NK-Cell Lymphomas of the Head and Neck

http://emedicine.medscape.com/article/871609-overview

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NK-Cell Lymphomas of the Head and Neck

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

Background
The natural killer (NK) cell is a cytolytic cell that is an important component of the body's immune system. These cells are capable of conducting immune surveillance for tumorous, bacterial, and viral invaders. NK-cell lymphoma is a type of non-Hodgkin lymphoma (NHL). Most NHLs (90%) are B cell in origin. In the past, the rarity of nonB-cell malignancies and their similar morphologic findings coupled with the previous unavailability of cell markers led to the inability to classify subtypes of nonB-cell NHL. This lack of knowledge also prevented clinicians from gathering meaningful information about the natural history of the disease and prognosis. This lack of knowledge is also demonstrated in previous classification systems, including the Lukes-Collins, Kiel, and Working Formulation systems, which did not identify subclasses of NK-/T-cell malignancies.

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.

Recent advances in tumor cell biology have led to the ability to subclassify NHL via the World Health Organization (WHO) classification of lymphomas. Previous terms for NK-cell malignancies and other forms of nonB-cell NHL included lethal midline granuloma, angiocentric lymphoma, malignant granuloma, malignant midline reticulosis, and polymorphic reticulosis. These terms were based on clinical and pathologic characteristics of the diseases encountered. Controversy still exists over the normal counterpart of NK-cell lymphoma. Whether NK-cell lymphoma represents the presence of a true NK cell or whether the malignancy represents the presence of a T cell with abnormal cell markers is under debate. This controversy has led many investigators to use the term NK-/T-cell lymphoma when classifying NK-cell lymphomas because of the absence of unequivocal proof of the exact lineage of these neoplasms. Further understanding of the development and identification of more specific cell markers of the NK cells and T cells will likely resolve this controversy in the future. Peripheral T- and NK-cell lymphomas classified by the WHO have many subclasses (see World Health Organization classification of lymphomas). The subgroupings, which primarily involve the head and neck region, include the nasal

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NK-Cell Lymphomas of the Head and Neck

http://emedicine.medscape.com/article/871609-overview

and nasal-type extranodal NK-/T-cell lymphomas. The term extranodal is used because these forms of malignancies are found outside of the traditional lymph node groupings. The nasal and nasal-type NK-/T-cell lymphomas have distinct presentations and prognoses, and they are believed to have different pathogeneses. Otolaryngologists should understand the importance of differentiating NK-/T-cell lymphoma from other similar pathologic entities found in the head and neck region, as the prognosis is greatly affected.

World Health Organization classification of lymphomas

B-cell neoplasms Precursor B-lymphoblastic leukemia/lymphoma Chronic lymphocytic leukemia/small lymphocytic lymphoma Lymphoplasmacytic lymphoma Plasma cell myeloma Extraosseous plasmacytoma Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma) Follicular lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma Intravascular large B-cell lymphoma B-cell proliferations of uncertain malignant potential Lymphomatoid granulomatosis Posttransplant lymphoproliferative disorder, polymorphic T-cell and NK-cell neoplasms Precursor T-lymphoblastic leukemia/lymphoma Blastic NK-cell lymphoma Adult T-cell leukemia/lymphoma Extranodal NK-/T-cell lymphoma, nasal type Subcutaneous panniculitislike T-cell lymphoma Mycosis fungoides Szary syndrome Primary cutaneous anaplastic large cell lymphoma Peripheral T-cell lymphoma Angioimmunoblastic T-cell lymphoma Anaplastic large cell lymphoma T-cell proliferation of uncertain malignant potential Lymphomatoid papulosis Hodgkin lymphoma Histiocytic and dendritic-cell neoplasms Mastocytosis

Pathophysiology
Extranodal nasal NK-/T-cell lymphoma manifests in the nasal cavity. Patients with this type tend to have earlier disease (stage I). However, later-stage presentations are observed and have an impact on survival rate. Nasal NK-/T-cell lymphomas are almost always (>95% of cases) associated with Epstein-Barr virus (EBV), irrespective of the ethnicity of the patient. The exact mechanism of malignant transformation via EBV has not been elucidated. Extranodal nasal-type NK-/T-cell lymphoma demonstrates predilection for the nasopharynx, palate, skin, soft tissues, orbit, gastrointestinal tract, and testes. Secondary lymph nodes may be involved in some cases; a disseminated leukemic picture is even possible. Lymphomas that manifest outside of the nose have a strong association with EBV in Asian patients, but the strong association is not present in whites. The pattern of involvement of the extranasal sites has been hypothesized to be related to the marker CD56. CD56 represents the neural cell adhesion molecule (NCAM) that has been shown to have homophilic binding properties. With the skin, gastrointestinal tract, and testes expressing the CD56 marker in large amounts, the neoplastic cells travel to these areas and set up foci of disease. Skin is the most common site of dissemination in NK-/T-cell lymphomas.

Epidemiology
Frequency
United States

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These lymphomas are very rare in whites. Prevalence is higher in people of Asian descent than in whites. In Western populations, the prevalence of nasal lymphomas is estimated at 0.17-1.5% of all NHLs, 45% of which are thought to be NK-/T-cell in origin. International Prevalence continues to be low, but this lymphoma is much more prevalent in Asia, Mexico, and Central and South America. Rates of nasal lymphoma in Hong Kong and South America have been reported to range from 2.6-8% of all NHLs, of which 45% are thought to represent NK-/T-cell lymphoma.

Mortality/Morbidity
When compared with other subtypes of lymphoma found in the head and neck region, NK-/T-cell lymphoma carries a much higher mortality rate and a decreased response to traditional chemotherapy and radiation therapy regimens. Overall, median survival time is reported as 12.5 months. Survival time for patients who present with a disseminated leukemic picture is reported to be less than 6 months. A complete response to primary treatment is reported in 56% of patients. Overall, the 2-year survival rate is 45%, and the 2-year disease-free survival rate is reported at 31%. Poor survival rates and response rates to treatment are theorized to be secondary to the CD56 cell marker and the presence of a multidrug resistance (P-glycoproteinpositive) phenotype. CD56 is thought to facilitate tumor cell dissemination because of its binding properties. NK-/T-cell lymphoma has a higher local relapse rate (21.4%) than that of T-cell lymphomas presenting in the nasopharynx (5%) or B-cell lymphomas presenting in the nasopharynx (0%). Fewer recurrences in the cervical nodes are reported (2.4%) than those reported for T-cell (10%) and B-cell (14.3%) malignancies. Hemophagocytic syndrome, associated with fever, marked pancytopenia, hemophagocytic histiocytes in the bone marrow, and rapid liver function deterioration, is a devastating complication of NHLs. This syndrome appears to be much more common in NK-/T-cell malignancies.

Sex
Men are more commonly affected with the disease than women, with a male-to-female ratio of almost 3:1.[1, 2]

Age
Patients with NK-/T-cell lymphoma commonly present in their sixth decade of life, which is almost a decade younger than people with B-cell neoplasms present. However, the disease has been seen in both the geriatric and pediatric populations.[1, 2]

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,

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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
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