Macrophage activation markers, specifically CD163 and CD169, play pivotal roles in the modulation of immune responses within the tumor microenvironment (TME), influencing the outcome of various cancers. These markers delineate the activation states of macrophages, with CD163 associated with the protumoral phenotype and CD169 with activation of tumor immunity. This review comprehensively explores the dualistic roles of these markers in cancer progression and immune suppression, and discusses the mechanisms through which these markers influence macrophage behavior, the impact of their expression on cancer progression, and the therapeutic potential of targeting these pathways to reprogram the TME toward enhancing antitumor immunity. This review aims to underscore the therapeutic potential of macrophage activation markers as targets for cancer treatment, highlighting emerging strategies and future directions in cancer immunotherapy.

Kawasaki disease presents dilation and occlusion of one or more coronary arteries in patients with early to late phases. Here we present the case of a 41-year-old Japanese male who underwent heart transplantation due to Kawasaki disease which was diagnosed at 3 years of age. The coronary arteries of the explanted heart showed pathological variations such as vascular remodeling, including aneurysm, intimal thickening, recanalization of occludes parts, and neovascularization of all vessels, especially developed vasa vasorum in the distal segments. Continuous vascular remodeling of coronary arteries may have developed progressive left ventricular dysfunction during the very late phase of Kawasaki disease.

Evaluation of bone marrow pathology can be challenging for nonspecialist pathologists due to its morphological complexities. Despite advances in artificial intelligence for other organ systems, research in bone marrow biopsy field remains limited. This study presents an artificial intelligence model developed to classify myeloid diseases based on morphologically normal megakaryocytes in hematoxylin-eosin-stained bone marrow biopsy specimens. The model integrates two deep learning components: one for detecting bone marrow regions, and the other for identifying megakaryocytes, along with an XGBoost-based classifier that leverages extracted features to differentiate between normal cases, myelodysplastic neoplasm, and immune thrombocytopenic purpura. The model achieved exceptional accuracy, with area under the curve values of 0.9996 (bone marrow detection) and 0.9997 (megakaryocyte detection). For disease classification, myelodysplastic neoplasm versus normal performed well, with an area under the curve of 0.879. Feature analysis revealed that the percentage of megakaryocyte among all cells and the number of adjacent megakaryocytes within various distances were significantly correlated with disease prediction. This study introduces the first artificial intelligence model capable of classifying myelodysplastic neoplasm versus normal based on normal megakaryocyte morphology. This model demonstrates potential not only for diagnostic assistance but also for uncovering novel histological features.

We report a case of pancreatic ductal adenocarcinoma (PDAC) in a 51-year-old woman with PRSS1-associated hereditary pancreatitis (HP) and a history of chronic alcohol and tobacco use. Following neoadjuvant chemotherapy, she underwent total pancreatectomy. Histological analysis of the entire pancreas revealed no high-grade PanINs and scattered low-grade PanINs, with and without KRAS mutations, indicating molecular heterogeneity. Genomic profiling identified multiple driver alterations, comprising both clonal and subclonal events, including mutations in KRAS, CDKN2A/B, SMAD4, ATRX, MSH3, and the TERT promoter. Immunohistochemistry showed strong nuclear p53 overexpression despite the absence of TP53 mutation, suggesting a chromosomal instability phenotype. These findings support the hypothesis of a chromothripsis-like catastrophic genomic event contributing to rapid oncogenesis, bypassing the conventional PanIN sequence. The background of chronic inflammation, advanced lipomatous atrophy, and environmental exposures may have facilitated this transformation. This case underscores the need to consider alternative, nonlinear pathways of PDAC development in genetically predisposed individuals and highlights the potential utility of molecular surveillance for early detection and risk stratification.

Germinomas constitute two-thirds of intracranial germ cell neoplasms, with a woman: male ratio of 8:22. A characteristic of this tumor is its adequate vascularity, which has not been previously studied with markers such as Nestin, YAP and CD15, and which can provide valuable information about the biology of this tumor. These markers were analyzed by immunohistochemistry, showing tumor blood vessels cytoplasmic staining for nestin and for CD15, demonstrating angiogenesis as an important mechanism in germinomas.

Recent reports have revealed various morphological features of ALK-rearranged mesenchymal neoplasms but their characteristics remain to be elucidated. Here, we report a case of ALK-rearranged mesenchymal neoplasm with novel morphological features. A 32-year-old man had an intra-abdominal mass measuring 75 mm in diameter. Histologically, the tumor consisted of many lymphoid follicles with wide fibrosis or hyalinization. The follicles were characterized by regressed germinal centers and expanded mantle zones. Hyalinized blood vessels were distributed in the follicular and interfollicular areas. These histological findings resembled those of hyaline-vascular type unicentric Castleman disease (HV-UCD). However, the fibrous areas exhibited histological findings similar to inflammatory myofibroblastic tumor (IMT), which is characterized by the proliferation of spindle or stellate-shaped fibroblastic cells accompanied by lymphoid, eosinophil, and plasma cell infiltration. Immunohistochemically, ALK-positive spindle cells were observed in the follicular, interfollicular, and fibrous areas. Molecular analysis revealed fusion between ATIC (exon 7) and ALK (exon 20). Immunofluorescence staining suggested that ALK-positive tumor cells in follicular areas were derived from CD23-positive follicular dendritic cells, and those in interfollicular areas were derived from α-SMA-positive fibroblastic reticular cells or myofibroblasts. Therefore, we report an extremely rare case of ALK-rearranged mesenchymal neoplasm with features of both HV-UCD and IMT.

Anaplastic pancreatic carcinoma (APC) arising from mucinous cystic neoplasm (MCN) is rare, with only 12 cases reported. The relationship between pregnancy-associaed hormonal changes and MCN progression remains poorly understood, particularly regarding hormone receptor expression patterns during malignant transformation. A 34-year-old woman presented with persistent abdominal pain 9 months post-delivery. Imaging revealed an 11 cm multilocular cystic mass in the pancreatic body and tail with mural nodules showing blood flow signals. Laboratory findings demonstrated normal. She underwent distal pancreatectomy and splenectomy and no recurrence at 6-month follow-up. Histopathological examination revealed MCN with ovarian-type stroma progressing from low-to-high grade dysplasia, invasive ductal carcinoma, and anaplastic carcinoma with osteoclast-like giant cells. Immunohistochemically, estrogen receptor (ER) expression showed stepwise pattern: negative in low-grade dysplasia, strongly positive in high-grade dysplasia and anaplastic components. Progesterone receptor positivity was observed in stromal and epithelial components, with elevated Ki-67 correlating with ER expression. This represents first documentation of progressive ER acquisition during MCN malignant transformation, suggesting autonomous hormone production by ovarian‑type stroma may help sustain tumor growth beyond pregnancy. Stepwise ER expression may serve as a biomarker for risk stratification and a potential target for therapy in hormone-sensitive pancreatic neoplasms.

Although rare, thyroid follicular nodular disease (TFND) may exhibit a nodule-in-nodule (NN) appearance with solid/trabecular (ST) components (STc). While the STc has histologically aggressive features compared to the outer nodule (Out-N) in TFND, its pathological significance remains unclear. We present a case of TFND with STc in a 63-year-old man who developed skin implantation and lung metastases 3 years after lobectomy. Histologically, the skin tumor resembled STc with high mitotic activity. Molecular analysis revealed EZH1 mutations in both the Out-N and STc of TFND, while KRAS and TERT promoter mutations were restricted to STc and the skin tumor. These findings suggest that the STc of NN may be a precursor to poorly differentiated thyroid carcinoma arising from well-differentiated components through stepwise mutations. This case highlights the malignant potential of certain Noninvasive TFNDs and suggests the need for further analyses to clarify this hypothesis and reconsider their classification and management.

A 64-year-old female presenting with multiple cystic lesions in bilateral parotid glands was clinically considered to be benign. The surgically resected specimen revealed that the lesions met the diagnostic criteria of lymphoepithelial cysts (LECs). What's unique is that Langerhans cell histiocytosis (LCH) were identified in the LECs by immunohistochemistry (IHC) and molecular test. The inconspicuous LCH cells distributed along and mimicked the epithelial lining of cyst walls and were possibly to be missed in diagnosis. To date, there has no documented report of primary LCH originating within LECs. This study presents for the first time of a unique growth pattern. In addition, we reviewed published articles and attempt to make tentative discussion on pathogenesis.

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.

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.

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.