A Clinicopathological Study of Cytomegalovirus Lymphadenitis and Tonsillitis and Their Association with Epstein-Barr Virus

Abstract

Introduction: Histopathological characteristics of cytomegalovirus (CMV) lymphadenitis have been well described. Rare studies have reported the immune status and clinical features. Clinically, experts believed that CMV lymphadenitis develops in immunocompromised and immunocompetent patients. Infectious mononucleosis (IM)-like syndrome is the most well-known clinical presentation.

Methods: We reviewed archived CMV immunohistochemical stains on lymphoid tissues. The clinicopathological features of CMV-positive cases were studied.

Results: For lymph nodes, we detected CMV in 29% (5/17) allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) recipients, 29% (4/14) post-autologous PBSCT patients, 13% (6/47) patients treated with intravenous chemotherapy, and 9% (9/96) immunocompetent patients. We detected CMV in 7% (2/24) of tonsils but not in the nasopharynx, tongue base, or spleen specimens. The patients with iatrogenic immunodeficiency ranged from 37 to 76 years old. CMV infections developed a few years after lymphoma treatment (median duration after allogeneic PBSCT, 932 days; after autologous PBSCT, 370 days; and after chemotherapy, 626 days). The most common clinical presentation was neck mass (13/25, 42%), followed by asymptomatic image finding (10/25, 40%). Positron emission tomography/computed tomography (PET/CT) scan showed increased uptake compared to the liver in all patients (11/11, 100%). Of 10 lymphoma patients, 8 (80%) had a Deauville score of 4-5; they accounted for 30% (8/27) of lymphoma patients with false-positive PET/CT scan results. All cases were self-limiting. 96% (23/25) cases had Epstein-Barr virus coinfection, and EBER-positive cells were predominantly in a few germinal centers.

Conclusions: Cytomegalovirus (CMV) lymphadenitis and tonsillitis were subclinical infections, not primary CMV infection with IM-like syndrome. The lymphadenopathy typically developed a few years after lymphoma treatments in the middle-aged and the elderly. The lesions mimicked lymphoma relapse in PET scans. Therefore, recognizing CMV infection in lymphoid tissues is of clinical importance.

Keywords: Cytomegalovirus; Epstein–Barr virus; Lymphadenopathy; Lymphoma; Positron emission tomography; Reactive lymphoid hyperplasia.

Fig. 1

Positron emission tomography of Case 4 showed high and focal FDG uptake (SUVmax = 7.4) in the left superior jugular node (arrow), suspicious for relapse

Fig. 2

Pathological findings of the 25 cases (from left to right, Cases 1–25). Hematoxylin-and-eosin staining is shown in the upper three rows (blue); cytomegalovirus (CMV) immunohistochemical (IHC) staining is shown in the middle two rows (red); EBER in situ hybridization (ISH) is shown in the lower two rows (green)

Fig. 3

Hematoxylin-and-eosin staining of Case 9, showing monocytoid cell proliferation (asterisks) and follicular hyperplasia

Fig. 4

A Cytomegalovirus (CMV) immunohistochemical staining revealed positive cells in the monocytoid cell region (circled with dashed lines) (Case 10). B The CMV-positive cells were variable in size and shape (Case 16). C EBER-positive cells predominantly in the germinal centers (Case 14). D a germinal center with numerous positive cells (Case 13)