Pathology International最新文献

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.

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.

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.

The glycoform of heart development protein with EGF-like domains 1 (HEG1) recognized by the SKM9-2 monoclonal antibody is a useful diagnostic marker for malignant pleural mesothelioma (MPM). The putative glycoform includes core 2 O-glycans carrying sialyl poly-N-acetyllactosamine (LacNAc), but sulfation modifications are undetermined. Since sialyl 6-sulfo LacNAc-capped core 2 O-glycans are expressed in MPM and their structure overlaps with low-sulfated keratan sulfate (KS), we asked whether low-sulfated KS is expressed in MPM and whether HEG1 is decorated with low-sulfated KS. We performed immunohistochemical analysis of 41 MPM cases using anti-KS monoclonal antibodies and endoglycosidases, reversed-phase ion-pair high-performance liquid chromatography analysis of KS/sulfated LacNAc isolated from human pleural tissue, and western blot analysis of HEG1·IgG recombinant fusion proteins secreted from low-sulfated KS-expressing human embryonic kidney cells. Most MPM tissues were stained with anti-low-sulfated KS antibodies and staining was eliminated by endo-β-galactosidase and keratanase II but not by peptide-N-glycosidase F. Disaccharide composition analysis revealed that mono-sulfated LacNAc disaccharide and di-sulfated LacNAc disaccharide accounted for 83.1% and 16.9% of pleural KS/sulfated LacNAc, respectively. Western blot analysis of HEG1·IgG glycoforms indicated that HEG1 functions as a core protein for low-sulfated KS. Thus, HEG1 protein decorated with low-sulfated KS is expressed in MPM.

Orbital solitary fibrous tumor (SFT) is an extremely rare variant of systemic SFTs. However, the relationship between the biological/clinical characteristics, histological malignancies, and known oncogenes of systemic SFTs has not yet been elucidated. Therefore, we investigated these features and explored the prognostic factors of orbital SFTs by analyzing a series of orbital SFT cases. Six orbital SFT and one meningeal SFT were analyzed for comparison. NAB2::STAT6 variants were identified in five of the six orbital SFTs cases and one meningeal SFT case. There was no correlation between the exon composition of NAB2::STAT6 variants and the time of relapse after surgery or histological malignancy. Nuclear STAT6 staining by immunohistochemistry was observed in all cases, whereas cytosolic STAT6 staining was confirmed in three orbital SFT cases. The presence of histological malignancies and positive cytosolic STAT6 staining were mutually exclusive. The diffuse strong expressions of p53 and p16 were confirmed only in a case with the worst clinical course. No TERT promoter mutations were observed in any of these cases. Our study suggests that positivity of cytosolic STAT6 staining and high p53/p16 expression may be a predictor of histological/clinical malignancy in orbital SFT. Further evidence is necessary to confirm our results.

T follicular helper cell lymphoma (TFHL) is a systemic T-cell lymphoma with a phenotype reminiscent of TFH cells and frequent RHOA p.G17V mutation. Here, we report a case of TFHL with spatially multiple and clonally independent B-/plasma cell proliferations (B/PC-Ps), which posed diagnostic difficulties. An 87-year-old female presented with a skin rash, and a skin biopsy from the chest was initially diagnosed as low-grade B-cell lymphoma with plasmacytic differentiation. Three months after rituximab monotherapy, bilateral pleural effusions developed. Cytology of the pleural effusion revealed abnormal lymphocytes and plasma cells. The abnormal T-cells were positive for CD3, CD4, CD10, and PD1, while the neoplastic plasma cells showed kappa-predominant light-chain restriction. Additional cutaneous biopsies from the left forearm and upper arm revealed Epstein-Barr virus-positive and -negative B/PC-Ps, respectively. Polymerase chain reaction identified RHOA p.G17V and the same monoclonal rearrangement of T-cell receptor gamma gene (TRG) in all the four specimens. In addition, three cutaneous lesions showed distinct monoclonal immunoglobulin heavy chain gene (IGH) rearrangements. This case demonstrates phenotypic and clonal diversity of monoclonal B/PC-Ps in TFHL, which can obscure the neoplastic TFH proliferation. In such cases, careful clinicopathological correlation and the integration of immunophenotypic and genetic analyses may aid in the diagnosis.