A 15-year-old girl is evaluated due to persistent fever, fatigue, and sore throat. Physical examination reveals splenomegaly and symmetric posterior cervical lymphadenopathy. Peripheral blood smear results are shown in the image below: The atypical cells seen here are most likely an activated form of which of the following?

Question

A 15-year-old girl is evaluated due to persistent fever, fatigue, and sore throat.  Physical examination reveals splenomegaly and symmetric posterior cervical lymphadenopathy.  Peripheral blood smear results are shown in the image below:  The atypical cells seen here are most likely an activated form of which of the following?

Quizplus · Accepted Answer

11ec160b_3982_affc_9249_312b639d3a40_MD0001_00 This patient's fever, fatigue, sore throat, splenomegaly, symmetric posterior cervical lymphadenopathy, and atypical lymphocytosis are characteristic of infectious mononucleosis (IM). After entering the bloodstream through the pharyngeal mucosa and tonsillar crypts, the Epstein-Barr virus (EBV) preferentially infects B lymphocytes by binding to CD21 cell surface receptors. EBV-infected B lymphocytes then activate cytotoxic T lymphocytes (CD8⁺) through the presentation of viral antigens on major histocompatibility complex class I molecules. These reactive (atypical) CD8⁺ T lymphocytes are the primary immune response to EBV and clonally expand to destroy virus-infected cells. Atypical lymphocytes make up more than 10% of the cells in a peripheral blood smear in IM, and most (>95%) of those cells are CD8⁺ T lymphocytes. They classically appear much larger than quiescent lymphocytes, with abundant basophilic cytoplasm and a cell membrane that conforms to the borders of neighboring cells. Although activated CD21⁺ B lymphocytes and CD4⁺ helper T lymphocytes can have a similar appearance in response to EBV infection, they make up <5% of the atypical lymphocytes in the peripheral circulation (Choices A and D). (Choice C) Monocytosis can be seen with chronic infections and may be associated with persistent fever, fatigue, and splenomegaly; however, monocytes typically have vacuolated, grayish cytoplasm. (Choice E) Activated plasma cells appear as ovoid cells with abundant cytoplasm and an eccentric nucleus with a spoke-wheel chromatin pattern. A zone of perinuclear clearing within the cytoplasm may also be noted, corresponding to the active Golgi body. Educational objective: The primary immune response to Epstein-Barr virus is mediated by CD8⁺ T lymphocytes, which are activated through the presentation of viral antigens on infected CD21⁺ B lymphocytes. These reactive (atypical) CD8⁺ T lymphocytes can be observed in the peripheral blood smears of patients with infectious mononucleosis.

A 15-Year-Old Girl Is Evaluated Due to Persistent Fever, Fatigue