infectious mononucleosis

Digital cases

 HPC:193 : EBV-associated infectious mononucleosis
 HPC:308 : EBV-associated infectious mononucleosis (Bilateral tonsillar hypertrophy)
 HPC:333 : EBV-associated infectious mononucleosis (Lymph node)

Primary infection by EBV usually occurs in children, and in many areas of the world greater than 90% of individuals are infected by age 5.

Acute EBV infection is usually asymptomatic or self-limited in children. In developed countries, primary acute infection can occur later in life and may cause symptoms of infectious mononucleosis. Waldeyer ring and cervical lymph nodes are often involved by EBV in acute primary EBV infection. A positive monospot (Paul-Bunnell heterophile antibody test) or specific serological tests are important in evaluating the presence of infection, and in determining whether it is recent or remote.

There is a primary immune response involving T cells to the EBV infected B cells. The biggest pitfall in examining tissue of a patient with acute EBV infection is mistaking the process for lymphoma.

Infectious mononucleosis shows a spectrum of morphologic changes including extensive proliferation of immunoblasts some with marked atypia resembling Reed-Sternberg (RS) cells. These RS-like cells tend to cluster around necrosis which may also be prominent. Monocytoid B cells may also be observed.

The histological findings in the tonsils are similar to those of the lymph node. Changes occur most often in palatine tonsils but lingual tonsils can also be enlarged. At least partial preservation of the architecture is usually present and there is usually a polymorphous background of lymphocytes.

Early on in the process CD8+ lymphocytes outnumber CD4+ T cells causing an inverse CD4:CD8 ratio. CD30 is often positive in the immunoblasts without CD15 staining. The immunoblasts are also reactive for B cell markers including CD20, Pax5 and CD79a.

In situ hybridization for EBER consistently reveals numerous positive immunoblastic cells in the interfollicular areas. EBV staining with in situ hybridization for EBER is helpful and usually shows a diffuse positivity.

Latent membrane protein (LMP-1) may be positive in a smaller number of cells. For this reason in situ staining for EBER may be more helpful than LMP-1 staining. Molecular studies are sometimes performed and show a polyclonal pattern for IGH gene rearrangement, and may show a restricted or oligoclonal pattern in the TCR gene rearrangements.

The host response in acute EBV infection is important to controlling the infection. In a normal asymptomatic rapid response to acute EBV infection, T cells recognize a wide variety of EBV epitopes and the T cell repertoire is expanded. But in individuals who exhibit symptoms of infectious mononucleosis the T cell repertoire is limited.

Persistence of latent EBV genes in B cells results in a carrier state and in the correct environment transformation to B cell lymphoma.

Synopsis

 centroblasts and immunoblasts
 Reed-Sternberg (RS)-like cells
 geographic necrosis containing cytologically atypically B-cells (15157051)
 angiocentric lymphoproliferative lesion (AIL)
 retention of the architecture and residual reactive germinal centers
 diffuse interfollicular hyperplasia of immunoblastic cells
 Immunoblastic hyperplasia
 Immunoblasts with vesicular chromatin and distinct nucleoli showing atypia.
 LMP1 positivity in the immunoblastic cells.
 EBER positivity in the EBV infected B cells.
 Focal residual germinal center formation and diffuse proliferation of cells in the interfollicular areas.
 Large cells resembling Reed-Sternberg cells and immunoblasts are present.

Immunochemistry

Reed-Sternberg-like cells are CD30+, CD15-, BOB.1+ and OCT-2+.

Differential diagnosis

 B-cell lymphoma
 lymphomatoid granulomatosis of the lymph node
 EBV+ B-cell lymphoproliferative disorders associated with immunodeficiency

The diagnosis of infectious mononucleosis (acute Epstein-Barr virus (EBV) infection) is usually made on the basis of clinical and laboratory findings. However, an atypical clinical presentation occasionally results in a lymph node or tonsillar biopsy. The morphological features of EBV-infected lymphoid tissue can easily mimic lymphoma.

An atypical lymphoid infiltrate with numerous MUM1+, CD10-, BCL-6- immunoblasts should raise the suspicion of a reactive process, such as infectious mononucleosis, and warrants additional consideration before a diagnosis of lymphoma is made.

Association

 sarcoidosis
 arthritis

See also

 IMN-like PTLD (infectious mononucleosis-like PTLD)

References

 http://www.semdiagpath.com/article/S0740-2570(14)00108-7/fulltext

 Infectious mononucleosis mimicking lymphoma: distinguishing morphological and immunophenotypic features. Louissaint A Jr, Ferry JA, Soupir CP, Hasserjian RP, Harris NL, Zukerberg LR. Mod Pathol. 2012 May 25. PMID: 22627742