Clinical manifestations, pathologic features, and diagnosis of extranodal NK/T cell lymphoma, nasal type
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
The peripheral T cell lymphomas (PTCL) are a heterogeneous group of generally aggressive neoplasms that constitute less than 15 percent of all non-Hodgkin lymphomas (NHLs) in adults [1,2]. (See "Classification of the hematopoietic neoplasms".)
Among these, in decreasing frequency of occurrence, are:
●Peripheral T cell lymphoma, not otherwise specified (NOS)
●Anaplastic large cell lymphoma, primary systemic type
●Angioimmunoblastic T cell lymphoma
- World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL (Eds), IARC Press, Lyon 2008.
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
- Jaffe ES, Chan JK, Su IJ, et al. Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol 1996; 20:103.
- Arber DA, Weiss LM, Albújar PF, et al. Nasal lymphomas in Peru. High incidence of T-cell immunophenotype and Epstein-Barr virus infection. Am J Surg Pathol 1993; 17:392.
- Li CC, Tien HF, Tang JL, et al. Treatment outcome and pattern of failure in 77 patients with sinonasal natural killer/T-cell or T-cell lymphoma. Cancer 2004; 100:366.
- Barrionuevo C, Zaharia M, Martinez MT, et al. Extranodal NK/T-cell lymphoma, nasal type: study of clinicopathologic and prognosis factors in a series of 78 cases from Peru. Appl Immunohistochem Mol Morphol 2007; 15:38.
- Liang R. Advances in the management and monitoring of extranodal NK/T-cell lymphoma, nasal type. Br J Haematol 2009; 147:13.
- Au WY, Weisenburger DD, Intragumtornchai T, et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood 2009; 113:3931.
- Au WY, Ma SY, Chim CS, et al. Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years. Ann Oncol 2005; 16:206.
- Laurini JA, Perry AM, Boilesen E, et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood 2012; 120:4795.
- Chihara D, Ito H, Matsuda T, et al. Differences in incidence and trends of haematological malignancies in Japan and the United States. Br J Haematol 2014; 164:536.
- Adams SV, Newcomb PA, Shustov AR. Racial Patterns of Peripheral T-Cell Lymphoma Incidence and Survival in the United States. J Clin Oncol 2016; 34:963.
- Chim CS, Ma SY, Au WY, et al. Primary nasal natural killer cell lymphoma: long-term treatment outcome and relationship with the International Prognostic Index. Blood 2004; 103:216.
- Li YX, Liu QF, Fang H, et al. Variable clinical presentations of nasal and Waldeyer ring natural killer/T-cell lymphoma. Clin Cancer Res 2009; 15:2905.
- Kanavaros P, Lescs MC, Brière J, et al. Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. Blood 1993; 81:2688.
- Quintanilla-Martinez L, Kremer M, Keller G, et al. p53 Mutations in nasal natural killer/T-cell lymphoma from Mexico: association with large cell morphology and advanced disease. Am J Pathol 2001; 159:2095.
- Quintanilla-Martinez L, Franklin JL, Guerrero I, et al. Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru: high prevalence of p53 overexpression. Hum Pathol 1999; 30:849.
- Li T, Hongyo T, Syaifudin M, et al. Mutations of the p53 gene in nasal NK/T-cell lymphoma. Lab Invest 2000; 80:493.
- Siu LL, Chan JK, Wong KF, Kwong YL. Specific patterns of gene methylation in natural killer cell lymphomas : p73 is consistently involved. Am J Pathol 2002; 160:59.
- Karube K, Nakagawa M, Tsuzuki S, et al. Identification of FOXO3 and PRDM1 as tumor-suppressor gene candidates in NK-cell neoplasms by genomic and functional analyses. Blood 2011; 118:3195.
- Proulx GM, Caudra-Garcia I, Ferry J, et al. Lymphoma of the nasal cavity and paranasal sinuses: treatment and outcome of early-stage disease. Am J Clin Oncol 2003; 26:6.
- Liu QF, Wang WH, Wang SL, et al. Immunophenotypic and clinical differences between the nasal and extranasal subtypes of upper aerodigestive tract natural killer/T-cell lymphoma. Int J Radiat Oncol Biol Phys 2014; 88:806.
- Li YX, Fang H, Liu QF, et al. Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring. Blood 2008; 112:3057.
- Chan JK, Sin VC, Wong KF, et al. Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 1997; 89:4501.
- Chan JK, Ng CS, Lau WH, Lo ST. Most nasal/nasopharyngeal lymphomas are peripheral T-cell neoplasms. Am J Surg Pathol 1987; 11:418.
- Ferry JA, Sklar J, Zukerberg LR, Harris NL. Nasal lymphoma. A clinicopathologic study with immunophenotypic and genotypic analysis. Am J Surg Pathol 1991; 15:268.
- Lei KI, Chan LY, Chan WY, et al. Diagnostic and prognostic implications of circulating cell-free Epstein-Barr virus DNA in natural killer/T-cell lymphoma. Clin Cancer Res 2002; 8:29.
- Ho FC, Srivastava G, Loke SL, et al. Presence of Epstein-Barr virus DNA in nasal lymphomas of B and 'T' cell type. Hematol Oncol 1990; 8:271.
- Lipford EH Jr, Margolick JB, Longo DL, et al. Angiocentric immunoproliferative lesions: a clinicopathologic spectrum of post-thymic T-cell proliferations. Blood 1988; 72:1674.
- Chim CS, Au WY, Shek TW, et al. Primary CD56 positive lymphomas of the gastrointestinal tract. Cancer 2001; 91:525.
- Lan SK, Lin CW, Ho HC, et al. Penile metastasis secondary to nasal NK/T-cell lymphoma. Urology 2008; 72:1014.
- Falini B, Pileri S, De Solas I, et al. Peripheral T-cell lymphoma associated with hemophagocytic syndrome. Blood 1990; 75:434.
- Okuda T, Sakamoto S, Deguchi T, et al. Hemophagocytic syndrome associated with aggressive natural killer cell leukemia. Am J Hematol 1991; 38:321.
- Han L, Li L, Wu J, et al. Clinical features and treatment of natural killer/T cell lymphoma associated with hemophagocytic syndrome: comparison with other T cell lymphoma associated with hemophagocytic syndrome. Leuk Lymphoma 2014; 55:2048.
- Soler J, Bordes R, Ortũno F, et al. Aggressive natural killer cell leukaemia/lymphoma in two patients with lethal midline granuloma. Br J Haematol 1994; 86:659.
- Jaffe ES. Classification of natural killer (NK) cell and NK-like T-cell malignancies. Blood 1996; 87:1207.
- Elenitoba-Johnson KS, Zarate-Osorno A, Meneses A, et al. Cytotoxic granular protein expression, Epstein-Barr virus strain type, and latent membrane protein-1 oncogene deletions in nasal T-lymphocyte/natural killer cell lymphomas from Mexico. Mod Pathol 1998; 11:754.
- Ho FC, Choy D, Loke SL, et al. Polymorphic reticulosis and conventional lymphomas of the nose and upper aerodigestive tract: a clinicopathologic study of 70 cases, and immunophenotypic studies of 16 cases. Hum Pathol 1990; 21:1041.
- Chan JK, Yip TT, Tsang WY, et al. Detection of Epstein-Barr viral RNA in malignant lymphomas of the upper aerodigestive tract. Am J Surg Pathol 1994; 18:938.
- Siu LL, Chan V, Chan JK, et al. Consistent patterns of allelic loss in natural killer cell lymphoma. Am J Pathol 2000; 157:1803.
- Sun HS, Su IJ, Lin YC, et al. A 2.6 Mb interval on chromosome 6q25.2-q25.3 is commonly deleted in human nasal natural killer/T-cell lymphoma. Br J Haematol 2003; 122:590.
- Quintanilla-Martinez L, Ridaura C, Nagl F, et al. Hydroa vacciniforme-like lymphoma: a chronic EBV+ lymphoproliferative disorder with risk to develop a systemic lymphoma. Blood 2013; 122:3101.
- Dojcinov SD, Venkataraman G, Raffeld M, et al. EBV positive mucocutaneous ulcer--a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 2010; 34:405.
- Mansoor A, Pittaluga S, Beck PL, et al. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series. Blood 2011; 117:1447.
- Takeuchi K, Yokoyama M, Ishizawa S, et al. Lymphomatoid gastropathy: a distinct clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation. Blood 2010; 116:5631.
- CLINICAL FEATURES
- PATHOLOGIC FEATURES
- Morphologic features
- - Growth pattern
- - Cell morphology
- Genetic features
- DIFFERENTIAL DIAGNOSIS
- NK cell leukemia
- Lymphomatoid granulomatosis
- EBV-positive mucocutaneous ulcer
- EBV-positive diffuse large B cell lymphoma, NOS
- Peripheral T cell lymphoma, unspecified
- Hepatosplenic T cell lymphoma
- Squamous cell carcinoma
- Nonkeratinizing nasopharyngeal carcinoma
- NK cell enteropathy