Pathology International最新文献

Although it has been known for over 40 years that lung cancer can progress by spreading through alveolar spaces, the WHO formally published the term "spread through air spaces" (STAS) only 10 years ago, in 2015. Numerous studies have proven that STAS is a poor prognostic factor in all histological types of lung cancer and affects surgical procedure selection and stage classification. While it is clear that STAS should be reported in the routine diagnosis of lung cancer, diagnosis can sometimes be challenging, and pathologists need to be aware of the diagnostic and exclusion criteria. Clinicians also need to recognize the importance of STAS and cooperate in improving diagnosis using frozen sections, which has become a topic of discussion in recent years. In this review, we summarize the current status of research on STAS from various perspectives, including clinical, morphological, genetic, molecular, and tumor immune microenvironmental properties, and discuss future prospects.

Pathological autopsies are essential for medical education and medical progress, yet their numbers have been declining globally. Annual of the Pathological Autopsy Cases in Japan (APAC-J), established in 1958, is a comprehensive nationwide database of autopsies performed in Japan. This study analyzed APAC-J data from 1958 to 2023, encompassing over 1.49 million cases. The number of autopsies peaked at 40,680 in 1985 but declined significantly to 10,020 in 2019, and further to 6,557 in 2022 largely due to the COVID-19 pandemic. Autopsy rates declined after the medical school conflicts in the late 1960s, with temporary increases following the introduction of board certification for pathologists. The number of data-reporting facilities rose to 934 by 2019. Since 2000, the proportion of brain dissections has slightly increased, while limited autopsies have decreased (24% and 3.9%, respectively, in 2023). The male-to-female ratio is over 2.0, and average ages of autopsy cases remain over 10 years younger than Japanese life expectancy. Autopsy rates were higher among individuals from childhood to middle age. This study demonstrates that social dynamics and healthcare system reforms have influenced autopsy practices. Interpretation of autopsy case groups must consider demographic characteristics and shifts in autopsy implementation over time.

Breast cancer in adolescents and young adults has poorer clinical outcomes, but the role of MYC in this group remains unclear. We aimed to elucidate the characteristics of MYC expression in breast cancer among adolescents and young adults. MYC expression in 42 adolescents and young adults and 110 older adults were analyzed using immunohistochemistry, fluorescence in situ hybridization, quantitative polymerase chain reaction, and RNA sequencing. Immunohistochemical c-myc expression was higher in adolescents and young adults group compared to older adults, without MYC gene amplification. In older adults, c-myc expression was associated with more aggressive features. Adolescents and young adults group showed higher c-myc expression even in tumors with less aggressive features, such as estrogen receptor positive, low Ki-67 labeling index, and early clinical stage, than older adults. RNA sequencing revealed higher expression of cholecystokinin B receptor and lower expression of uridine diphosphate glucuronosyltransferase 2 family member B4 in c-myc positive tumors of adolescents and young adults group. The preference of positive cases for both c-myc and cholecystokinin B receptor was significantly higher in adolescents and young adults group. In conclusion, c-myc overexpression makes adolescents and young adults breast cancer more aggressive through multifaceted roles including relevantly expressed cholecystokinin B receptor. Clinical trial registration: This study is not a clinical trial.

This study aimed to clarify the risk factors for recurrence in epidermal growth factor receptor (EGFR) mutated and wild-type lung adenocarcinomas, with a focus on the newly proposed International Association for the Study of Lung Cancer (IASLC) grading system. We enrolled 2106 patients who underwent complete anatomical radical resection and had a known EGFR mutational status and IASLC grade. Patient characteristics and pathological features were analyzed to assess the cumulative incidence of recurrence (CIR). No significant differences were found in the CIR between the EGFR mutated (EGFRm) and wild-type groups. In the EGFRm group, multivariate analysis identified IASLC grade 2, grade 3 (reference: grade 1), pathological stage II/III, lymphatic invasion (ly), vessel invasion (v), and plural invasion as independent risk factors for recurrence. In the wild-type group, IASLC grades 2 and 3, pathological stage II/III, ly, and v were identified as independent risk factors for recurrence. Patients with any independent risk factor had a significantly poorer overall survival and a higher CIR compared with those without a risk factor in both the EGFRm and wild-type groups. The IASLC grading system is a valuable prognostic factor for recurrence in patients with lung adenocarcinoma harboring EGFRm.

A 57-year-old male underwent an incidental left adrenal tumor resection because of malignancy concerns. The tumor demonstrated a heterogeneous yellowish-white color. Histological features were characterized by nuclear atypia, diffuse growth, sinusoidal invasion, and mucin deposition in most stromal regions, leading to the diagnosis of a myxoid adrenocortical carcinoma (ACC). Whole exome sequencing analysis revealed 1p deletion and other several mutations without TP53 nor CTNNB1 mutations. Following surgery and adjuvant mitotane therapy, the patient showed no recurrence at a 5-year follow-up. Myxoid ACC is an exceedingly rare tumor characterized by mucus deposits in tumor stroma with high malignant potential. Despite the identification of crucial driver gene mutations such as TP53 and CTNNB1 in ACC, the genetic background of the myxoid ACC remains unclear. This case was the first case report of myxoid ACC with a 1p deletion, which was reported to be detected in 67% of ACC and 9% of adenoma but not in hyperplasia, supporting the correlation of this aberration with tumorigenesis. In conclusion, 1p deletion may be relevant to tumorigenesis in myxoid ACC.

Nuclear receptors (NRs) are lipid ligand-binding transcription factors, with 48 members having been identified in humans to date. They are involved in diverse physiological processes, including development and homeostasis, and are also implicated in the pathogenesis of various diseases, most notably cancer. While NR activity is primarily regulated by specific ligand binding, posttranslational modifications, particularly phosphorylation, also play a critical role in modulating their function. Recently, we identified a novel signaling pathway linking claudins (CLDNs), cell-cell adhesion proteins, to NRs. CLDN-mediated cell-cell adhesion activates Src family kinases (SFKs), leading to serine phosphorylation of several NRs. This newly-discovered CLDN-NR pathway contributes to epithelial differentiation in stem cells and promotes cancer progression. In this review, we discuss the biological significance and underlying mechanisms of this, tracing the development of our research.

Primary salivary gland-type tumors may rarely be accompanied by hyperplastic alveolar cells, a pattern referred to as pneumocytic adenomyoepithelioma (PAM). Most previously reported cases have relied solely on immunohistochemical findings. In this report, we present a case involving three distinct types of epithelial cell components, identified through dual immunohistochemical staining for p40/TTF-1, in addition to the detection of HRAS mutation using next-generation sequencing. The female patient, in her 70s, underwent left lower lobectomy after a chest CT scan revealed a 20 mm solid mass in the left lower lobe. The final histopathological diagnosis was a primary pulmonary epithelial-myoepithelial carcinoma (EMEC). This paper presents a case of a primary pulmonary EMEC exhibiting so-called PAM morphology and includes a brief review of the literature.

Cancer cells reprogram their metabolism during progression to adapt to the tumor microenvironment, which is characterized by distinct differences in nutrient availability, oxygen concentrations, and acidity. This metabolic reprogramming can simultaneously create metabolic vulnerabilities unique to cancer cells, making cancer metabolism a promising therapeutic target. Since the clinical application of folate antimetabolites in the 1940s, numerous therapeutic strategies targeting cancer metabolism have been developed. In recent years, advancements in technologies such as metabolome analysis have facilitated the development of agents that more specifically target cancer cell metabolism. However, these newly developed agents often face challenges in demonstrating efficacy as monotherapies in clinical trials. Nevertheless, combination therapies, designed based on precise mechanistic insights and incorporating agents such as immune-checkpoint and signaling-pathway inhibitors, have shown promising efficacy. This review provides an overview of the current landscape of therapeutic strategies targeting cancer metabolism, with a particular focus on approaches targeting amino acid, fatty acid, and glucose metabolism in cancer cells.