{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:44:08Z","timestamp":1793411048155,"version":"4.5.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>Extranodal NK\/T-cell lymphoma (ENKTL) is a non-Hodgkin lymphoma associated with the Epstein-Barr virus that primarily affects individuals in East Asia and indigenous populations in Central and South America. Morphologically, ENKTL typically consists of medium-sized cells or a combination of small and large cells. This report presents 10 cases characterized by predominantly anaplastic cells with diffuse expression of CD30, resembling anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK-negative ALCL) and demonstrating highly aggressive behavior. The cohort included 9 males and 1 female, ranging in age from 29 to 65 years (median age: 47\u00a0y). Eight patients presented with nasal disease, while 2 had non-nasal disease. Five patients had stage I\/II disease, and the remaining 5 had stage III\/IV disease. Morphologically, necrosis was observed in 9 cases, angiocentric-angiodestructive growth in 3 cases, and pseudoepitheliomatous hyperplasia in 2 cases. Anaplastic cells predominated in all cases, with some displaying eccentric, horseshoe-shaped, or kidney-shaped nuclei (referred to as \u201cHallmark\u201d cells). The morphology profile was monomorphic in 3 cases and polymorphic in 7 cases. Immunohistochemically, all cases tested positive for cytotoxic granule markers (TIA1 and granzymeB) and Epstein-Barr virus-encoded RNA. Cytoplasmic expression of CD3\u03b5 and CD56 was observed in 9 of 10 cases. Interestingly, most cases (7 of 8) exhibited variable expression of MuM1, ranging from 10% to 90%. All cases showed diffuse positivity for CD30 but were negative for ALK, resulting in 3 cases being initially misdiagnosed as ALK-negative ALCL. Compared with nonanaplastic cases, anaplastic cells predominant ENKTL had a significantly higher frequency of \u201cB\u201d symptoms, bone marrow involvement, hemophagocytic lymphohistiocytosis, and higher Ki67 proliferative index. These findings provide valuable information for pathologists, expanding their understanding of the cytologic spectrum of ENKTL. This rare variant of ENKTL, characterized by the predominance of anaplastic cells and diffuse CD30 expression, exhibits high aggressiveness and should be differentiated from ALK-negative ALCL. Awareness of this uncommon variant is crucial in preventing misdiagnosis and ensuring the timely initiation of therapy.<\/jats:p>","DOI":"10.1097\/pas.0000000000002156","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T13:01:07Z","timestamp":1700485267000},"page":"174-182","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Extranodal NK\/T-Cell Lymphoma Predominantly Composed of Anaplastic Cells"],"prefix":"10.1097","volume":"48","author":[{"given":"Yujia","family":"Zhong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine"},{"name":"Department of Pathology, Sun Yat-sen University Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Friendship Hospital, Capital Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jierong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine"},{"name":"Department of Pathology, Sun Yat-sen University Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Ping","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine"},{"name":"Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengbing","family":"Zang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine"},{"name":"Department of Pathology, Sun Yat-sen University Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine"},{"name":"Department of Pathology, Sun Yat-sen University Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfen","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine"},{"name":"Department of Pathology, Sun Yat-sen University Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine"},{"name":"Department of Pathology, Sun Yat-sen University Cancer Center"},{"name":"Department of Pathology, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, Gansu, Chiina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"R2-20250608","doi-asserted-by":"crossref","first-page":"20160271","DOI":"10.1098\/rstb.2016.0271","article-title":"Epstein-Barr virus-associated lymphomas","volume":"372","author":"Shannon-Lowe","year":"2017","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"R3-20250608","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1200\/JCO.2008.16.4558","article-title":"International peripheral T-cell and natural killer\/T-cell lymphoma study: pathology findings and clinical outcomes","volume":"26","author":"Vose","year":"2008","journal-title":"J Clin Oncol"},{"key":"R4-20250608","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s12185-008-0021-7","article-title":"Nasal NK\/T-cell lymphoma: epidemiology and pathogenesis","volume":"87","author":"Aozasa","year":"2008","journal-title":"Int J Hematol"},{"key":"R5-20250608","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s11899-016-0355-9","article-title":"Extranodal NK\/T cell lymphoma, nasal type (ENKTL-NT): an update on epidemiology, clinical presentation, and natural history in North American and European Cases","volume":"11","author":"Haverkos","year":"2016","journal-title":"Curr Hematol Malig Rep"},{"key":"R6-20250608","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13045-022-01293-5","article-title":"How we treat NK\/T-cell lymphomas","volume":"15","author":"Tse","year":"2022","journal-title":"J Hematol Oncol"},{"key":"R7-20250608","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.3390\/microorganisms9071381","article-title":"Extranodal NK\/T-cell lymphoma, nasal type: genetic, biologic, and clinical aspects with a central focus on Epstein-Barr virus relation","volume":"9","author":"Takahara","year":"2021","journal-title":"Microorganisms"},{"key":"R8-20250608","first-page":"73","article-title":"The pathologic and genetic characteristics of extranodal NK\/T-cell lymphoma","volume":"12","author":"Kim","year":"2022","journal-title":"Life (Basel)"},{"key":"R9-20250608","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/01.pai.0000205062.27174.56","article-title":"Extranodal NK\/T-cell lymphoma, nasal type: study of clinicopathologic and prognosis factors in a series of 78 cases from Peru","volume":"15","author":"Barrionuevo","year":"2007","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"R10-20250608","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1177\/106689690401200410","article-title":"Nasal NK\/T cell lymphoma in Taiwan: a clinicopathologic study of 22 cases, with analysis of histologic subtypes, Epstein-Barr virus LMP-1 gene association, and treatment modalities","volume":"12","author":"Kuo","year":"2004","journal-title":"Int J Surg Pathol"},{"key":"R11-20250608","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/his.12990","article-title":"Small-cell predominant extranodal NK\/T cell lymphoma, nasal type: clinicopathological analysis of a series of cases diagnosed in a Western population","volume":"69","author":"McKelvie","year":"2016","journal-title":"Histopathology"},{"key":"R12-20250608","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/dc.24388","article-title":"Malignant effusions from extranodal NK\/T-cell lymphomas are frequently of anaplastic morphology with azurophilic granules and of T-cell lineage","volume":"48","author":"Liu","year":"2020","journal-title":"Diagn Cytopathol"},{"key":"R13-20250608","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1093\/ajcp\/aqv010","article-title":"Extranodal natural killer\/T-cell lymphoma in children and adolescents: a report of 17 cases in China","volume":"145","author":"Huang","year":"2016","journal-title":"Am J Clin Pathol"},{"key":"R14-20250608","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1097\/PAS.0000000000001210","article-title":"De novo testicular extranodal NK\/T-cell lymphoma: a clinicopathologic study of 21 cases with review of additional 18 cases in the literature","volume":"43","author":"Huang","year":"2019","journal-title":"Am J Surg Pathol"},{"key":"R15-20250608","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1097\/PAS.0b013e31824433d8","article-title":"Extranodal NK\/T-cell lymphoma, nasal type, includes cases of natural killer cell and \u03b1\u03b2, \u03b3\u03b4, and \u03b1\u03b2\/\u03b3\u03b4 T-cell origin: a comprehensive clinicopathologic and phenotypic study","volume":"36","author":"Pongpruttipan","year":"2012","journal-title":"Am J Surg Pathol"},{"key":"R16-20250608","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.3390\/cancers14071650","article-title":"Anaplastic large cell lymphoma: molecular pathogenesis and treatment","volume":"14","author":"Zhang","year":"2022","journal-title":"Cancers (Basel)"},{"key":"R17-20250608","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1182\/blood-2017-12-791418","article-title":"Advances in the treatment of extranodal NK\/T-cell lymphoma, nasal type","volume":"131","author":"Yamaguchi","year":"2018","journal-title":"Blood"},{"key":"R18-20250608","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3960\/jslrt.17023","article-title":"Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects","volume":"57","author":"Tsuyama","year":"2017","journal-title":"J Clin Exp Hematop"},{"key":"R19-20250608","doi-asserted-by":"crossref","first-page":"103237","DOI":"10.1016\/j.critrevonc.2021.103237","article-title":"Extranodal NK\/T cell lymphoma, nasal type: an updated overview","volume":"159","author":"Sanchez-Romero","year":"2021","journal-title":"Crit Rev Oncol Hematol"},{"key":"R20-20250608","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1053\/j.semdp.2019.12.002","article-title":"Pathology and genetics of anaplastic large cell lymphoma","volume":"37","author":"Leventaki","year":"2020","journal-title":"Semin Diagn Pathol"},{"key":"R21-20250608","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.humpath.2003.10.013","article-title":"Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria","volume":"35","author":"Herling","year":"2004","journal-title":"Hum Pathol"},{"key":"R22-20250608","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.3324\/haematol.2021.280003","article-title":"Immune pathway upregulation and lower genomic instability distinguish EBV-positive nodal T\/NK-cell lymphoma from ENKTL and PTCL-NOS","volume":"107","author":"Wai","year":"2022","journal-title":"Haematologica"},{"key":"R23-20250608","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3324\/haematol.2017.180430","article-title":"Epstein-Barr virus-associated primary nodal T\/NK-cell lymphoma shows a distinct molecular signature and copy number changes","volume":"103","author":"Ng","year":"2018","journal-title":"Haematologica"},{"key":"R24-20250608","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/hon.2482","article-title":"Frequent expression of CD30 in extranodal NK\/T-cell lymphoma: potential therapeutic target for anti-CD30 antibody-based therapy","volume":"36","author":"Kawamoto","year":"2018","journal-title":"Hematol Oncol"},{"key":"R25-20250608","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s40880-017-0212-9","article-title":"CD30 expression in extranodal natural killer\/T-cell lymphoma, nasal type among 622 cases of mature T-cell and natural killer-cell lymphoma at a single institution in South China","volume":"36","author":"Feng","year":"2017","journal-title":"Chin J Cancer"},{"key":"R26-20250608","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.3109\/10428194.2014.974048","article-title":"Prognostic implications of CD30 expression in extranodal natural killer\/T-cell lymphoma according to treatment modalities","volume":"56","author":"Kim","year":"2015","journal-title":"Leuk Lymphoma"},{"key":"R27-20250608","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1186\/1471-2407-14-890","article-title":"CD30 expression is a novel prognostic indicator in extranodal natural killer\/T-cell lymphoma, nasal type","volume":"14","author":"Li","year":"2014","journal-title":"BMC Cancer"},{"key":"R28-20250608","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1111\/j.1365-2133.2008.08566.x","article-title":"MUM1 expression in cutaneous CD30+ lymphoproliferative disorders: a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma","volume":"158","author":"Kempf","year":"2008","journal-title":"Br J Dermatol"},{"key":"R29-20250608","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/sj.leu.2401696","article-title":"MUM1\/IRF4 expression as a frequent event in mature lymphoid malignancies","volume":"14","author":"Tsuboi","year":"2000","journal-title":"Leukemia"},{"key":"R30-20250608","first-page":"5086","article-title":"Histological type distribution and expression of nm23, VEGF, TOP2A and MUM-1 in peripheral T-cell and NK-cell lymphomas in Chinese: analysis of 313 cases","volume":"11","author":"Huang","year":"2018","journal-title":"Int J Clin Exp Pathol"},{"key":"R31-20250608","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.critrevonc.2012.06.004","article-title":"Anaplastic large cell lymphoma, ALK-negative","volume":"85","author":"Ferreri","year":"2013","journal-title":"Crit Rev Oncol Hematol"},{"key":"R32-20250608","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/labinvest.3780055","article-title":"Mutations of the p53 gene in nasal NK\/T-cell lymphoma","volume":"80","author":"Li","year":"2000","journal-title":"Lab Invest"},{"key":"R33-20250608","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.humpath.2018.05.026","article-title":"TP53 mutations in peripheral mature T and NK cell lymphomas: a whole-exome sequencing study with correlation to p53 expression","volume":"80","author":"Huang","year":"2018","journal-title":"Hum Pathol"},{"key":"R34-20250608","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0002-9440(10)63061-1","article-title":"p53 Mutations in nasal natural killer\/T-cell lymphoma from Mexico: association with large cell morphology and advanced disease","volume":"159","author":"Quintanilla-Martinez","year":"2001","journal-title":"Am J Pathol"},{"key":"R35-20250608","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1309\/V561QTM6854W4WAV","article-title":"Immunohistochemical characterization of nasal-type extranodal NK\/T-cell lymphoma using a tissue microarray: an analysis of 84 cases","volume":"130","author":"Schwartz","year":"2008","journal-title":"Am J Clin Pathol"},{"key":"R36-20250608","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.prp.2014.02.004","article-title":"Both c-Myc and Ki-67 expression are predictive markers in patients with extranodal NK\/T-cell lymphoma, nasal type: a retrospective study in China","volume":"210","author":"Huang","year":"2014","journal-title":"Pathol Res Pract"},{"key":"R37-20250608","doi-asserted-by":"crossref","first-page":"793","DOI":"10.7150\/jca.17766","article-title":"Overexpression of MYC and BCL2 predicts poor prognosis in patients with extranodal NK\/T-cell lymphoma, nasal type","volume":"8","author":"Wang","year":"2017","journal-title":"J Cancer"},{"key":"R38-20250608","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/path.2823","article-title":"Activated oncogenic pathways and therapeutic targets in extranodal nasal-type NK\/T cell lymphoma revealed by gene expression profiling","volume":"223","author":"Ng","year":"2011","journal-title":"J Pathol"},{"key":"R39-20250608","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1038\/leu.2017.40","article-title":"RUNX3 is oncogenic in natural killer\/T-cell lymphoma and is transcriptionally regulated by MYC","volume":"31","author":"Selvarajan","year":"2017","journal-title":"Leukemia"}],"container-title":["American Journal of Surgical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/PAS.0000000000002156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T20:04:18Z","timestamp":1749413058000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/PAS.0000000000002156"}},"subtitle":["A Frequently Misdiagnosed and Highly Aggressive Variant"],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.1097\/pas.0000000000002156","relation":{},"ISSN":["0147-5185"],"issn-type":[{"value":"0147-5185","type":"print"}],"subject":[],"published":{"date-parts":[[2023,11,20]]}}}