A 15-year-old transgender male patient with a history of asthma receiving no treatment was admitted with worsening fever and sinusitis not responding to outpatient antibiotic therapy. Functional endoscopic sinus surgery showed inflammatory sinus tissue. A biopsy demonstrated fibrinopurulent exudate with necrosis and atypical lymphoid infiltrate with scattered large atypical cells, some with prominent nucleoli, vesicular chromatin, and bi/multinucleation resembling Hodgkin/Reed-Sternberg cells (panel A; hematoxylin and eosin stain, original magnification ×40]). By immunohistochemistry, the infiltrate was composed of B cells expressing CD20 (panel B; CD20 stain, original magnification ×10]), PAX5 (panel C; PAX5 stain, original magnification ×40]), and CD30 (panel D; CD30stain, original magnification ×40]). Epstein-Barr virus (EBV)-encoded RNA–in situ hybridization (EBER-ISH) highlighted small lymphocytes as well as Hodgkin/Reed-Sternberg–like cells (panel E; EBER-ISH stain, original magnification ×20]). The background was composed of reactive T cells (CD4 << CD8; panel F, CD8 stain, original magnification ×10]). The lymphoid cells were negative for CD56, ALK1, AE1/AE3, synaptophysin, S100, and myogenin. Further laboratory testing showed positive heterophile antibodies. Overall, the findings were consistent with acute infectious mononucleosis.

CD30+ Reed-Stenberg–like cells are seen in acute EBV infection with increased CD8+ cells and an inversed CD4-to-CD8 ratio. These findings pose a challenge in diagnosing this entity and ruling out the possibility of a neoplastic process such as large B-cell lymphoma or Hodgkin lymphoma, which require different courses of treatment. Clinical history, serologic findings, and follow-up are important in patients with acute EBV infection.

A 15-year-old transgender male patient with a history of asthma receiving no treatment was admitted with worsening fever and sinusitis not responding to outpatient antibiotic therapy. Functional endoscopic sinus surgery showed inflammatory sinus tissue. A biopsy demonstrated fibrinopurulent exudate with necrosis and atypical lymphoid infiltrate with scattered large atypical cells, some with prominent nucleoli, vesicular chromatin, and bi/multinucleation resembling Hodgkin/Reed-Sternberg cells (panel A; hematoxylin and eosin stain, original magnification ×40]). By immunohistochemistry, the infiltrate was composed of B cells expressing CD20 (panel B; CD20 stain, original magnification ×10]), PAX5 (panel C; PAX5 stain, original magnification ×40]), and CD30 (panel D; CD30stain, original magnification ×40]). Epstein-Barr virus (EBV)-encoded RNA–in situ hybridization (EBER-ISH) highlighted small lymphocytes as well as Hodgkin/Reed-Sternberg–like cells (panel E; EBER-ISH stain, original magnification ×20]). The background was composed of reactive T cells (CD4 << CD8; panel F, CD8 stain, original magnification ×10]). The lymphoid cells were negative for CD56, ALK1, AE1/AE3, synaptophysin, S100, and myogenin. Further laboratory testing showed positive heterophile antibodies. Overall, the findings were consistent with acute infectious mononucleosis.

CD30+ Reed-Stenberg–like cells are seen in acute EBV infection with increased CD8+ cells and an inversed CD4-to-CD8 ratio. These findings pose a challenge in diagnosing this entity and ruling out the possibility of a neoplastic process such as large B-cell lymphoma or Hodgkin lymphoma, which require different courses of treatment. Clinical history, serologic findings, and follow-up are important in patients with acute EBV infection.

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