Extranodal NK/T-cell Lymphoma, Nasal Type



Extranodal NK/T-cell Lymphoma, Nasal Type


Aaron Auerbach, MD, PhD





Key Facts


Terminology



  • Tumor of NK cells or T cells, with necrosis, Epstein-Barr virus infection, and angioinvasion


Etiology/Pathogenesis



  • Epstein-Barr virus


Clinical Issues



  • Common in adults in South America, Central America, and Asia


  • Nasopharynx most common site, skin is 2nd


Microscopic Pathology



  • Diffuse dermal/subcutaneous infiltrate of variably sized tumor cells, angiocentric with necrosis


  • Dense chromatin, can be vesicular in large cells


  • Coagulative necrosis in most cases


Ancillary Tests



  • Epstein-Barr virus antigen (+)


  • Mostly NK-cell markers phenotype



    • βF1(−), CD2(+), cytoplasmic CD3-ε(+), CD56(+/-), cytotoxic markers(+)


  • Less often T-cell marker phenotype



    • βF1(+), CD2(+), cytoplasmic CD3-ε(+), CD56(-/+), cytotoxic markers(+)


  • No specific cytogenetic abnormalities


Top Differential Diagnoses



  • Wegener granulomatosis


  • Infection


  • B-cell lymphomas (DLBCL, lymphomatoid granulomatosis)


  • PTCL-NOS, NK-cell leukemia







Clinical photograph of ENNKTCL, nasal type shows extensive destruction of the nasolabial region (above). High magnification of this lesion shows an atypical lymphoid infiltrate with vascular destruction.






This is a nasal-type extranodal NK/T-cell lymphoma of NK cell lineage involving the skin. The neoplastic cells are enlarged and show nuclear hyperchromasia. (Courtesy L. J. Medeiros, MD.)


TERMINOLOGY


Abbreviations



  • Extranodal NK/T-cell lymphoma, nasal type (ENNKTCL)


Synonyms



  • Angiocentric T-cell lymphoma, malignant midline reticulosis, lethal midline granuloma, polymorphic reticulosis


Definitions



  • Lymphoma composed of NK cells or T cells that is characterized by necrosis, Epstein-Barr virus infection, and often angioinvasion



    • Usually extranodal


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Epstein-Barr virus



    • Epstein-Barr virus antigens are identified by immunohistochemistry and in situ hybridization


  • Immunosuppression



    • Subset of patients are immunosuppressed



      • Including post transplant


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare in United States; more common in South America, Central America, and Asia


  • Age



    • Usually adults


Site



  • Nasal



    • Most common location of disease


    • Anywhere in upper aerodigestive tract



      • Includes nasal cavity, nasopharynx, sinuses, and palate


  • Extranasal



    • Skin



      • Most common extranasal site


      • Skin can be primary disease or secondary to disease elsewhere


      • Often extremities or torso


    • Other sites include gastrointestinal tract, lymph nodes, and testes


Presentation



  • Skin



    • Nodules &/or plaques on skin



      • Often ulcerated


  • Nasal



    • Obstruction or epistaxis


  • Gastrointestinal tract



    • Perforation or mass


  • B symptoms including fever &/or weight loss


  • Hemophagocytic syndrome in some cases Laboratory Tests


  • EBV DNA can be assessed to check disease activity


Natural History



  • Can spread to regional lymph nodes



    • Tumor only in lymph nodes and not other anatomic sites is uncommon


    • Primary lymph node involvement is very rare


  • Can involve bone marrow


Treatment



  • Chemotherapy and radiation therapy Prognosis


  • Median survival < 15 months



    • Better survival with intense radiotherapy and chemotherapy


  • Poor prognostic indicators




    • High stage of disease


    • Bone marrow with EBV(+) cells


    • High International or Korean Prognostic Index



      • B symptoms, serum LDH, regional lymph nodes, stage


    • ↑ EBV DNA


    • ↑ C-reactive protein, thrombocytopenia


    • ↑ Ki-67 > 50%


  • Better prognostic indicators



    • More favorable for nasal disease than extra-nasal


    • High absolute lymphocyte count


    • CD56(+), CD30(+) coexpression has been reported


IMAGE FINDINGS


General Features



  • Mass lesion that can destroy bone, especially in nasal tumors


MACROSCOPIC FEATURES


General Features



  • 1 or more firm nodules


MICROSCOPIC PATHOLOGY


Histologic Features



  • Skin/mucosa



    • Diffuse pattern of infiltration



      • Mostly dermal infiltrate, sometimes subcutis


      • Rare foci of epidermotropism in 30%


    • Tumor cells can be small, medium, or large



      • Irregular nuclear shapes


      • Dense chromatin, can be vesicular in large cells


      • Sometimes ↑ clear cytoplasm


    • Coagulative necrosis in most cases


    • Tumor cells are angiocentric and angiodestructive


    • Overlying epithelium/mucosa



      • ± ulceration


      • Often shows pseudoepitheliomatous hyperplasia


    • ↑ mitoses


    • Erythrophagocytosis is sometimes seen


  • Lymph node



    • Tumor tends to involve paracortical areas


  • Bone marrow



    • Usually interstitial infiltrate



      • Lacking large tumor aggregates


    • Involved in 15% of cases


Cytologic Features



  • Rarely, diagnosis can be made by fine needle aspirate



    • Azurophilic granules in some tumor cells


ANCILLARY TESTS


In Situ Hybridization



  • In situ hybridization for EBV small-encoded RNA (EBER)


Immunohistochemistry

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Extranodal NK/T-cell Lymphoma, Nasal Type

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