Re-challenging immune checkpoint inhibitor in a patient with advanced non-small cell lung cancer: a case report

Abstract Background Currently, immune checkpoint (ICP) inhibitors are essential drugs for the treatment of non-small cell lung cancer (NSCLC). However, in patients previously treated with ICP inhibitors, the efficacy and safety of re-challenging the same or another ICP inhibitor remain unclear. Case presentation We present the case of a patient treated with nivolumab for advanced NSCLC who was previously treated with an ICP inhibitor as the first-line chemotherapy along with heavy cytotoxic chemotherapy. After the failure of five lines of chemotherapy, 3 cycles of nivolumab, as the ICP inhibitor re-challenge, the patient achieved a partial response. Conclusions This case might suggest that re-challenging an ICP inhibitor could be clinically active in selected patients with advanced NSCLC who progress after achieving an initial clinical benefit with an ICP inhibitor

Molecular and Morphological Profiling of Lung Cancer: A Foundation for “Next-Generation” Pathologists and Oncologists

The pathological diagnosis of lung cancer has largely been based on the morphological features observed microscopically. Recent innovations in molecular and genetic technology enable us to compare conventional histological classifications, protein expression status, and gene abnormalities. The introduction of The Cancer Genome Atlas (TCGA) project along with the widespread use of the next-generation sequencer (NGS) have facilitated access to enormous data regarding the molecular profiles of lung cancer. The World Health Organization classification of lung cancer, which was revised in 2015, is based on this progress in molecular pathology; moreover, immunohistochemistry has come to play a larger role in diagnosis. In this article, we focused on genetic and epigenetic abnormalities in non-small cell carcinoma (adenocarcinoma and squamous cell carcinoma), neuroendocrine tumor (including carcinoids, small cell carcinoma, and large cell neuroendocrine carcinoma), and carcinoma with rare histological subtypes. In addition, we summarize the therapeutic targeted reagents that are currently available and undergoing clinical trials. A good understanding of the morphological and molecular profiles will be necessary in routine practice when the NGS platform is widely used

A cotyledonoid dissecting leiomyoma with an intravascular component and adenomyosis accompanied with possible multiple lung metastases: A case report

A cotyledonoid dissecting leiomyoma (CDL) is a rare variant of a uterine smooth muscle cell tumor and is characterized by intramural and extrauterine growth patterns with dissection of the uterine myometrium.We encountered a case of a CDL with multiple lung nodules. Computed tomographic and magnetic resonance imaging results revealed the presence of a multilobulated abdominal mass with cystic components contiguous to the uterine corpus and well-demarcated nodules measuring ≤2 cm in diameter in the bilateral lungs. Simple hysterectomy and bilateral salpingo-oophorectomy were performed.Macroscopically, a placenta-like tumor protruded from the medial fundus of the uterine corpus toward the intraluminal and peritoneal cavities. Histologically, the tumor was composed of neoplastic spindle cells with hyalinized degeneration and vascular proliferation. Endometrial glands with stroma and vascular invasion were also noted.This is the first report of a CDL with possible metastasis. Histological features, including intravascular growth, may predict the aggressive behavior of this tumor. Keywords: Adenomyosis, Leiomyoma, Smooth muscle tumo

Genetic and immunohistochemical analyses of ciliated muconodular papillary tumors of the lung: A report of five cases

Ciliated muconodular papillary tumors are benign lesions located in the peripheral lung field. Recent studies revealed BRAF and epidermal growth factor receptor gene mutations and anaplastic lymphoma kinase gene rearrangement. Five ciliated muconodular papillary tumors were screened for the BRAF V600E and EGFR mutations via polymerase chain reaction. Immunohistochemical analysis was performed for the detection of the BRAF V600E and anaplastic lymphoma kinase proteins, as well as other markers including phosphorylated extracellular signal-regulated protein kinase. Three tumors (60%) harbored the BRAF V600E mutation. Immunohistochemical analysis confirmed this mutation in all of the tumor cell types. EGFR mutation and immunoactivity of the anaplastic lymphoma kinase protein were not detected. Phosphorylated extracellular signal-regulated protein kinase was negative both in the cytoplasm and nucleus of the BRAF V600E–positive tumors. Mucin 1, mucin 4, thyroid transcription factor 1, and cytokeratin 7 were positive, and mucin 5AC was partially positive, whereas napsin A and cytokeratin 20 were negative. Ciliated muconodular papillary tumor may originate from the terminal bronchioles, and the status of ERK activation reflects its benign behavior

A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor

Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness

Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5

Abstract The unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates ongoing control measures. Given its rapid spread, the new Omicron subvariant BA.5 requires urgent characterization. Here, we comprehensively analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1. Although in vitro growth kinetics of BA.5 was comparable among the Omicron subvariants, BA.5 was much more fusogenic than BA.1 and BA.2. Airway-on-a-chip analysis showed that, among Omicron subvariants, BA.5 had enhanced ability to disrupt the respiratory epithelial and endothelial barriers. Furthermore, in our hamster model, in vivo pathogenicity of BA.5 was slightly higher than that of the other Omicron variants and less than that of ancestral B.1.1. Notably, BA.5 gains efficient virus spread compared with BA.1 and BA.2, leading to prompt immune responses. Our findings suggest that BA.5 has low pathogenicity compared with the ancestral strain but enhanced virus spread /inflammation compared with earlier Omicron subvariants