
Adrenal incidentaloma ; Lung Neoplasms

BACKGROUND AND OBJECTIVES

Cell lines serve as invaluable tools in studying lung cancer biology and developing new therapies to combat the disease. However, commercially available cell lines are typically of Caucasian origin and may be less representative of the local genetic background. To address this, our lab previously immortalized cells from pleural fluid of a Filipino non-small cell lung cancer (NSCLC) patient via CDK4 transduction. Copy number variations (CNVs) are a type of genetic variation which may affect physiology and disease by disrupting gene function or altering gene expression, and in cancer, these may be associated with patient outcomes. CNV profiling can be valuable for understanding the biology of our immortalized cells and identifying genes that could serve as potential targets for diagnostic, prognostic, and therapeutic interventions. This study aimed to characterize previously immortalized NSCLC-derived cells, GL01, in comparison with an established lung adenocarcinoma (LUAD) cell line, A549, through whole-genome microarray-based copy number profiling.

METHODS

DNA was extracted from GL01 and A549 cells using a commercially-available silica-based DNA extraction kit. DNA extracts were quantified and normalized for microarray analysis. Whole-genome copy number profiling was done using the OncoScan CNV Plus Assay following the manufacturer’s protocols, and data was analyzed using the Chromosome Analysis Suite software. Functional analysis of genes identified to be involved in copy number aberrations was done using the PANTHER Classification System.

RESULTS

Copy number aberrations span 1,592,737,105 bp in GL01 and 1,715,708,552 bp in A549, with a high degree of concordance between the two. Large-scale and focal copy number aberrations previously identified to be recurrent in various LUAD cohorts were present in both GL01 and A549. Focal copy number aberrations associated with previously described lung cancer-related genes involve the PDE4D gene in GL01 and the SKIL and CDKN2A/CDKN2B genes in both GL01 and A549. PANTHER Pathway analysis of genes positively correlated with mRNA expression showed that the ubiquitin proteasome pathway was significantly overrepresented in both GL01 (FDR p = 0.000074) and A549 (FDR p = 0.000075), with 20 genes involved. Additionally, the KRAS:p.G12C/S:c.34G>T/A somatic mutation variant was detected in both GL01 and A549.

CONCLUSION

This study provides a method for identifying potentially clinically-relevant genes associated with a sample’s copy number aberrations and the pathways they represent, providing personalized mechanistic, prognostic, and therapeutic insights into the cancer biology of our cells.

Human ; Carcinoma, Non-small-cell Lung ; Adenocarcinoma Of Lung

BACKGROUND

COVID-19 infection poses a continuing challenge especially to those already with prior lung disease. To analyze such patients’ profile is essential in today’s health care management.

OBJECTIVE

The study aimed to compare the outcomes of COVID-19 confirmed patients with and without primary lung cancer in terms of hospital stay, recovery, and mortality.

METHODS

The study employed a retrospective cohort design. Chart review of all adult COVID-19 patients in Philippine General Hospital from January 2021 to June 2021 was done. A matched cohort study was conducted between COVID-19 patients with and without primary lung cancer.

RESULTS

Among the 953 COVID-19 patients, there were 14 patients with primary lung cancer. In terms of length of hospital stay, patients with primary lung cancer had shorter days from 1.32 to 15.1 days compared to 2.28 to 18.36 days in patients without primary lung cancer (p-value 0.271). Furthermore, they had 64% recovery rate compared to 78% in those without primary lung cancer (p-value 0.118). In terms of overall mortality rate, primary lung cancer patients had 36% rate as compared to 22% in the non-lung cancer group (p-value 0.119). Diabetes mellitus, mild to severe COVID, Remdesivir, and antibiotic use were associated with longer hospital stay while oxygen support via nasal cannula and invasive ventilation led to shorter hospital stay. Age above 50 years, chronic liver disease, other malignancy, shortness of breath, oxygen support via face mask, high flow nasal cannula, invasive ventilation, antibiotic use, hemoperfusion and nebulization showed a decrease chance of recovery while on contrary, Remdesivir showed an increase chance of recovery. An increase mortality rate was seen among age above 50 years, chronic liver disease, other malignancy, shortness of breath, oxygen support via facemask, high flow nasal cannula, invasive ventilation, antibiotics, hemoperfusion, and nebulization, in contrast to a decrease in Remdesivir therapy.

CONCLUSIONS

Among all admitted COVID-19 patients, primary lung cancer patients were associated with shorter hospital stay (8.21+6.89days), lower rate of recovery (64%), and higher mortality rate (36%) as compared to those without primary lung cancer. However, based on the computed p-values for each outcome, these differences are not statistically significant.

Covid-19 ; Lung Cancer ; Lung Neoplasms

Lung cancer is the malignancy with the highest incidence and mortality burden globally, ranking first in both morbidity and mortality among all types of malignant tumors. Pathologically, lung cancer is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for approximately 85% of cases. Due to the often subtle or nonspecific clinical manifestations in early-stage disease, many patients are diagnosed at a locally advanced or metastatic stage, where treatment options are limited and prognosis remains poor. Therefore, molecular targeted therapy focusing on driver genes has become a key strategy to improve the survival outcomes of patients with advanced NSCLC. The epidermal growth factor receptor (EGFR) is one of the most common driver genes in NSCLC. While EGFR mutations occur in approximately 12% of advanced NSCLC patients globally, the incidence rises to 55.9% in Chinese patients. Among EGFR mutations, P-loop and αC-helix compressing (PACC) mutations account for about 12.5%. Currently, EGFR tyrosine kinase inhibitors (TKIs) have become the first-line standard treatment for advanced NSCLC patients with classical EGFR mutations, with efficacy well-established through clinical studies and real-world evidence. However, with rapid advancements in NSCLC precision medicine and deeper exploration of the EGFR mutation spectrum, EGFR PACC mutations have emerged as a key clinical focus. The structural characteristics of these mutations lead to significant variability in responses to EGFR TKIs, leaving therapeutic options still limited, while detection challenges persist due to the sensitivity constraints of current testing technologies, driving increasing demand for improved diagnostic and treatment approaches. The current clinical evidence primarily stems from retrospective analyses and small-scale exploratory studies, while prospective, large-scale, high-level evidence-based medical research specifically targeting this mutation subtype remains notably insufficient. This evidence gap has consequently led to the absence of standardized guidelines or expert consensus regarding optimal treatment strategies for advanced NSCLC with EGFR PACC mutations. As a clinical consensus specifically addressing EGFR PACC-mutant NSCLC, this document provides a comprehensive framework encompassing the clinical rationale for EGFR PACC mutation testing, therapeutic strategies for advanced-stage disease, management of treatment-related adverse events, and follow-up protocols. The consensus underscores the pivotal role of EGFR PACC mutation detection in precision medicine implementation while offering evidence-based recommendations to guide personalized therapeutic decision-making. By establishing clear clinical pathways encompassing molecular testing, therapeutic intervention, and long-term monitoring for EGFR PACC-mutant NSCLC, this consensus aims to meaningfully improve patient survival outcomes while serving as a robust, evidence-based foundation for developing personalized clinical management approaches.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; ErbB Receptors/antagonists & inhibitors* ; Mutation ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Molecular Targeted Therapy ; Consensus

Mutations in the human epidermal growth factor receptor 2 (HER-2) gene are recognized as significant but relatively rare driver alterations in non-small cell lung cancer (NSCLC). These mutations predominantly manifest as gene mutation, amplification, and protein overexpression, with an estimated prevalence from 2.8% to 15.4% among NSCLC patients in China. Research indicates that HER-2 mutations, particularly exon 20 insertions (ex20ins), are strongly correlated with aggressive tumor biology, poor prognosis, and limited responsiveness to immunotherapy, thereby exhibiting characteristics of "cold tumors". Overexpression and amplification of HER-2 are also indicative of a heightened risk of chemotherapy resistance and unfavorable survival outcomes, suggesting a distinct molecular subtype with unique biological behaviors. In recent years, novel antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), have demonstrated groundbreaking efficacy in HER-2-mutant advanced NSCLC patients. These ADCs have shown significant clinical benefits, including high objective response rates and progression-free survival advantages, making T-DXd the first targeted therapy approved for this patient population globally. Additionally, ADCs have exhibited therapeutic potential in patients with HER-2 overexpression, thus broadening the scope of their indications. To standardize the clinical diagnosis and treatment of HER-2 variant NSCLC, the Chinese Anti-cancer Association convened multidisciplinary experts from oncology, pulmonology, thoracic surgery, pathology, and molecular diagnostics to develop this consensus based on the latest evidences from both domestic and international studies, coupled with China's clinical practice experience. This consensus focuses on the molecular characteristics, clinical significance, diagnostic strategies, treatment options, and safety management of HER-2 alterations, addressing ten critical clinical questions in a systematic manner. It is recommended that HER-2 status be routinely tested at initial diagnosis, disease progression, or recurrence in NSCLC. Mutation detection should prioritize next-generation sequencing (NGS), while protein overexpression may be assessed using immunohistochemistry (IHC) standards for gastric cancer. Fluorescence in situ hybridization (FISH) is recommended for detecting HER-2 amplification. Regarding treatment, for HER-2-mutant patients, first-line therapy may involve chemotherapy with or without immune checkpoint inhibitors (ICIs), similar to treatment approaches for driver-gene negative populations. Upon failure of first-line treatment, trastuzumab deruxtecan, may be considered as alternative therapeutic options. For patients with HER-2 overexpression, ADCs should be considered after failure of standard systemic therapy. However, the management of HER-2 amplification remains insufficiently supported by evidence, necessitating a cautious, individualized approach. The consensus also includes detailed recommendations for screening and managing adverse effects associated with ADCs, such as interstitial lung disease (ILD), emphasizing the crucial role of safety management in ensuring treatment efficacy. The publication of this consensus aims to drive the standardization of molecular diagnosis and treatment pathways for HER-2 variant NSCLC, improve clinical outcomes and quality of life for patients, and facilitate the implementation of personalized precision treatment strategies.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Receptor, ErbB-2/metabolism* ; Mutation ; Immunoconjugates/therapeutic use* ; Consensus ; Trastuzumab/therapeutic use* ; Camptothecin/analogs & derivatives*

Objective To investigate the regulatory effect of tumor necrosis factor-α-induced protein-8-like factor 2 (TIPE2) on the phenotype of lung cancer tumor-associated macrophages (TAM) and its influence on the stemness of lung cancer cells. Methods Mouse macrophage cell line RAW264.7 was cultured and infected with either LV-TIPE2 lentivirus or negative control LV-NC lentivirus. The TIPE2 expression in infected cells was assessed by real-time quantitative PCR (RT-qPCR) and Western blotting to verify transfection efficiency. The infected RAW264.7 cells were co-cultured with lung cancer cell line A549, and were divided into four groups: control group (RAW264.7 cells or A549 cells cultured alone), TAM group (RAW264.7 cells co-cultured with A549 cells), LV-NC group (RAW264.7 cells infected with LV-NC and co-cultured with A549 cells), LV-TIPE2 group (RAW264.7 cells infected with LV- TIPE2 and co-cultured with A549 cells). The RAW264.7 cells were collected after co-culture, and the expression of mannose receptor (CD206) protein of M2 macrophages was detected by cellular immunofluorescence staining. The proportions of M1 and M2 macrophages were detected by flow cytometry. After co-culture, A549 cells were collected, and their activity was assessed by CCK-8 assay. Self-renewal ability was evaluated using tumor cell pelleting experiment. The expression of stemness marker proteins-including cluster of differentiation 133 (CD133), transmembrane adhesion molecule (CD44), sex-determining region Y-box protein 2 (SOX2) and octamer-binding transcription factor 4 (OCT4)-was detected by Western blot. Results Compared with the control group or LV-NC group, the relative mRNA and protein expression levels of TIPE2 in RAW264.7 cells from the LV-TIPE2 group were significantly upregulated. Compared with the control group, the fluorescence intensity of M2-type macrophage marker CD206 protein in RAW264.7 cells from the TAM group was significantly increased, the proportion of M1-type macrophages was significantly decreased, and the proportion of M2-type macrophages was significantly increased. In contrast, compared with the TAM group, the fluorescence intensity of CD206 protein in RAW264.7 cells from the LV-TIPE2 group was significantly decreased, the proportion of M1-type macrophages was significantly increased, and the proportion of M2-type macrophages was significantly decreased. Compared with the control group, the proliferation activity of A549 cells in TAM group was significantly increased, the number of tumor pellet formation was significantly increased, and the relative expression levels of CD133, CD44, SOX2 and OCT4 were significantly up-regulated. However, compared with the TAM group, the proliferation activity of A549 cells from the LV-TIPE2 group was significantly decreased, the number of tumor pellet formation was significantly decreased, and the relative expression levels of CD133, CD44, SOX2 and OCT4 were significantly decreased. Conclusion TIPE2 can suppress the stemness of lung cancer cells by inhibiting the polarization of macrophages to M2-type, thereby exerting an anticancer effect.
Animals ; Mice ; Humans ; Tumor-Associated Macrophages/metabolism* ; Lung Neoplasms/genetics* ; Intracellular Signaling Peptides and Proteins/metabolism* ; RAW 264.7 Cells ; A549 Cells ; Phenotype ; Coculture Techniques ; Receptors, Cell Surface/metabolism* ; Neoplastic Stem Cells/metabolism* ; Mannose Receptor ; Mannose-Binding Lectins/metabolism* ; Lectins, C-Type/metabolism* ; Cell Polarity ; Macrophages/metabolism*

A 12-year-old boy was admitted with symptoms of cough and fever lasting over a month, accompanied by weight loss 2 kg. Prior anti-infective treatments proved ineffective in alleviating the symptoms. Chest imaging revealed diffuse interstitial pulmonary edema in the right lung with obstructed lymphatic drainage. Combined with histopathological examinations, the diagnosis was confirmed as lung cancer with pulmonary lymphangitic carcinomatosis. The patient underwent chemotherapy with docetaxel and carboplatin, yet the disease progressively worsened, resulting in death three months after diagnosis. This case highlights lung cancer should not be overlooked in patients with persistent respiratory symptoms of unknown etiology. Early imaging examinations, along with necessary pathological evaluations, are crucial for timely detection and diagnosis. The presence of pulmonary lymphangitic carcinomatosis often indicates an advanced-stage of cancer, associated with a poor prognosis.
Humans ; Male ; Lung Neoplasms/complications* ; Child ; Carcinoma/drug therapy*

OBJECTIVE: To investigate the clinical characteristics and prognosis of primary pulmonary lymphoma (PPL). METHODS: The clinical data of 17 patients with PPL admitted to Gansu Provincial Hospital from January 2013 to June 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: The median age of the 17 patients was 56 (29-73) years old. There were 8 males and 9 females. According to Ann Arbor staging system, there were 9 patients with stage I-II and 8 patients with stage III-IV. There were 14 patients with IPI score of 0-2 and 3 patients with IPI score of 3-4. All 17 patients had symptoms at the initial diagnosis, most of the first symptoms were cough, and 6 patients had B symptoms.Among the 17 patients, there were 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, 1 case of gray zone lymphoma (GZL), and 3 cases of Hodgkin's lymphoma (HL). 15 patients received chemotherapy, of which 3 cases received autologous hematopoietic stem cell transplantation(ASCT) and 3 cases received radiotherapy; 2 patients did not receive treatment. The median number of chemotherapy courses was 6(2-8). The short-term efficacy was evaluated, 12 patients achieved complete remission (CR) and 3 patients achieved partial remission (PR). The age, pathological subtype, sex, Ann Arbor stage, β₂-microglobulin(β₂-MG) level, lactate dehydrogenase(LDH) level were not correlated with CR rate (P >0.05), while IPI score was correlated with recent CR rate (P < 0.05 ). The median follow-up time was 31(2-102) months. One of the 12 CR patients died of COVID-19, and the rest survived. Among the 3 patients who did not reach CR, 1 died after disease progression, while the other 2 survived. One of the 2 untreated patients died one year after diagnosis. Both the median progression-free survival (PFS) time and overall survival (OS) time of the 17 patients were both 31 (2-102) months. CONCLUSION The incidence of PPL is low, and the disease has no specific clinical manifestations, which is easily missed and misdiagnosed. The pathological subtypes are mainly MALT lymphoma and DLBCL, and the treatment is mainly combined chemotherapy. The IPI score is related to the treatment efficacy.
Humans ; Middle Aged ; Male ; Female ; Adult ; Prognosis ; Aged ; Lung Neoplasms/therapy* ; Retrospective Studies ; Neoplasm Staging ; Lymphoma/therapy* ; Lymphoma, Large B-Cell, Diffuse

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation