Lester Daron Robert Thompson, MD

TONSIL

Lymphoid changes of the nasopharyngeal and palatine tonsils that are indicative of human immunodeficiency virus infection. A clinicopathologic study of 12 cases.

Wenig BM, Thompson LD, Frankel SS, Burke AP, Abbondanzo SL, Sesterhenn I, Heffner DK.

Am J Surg Pathol. 1996 May;20(5):572-87.

We report 12 cases in which the histomorphologic changes of the nasopharyngeal tonsils (adenoids) or palatine tonsils suggest infection with the human immunodeficiency virus (HIV). The patients included 10 men and two women, aged 20 to 42 years (median, 33 years). The clinical presentation included airway obstruction, pharyngitis, fever, and a tonsillar or adenoidal mass lesion. Histologic evaluation of the excised adenoids or tonsils in 10 of the cases demonstrated a spectrum of changes including florid follicular hyperplasia, follicle lysis, attenuated mantle zone, and the presence of multinucleated giant cells (MGC). The latter characteristically localized adjacent to the surface or tonsillar crypt epithelium. Two of the 12 cases showed marked lymphoid depletion with absent germinal centers, plasmacytosis, and stromal vascular proliferation. Immunohistochemical evaluation for HIV p24 core protein showed reactivity in 10 of 12 cases localized to follicular dendritic cell network (FDC), the MGC, scattered interfollicular lymphoid cells, and cells identified within the surface or crypt epithelium. Localization of viral RNA by in situ hybridization paralleled the HIV p24 immunohistochemical findings. Additional significant findings included the presence of both CD-68 and S-100 protein in the MGC and the presence of S-100 protein in dendritic cells. Other than HIV, no microorganisms were identified. At the time of presentation, eight patients were not known to be a risk for HIV infection, nor were they known to be HIV infected or suffering from AIDS. In these patients, HIV infection was suspected on the basis of the histologic changes seen in the resected tonsillar and adenoidal tissue. Serologic evaluation (by enzyme-linked immunosorbent assay), confirmed the presence of HIV infection. Our findings suggest the possibility of HIV dissemination through the upper aero-digestive tract mucosa via target cells, such as intraepithelial dendritic cells, submucosal macrophages, and T-lymphocytes. Subsequent presentation of viral antigens to the tonsillar and adenoidal lymphoid tissues results in enlargement of these structures that clinically may simulate a neoplastic proliferation but causes histomorphologic changes that are highly suspicious for HIV infection even in asymptomatic HIV-positive patients.

PMID: 8619422

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Replication of HIV-1 in dendritic cell-derived syncytia at the mucosal surface of the adenoid.

Frankel SS, Wenig BM, Burke AP, Mannan P, Thompson LDR, Abbondanzo SL, Nelson AM, Pope M, Steinman RM

Science 1996;272:115-117

Human immunodeficiency virus-type 1 (HIV-1) replicates actively in infected individuals, yet cells with intracellular depots of viral protein are observed only infrequently. Many cells expressing the HIV-1 Gag protein were detected at the surface of the nasopharyngeal tonsil or adenoid. This infected mucosal surface contained T cells and dendritic cells, two cell types that together support HIV-1 replication in culture. The infected cells were multinucleated syncytia and expressed the S100 and p55 dendritic cell markers. Eleven of the 13 specimens analyzed were from donors who did not have symptoms of acquired immunodeficiency syndrome (AIDS). The interaction of dendritic cells and T cells in mucosa may support HIV-1 replication, even in subclinical stages of infection.

PMID: 8600520

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Tonsillar lymphangiomatous polyps: a clinicopathologic series of 26 cases.

Kardon DE, Wenig BM, Heffner DK, Thompson LD.

Mod Pathol. 2000 Oct;13(10):1128-33.

BACKGROUND: Lymphangiomatous polyps are uncommon benign tumors of the tonsils.

METHODS: Twenty-six cases of lymphangiomatous polyps diagnosed between 1980 and 1999 were retrieved from the files of the Otorhinolaryngic-Head and Neck Tumor Registry of the Armed Forces Institute of Pathology. Hematoxylin and eosin-stained slides were reviewed to characterize the histologic features of these tumors. Immunohistochemical stains were performed on 15 cases. Clinical follow-up data were obtained.

RESULTS: The patients included 13 males and 13 females, ages 3 to 63 years (mean, 25.2 years). Patients experienced dysphagia, sore throat, and the sensation of a mass in the throat. Symptoms were present from a few weeks to years. The tonsillar masses were unilateral in all cases. Clinically, the lesions were frequently mistaken for a neoplasm (n = 18 patients). Grossly, all of the lesions were polypoid and measured 0.5 to 3.8 cm (mean, 1.6 cm). Histologically, the polyps were covered by squamous epithelium showing variable epithelial hyperplasia, dyskeratosis, and lymphocytic epitheliotropism. The masses showed a characteristic submucosal proliferation of small to medium-sized, endothelial-lined, lymph-vascular channels lacking features of malignancy. Collagen, smooth muscle, and adipose tissue were present in the stroma. Intravascular proteinaceous fluid and lymphocytes were noted. Immunohistochemical findings confirmed the endothelial origin of the vascular proliferation and a mixed lymphoid population. The differential diagnosis included fibroepithelial polyp, lymphangioma, juvenile angiofibroma, and squamous papilloma. In all patients with follow-up, complete surgical excision was curative (mean follow-up, 5.4 years; range, 1 mo to 14 years).

CONCLUSIONS: We detail the clinical and pathologic features of tonsillar lymphangiomatous polyps. These tumors are uncommon and may clinically be mistaken for a malignant neoplasm. The characteristic histologic features should allow for its correct diagnosis and differentiation from similar appearing tonsillar lesions.

PMID: 11048808

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A clinicopathologic series of 22 cases of tonsillar granulomas.

Kardon DE, Thompson LD.

Laryngoscope. 2000 Mar;110(3 Pt 1):476-81.

OBJECTIVES: Tonsils are uncommonly affected by granulomatous inflammation, often with an obscure cause. This study attempts to elucidate the nature of tonsillar granulomatous inflammation.

DESIGN: Retrospective clinicopathologic review.

METHODS: Twenty-two cases of tonsillar granulomas diagnosed between 1940 and 1999 were retrieved from the files of the Armed Forces Institute of Pathology. H&E slides and a series of histochemical stains were reviewed, and patient follow-up was obtained.

RESULTS: There were 11 males and 11 females, aged 7 to 64 years (mean, 29.9 y). Most of the cases presented bilaterally (n = 19) with sore throat, dysphagia, and/or nasal obstruction. The clinical differential included chronic tonsillitis, tuberculosis, nonspecific infection, sarcoidosis, and a neoplasm. Histologically, the granulomas were focal and scattered, or diffuse, identified in the interfollicular zones (n = 16) and/or the germinal centers (n = 13), and occasionally associated with necrosis (n = 6). Based on histochemical and clinical follow-up information, the etiology of the granulomas included sarcoidosis (n = 8), tuberculosis (n = 3), Hodgkin's lymphoma (n = 2), toxoplasmosis (n = 1), squamous cell carcinoma (n = 1), and no specific known cause (n = 7). Twelve patients were either alive at last follow-up or had died with no evidence of disease (mean, 12.4 y), and 9 were either alive at last follow-up or had died with disease (mean, 24.9 y). One patient was alive with unknown disease status (lost to follow-up after 13.3 y).

CONCLUSIONS: Although a cause for tonsillar granulomas is frequently identified, a number may not develop an identifiable etiology, with the granulomas probably representing an exaggerated immune response to chronic tonsillitis. However, a careful work-up must be conducted to exclude specific causes and avoid clinical mismanagement.

PMID: 10718441

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Acute Necrotizing Herpetic Tonsillitis: A Report of Two Cases.

Borhan WM, Dababo MA, Thompson LD, Saleem M, Pashley N

Head and Neck Pathol accepted 2013 Dec 6. [Epub ahead of print]

The finding of herpetic tonsillitis is rare. Tonsillectomies are usually done for children with recurrent chronic tonsillitis, while viral throat infections are generally self-limiting. We present two cases: A 5 yearold girl, with atypical hemolytic anemia managed with Eculizumab, who presented with a pharyngeal infection and tonsillar enlargement that did not respond to intravenous antibiotics or antifungal therapies; and a 30 yearold man who presented with upper airway obstruction and fever; bilateral tonsillectomies were performed. Histopathological examination showed a necrotizing tonsillitis with numerous ground-glass intranuclear inclusions, characteristic of herpes viral infection, further confirmed by Herpes simplex virus in situ hybridization. Both patients were managed by intravenous Acyclovir, with dramatic improvement.

PMID: 24338612

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Routine histologic examination is unnecessary for tonsillectomy or adenoidectomy.

Randall DA, Martin PJ, Thompson LD

Laryngoscope. 2007 Sep;117(9):1600-4

OBJECTIVE: To determine whether the current practice and incurred cost of histologic examination of tonsillectomy and adenoidectomy specimens is warranted.

STUDY DESIGN: Review article based on medical literature.

SUBJECTS AND METHODS: A retrospective PubMed review of all pertinent literature regarding tonsillectomy, adenoidectomy, and related surgical pathology was conducted. References of the articles obtained were reviewed for additional sources.

RESULTS: Twenty studies report 54,901 patients and found 54 malignancies (0.087% prevalence). Of these, 48 (88% of the patients) had suspicious features such as tonsillar asymmetry, cervical lymphadenopathy, or abnormal tonsil appearance, preoperatively. The remaining six patients without any suspicious features (better representing true occult malignancy) were 0.011% of the total cases.

CONCLUSION: Submission of tonsillectomy, adenoidectomy, or both specimens is warranted only when patients demonstrate findings associated with malignancy: tonsillar asymmetry, history of cancer, neck mass, tonsil firmness or lesion, weight loss, and constitutional symptoms.

PMID: 17762791

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Tonsil with Tangier disease.

Nelson BL, Thompson LD.

Ear Nose Throat J. 2003 Mar;82(3):178.

FIRST PARAGRAPH: Tangier disease is a rare autosomal-recessive inherited disorder that is caused by a defect in chromosome 9q31. It is characterized by a severe deficiency or absence of high-density lipoproteins in plasma. A defect in cellular cholesterol removal results in the massive, abnormal accumulation of cholesterol esters in macrophages in many tissues. Although this accumulation is most conspicuous in the tonsils, progressive accretion of these esters also occurs in nerves (neuropathy) and vessels (atherosclerosis). The pathognomonic finding is a low plasma cholesterol concentration accompanied by normal or elevated triglyceride levels and large, lobulated, hyperplastic, bright orange-yellow tonsils and adenoid tissue. Affected families have been identified on Tangier Island, Va., in Chesapeake Bay as well as in Missouri, Kentucky, and Europe.

PMID: 12696235

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