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    Extranodal NK/T Cell Lymphoma, Nasal Type

    Definition

    • Polymorphic extranodal lymphoma, expressing NK or rarely cytotoxic T cell phenotype

    Alternate/Historical Names

    • Polymorphic reticulosis
    • Lethal midline granuloma
    • Angiocentric T cell lymphoma

    Diagnostic Criteria

    • Primarily extranodal
      • Most common site is nose
      • Nodes may be involved secondarily
    • Necrosis nearly always present
      • Vascular destruction may be seen
      • Ulceration common
      • Pseudoepitheliomatous hyperplasia may be seen
    • Wide range of appearance from small to large cell
      • Frequently mixed
      • Inflammatory cells may be prominent
      • Cytoplasm may be clear with azurophilic granules on Giemsa stained cytologic preparations
    • CD56 positive
      • Rare cases may lack CD56, but must then be EBV+, CD3+ and cytotoxic protein+
    • EBV positive
      • May be lacking in some extranasal, North American or Western European cases
    • Note that the term "nasal type" originally applied only to lymphomas of this type that occurred in sites other than the nasal cavity; it now includes nasal and extra-nasal locations

    Dita Gratzinger MD PhD
    Yasodha Natkunam MD PhD
    Robert V Rouse MD

    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Initial posting : September 1, 2007

    Supplemental studies

    Immunohistology and Flow

    NK type
    CD56 100%
    EBV LMP Positive, less sensitive than in situ hybridization
    CD3 Cytoplasmic positive, membrane negative
    Cytotoxic granule proteins: granzyme B, TIA1, perforin Generally positive
    CD43, CD45RO Generally positive
    CD20, CD79a Rare positive cases reported
    CD30 Occasionally positive
    CD4, CD5, CD8 Negative

    T cell type

    CD56 Negative
    CD3 Positive
    CD5, CD8 May be positive
    Cytotoxic granule proteins: granzyme B, TIA1, perforin Required for diagnosis
    EBV Required for diagnosis
    • CD56 is not specific, it may be seen in other lymphomas and non-lymphoid neoplasms

    Genetic analysis

    • EBV EBER positive by in situ hybridization 25-95%
      • Depends on geographic location
      • In endemic areas 95%
    • Cases with NK phenotype will have germline T cell receptor gene configuration

    Differential Diagnosis

    Nonspecific Inflammatory Process vs. Extranodal NK/T Cell Lymphoma

    • Identification of aytypical cells with the following phenotypes establishes the diagnosis of nasal type NK/T lymphoma
      • CD56+, EBV+, CD3+ or
      • CD56-, EBV+, CD3+ and cytotoxic protein+
    • Infiltration of bony trabeculae of nasal septum is highly suggestive of malignancy

    Peripheral T Cell Lymphoma vs. Extranodal NK/T Cell Lymphoma, Nasal Type

    • Identification of aytypical cells with the following phenotypes establishes the diagnosis of nasal type NK/T lymphoma
      • CD56+, EBV+, CD3+ or
      • CD56-, EBV+, CD3+ and cytotoxic protein+

    Extranodal NK/T Cell Lymphoma Enteropathy Type T Cell Lymphoma
    CD56 100% CD56 20%
    EBV 100% in nasal sites but variable in other sites and outside endemic areas EBV variable, possibly by geography
    No adjacent enteropathy Adjacent enteropathy 75%
    Both may involve the GI tract and both express cytotoxic T markers

     

    Lymphomatoid Granulomatosis vs. Extranodal NK/T Cell Lymphoma

    • Lymphomatoid granulomatosis was originally considered an angiocentric T cell lymphoma
      • It is now recognized as an EBV+ B cell process with a marked T cell response

    Aggressive NK cell Leukemia

    • Cases involving bone marrow overlap with aggressive NK cell leukemia, which may represent the leukemic counterpart of this lymphoma

    Clinical

    • Most common in Asia and Latin America
      • Sporadic cases in North America and Western Europe
    • Most often presents with nasal obstruction and/or destruction of adjacent structures
      • May extend into sinuses but does not primarily involve them
      • Marrow and nodes involved only if disseminated
    • Other sites
      • Skin, soft tissue, GI tract, testis
    • May have fever, malaise, weight loss
    • Hemophagocytic syndrome may be present in disseminated cases
    • Cases involving bone marrow overlap with aggressive NK cell leukemia, which may represent the leukemic counterpart of this lymphoma

    Grading / Staging / Report

    • Grading is not applicable

    Ann Arbor Staging System

    • Stage I
      • I if involvement of a single lymph node region
      • IE if involvement of a single extralymphatic organ or site
    • Stage II
      • II if two or more lymph node regions on same side of diaphragm
      • IIE if localized involvement of an extralymphatic organ or site and one or more lymph node regions on the same side of the diaphragm
    • Stage III
      • III if Involvement of lymph node regions on both sides of the diphragm
      • IIIS if spleen involved
      • IIIE if extralymphatic site involved
    • Stage IV
      • Diffuse or disseminated involvement of one or more extralymphatic organs or tissues, with or without associated lymph node involvement
    • Systemic Symptoms in 6 months preceding admission
      • Fever, night sweats, 10% weight loss
      • A = absent
      • B = present
    • Extranodal sites are also designated
      • M+ = marrow
      • L+ = lung
      • H+ = liver
      • P+ = pleura
      • O+ = bone
      • D+ = skin and subcutaneous tissue
    • Although originally designed for Hodgkin lymphoma, the Ann Arbor System is also used for non-Hodgkin lymphomas.

    The pathology report should contain the following information:

    • Diagnosis in the World Health Organization (WHO) classification
      • Equivalent diagnosis in other classifications used by relevant clinicians
    • Results of supplementary studies if performed
    • Relationship to other specimens from the same patient
    • Information relevant to staging if available

     

    Lists

    Mature T and NK cell neoplasms (WHO classification)

    CD56 positive lymphoid neoplasms

    CD56 positive non-lymphoid neoplasms (>25% positive)

    Gastrointestinal tract lymphomas

    Bibliography

    • Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
    • Jaffe ES, Harris NL Stein H, Vardiman JW eds. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2001
    • Chan JK, Sin VC, Wong KF, Ng CS, Tsang WY, Chan CH, Cheung MM, Lau WH. Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood. 1997 Jun 15;89(12):4501-13.
    • Blakolmer K, Vesely M, Kummer JA, Jurecka W, Mannhalter C, Chott A. Immunoreactivity of B-cell markers (CD79a, L26) in rare cases of extranodal cytotoxic peripheral T- (NK/T-) cell lymphomas. Mod Pathol 2000 Jul;13(7):766-72
    • Cheung MM, Chan JK, Lau WH, Foo W, Chan PT, Ng CS, Ngan RK. Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients. J Clin Oncol 1998 Jan;16(1):70-7
    • Chan JK, Sin VC, Wong KF, Ng CS, Tsang WY, Chan CH, Cheung MM, Lau WH. Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 1997 Jun 15;89(12):4501-13
    • Kwong YL, Chan AC, Liang R, Chiang AK, Chim CS, Chan TK, Todd D, Ho FC. CD56+ NK lymphomas: clinicopathological features and prognosis. Br J Haematol 1997 Jun;97(4):821-9
    • Jaffe ES, Chan JK, Su IJ, Frizzera G, Mori S, Feller AC, Ho FC. 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 Jan;20(1):103-11
    • Nakamura S, Suchi T, Koshikawa T, Kitoh K, Koike K, Komatsu H, Iida S, Kagami Y, Ogura M, Katoh E, et al. Clinicopathologic study of CD56 (NCAM)-positive angiocentric lymphoma occurring in sites other than the upper and lower respiratory tract. Am J Surg Pathol 1995 Mar;19(3):284-96
    • Wong KF, Chan JK, Ng CS, Lee KC, Tsang WY, Cheung MM. CD56 (NKH1)-positive hematolymphoid malignancies: an aggressive neoplasm featuring frequent cutaneous/mucosal involvement, cytoplasmic azurophilic granules, and angiocentricity. Hum Pathol 1992 Jul;23(7):798-804
    • Teruya-Feldstein J, Jaffe ES, Burd PR, Kanegane H, Kingma DW, Wilson WH, Longo DL, Tosato G. The role of Mig, the monokine induced by interferon-gamma, and IP-10, the interferon-gamma-inducible protein-10, in tissue necrosis and vascular damage associated with Epstein-Barr virus-positive lymphoproliferative disease. Blood 1997 Nov 15;90(10):4099-105
    • Liang R, Todd D, Chan TK, Chiu E, Lie A, Kwong YL, Choy D, Ho FC. Treatment outcome and prognostic factors for primary nasal lymphoma. J Clin Oncol 1995 Mar;13(3):666-70
    • Quintanilla-Martinez L, Franklin JL, Guerrero I, Krenacs L, Naresh KN, Rama-Rao C, Bhatia K, Raffeld M, Magrath IT. Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru : high prevalence of p53 overexpression. Hum Pathol 1999 Jul;30(7):849-55
    • van de Rijn M, Bhargava V, Molina-Kirsch H, Carlos-Bregni R, Warnke RA, Cleary ML, Kamel OW. Extranodal head and neck lymphomas in Guatemala : high frequency of Epstein-Barr virus-associated sinonasal lymphomas. Hum Pathol 1997 Jul;28(7):834-9
    • Elenitoba-Johnson KS, Zarate-Osorno A, Meneses A, Krenacs L, Kingma DW, Raffeld M, Jaffe ES. 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 Aug;11(8):754-61
    • Ho FC, Choy D, Loke SL, Kung IT, Fu KH, Liang R, Todd D, Khoo RK. 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 Oct;21(10):1041-50
    • Arber DA, Weiss LM, Albujar PF, Chen YY, Jaffe ES. Nasal lymphomas in Peru . High incidence of T-cell immunophenotype and Epstein-Barr virus infection. Am J Surg Pathol 1993 Apr;17(4):392-9
    • Jaffe ES, Krenacs L, Kumar S, Kingma DW, Raffeld M. Extranodal peripheral T-cell and NK-cell neoplasms. Am J Clin Pathol 1999 Jan;111(1 Suppl 1):S46-55
    • Cuadra-Garcia I, Proulx GM, Wu CL, Wang CC, Pilch BZ, Harris NL, Ferry JA. Sinonasal lymphoma: a clinicopathologic analysis of 58 cases from the Massachusetts General Hospital . Am J Surg Pathol 1999 Nov;23(11):1356-69
    • Shipley WR, Hammer RD , Lennington WJ, Macon WR. Paraffin immunohistochemical detection of CD56, a useful marker for neural cell adhesion molecule (NCAM), in normal and neoplastic fixed tissues. Appl Immunohistochem 1997;5:87-93
    • Hasserjian RP, Harris NL. NK-cell lymphomas and leukemias: a spectrum of tumors with variable
      manifestations and immunophenotype. Am J Clin Pathol. 2007 Jun;127(6):860-8
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