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Katoh, Hiroto; Komura, Daisuke; Furuya, Genta; Ishikawa, Shumpei
doi: 10.1111/pin.13284pmid: 36342353
Lymphocytes consist of highly heterogeneous populations, each expressing a specific cell surface receptor corresponding to a particular antigen. Lymphocytes are both the cause and regulator of various diseases, including autoimmune/allergic diseases, lifestyle diseases, neurodegenerative diseases, and cancers. Recently, immune repertoire sequencing has attracted much attention because it helps obtain global profiles of the immune receptor sequences of infiltrating T and B cells in specimens. Immune repertoire sequencing not only helps deepen our understanding of the molecular mechanisms of immune‐related pathology but also assists in discovering novel therapeutic modalities for diseases, thereby shedding colorful light on otherwise tiny monotonous cells when observed under a microscope. In this review article, we introduce and detail the background and methodology of immune repertoire sequencing and summarize recent scientific achievements in association with human diseases. Future perspectives on this genetic technique in the field of histopathological research will also be discussed.
doi: 10.1111/pin.13293pmid: 36484765
The fifth edition of the World Health Organization classification of soft tissue and bone tumors redefined Ewing sarcoma by fusions between EWSR1/FUS and ETS family of transcription factors, and recognized three tumor groups among Ewing‐like sarcoma: CIC‐rearranged sarcoma, sarcoma with BCOR genetic alterations, and round cell sarcoma with EWSR1::non‐ETS fusions. Although this classification underscores the critical role of molecular genetics in the diagnosis of small round cell sarcoma, each entry is recognized as a specific entity not only because they have different genetics but because their phenotypes are distinct and reasonably robust to support the diagnosis. This review focuses on the morphological aspects of Ewing sarcoma and a subset of Ewing‐like sarcomas (CIC‐rearranged sarcoma, BCOR‐associated sarcoma, and EWSR1::NFATC2 sarcoma) for which phenotypic characteristics have been well established. Classic histological findings, uncommon variations, and recurrent diagnostic pitfalls are addressed, along with the utility of recently developed immunohistochemical markers (NKX2.2, PAX7, ETV4, BCOR, CCNB3, and NKX3.1). Phenotypic expertise would significantly expedite the diagnostic process and complement (or sometimes outperform) genetic testing, even in well‐resourced settings. Morphological knowledge plays an even more substantial role in facilities that do not have easy access to molecular testing.
Jung, Joon Min; Lee, Mi Young; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Lee, Woo Jin
doi: 10.1111/pin.13292pmid: 36468840
The diagnostic role of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has not been thoroughly evaluated for acral melanocytic tumors. The objective of this study was to evaluate the utility of this modality for the diagnosis of acral melanocytic tumors compared with other potential markers. Melanocytic tumors were classified as either acral nevi, challenging melanocytic tumors (superficial atypical melanocytic proliferation of uncertain significance (SAMPUS)‐favor benign (SAMPUS‐FB), SAMPUS‐favor malignant (SAMPUS‐FM)) or acral melanomas. A total of 106 acral melanocytic tumors including acral nevi (n = 32), SAMPUS‐FB (n = 17), SAMPUS‐FM (n = 20), and acral melanomas (n = 37) were included. Diagnostic power, assessed using an area under the receiver operating characteristic curve (AUC) for distinguishing acral melanomas and acral nevi, was highest for PRAME (AUC = 0.997), followed by c‐Myc (AUC = 0.755), cyclin D1 (AUC = 0.652), and c‐Kit (AUC = 0.573). At a PRAME expression level ≥30% as a positive test for acral melanoma, the sensitivity and specificity of this marker for discriminating acral melanoma from acral nevus were 100% and 96.9%, respectively. PRAME immunohistochemistry also discriminated SAMPUS‐FM from SAMPUS‐FB with a sensitivity and specificity of 90.0% and 76.5%, respectively. In conclusion, PRAME immunohistochemistry can be used effectively to distinguish between various spectra of acral melanocytic neoplasms.
Yorozu, Keigo; Kurasawa, Mitsue; Iino, Yuki; Nakamura, Yuka; Hashizume, Kaoru; Harada, Naoki; Ochiai, Atsushi
doi: 10.1111/pin.13288pmid: 36398869
Gene amplification and protein overexpression of human epidermal growth factor receptor type 2 (HER2) are specific targets for HER2‐targeting drugs in breast, gastric, salivary gland, and colorectal cancers. The histopathological determination of HER2 status is crucial for treatment, highlighting the importance of improving HER2 detection accuracy in clinical practice. We prepared tissue microarray (TMA) slides for use as control slides for the standardization of gastric HER2 testing. Four human gastric cancer cell lines with HER2 scores of 3+, 2+, 1+, and 0 were xenografted in NOG mice. The TMA slides were constructed using samples from three different areas in these tumors. Staining properties were determined using six clinical kits for HER2. In TMA, HER2‐positive tumors with HER2 scores of 3+ and 2+ showed good staining with all diagnostic kits, and the tissue images were similar to those of clinical samples. Xenograft tumor slides could potentially be used as external controls to standardize staining conditions for a variety of kits and may improve the accuracy of HER2 detection in clinical practice.
Sugino, Takashi; Kakuda, Yuko; Yasui, Haruna; Oishi, Takuma; Norose, Tomoko; Kawata, Takuya; Tadokoro, Yukiko; Nishimura, Seiichiro
doi: 10.1111/pin.13302pmid: 36579416
Acinic cell carcinoma (ACC) is an exceptionally rare type of breast carcinoma with a low‐grade morphology and a favorable prognosis. It is postulated to be a type of invasive carcinoma arising in microglandular adenosis (MGA). We report a case of extensively spreading ACC of the breast with MGA‐like features. Macroscopically, yellowish nodules were widely distributed throughout the right breast, up to the axilla, without mass formation. Microscopically, the tumor consisted of two distinct carcinoma components: one was multiple nodular lesions showing invasive carcinoma with fused solid nests, and the other was a widely spreading lesion exhibiting MGA‐like features with uniform small single glands. Immunohistochemically, both components were negative for ER, PR, and HER2, and expressed EMA, S100 and lysozyme. The distinct morphology and molecular expression indicated ACC. The single glands in the MGA‐like area lacked myoepithelial cells but were linearly surrounded by type IV collagen, a basement membrane component. This case supports the hypothesis that ACC and MGA have the same lineage and indicates that ACC is not necessarily a low‐grade malignancy and can be aggressive.
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