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Lymphoid Lesions of the Head and Neck: a Model of Lymphocyte Homing and Lymphomagenesis Elaine S

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Lymphoid Lesions of the Head and Neck: a Model of Lymphocyte Homing and Lymphomagenesis Elaine S Lymphoid Lesions of the Head and Neck: A Model of Lymphocyte Homing and Lymphomagenesis Elaine S. Jaffe, M.D. Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland Lymphomagenesis is not a random event but is Lymphoid lesions of the head and neck mainly affect usually site specific. It is dependent on lymphocyte the nasopharynx, nasal and paranasal sinuses, and homing, as well as the underlying biology and func- salivary glands. These three compartments each are tion of the resident lymphoid tissues. The head and affected by a different spectrum of lymphoid malig- neck region contains several compartments: the na- nancies and can serve as model for mechanisms of sopharynx, nasal and paranasal sinuses, and sali- lymphomagenesis. The type of lymphoma seen re- vary glands, each of which is affected by a different flects the underlying biology and function of the par- subset of benign and neoplastic lymphoid prolifer- ticular site involved. The nasopharynx and Waldeyer’s ations (Table 1). These three sites can serve as a ring are functionally similar to the mucosal associated model of lymphomagenesis that can be extended to lymphoid tissue (MALT) of the gastrointestinal tract other organ systems. Indeed, the head and neck and are most commonly affected by B-cell lympho- region can serve as a microcosm for understanding mas, with mantle cell lymphoma being a relatively the principles of lymphoma classification and the frequent subtype. The most prevalent lymphoid lesion distribution of lymphoma subtypes in other organ of the salivary gland is lymphoepithelial sialadenitis, systems. associated with Sjögren’s syndrome. Lymphoepithe- The nasopharynx normally contains abundant lial sialadenitis is a condition in which MALT is ac- lymphoid tissue. This site is functionally equivalent quired in a site not normally containing lymphoid to the lymphoid tissue of the gastrointestinal tract tissue. Patients with Sjögren’s syndrome are at in- or mucosal-associated lymphoid tissue (MALT). creased risk to develop B-cell lymphomas, most com- The most common benign process is follicular hy- monly MALT lymphomas. The nasal and paranasal perplasia, and the most common lymphomas are sinuses are the prototypical site for the development the “small B-cell lymphomas,” most commonly of extranodal natural killer (NK) /T-cell lymphoma, mantle cell lymphoma. By contrast, the nasal re- nasal type. This condition must be distinguished from gion and paranasal sinuses do not contain lym- other conditions causing the clinical picture of lethal phoid tissue normally. NK/T-cell lymphomas are midline granuloma, including Wegener’s granuloma- most common in this site, nearly always associated tosis and infectious disorders. Lymphomatoid granu- with Epstein-Barr virus (EBV). The prevalence of EBV lomatosis is common in the lung but is rarely seen in in this subset of lymphomas may relate to the fact that the midline facial structures. the nasopharynx is a reservoir for EBV infection. In- terestingly, however, most nasopharyngeal lympho- KEY WORDS: B-cell, Epstein Barr virus, Follicular mas are negative for EBV sequences. lymphoma, Immunophenotyping, Lymphocyte The salivary gland does not normally contain homing, Lymphoma, Lymphomagenesis, MALT lymphoid tissue but is a site predisposed to the lymphoma, NK-cell lymphoma, T-cell. acquisition of acquired MALT upon appropriate an- Mod Pathol 2002;15(3):255–263 tigenic stimulation. It is a frequent target in patients with autoimmune disease, such as Sjögren’s syn- drome (SS). The most common lymphoma of the salivary gland is MALT lymphoma. NASOPHARYNGEAL LYMPHOID HYPERPLASIA Copyright © 2002 by The United States and Canadian Academy of Pathology, Inc. AND LYMPHOMA VOL. 15, NO. 3, P. 255, 2002 Printed in the U.S.A. Date of acceptance: September 27, 2001. As Waldeyer’s ring is the site of abundant lym- Address reprint requests to: Elaine S. Jaffe, M.D., Building 10, Room 2N202, 10 Center Drive MSC-1500, Bethesda, MD 20892; e-mail: phoid tissue, the nasopharyngeal lymphoid tissues [email protected]; fax: 301-402-2415. can be the sites of both lymphoid hyperplasia and 255 TABLE 1. Common Lymphoid Lesions of the Head and TABLE 2. World Health Organization Classification of Neck Lymphoid Neoplasms Nasopharynx and Waldeyer’s ring B-cell neoplasms Lymphoid hyperplasia Precursor B-cell neoplasm Lymphomas, B cell ϾϾ T cell Precursor B-lymphoblastic leukemia/lymphoma Mantle cell lymphoma Mature (peripheral) B-cell neoplasms Follicular lymphoma Chronic lymphocytic leukemia/small lymphocytic lymphoma Small lymphocytic lymphoma B-cell prolymphocytic leukemia Nasal and paranasal sinuses, palate Lymphoplasmacytic lymphoma Extranodal natural killer/T-cell lymphoma, nasal type Splenic marginal zone B-cell lymphoma Wegener’s granulomatosis Hairy cell leukemia Oral cavity and gingiva Plasma cell myeloma/plasmacytoma Plasmablastic lymphoma Extranodal marginal-zone B-cell lymphoma of mucosa-associated Lymphomatoid granulomatosis lymphoid tissue type Burkitt lymphoma (usually extension from bone) Nodal marginal-zone B-cell lymphoma/follicular lymphoma Salivary gland Mantle cell lymphoma HIV-associated cystic hyperplasia Diffuse large B-cell lymphoma Lymphoepithelial sialadenitis Mediastinal large B-cell lymphoma Marginal-zone B-cell lymphoma of mucosa-associated lymphoid Primary effusion lymphoma tissue type Intravascular large B-cell lymphoma Warthin’s tumor Burkitt lymphoma/Burkitt cell leukemia T- and natural killer cell neoplasms Precursor T-cell neoplasm Precursor T-lymphoblastic lymphoma/leukemia Mature (peripheral) T-cell neoplasms lymphoma. In many respects, the lymphoid tissue T-cell prolymphocytic leukemia of the nasopharynx is functionally similar to the T-cell large granular lymphocytic leukemia Aggressive natural killer cell leukemia lymphoid tissues of the gastrointestinal tract and is Adult T-cell lymphoma/leukemia considered part of the MALT system. Follicular hy- Hepatosplenic T-cell lymphoma perplasia is the most common pattern of lymphoid Extranodal natural killer/T-cell lymphoma, nasal type Enteropathy-type T-cell lymphoma reaction seen. Lymphocytes often infiltrate the Subcutaneous panniculitis-like T-cell lymphoma overlying epithelium, producing lymphoepithelial Mycosis fungoides/Sezary syndrome lesions, and should not be considered suspicious Primary cutaneous anaplastic large-cell lymphoma Peripheral T-cell lymphoma, not otherwise characterized for evolving lymphomas. Lymphoepithelial lesions Angioimmunoblastic T-cell lymphoma are common in sites containing normal MALT, such Anaplastic large-cell lymphoma as the tonsil and ileum. In contrast, when lympho- epithelial lesions are seen in acquired MALT, such as in the stomach, they are more often an indica- usually negative for CD23. They are cyclin D1 pos- tion for an evolving lymphoproliferative process (1). itive as a result of the associated chromosomal The most common lymphomas of the nasophar- translocation, t(11;14) (5). Immunophenotypic ynx are the small B-cell lymphomas, mantle cell studies are very helpful in differential diagnosis, as lymphoma (MCL), small lymphocytic lymphoma/ especially in small biopsy specimens, morphologic chronic lymphocytic leukemia (SLSL/CLL), and fol- details of architecture and cytology may be limited. licular lymphoma (FL; Table 2). The histologic and Follicular lymphoma is not uncommon in the immunophenotypic features of these lymphomas palatine tonsils but is more infrequent in the naso- mirror those of other sites. pharynx. Although follicular lymphomas are gener- MCL is among the more common lymphomas ally rare in children, the nasopharyngeal and pala- affecting the nasopharynx. It frequently involves tine tonsils are among the most common sites of the gastrointestinal tract, producing polypoid le- follicular lymphomas in children (6). In contrast to sions throughout the small bowel. This pattern of follicular lymphomas in adults, these tumors are gastrointestinal tract involvement has been referred usually bcl-2 protein negative and lack BCL-2 gene to as lymphomatous polyposis (2). Twenty percent rearrangements (Table 3). They are typically Grade of patients with MCL present with overt gastroin- 3, with a predominance of centroblasts, and a high testinal tract involvement, but with endoscopic mitotic rate. The differential diagnosis with florid evaluation, the incidence increases to 88% (3, 4). As follicular hyperplasia can be difficult. Stains for the nasopharynx is functionally and developmen- bcl-2, commonly employed in the diagnosis of FL, tally linked to the gastrointestinal tract, it is not are not helpful. Documentation of monoclonality, surprising that this site is commonly involved as either by light-chain expression or molecular stud- well. Waldeyer’s ring is involved at presentation in ies, is most useful in diagnosis. Some cases appear 20% of patients, but the incidence may be greater to show evidence of plasmacytoid differentiation, with a thorough ear, nose, and throat exam and and therefore, immunohistochemistry in paraffin blind biopsies of nasopharyngeal lymphoid tissue sections may be useful. FL in children usually pre- (3). The overlying mucosal epithelium is commonly sents with localized disease and has an excellent undisturbed. MCL is composed of CD5ϩ,BϪcells, prognosis (7). It is more common in males than 256 Modern Pathology TABLE 3. Characteristics of Pediatric Follicular this site is nasal NK/T-cell lymphoma. However, Lymphoma: a Distinctive Disease Entity
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