Andrea Maria Schmidt-Westhausen, in
Maxillofacial Surgery (Third Edition), 2017 Infectious mononucleosis is also known as
Pfeiffer disease, glandular fever, kissing or students' disease, and usually occurs in early adulthood following oral transmission. Putrid inflammation of the tonsils with foetor and lymph node swelling is one of the prominent features.43 The Epstein-Barr virus (EBV) is also associated with lymphomas and nasopharyngeal carcinomas. Especially in patients with immunosuppression and human immunodeficiency virus (HIV), EBV can be associated with oral
hairy leukoplakia. Because infectious mononucleosis is a self-limiting condition, symptomatic treatment is recommended. Given the adverse reactions and lack of evidence, supportive corticosteroid administration to relieve pharyngeal and laryngeal symptoms is controversial.44 Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780702060564001039 Lymph NodesKAREN L. CHANG, ... LAWRENCE M. WEISS, in Modern Surgical Pathology (Second Edition), 2009 INFECTIOUS MONONUCLEOSISInfectious mononucleosis is the prototypic reactive paracortical hyperplasia. Clinical and serologic findings as well as the presence of atypical lymphocytes in the peripheral blood usually lead to the diagnosis. Thus, the surgical pathologist is confronted with a tissue specimen of infectious mononucleosis only in rare patients whose disease is clinically aberrant or whose adenopathy is persistent. Because of the rareness of infectious mononucleosis cases among surgical pathologists, the disease in its late stages may easily be confused with malignant neoplasms. Immunohistochemical study of EBV latent membrane protein and EBV in situ hybridization studies generally have positive results and are therefore not useful in distinguishing between infectious mononucleosis and Hodgkin's lymphoma, except as noted before.132 Anaplastic large cell lymphoma is also in the differential diagnosis of infectious mononucleosis. Both lesions have large immunoblasts that show immunohistochemical staining for CD30 and CD43. However, in contrast to the reactive lesion, the malignant cells of anaplastic large cell lymphoma test positive for anaplastic lymphoma kinase (ALK) protein and CD3 (majority of cases) and are present predominantly as large clusters in the sinuses or as a diffuse proliferation. The malignant cells do not usually stain for CD20, whereas test results for CD20 are positive in the large immunoblasts of infectious mononucleosis. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9781416039662000412 Epstein-Barr VirusJennifer M. Geris, ... Henry H. BalfourJr, in Encyclopedia of Infection and Immunity, 2022 Incidence of primary EBV infection and infectious mononucleosisInfectious mononucleosis most commonly affects those who have primary EBV infection during adolescence or adulthood. The overall incidence of infectious mononucleosis in the U.S. is about 500 cases per 100,000 persons per year, with the highest incidence among persons aged 15–24 years (reviewed in Luzuriaga and Sullivan, 2010). Interestingly, our prospective studies of students attending the University of Minnesota have shown the incidence of primary EBV infection during the four undergraduate years was 14.4 cases per 100 person-years. Among those with primary infection, nearly 78% (62/80) developed infectious mononucleosis (Balfour et al., 2013b; Grimm et al., 2016). Our findings are consistent to those reported by Crawford et al., who found a rate of 15.2 cases per 100 person-years of primary EBV infection among undergraduates at Edinburgh University, Scotland. However, only 24.5% (27/110) developed infectious mononucleosis (Crawford et al., 2006). Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780128187319000744 Epstein–Barr Virus, Infection and ImmunityMartin Rowe, in Encyclopedia of Immunology (Second Edition), 1998 Infectious mononucleosisInfectious mononucleosis (IM) occurs mainly in affluent Western societies where primary infection with EBV generally occurs at a later age. IM is a self-limiting lymphoproliferative disease that is characterized clinically by fever, sore throat, lymphadenopathy, hepatosplenomegaly and abnormal liver functions. Many of the manifestations in IM are probably a consequence of ineffective cellular immune responses to EBV-induced proliferation of B cells or due to inadvertent tissue damage by autoimmune processes. The majority of atypical lymphocytes in the blood of these patients are T cells, and elevated numbers of suppressor T cells, CTLs and natural killer (NK) cells are present. The cytotoxic response shows a broad specificity that is largely non-HLA-restricted, although a minor population of EBV-specific HLA-restricted CTLs is detectable and this subsequently dominates the cellular immune response as the disease resolves itself. The serological picture in IM patients is distinct from that seen in asymptomatic primary infection in children. In addition to IgM antibodies to VCA, IM patients also show a transient (2–3 weeks) IgM heterophile antibody response of the Paul–Bunnell type. Furthermore, the IgG antibodies to EA are usually directed to the diffuse (EA-D) components rather than to the EA-R as in silent primary infection. The presence of IgG antibodies to EA-D may correlate with lymph node involvement, which is consistent with the elevated incidence of these antibodies in nasopharyngeal carcinoma, where invasion of draining lymph nodes commonly occurs, and their initial absence in Burkitt's lymphoma, when lymph nodes are not usually involved (see below). Unlike silent primary infection, where IgG antibodies to EA and VCA are transient, these antibodies may remain elevated in IM patients for up to 2 years after the clinical symptoms resolve themselves, which is indicative of increased levels of virus production. The antibody response to the gp340/220 MA components is delayed, which is consistent with the relatively low virus-neutralizing titers observed in IM sera. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B0122267656002309 Epstein-Barr Virus (Mononucleosis and Lymphoproliferative Disorders)Ben Z. Katz, in Principles and Practice of Pediatric Infectious Diseases (Fifth Edition), 2018 Laboratory Findings and DiagnosisIM usually is diagnosed on the basis of typical clinical features, hematologic abnormalities, and a positive heterophil antibody agglutination test. Antibodies to specific EBV antigens can be used to confirm the diagnosis. Younger children often experience primary EBV infection in the absence of characteristic symptoms, hematologic abnormalities, and heterophil antibody response; a specific antibody response to EBV antigens is present, however.89,90 Histology of lymph nodes can resemble that of a lymphoma.91 During the first week of illness, leukopenia or leukocytosis can be so prominent that leukemia is suspected. Absolute increase in the number of atypical lymphocytes is characteristic during the second week of illness. Atypical lymphocytes (Downey cells) are a hallmark of IM. Cells vary markedly in size and shape, and after Wright staining, the cytoplasm is dark blue and vacuolated, with a foamy appearance. Nuclei are round, bean-shaped, or lobulated and contain no nucleoli. Presence of >10% atypical lymphocytes is characteristic, although not specific, for IM. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780323401814002085 HerpesvirusesI. Johannessen, M.M. Ogilvie, in Medical Microbiology (Eighteenth Edition), 2012 Infectious mononucleosis/glandular feverInfectious mononucleosis (IM; or glandular fever, GF) is seen predominantly in the 15–25 years age group when primary EBV infection is delayed into adulthood. The incubation period is 30–50 days, and the onset is abrupt with a triad of sore throat, cervical lymphadenopathy and fever, often accompanied by malaise, headache, sweating (particularly at night) and gastrointestinal discomfort. A mononucleosis of atypical lymphocytes is observed in blood. Pharyngitis may be severe, accompanied by a greyish-white membrane and gross tonsillar enlargement. Lymphadenopathy becomes generalized, often with splenic enlargement and tenderness, mild hepatomegaly (and biochemical hepatitis) in some individuals and clinical jaundice in 5–10% of cases. Intermittent fevers with drenching sweats may occur daily over 2 weeks. A faint transient morbilliform rash may be seen; a maculopapular rash may follow ampicillin administration, due to immune complexes with antibody to ampicillin. The illness can last for several weeks, and prolonged and debilitating fatigue and lack of concentration are common in the aftermath. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780702040894000585 Otolaryngologic DisordersLisa M. Elden, ... William P. Potsic, in Pediatric Surgery (Seventh Edition), 2012 Recurrent pharyngotonsillitisRecurrent infection of the pharynx may be either viral or bacterial. GABHS are the most worrisome bacterial organisms, because recurrent infection may lead to complications such as scarlet fever, acute rheumatic fever, septic arthritis, and acute glomerulonephritis. In addition to a history of multiple positive cultures for S. pyogenes, elevated antistreptolysin-O (ASO) titers may identify patients with chronic infection who are at risk for developing complications. Some asymptomatic children may be chronic carriers of GABHS, and elevated ASO titers may not be a reliable indicator for distinguishing between an active infection and the carrier state. Treatment of recurrent streptococcal infection or the child who is a carrier should include a trial course of an antibiotic shown to reduce carriage (e.g., clindamycin, vancomycin, or rifampin). Children with recurrent pharyngotonsillitis unresponsive to medical therapy or those who suffer a complication should be considered for surgical management. Whereas treatment of each child should be individualized, suggested guidelines for surgical candidates include seven infections in 1 year, five or more infections per year for 2 years, or three or more infections per year for 3 years.20 Other factors to be considered in using a surgical option include severity of infection, response to antibiotic therapy, loss of time from school, and need for hospitalization. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780323072557000556 Lymph NodesPaul E. WakelyJr., Edmund S. Cibas, in Cytology (Third Edition), 2009 Infectious MononucleosisInfectious mononucleosis is caused by the EBV and spread through person-to-person contact, most commonly in adolescents and young adults. The clinical presentation may include fever, malaise, pharyngitis, rash, and peripheral lymphadenopathy, typically cervical, but axillary and inguinal lymphadenopathy also occur. Lymph nodes are often tender and movable. Splenomegaly is common, and splenic rupture is a potential complication. Laboratory findings include peripheral blood atypical lymphocytosis, and a positive heterophil (Monospot) test. CYTOMORPHOLOGY OF INFECTIOUS MONONUCLEOSIS: •increased percentage of immunoblasts, plasmacytoid lymphocytes, and plasma cells •few dendritic-lymphocytic aggregates and tingible-body macrophages Aspirates contain predominantly small lymphocytes, accompanied by an increased number of immunoblasts, centroblasts, plasmacytoid lymphocytes, and occasionally plasma cells73,74 (Fig. 11.11). Binucleated immunoblasts simulating RS cells may be found but are rare. IP confirms the polyclonal nature of the B-cells, and often shows a reversed CD4/CD8 ratio. DIFFERENTIAL DIAGNOSIS OF INFECTIOUS MONONUCLEOSIS: •reactive lymphoid hyperplasia •other lymphadenopathy associated with increased immunoblasts •large cell lymphoma •Hodgkin lymphoma A high percentage of immunoblasts, centroblasts, and plasmacytoid lymphocytes are typical of infectious mononucleosis, but the amount depends on the stage of the disease. In the early stages of infectious mononucleosis, immunoblast proliferation is barely perceptible, and FNA is indistinguishable from reactive lymphoid hyperplasia.74 The immunoblast proliferation in other lymphadenopathies (e.g., anticonvulsant-associated lymphadenopathy, herpes simplex, cytomegalovirus, and postvaccinial lymphadenitis) and drug hypersensitivity is indistinguishable from that of infectious mononucleosis. A detailed clinical history, serologic studies, or excisional biopsy may be necessary to exclude these other entities. Most patients who develop anticonvulsant-related lymphadenopathy (principally to phenytoin) usually do so within 6 months of the onset of therapy. Herpetic lymphadenitis usually occurs in the setting of disseminated infection in a patient who is immunosuppressed, and diagnosis is usually made by association with the cutaneous lesions. In addition to increased immunoblasts, herpes simplex and cytomegalovirus lymphadenitis may contain cells with diagnostic viral inclusions. Because infectious mononucleosis induces a discernible increase in large cells and there is a scarcity of tingible-body macrophages and dendritic-lymphocytic aggregates, one of the “large cell” NHLs needs to be considered. Immunophenotypic studies are helpful in problematic cases to confirm the polyclonal nature of the immunoblasts in infectious mononucleosis. Immunoblasts are occasionally mistaken for mononuclear RS cell variants. Unlike RS cells, immunoblasts are smaller, have smaller nucleoli, greater cytoplasmic basophilia, and sometimes contain a perinuclear zone of clearing. Binucleated immunoblasts mimicking classic RS cells are extremely rare. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9781416053293000116 LymphadenopathyEthan Rubinstein, Yoav Keynan, in Infectious Diseases (Fourth Edition), 2017 Infectious MononucleosisInfectious mononucleosis is a disease of teenagers and young adults. It is classically characterized by fever, tonsillopharyngitis, lymphadenopathy, splenomegaly and atypical lymphocytes on peripheral blood smear. Epstein–Barr virus (EBV) is the cause in 80–90% of cases, followed by cytomegalovirus (CMV; 8–16%) and toxoplasmosis (1–2%).51 It is usually a benign and self-limiting process. Patients exhibit generalized lymphadenopathy and localized lymph node enlargement with or without systemic manifestations. Lymphadenopathy is observed in the vast majority of children and young adults with infectious mononucleosis but only in approximately 45% of patients older than 40 years.52 Lymph nodes are usually moderately enlarged and not very tender; they can be found at the posterior cervical, axillary, epitrochlear, submandibular, submental and groin regions. Lymph node histology demonstrates paracortical immunoblastic proliferation as seen in many viral infections.53 Serious complications of infectious mononucleosis include meningoencephalitis with seizures, myelitis, peripheral neuropathy, splenic rupture, upper airway obstruction, interstitial pneumonitis and severe hepatitis with liver failure. Death is rather rare. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9780702062858000150 Infectious LymphadenitisJudith A. Ferry, in Diagnostic Pathology of Infectious Disease, 2010 Infectious MononucleosisInfectious mononucleosis is defined as symptomatic primary infection by Epstein-Barr virus (EBV). Infectious mononucleosis was first described as a distinct entity in 1920, when six college students with pharyngitis, fever, and lymphadenopathy (a syndrome then referred to as glandular fever) were all found to have an absolute lymphocytosis in the peripheral blood, with mononuclear cells with unusually abundant cytoplasm. Subsequently, Paul and Bunnell found that the serum of patients with infectious mononucleosis caused sheep red blood cells to agglutinate due to the presence of what they called a heterophile antibody, and this provided a laboratory test for the diagnosis of infectious mononucleosis. The definition of infectious mononucleosis was further refined when a laboratory worker exposed to EBV, which had only recently been discovered and identified as being associated with endemic Burkitt's lymphoma,1 developed heterophile-positive infectious mononucleosis, establishing EBV as the causative agent.2 Currently, the diagnosis of infectious mononucleosis is usually established clinically, but if enlarged lymph nodes or tonsils are biopsied, problems in differential diagnosis may arise. Clinical FeaturesInfectious mononucleosis is a fairly common disease of adolescents and young adults. Cases of infectious mononucleosis in young children have been reported, although EBV infection in this age group is usually subclinical. Rare cases are also described in older adults. Males and females are affected equally. Infectious mononucleosis is more commonly encountered among individuals in higher socioeconomic groups, who are less likely to be exposed to EBV during early childhood. Transmission is through close contact with another individual who is EBV infected. The classic findings at presentation are fever, pharyngitis, and cervical lymphadenopathy accompanied by an atypical peripheral blood lymphocytosis and a positive heterophile antibody (Monospot) test. Lymphadenopathy is usually symmetric and tender.2 Splenomegaly is also common. A maculopapular or urticarial rash may develop, mainly among patients who are treated with a β-lactam antibiotic.2 Supportive therapy is usually sufficient, and spontaneous recovery is the rule in almost all cases, except for those with serious complications. In more severe cases, generalized lymphadenopathy, hepatomegaly with hepatic dysfunction, splenic rupture, peripheral cytopenias, and development of a hemophagocytic syndrome may occur. In most cases, the illness is self-limited, but rarely, intercurrent infection, Guillain-Barré syndrome, or splenic rupture with hemorrhage results in death. Problems in establishing a diagnosis on clinical and laboratory grounds sometimes arise because the heterophile antibody test may not be positive, especially early in the illness and among children; repeated Monospot testing is sometimes required. In some individuals, particularly those at the extremes of age, the heterophile antibody is never detected.2 In such cases, serologic studies for EBV-associated antigens help establish a diagnosis. Another scenario creating diagnostic difficulties is the patient who has clinical features diverging from the classic presenting symptoms, such as a presentation with diffuse lymphadenopathy without prominent pharyngitis. Patients with unusual clinical or laboratory features are more likely than those with classic infectious mononucleosis to undergo lymph node excision to establish a diagnosis. Pathologic FeaturesThe lymph nodal architecture is typically distorted but not effaced by an expanded paracortex containing a polymorphous population of lymphoid cells, including small lymphocytes, intermediate-sized lymphoid cells, immunoblasts, tingible body macrophages, and mature and immature plasma cells. The immunoblasts may be atypical, with pleomorphic or lobated nuclei. Binucleated cells resembling Reed-Sternberg cells may be identified. Mitotic figures may be numerous. Apoptosis is common, and zonal necrosis may be present. Primary follicles or reactive follicles are often present at the periphery of the lymph node, but follicular hyperplasia is not usually a prominent feature. Sinuses are patent in at least some areas, and frequently they are dilated. Sinuses contain histiocytes and a polymorphous population of lymphoid cells similar to that found in the paracortex, including immunoblasts. Lymphoid cells sometimes infiltrate the capsule and extend into perinodal fat. Similar histologic features are found in the tonsils of patients with infectious mononucleosis (Fig. 11-1). In tonsils, crypts are usually present, although the epithelium lining them may be necrotic.3-7 The small and intermediate-sized cells in the paracortex are predominantly T cells, including many that are activated in response to the presence of the virus. The CD4/CD8 ratio is decreased. The paracortical immunoblasts are CD20+ B cells. They typically coexpress MUM1/IRF4 but not bcl6 or CD10; some are bcl2+. Therefore, the EBV+ immunoblasts have a post–germinal center immunophenotype.8 With the use of immunostains or in situ hybridization for κ and λ immunoglobulin light chains, the plasma cells are demonstrated to be polytypic. Polytypic light chain expression can often be demonstrated in the immunoblasts as well.8 The blasts typically show focal staining for the activation antigen CD30; they are CD15−.3,4,9-11 With in situ hybridization, EBV-encoded RNA (EBER) can be detected in the paracortical immunoblasts.9 Rarely, patients with acute infectious mononucleosis or a recent history of infectious mononucleosis have florid follicular hyperplasia with large follicles, rather than the more common paracortical immunoblastic reaction. EBER+ cells may be found in follicles and in the interfollicular areas in such cases.12 Differential DiagnosisThe differential diagnosis of infectious mononucleosis is broad. A variety of infectious processes can be associated with an infectious mononucleosis–like illness, including cytomegalovirus (CMV), Human herpesvirus 6 (HHV-6), herpes simplex virus type 1 (HSV-1), human immunodeficiency virus (HIV), group A β-hemolytic Streptococcus pyogenes (strep throat), Toxoplasma gondii, and others.2 Careful clinical evaluation, augmented by laboratory studies, is required to establish a diagnosis. The differential diagnosis based on pathologic features includes a variety of reactive and neoplastic conditions. If immunoblasts are numerous, the possibility of diffuse large B-cell lymphoma is often a consideration. In favor of infectious mononucleosis are lack of architectural effacement, presence of areas readily recognizable as reactive hyperplasia, a polymorphous background of lymphoid cells, patent sinuses containing lymphoid cells including immunoblasts, and lack of monotypic immunoglobulin expression on immunophenotyping.4,7 The typical immunophenotype of the immunoblasts (CD10−, bcl6−, bcl2+/−, MUM1+) may also be helpful, because the majority of diffuse large B-cell lymphomas express bcl6. Diffuse large B-cell lymphomas are usually EBV− unless the patient is immunocompromised, so the presence of EBV should raise the possibility of infectious mononucleosis. Classic Hodgkin lymphoma is often included in the differential diagnosis, because Reed-Sternberg–like cells are often seen in infectious mononucleosis (see Fig. 11-1C); however, most large cells in infectious mononucleosis have the appearance of immunoblasts rather than Reed-Sternberg cells or variants. Hodgkin lymphoma is more often associated with obliteration of the lymph nodal architecture. The polymorphous background of lymphoid cells ranging from small to intermediate and large in the paracortex and sinuses in infectious mononucleosis is very helpful in excluding Hodgkin lymphoma, in which background lymphocytes are all typically small. Granulocytes, especially eosinophils, and a background of fibrosis are more common in Hodgkin lymphoma. Immunoblasts in infectious mononucleosis are CD20+, CD15−, in contrast to the CD20−, CD15+ status typically found with Reed-Sternberg cells. The CD4/CD8 ratio is usually normal or elevated in Hodgkin lymphoma, in contrast to the CD8 predominance typically seen in infectious mononucleosis. Reed-Sternberg cells in approximately 50% of cases of classic Hodgkin lymphoma are EBV+, so the presence of EBV does not exclude Hodgkin lymphoma. Obtaining adequate clinical information is important to make the correct diagnosis. If the patient is known to have clinical or laboratory evidence of infectious mononucleosis, a diagnosis of Hodgkin disease or non-Hodgkin lymphoma should be made with caution. Other viral infections, vaccination, certain drugs, and acute reaction to severe necrotizing processes can produce lymphadenopathy with histologic features similar to or indistinguishable from those of infectious mononucleosis. Clinical information can be helpful in investigating the cause of the lymphadenopathy. In addition, in infectious mononucleosis, EBV+ immunoblasts are typically present in large numbers, whereas in other conditions, EBV+ cells are usually absent.9,13-16 The Monospot test and serologic testing for EBV-specific antibodies can be helpful in establishing a diagnosis. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B9781416034292000110 What is the hallmark of infectious mononucleosis?Swollen tonsils that appear red and with white lesions that may be oozing pus are a hallmark of infectious mononucleosis. It is considered highly contagious and is usually caused by the Epstein-Barr Virus (EBV). Mono spreads through saliva and therefore is sometimes called “kissing disease.”
Which of the following is contained in the primary granules of the neutrophil quizlet?granules of the neutrophil? and tertiary granules include lactoferrin, collagenase, NADPH oxidase, and alkaline phosphatase.
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