Viral-associated lymphoid proliferations☆
Introduction
In general, during the acute phase of a viral infection, there is an active viral replication (the lytic phase) and the host immune response is able to handle the infection, control replication, and eliminate the virus. Several forms of persistent, chronic, or latent infection have been recognized. We refer to a chronic infection when there is a continuous viral replication and high systemic viral load (Human Immunodeficiency Virus) and when the infections are not readily controlled by the host immune system (Hepatitis B and C Virus). Evidence of continued infection beyond 6 months is arbitrarily required for the process to be considered chronic. In cases of persistent or latent infection, no viral progeny is usually produced, since only limited transcription and translation of the viral genome occur, such as in Herpes viruses, Epstein–Barr Virus (EBV), Herpes Simplex Virus (HSV) and Varicella–Zoster Virus (VZV) infections; in reactivation usually a larger set of genes is transcribed, but it is often non-productive and clinically asymptomatic, and only occasionally can it lead to a full replicative phase with the expression of more than 80 viral genes and release of a new viral progeny.
Section snippets
EBV
EBV is a gamma herpes virus (HHV4) and linear double-stranded DNA virus, with worldwide distribution. It is orally transmitted and most people become infected in the course of their life. When the primary infection occurs in children (>90% positive by age 5) it is usually asymptomatic or a self-limited brief viral illness like many others. In the US and other developed countries, the primary acute infection often occurs later in life (adolescence or early adult) and causes acute infectious
Acute primary EBV infection, consistent with acute infectious mononucleosis
The histological features of tonsils or lymph nodes in patients with AIM vary greatly, ranging from follicular and paracortical hyperplasia to marked paracortical expansion, and occasionally to a worrisome proliferation of large immunoblasts with Reed–Sternberg-like (RS-like) cells. This range of changes may be observed even in the same biopsy (often tonsil) and may be helpful in reaching a diagnosis. In most cases, areas of necrosis are present and mitoses may be easily seen. Foci of
Chronic active EBV (CAEBV)
CAEBV was originally described by Dr. Stephen Straus13 as a disease related to chronic or persistent EBV infection. It was described as a severe illness lasting over 6 months subsequent to acute EBV infection, with persistent elevated titers of EBV and evidence of organ damage in patients without evidence of an underlying immunodeficiency. Based on the Western experience, it was initially viewed as a progressive EBV infection targeting B cells; however, over the years, the term CAEBV has been
Age-related EBV lymphoid proliferations
EBV reactivation also plays a central role in the development of lymphoid proliferative processes in the context of primary and iatrogenic immunodeficiencies. With aging, a reduced ability to handle infectious diseases also occurs and it is considered as part of the physiological aging process. However, the phenomenon of immunosenescence is multifactorial, involving both innate and adaptive arms of the immune system, and is still poorly understood. Numerous factors and complex mechanisms are
HHV6
Human herpes virus 6 (HHV6) is a beta herpes virus, nearly ubiquitous with a broad distribution worldwide with a seroprevalence approaching 100%. Two variants are recognized HHV6A and B, which are closely related. No disease is associated with type A, while type B is associated with exanthem roseola infantum (exanthem subitum) of infancy. Both are also opportunistic pathogens in immunocompromised hosts. The majority of infections in healthy infants are caused by HHV6B, which preferentially
Summary
The histological spectrum of viral-associated (EBV, HHV6) lymphoid proliferations is quite broad, ranging from reactive lymphadenitis to extremely atypical proliferations mimicking malignant lymphoma. However, by being aware of the histological, serologic, and molecular results that may occur in these viral-associated lymphoid proliferations and correlating this information with the specific clinical history, including family history and ethnic background, clinical presentation, symptoms, and
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Hematolymphoid disorders
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2021, Gattuso’s Differential Diagnosis in Surgical PathologyT-cell lymphoproliferative processes in the spleen
2020, Seminars in Diagnostic PathologyCitation Excerpt :After an acute EBV infection, patients can sometimes have persistent EBV infection without known underlying immunodeficiency. CAEBV is defined as a severe IM like illness of greater than 3 months duration with increased EBV DNA (102.5 copies/mg) in peripheral blood, histologic evidence of organ involvement including fever, lymphadenopathy, and hepatosplenomegaly, and EBV RNA or viral protein detected affected tissues without known immunodeficiency, malignancy or autoimmune disease.93,98 –100 Initially, chronic active Epstein-Barr virus infection was thought to be an infection of B cells, but it is now recognized that they can infect T-cells, NK cells and epithelial cells.95
EBV–Associated Lymphoproliferative Disorders: Update in Classification
2019, Surgical Pathology ClinicsCitation Excerpt :Some patients respond temporarily to immunomodulating agents, immunosuppressive therapy, or cytotoxic chemotherapy, but these treatments are not curative, and most patients succumb to their disease.19 For CAEBV of T/NK-cell type, EBV is uniformly expressed in many cytotoxic T cells in most cases.18 For CAEBV of B-cell type, the EBV expression pattern is similar to infectious mononucleosis, in which many small and large EBV-positive cells are identified with many EBV-negative cells present.
Epstein-Barr virus (EBV)–associated lymphoid proliferations, a 2018 update
2018, Human PathologyCitation Excerpt :Hemophagocytosis is commonly seen and the expanded activated histiocytes may alter the histologic picture in some cases. By in situ hybridization, EBV is uniformly expressed in many cytotoxic T cells in the majority of cases [24]. For CAEBV of B-cell type, it morphologically shows a PTLD-like picture but with an increased number of proliferating immunoblasts accompanied by increased plasma cells, occasional Reed-Sternberg-like cells, and paracortical hyperplasia.
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Supported in part by the Intramural Research Program, National Cancer Institute, NIH.