The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

Background: The Korean Society for Cytopathology introduced a digital proficiency test (PT) in 2021. However, many doubtful opinions remain on whether digitally scanned images can satisfactorily present subtle differences in the nuclear features and chromatin patterns of cytological samples. Methods: We prepared 30 whole-slide images (WSIs) from the conventional PT archive by a selection process for digital PT. Digital and conventional PT were performed in parallel for volunteer institutes, and the results were compared using feedback. To assess the quality of cytological assessment WSIs, 12 slides were collected and scanned using five different scanners, with four cytopathologists evaluating image quality through a questionnaire. Results: Among the 215 institutes, 108 and 107 participated in glass and digital PT, respectively. No significant difference was noted in category C (major discordance), although the number of discordant cases was slightly higher in the digital PT group. Leica, 3DHistech Pannoramic 250 Flash, and Hamamatsu NanoZoomer 360 systems showed comparable results in terms of image quality, feature presentation, and error rates for most cytological samples. Overall satisfaction was observed with the general convenience and image quality of digital PT. Conclusions As three-dimensional clusters are common and nuclear/chromatin features are critical for cytological interpretation, careful selection of scanners and optimal conditions are mandatory for the successful establishment of digital quality assurance programs in cytology.

Diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, exerts anti-inflammatory and antifibrotic effects in a variety of human chronic diseases. However, the role of DIZE in kidney fibrosis and the underlying mechanism remain unclear. Therefore, we investigated the effects of DIZE on the progression of renal fibrosis after unilateral ureteral obstruction (UUO), a well-established model of chronic kidney disease. Methods: C57BL/6 female or male mice were subjected to right UUO. Mice received 15 mg/kg DIZE or vehicle (saline) daily. On the 7th day after UUO, kidneys were collected for analysis of renal fibrosis (α-smooth muscle actin, phosphorylated SMAD3, transforming growth factor (TGF)-β, Masson’s trichrome, and Sirius red staining), inflammation (macrophage infiltration, proinflammatory cytokines/ chemokines), apoptosisecrotic cell death (TUNEL and periodic acid-Schiff staining), and ACE2 activity and messenger RNA (mRNA) expression. Results: Treatment with DIZE exacerbated renal fibrosis by upregulating the profibrotic TGF-β/SMAD3 pathway, proinflammatory cytokine/chemokines (interleukin [IL]-1β, monocyte chemoattractant protein-1, IL-6, and macrophage inflammatory protein-2) levels, M2 macrophage accumulation (CD206, IL-4, IL-10, and CX3CL1), and apoptoticecrotic cell death in the obstructed kidneys of female mice but not male mice. However, DIZE treatment had no effect on ACE2 activity or mRNA expression. Conclusion: DIZE exacerbates UUO-induced renal fibrosis by aggravating tubular damage, apoptosis, and inflammation through independent of angiotensin (1–7), angiotensin II levels, and ACE2 expression/activity, rather than protecting against renal fibrosis after UUO. DIZE also has powerful effects on recruiting macrophages, including the M2-polarized subtype, in female UUO mice.

Purpose: Smoking is a risk factor for the development of asthma and worsens the long-term prognosis of asthma. This study investigated the effect of cigarette smoke extract (CSE) on innate immune cells such as innate lymphoid cells (ILCs) and macrophages in a murine model of induced asthma. Methods: Six-week-old female BALB/C mice were exposed to ovalbumin (OVA) via an intranasal route with or without CSE for 8 weeks to establish a chronic murine asthma model. Airway hyperresponsiveness (AHR), airway inflammatory cells from bronchoalveolar lavage fluid, and the population of CD4 + T cells, ILCs, and macrophages in the lungs were studied to evaluate the effect of chronic CSE exposure on asthma. Results: Mice intranasally exposed to CSE along with OVA treatment (CSE/OVA) had significantly enhanced AHR, eosinophilic inflammation, increased IL-13 and IL-17 producing CD4 + T cells compared to mice intranasally exposed to OVA only. On the contrary, the frequency of Foxp3 + in CD4 + T cells was reduced in the CSE/OVA group. CSE enhanced the dendritic cell (DC) population, especially MHCII + DC with antigen-presenting capacity. Among ILCs, the CSE/OVA group showed a significant increase of IL-13-producing type 2 ILCs, but not interferon-γ+ ILC1s and IL-17 + ILC3s. . Among macrophages, alveolar macrophage and Ym-1 and FIZZ1 positive M2 macrophage populations were significantly induced by CSE exposure alone and when combined with OVA treatment. Conclusion In this study, we showed that long-term exposure to cigarette smoke contributes to the inception and aggravation of asthmatic inflammation by enhancing DCs, ILC2, and M2 alveolar macrophage populations in the mouse model.

Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma.MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF - CD11c - CD11b + monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c - monocytes in the lungs. While an intravenous adoptive transfer of Ly6c - monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c - monocytes did not. Ex vivo Ly6c - MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c - MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c - monocytes could be a therapeutic target for asthma management.

Background: Digital pathology (DP) using whole slide imaging is a recently emerging game changer technology that can fundamentally change the way of working in pathology. The Digital Pathology Study Group (DPSG) of the Korean Society of Pathologists (KSP) published a consensus report on the recommendations for pathologic practice using DP. Accordingly, the need for the development and implementation of a quality assurance program (QAP) for DP has been raised. Methods: To provide a standard baseline reference for internal and external QAP for DP, the members of the Committee of Quality Assurance of the KSP developed a checklist for the Redbook and a QAP trial for DP based on the prior DPSG consensus report. Four leading institutes participated in the QAP trial in the first year, and we gathered feedback from these institutes afterwards. Results: The newly developed checklists of QAP for DP contain 39 items (216 score): eight items for quality control of DP systems; three for DP personnel; nine for hardware and software requirements for DP systems; 15 for validation, operation, and management of DP systems; and four for data security and personal information protection. Most participants in the QAP trial replied that continuous education on unfamiliar terminology and more practical experience is demanding. Conclusions The QAP for DP is essential for the safe implementation of DP in pathologic practice. Each laboratory should prepare an institutional QAP according to this checklist, and consecutive revision of the checklist with feedback from the QAP trial for DP needs to follow.

Background: The Continuous Quality Improvement program for cytopathology in 2020 was completed during the coronavirus pandemic. In this study, we report the result of the quality improvement program. Methods: Data related to cytopathology practice from each institute were collected and processed at the web-based portal. The proficiency test was conducted using glass slides and whole-slide images (WSIs). Evaluation of the adequacy of gynecology (GYN) slides from each institution and submission of case glass slides and WSIs for the next quality improvement program were performed. Results: A total of 214 institutions participated in the annual cytopathology survey in 2020. The number of entire cytopathology specimens was 8,220,650, a reduction of 19.0% from the 10,111,755 specimens evaluated in 2019. Notably, the number of respiratory cytopathology specimens, including sputum and bronchial washing/ brushing significantly decreased by 86.9% from 2019, which could be attributed to the global pandemic of coronavirus disease. The ratio of cases with atypical squamous cells to squamous intraepithelial lesions was 4.10. All participating institutions passed the proficiency test and the evaluation of adequacy of GYN slides. Conclusions Through the Continuous Quality Improvement program, the effect of coronavirus disease 2019 pandemic, manifesting with a reduction in the number of cytologic examinations, especially in respiratory-related specimen has been identified. The Continuous Quality Improvement Program of the Korean Society for Cytopathology can serve as the gold standard to evaluate the current status of cytopathology practice in Korea.

Purpose: Asthma is a chronic airway inflammatory disorder and is associated with macrophages. Statin, a well-known lipid-lowering agent, has recently been noted for its anti-inflammatory effect on macrophage. This study was designed to evaluate the antiasthmatic effect of atorvastatin via modulation of macrophage activation by using an animal model of allergic asthma. Methods: Atorvastatin 40 mg/kg was given by gavage once a day for 3 days before challenge of ovalbumin (OVA); airway hyperresponsiveness (AHR), airway inflammatory cells, and cytokines were evaluated in the murine asthma model. The direct effect of atorvastatin on the activation of macrophages In vitro was determined using the alveolar macrophage cell line CRL-2456. Results: Administration of atorvastatin reduced the numbers of total inflammatory cells, macrophages, and eosinophils as well as lung histology enhanced in the murine asthma model. AHR measured by enhanced pause was significantly reduced after atorvastatin administration in the murine asthma model (P< 0.05). Atorvastatin administration resulted in the reduction in serum OVA-specific IgE levels and the increase in serum OVA-specific IgG2a levels (P< 0.05). The mRNA levels of Ccr3, Il-17, and Muc5ac enhanced by OVA challenge were decreased by treatment with atorvastatin (P< 0.05). Along with these improvement in allergic inflammatory changes, the population of CD11c-CD206+ macrophages as well as the expression of Ym-1 and Relm-α in the lungs were reduced with atorvastatin (P< 0.05). In vitro test with CRL-2456 showed that atorvastatin reduced the expression of Cd206, Arg-1, and Fgf-2 induced by IL-4 stimulation (P< 0.05). Conclusion This study highlighted the antiasthmatic effect of atorvastatin on the suppression of M2 macrophage activation in allergic asthma.

Background/Aims: Colorectal cancer (CRC) rate increases with aging. Aging-related proteins, such as sirtuins (SIRTs) may be a potential therapeutic target in the elderly patients with CRC. The clinical implications of SIRT1 and SIRT2 have not been reported for elderly patients with cancer. The aim of this study was to evaluate the impact of expression of SIRT1 and SIRT2 on clinical outcome in two extreme age groups of patients with CRC. Methods: The expression of SIRT1 and SIRT2 were evaluated in CRC tissues of 101 patients aged ≥ 80 years and 29 patients aged ≤ 40 years by immunohistochemistry. We defined the patients aged ≥ 80 years as the very elderly and patients aged ≤ 40 years as the young patients. Correlations between the expression of these proteins and clinicopathological features were analyzed. Results: The prognosis for the very elderly patients with high expressions of SIRT1 was significantly worse than that for patients showing low expression (median survival, 24.9 months vs. 38.6 months, p = 0.027) whereas high expression of SIRT2 better prognosis (median survival, 37.9 months vs. 17.3 months, p = 0.006). However, the young patients did not show any difference in prognosis according to expression of SIRT1 and SIRT2. In multivariate analysis, high SIRT1 expression retained statistical significance as a poor prognostic factor in the very elderly patients with CRC. Conclusions The results suggest that high SIRT1 expression could be predictive of a poor outcome for very elderly patients with CRC.