NK-Cell Lymphomas of the Head and Neck Workup

  • Author: Benjamin Daniel Liess, MD; Chief Editor: Arlen D Meyers, MD, MBA   more...
 
Updated: Oct 26, 2011
 

Laboratory Studies

  • The following laboratory studies should be performed:
    • CBC count: A CBC count may reveal anemia or lymphocytopenia.
    • Liver function tests including assessment of lactic dehydrogenase (LDH) levels: Elevated levels of LDH have been associated with poorer prognosis; these levels should be checked in every patient.
    • Renal function tests
    • Uric acid and calcium levels
    • EBV titers
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Imaging Studies

  • CT scanning of neck, chest, abdomen, and pelvis are indicated. Imaging studies are obtained to determine the full extent of disease for staging purposes. Neck CT scanning is important to detect skull base erosion and intracranial extension.[2, 3]
  • MRI of the head is performed in cases of suspected skull base invasion and intracranial extension.[2, 3]
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Procedures

  • The following procedures should be performed:
    • Flexible nasopharyngoscopy with direct laryngoscopy to characterize the extent of lesion.
    • Biopsy of primary site to characterize morphology and to allow genetic studies, immunohistochemical studies, and genetic (EBV) studies. Multiple large biopsies should be taken to provide adequate tissue for diagnosis. However, repeated biopsy may be necessary if too much necrosis is present.
    • Bone marrow biopsy to assess for disseminated disease.
    • Lumbar puncture to determine if intrathecal chemotherapy is indicated.
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Histologic Findings

The histologic features of NK-/T-cell lymphomas are similar at all sites of presentation. Morphologically, these malignancies demonstrate a broad cytologic spectrum. Size can include atypical cells that are small, medium, or large. Cells most commonly are medium-sized with irregular nuclei, granular chromatin, small nucleoli, and pale-to-clear cytoplasm. An inflammatory cell infiltrate may be observed and is most common with small-cell tumors. The infiltrate can include lymphocytes, plasma cells, histiocytes, and eosinophils, which explains the term polymorphic reticulosis in former classifications of these malignancies.

Atypical malignant cells possess moderate pale cytoplasm with azurophilic granules. Necrosis is almost always present along with evidence of angioinvasion, indicating a vascular pathogenesis (hence the name angiocentric lymphoma in previous classifications). Florid pseudoepitheliomatous hyperplasia may also be present and may lead to the misdiagnosis of squamous cell carcinoma.[1, 4, 5, 6, 7]

Immunophenotypical tests demonstrate the following patterns in detection of these malignancies. The most commonly present cell markers are CD2+, cytoplasmic CD3e+, and CD56+. Other markers that may be present include CD7, CD30, CD43, CD45RO, HLA-DR, interleukin-2 receptor, Fas (CD95), and Fas ligand. The following markers are known to be associated with NK cells and T cells but are not found in NK-/T-cell lymphomas: surface CD3, CD4, CD5, CD8, TCRg, TCRd, CD16, CD 20, and CD57.[8, 9, 3, 10, 4] Immunohistochemical testing of surface CD3-, cytoplasmic CD3e+, and CD56+ differentiate NKTCL from peripheral T-cell lymphoma.

Genetic tests find EBV in most tumor cells. The virus is found in a clonal episomal form. In most cases, T-cell receptor and immunoglobulin genes are in germline configuration. Various genetic abnormalities have been identified with the malignancies, but no specific chromosomal translocations have been identified.[3, 9]

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Staging

The Ann Arbor Classification stages NK-/T-cell lymphoma as follows:

  • Stage I - Involvement in a single lymph node region or single extralymphatic site
  • Stage II - Involvement of 2 or more lymph node regions on the same side of diaphragm, localized contiguous involvement of only one extralymphatic site and lymph node region
  • Stage III - Involvement of lymph node regions on both sides of diaphragm; may include spleen
  • Stage IV - Disseminated involvement of one or more extralymphatic organs with or without lymph node involvement

The addition of the letter E denotes extralymphatic sites. The letter B indicates the presence of B symptoms (ie, fever, night sweats, or weight loss).

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Contributor Information and Disclosures
Author

Benjamin Daniel Liess, MD  Assistant Professor, Department of Otolaryngology, University of Missouri-Columbia School of Medicine

Benjamin Daniel Liess, MD is a member of the following medical societies: American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American Laryngological Rhinological and Otological Society, American Medical Association, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Jerry W Templer, MD  Professor of Otolaryngology, University of Missouri Medical Center at Columbia

Jerry W Templer, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, Missouri State Medical Association, and Society of University Otolaryngologists-Head and Neck Surgeons

Disclosure: Nothing to disclose.

Specialty Editor Board

Benoit J Gosselin, MD, FRCSC  Associate Professor of Surgery, Dartmouth Medical School; Director, Comprehensive Head and Neck Oncology Program, Norris Cotton Cancer Center; Staff Otolaryngologist, Division of Otolaryngology-Head and Neck Surgery, Dartmouth-Hitchcock Medical Center

Benoit J Gosselin, MD, FRCSC is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, American Medical Association, American Rhinologic Society, Canadian Medical Association, Canadian Society of Otolaryngology-Head & Neck Surgery, College of Physicians and Surgeons of Ontario, New Hampshire Medical Society, North American Skull Base Society, and Ontario Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

M Sherif Said, MD, PhD  Associate Professor of Pathology, Director of Head and Neck Pathology, Department of Pathology, University of Colorado School of Medicine

M Sherif Said, MD, PhD is a member of the following medical societies: American Society for Clinical Pathology and College of American Pathologists

Disclosure: Nothing to disclose.

Christopher L Slack, MD  Private Practice in Otolaryngology and Facial Plastic Surgery, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders

Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA  Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society

Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation Unrestricted gift Unknown; Axis Three Corporation Ownership interest Consulting; Omni Biosciences Ownership interest Consulting; Sentegra Ownership interest Board membership; Syndicom Ownership interest Consulting; Oxlo Consulting; Medvoy Ownership interest Management position; Cerescan Imaging Honoraria Consulting; GYRUS ACMI Honoraria Consulting

Additional Contributors

The authors would like to acknowledge Young S. Paik, MD, for his assistance in the preparation and review of this manuscript.

References

  1. Khariwala SS, Litman DA, McQuone SJ, Hess JL, Thaler ER. Quiz case 2. Natural killer (NK) cell/peripheral T-cell lymphoma. Arch Otolaryngol Head Neck Surg. Nov 2000;126(11):1391, 1393. [Medline].

  2. Borges A, Fink J, Villablanca P, Eversole R, Lufkin R. Midline destructive lesions of the sinonasal tract: simplified terminology based on histopathologic criteria. AJNR Am J Neuroradiol. Feb 2000;21(2):331-6. [Medline].

  3. Ooi GC, Chim CS, Liang R, Tsang KW, Kwong YL. Nasal T-cell/natural killer cell lymphoma: CT and MR imaging features of a new clinicopathologic entity. AJR Am J Roentgenol. Apr 2000;174(4):1141-5. [Medline].

  4. Paik YS, Liess BD, Scheidt TD, Ingram EA, Zitsch RP 3rd. Extranodal nasal-type natural killer/T-cell lymphoma masquerading as recalcitrant sinusitis. Head Neck. Apr 9 2009;[Medline].

  5. 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. Jan 1 2004;103(1):216-21. [Medline].

  6. Sheahan P, Donnelly M, O'Reilly S, Murphy M. T/NK cell non-Hodgkin's lymphoma of the sinonasal tract. J Laryngol Otol. Dec 2001;115(12):1032-5. [Medline].

  7. Davison SP, Habermann TM, Strickler JG, DeRemee RA, Earle JD, McDonald TJ. Nasal and nasopharyngeal angiocentric T-cell lymphomas. Laryngoscope. Feb 1996;106(2 Pt 1):139-43. [Medline].

  8. Jaffe ES. Classification of natural killer (NK) cell and NK-like T-cell malignancies. Blood. Feb 15 1996;87(4):1207-10. [Medline].

  9. Rodrigo JP, Suarez C, Rinaldo A, et al. Idiopathic midline destructive disease: fact or fiction. Oral Oncol. Apr 2005;41(4):340-8. [Medline].

  10. Cuadra-Garcia I, Proulx GM, Wu CL, et al. Sinonasal lymphoma: a clinicopathologic analysis of 58 cases from the Massachusetts General Hospital. Am J Surg Pathol. Nov 1999;23(11):1356-69. [Medline].

  11. Kim BS, Kim TY, Kim CW, et al. Therapeutic outcome of extranodal NK/T-cell lymphoma initially treated with chemotherapy--result of chemotherapy in NK/T-cell lymphoma. Acta Oncol. 2003;42(7):779-83. [Medline].

  12. Luther N, Greenfield JP, Chadburn A, Schwartz TH. Intracranial nasal natural killer/T-cell lymphoma: immunopathologically-confirmed case and review of literature. J Neurooncol. Nov 2005;75(2):185-8. [Medline].

  13. Cheung MM, Chan JK, Lau WH, et al. Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients. J Clin Oncol. Jan 1998;16(1):70-7. [Medline].

  14. Greer JP, Kinney MC, Loughran TP Jr. T cell and NK cell lymphoproliferative disorders. Hematology Am Soc Hematol Educ Program. 2001;259-81. [Medline].

  15. Gutierrez M, Chabner BA, Pearson D, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8-year follow-up study of EPOCH. J Clin Oncol. Nov 1 2000;18(21):3633-42. [Medline].

  16. 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. Jan 1996;20(1):103-11. [Medline].

  17. Kim GE, Yang WI, Lee S, et al. The significance of granzyme B expression in patients with angiocentric lymphoma of the head and neck. Cancer. Jun 15 2001;91(12):2343-52. [Medline].

  18. Kwong YL, Chan AC, Liang RH. Natural killer cell lymphoma/leukemia: pathology and treatment. Hematol Oncol. May 1997;15(2):71-9. [Medline].

  19. Nathu RM, Mendenhall NP, Almasri NM, Lynch JW. Non-Hodgkin's lymphoma of the head and neck: a 30-year experience at the University of Florida. Head Neck. May 1999;21(3):247-54. [Medline].

  20. Ohshima K, Liu Q, Koga T, Suzumiya J, Kikuchi M. Classification of cell lineage and anatomical site, and prognosis of extranodal T-cell lymphoma -- natural killer cell, cytotoxic T lymphocyte, and non-NK/CTL types. Virchows Arch. Apr 2002;440(4):425-35. [Medline].

  21. Slater DN. The new World Health Organization classification of haematopoietic and lymphoid tumours: a dermatopathological perspective. Br J Dermatol. Oct 2002;147(4):633-9. [Medline].

  22. Takeshita M, Yoshida K, Suzumiya J, et al. Cases of cutaneous and nasal CD56 (NCAM)-positive lymphoma in Japan have differences in immunohistology, genotype, and etiology. Hum Pathol. Sep 1999;30(9):1024-34. [Medline].

  23. Yu KH, Yu SC, Teo PM, Chan AT, Yeo W, Chow J. Nasal lymphoma: results of local radiotherapy with or without chemotherapy. Head Neck. Jul 1997;19(4):251-9. [Medline].

 
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Coronal (left) and axial (right) CT scans of the sinus reveal severe pansinusitis with abnormal nasopharyngeal thickening, right facial edema and right temporal bone opacification.
MRI revealed a low, non enhancing T1 signal in the right maxillary, ethmoid and sphenoid sinuses. (left) A high and inhomogeneous T2 signal suggested tumor involvement and destruction of the middle and inferior turbinates. (right)
High-power photomicrograph of a nasopharyngeal mass that was diagnosed as natural killer (NK)–/T-cell lymphoma, nasal type. In this section stained with hematoxylin and eosin, a diffuse infiltrate of variably sized cells with irregularly shaped nuclei that contain coarsely granular chromatin is visible. In other areas of this tumor, necrosis and angiocentrism could be appreciated.
In this photomicrograph, immunohistochemical staining shows neoplastic cells to be positive for the pan T-cell antigen CD3 (positive cells have a brown tinge).
In this photomicrograph, immunohistochemical staining shows neoplastic cells to be positive for the natural killer (NK)–cell antigen CD56 (positive cells have a brown tinge).
In this photomicrograph, immunohistochemical staining shows neoplastic cells to be focally positive for granzyme B (positive cells have a brown tinge).
In this photomicrograph, in situ hybridization for Epstein-Barr virus RNA (EBER) shows positivity in neoplastic cells (positive cells have black nuclei).
 
 
 
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