Pathology of the Head and Neck

Nasopharynx and Waldeyer’s Ring Chapter 6 185causing acute necrotising tonsillitis include Clostridiumperfringens and Bartonella henselae with an unusual presentationof cat scratch disease [61, 121].6.3.3.2 Viral TonsillitisThe most common causes of upper respiratory tractinfections and pharyngo-tonsillitis in the general population,including infants and young children, are virusessuch as influenza virus, Coxsackie’s virus (groupA), adenovirus, and the ubiquitous herpes virus Epstein-Barrvirus [205]. EBV infects epithelial cells andB-lymphocytes of Waldeyer’s ring, which representthe reservoir for life-long viral persistence [104, 186].Primary infections with EBV occur early in infancyand childhood in developing countries and are generallyasymptomatic. In contrast, in developed countries,primary infection occurs in adolescents and youngadults. EBV infections may cause the mostly self-limitingacute disease infectious mononucleosis, affectingadolescents and young adults in the western world. InJapan, however, an endemic area for EBV, acute cases ofinfectious mononucleosis are commonly diagnosed inchildren less than 4 years of age [100]. The symptomsinclude enlarged swollen palatine tonsils, occasionallywith peritonsillar abscesses, sore throat, fever, malaise,cervical lymphadenopathy, lymphocytosis andoccasional hepato-splenomegaly [133]. The diagnosisin typical cases is made clinically and/or serologically[69]. Histologically, the changes of a primary EBV infectioncan be dramatic [30]. The surface epitheliumof the palatine tonsils is often necrotic. Follicular hyperplasiawith fused or bizarre-shaped follicles andnumerous tangible body macrophages and distendedinterfollicular areas with atypical immunoblasts, plasmacells, plasmacytoid lymphocytes and histiocytes,occasionally grouped around necrotic foci, are typical.Mitoses are numerous. Rare Reed-Sternberg-like cellswith single or multiple nuclei without nucleoli may bepresent beneath the crypt epithelium. The often atypicalimmunoblasts may simulate lymphoma, but in infectiousmononucleosis, they often merge with cells inthe reactive follicles and paracortex (Fig. 6.6). The proliferatinglymphoid cells are predominantly activatedT lymphocytes with CD8-positive T-cells dominatingover CD4-positive T-cells. The immunoblasts can be ofB-cell or T-cell type, and are occasionally CD30-positive,but CD15-negative [1]. Infected cells are reactivefor EBV nuclear antigen (EBNA) [2] and latent membraneprotein (LMP) [182, 186].The most important differential diagnosis of infectiousmononucleosis, especially in older patients, is theextranodal manifestation of Hodgkin’s lymphoma andnon-Hodgkin’s lymphoma (large cell and immunoblastictypes). Immunoglobulin rearrangements and T-cellreceptor gene rearrangements are lacking in infectiousmononucleosis. The differential diagnosis of ulceratingtonsillitis includes infections with herpes virus hominis(usually Herpes simplex virus type 1). Herpes simplexvirus can produce a vesiculo-bullous pharyngitisand may involve the palatine tonsils [106, 195]. Ruptureof the vesicles results in sharply circumscribed shallowulcers infiltrated by neutrophilic granulocytes. Infectedepithelial cells show the characteristic multinucleatedgiant cells with nuclear viral inclusion. The lymphoidinfiltrate and hyperplasia of a Herpes simplex virus infectionmay mimic a NK/T-cell lymphoma [184]. GroupA Coxsackie’s virus also produces punched-out vesiclesand is often associated with a concomitant Herpes simplexvirus infection. Rare systemic autoimmune diseases,like the anti-phospholipid antibody syndrome, maycause tonsillar ulcers [79].Chronic and recurrent tonsillitis are typically associatedwith respiratory syncytial virus, reactivation of latentEpstein-Barr virus, H. influenza and Staphylococcusaureus [44, 117, 204]. After episodes of recurrent tonsillitis,the palatine tonsils show extensive fibrosis at thesite of the former capsule and scarring with entrapped,“pulled up” skeletal muscle fibres at the base of the tonsiland atrophic lymphoid tissue with small lymphoid follicleswith atrophic germinal centres. Granulomas maybe present. The crypts are distended and filled with keratinousdebris, inflammatory cells and occasional aggregatesof actinomyces. Retention cysts can be formedwithin the deep crypts of chronically irritated palatinetonsils after occlusion of the orifice. The crypt epitheliumbecomes keratinised. Calcification of the desquamateddebris following deposition of inorganic saltsmay result in tonsillar calculi, so-called tonsilloliths. Thepresence of actinomyces is not associated causally withrecurrent tonsillitis [57, 120].Human immunodeficiency virus 1 (HIV-1) infectslymphocytes of lymph nodes and extranodal lymphoidtissue. Hypertrophy of the nasopharyngeal and palatinetonsils is among the earliest clinical manifestations ofHIV-1 infections. Enlargement of the palatine tonsils isusually bilateral and large ulcers may lead to completedestruction of the tonsils [28]. The histological changesin HIV-induced tonsillar hypertrophy vary with stageand progression of the infection. The earliest changes includeflorid reactive follicular hyperplasia with irregularlyshaped germinal centres with an attenuated or absentmantle cell zone. Another early change suggesting HIVinfection is “follicle lysis”, with permeation and disruptionof germinal centres by “infiltrating” small lymphocytescreating a “moth eaten” appearance. Follicle lysis/follicular involution involves loss of tangible body macrophagesas well as the mantle zone of lymph follicles. Interfollicularhaemorrhage is another feature of follicularinvolution. Multinucleated giant cells are a typical andspecific feature of HIV tonsillitis. The multinucleated gi-