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  • Surgical Pathology Criteria

    Extranodal NK/T Cell Lymphoma, Nasal Type


    • 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


    • 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



    Mature T and NK cell neoplasms (WHO classification)

    CD56 positive lymphoid neoplasms

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

    Gastrointestinal tract lymphomas


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