Infectious mononucleosis mimicking lymphoma: distinguishing morphological and immunophenotypic features

Abstract

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. Furthermore, the immunophenotype of the immunoblasts has not been well characterized. To assess the morphological spectrum of acute EBV infection and the utility of immunohistochemistry in diagnosing difficult cases that resemble lymphoma, we reviewed 18 cases of acute EBV infection submitted in consultation to our institution with an initial diagnosis of/or suspicion for lymphoma. Patients included nine male and nine female individuals with a median age of 18 years (range 9-69). Biopsies were obtained from lymph nodes (3/18) or Waldeyer's ring (15/18). Infectious mononucleosis was confirmed by monospot or serological assays in 72% of cases (13/18). All cases featured architectural distortion by a polymorphous infiltrate with an immunoblastic proliferation, sometimes forming sheets. Reed-Sternberg-like cells were present in 8/18 (44%) of the cases. Infiltrates were often accompanied by necrosis (10/18) and mucosal ulceration (6/15). The majority of immunoblasts in all cases were CD20 þ B cells with a post-germinal center immunophenotype (strongly positive for MUM1/IRF4 (18/18), CD10À (18/18 negative) and BCL-6À (16/18 negative; 2/18 faint BCL-6 expression in o10% of immunoblasts)). Immunoblasts showed variable weak expression of BCL-2 and polyclonal expression of j and k immunoglobulin light chains in 81% cases. ReedSternberg-like cells in 8/8 cases were CD30 þ , CD15À, BOB.1 þ and OCT-2 þ . In conclusion, an atypical lymphoid infiltrate with numerous MUM1 þ , CD10À, BCL-6À immunoblasts should raise the suspicion of a reactive process, such as infectious mononucleosis, and warrants additional consideration before a diagnosis of lymphoma is made.

T cell-rich lymphoid infiltrates with large B cells: a review of key entities and diagnostic approach

“…In lymph nodes and tonsils, there is follicular and paracortical hyperplasia, with a prominent immunoblastic reaction, usually of activated B-immunoblasts, which frequently express CD30 in varying degrees (figure 1B, inset), intermingled with plasma cells and predominantly cytotoxic T cells 5 6 8 9. Immunoblasts may occur in sheets and show high proliferative activity and necrosis, sometimes resulting in a resemblance to diffuse large B cell lymphoma (DLBCL) 5 9.…”

“…In lymph nodes and tonsils, there is follicular and paracortical hyperplasia, with a prominent immunoblastic reaction, usually of activated B-immunoblasts, which frequently express CD30 in varying degrees (figure 1B, inset), intermingled with plasma cells and predominantly cytotoxic T cells 5 6 8 9. Immunoblasts may occur in sheets and show high proliferative activity and necrosis, sometimes resulting in a resemblance to diffuse large B cell lymphoma (DLBCL) 5 9. Another potential diagnostic pitfall is that the CD30-positive immunoblasts can sometimes resemble Hodgkin/Reed-Sternberg (HRS-like) cells (figure 1B), and coupled with a loss of CD45/leucocyte common antigen (LCA) and B cell markers and transcription factor expression that sometimes occurs in these cells,5 8 10 11 this can result in misdiagnosis of CHL 5 6 9…”

“…Immunoblasts may occur in sheets and show high proliferative activity and necrosis, sometimes resulting in a resemblance to diffuse large B cell lymphoma (DLBCL) 5 9. Another potential diagnostic pitfall is that the CD30-positive immunoblasts can sometimes resemble Hodgkin/Reed-Sternberg (HRS-like) cells (figure 1B), and coupled with a loss of CD45/leucocyte common antigen (LCA) and B cell markers and transcription factor expression that sometimes occurs in these cells,5 8 10 11 this can result in misdiagnosis of CHL 5 6 9…”

LMP1 mediates multinuclearity through downregulation of shelterin proteins and formation of telomeric aggregates

“…17 Our recent observations document that very short telomeres are a hallmark of LMP1-expressing RS cells, even in young patients. 18 Short-term cultures of ex vivo EBV-infected normal human B lymphocytes show partial displacement of the telomeric protein TRF2, which is associated with a high level of nonclonal structural aberrations, namely Robertsonian translocations, unbalanced translocations, and chromatid gaps.…”

Atypical lymphoid proliferations: the pathologist’s viewpoint

“…For these challenging cases, the separation of AtLP from lymphomas depends on morphologic and molecular analysis [23][24][25]. of AtLP are not as large as mononuclear Reed-Sternberg cells, their nucleoli tend to be basophilic rather than eosinophilic and their cytoplasm is basophilic/amphophilic rather than eosinophilic [37]. Reed-Sternberg cells have a tendency for clustering versus even distribution of the reactive immunoblasts in AtLP.…”