A 13-year-old boy is admitted to the hospital due to fever and fatigue for the past week. The patient recently received a cadaveric renal transplant for glomerulonephritis, and his immunosuppressive medication regimen was increased a month ago due to early evidence of rejection. Temperature is 37.7 C (99.9 F). Heart and lung examinations are unremarkable. The liver is mildly enlarged, and the spleen tip is palpable. There is notable adenopathy of the bilateral inguinal and axillary regions. A complete blood count shows mild leukopenia. Histopathology findings from biopsy of one of the enlarged lymph nodes are shown in the image below. Which of the following is the most likely cause of this patient's presentation?

Question

A 13-year-old boy is admitted to the hospital due to fever and fatigue for the past week.  The patient recently received a cadaveric renal transplant for glomerulonephritis, and his immunosuppressive medication regimen was increased a month ago due to early evidence of rejection.  Temperature is 37.7 C (99.9 F).  Heart and lung examinations are unremarkable.  The liver is mildly enlarged, and the spleen tip is palpable.  There is notable adenopathy of the bilateral inguinal and axillary regions.  A complete blood count shows mild leukopenia.  Histopathology findings from biopsy of one of the enlarged lymph nodes are shown in the image below.  Which of the following is the most likely cause of this patient's presentation?

Quizplus · Accepted Answer

11ec160b_3b17_80fd_9249_47e140b5c0e5_MD0001_00 This patient underwent solid organ transplantation and is on high-dose immunosuppressive medications due to acute graft rejection. He subsequently developed mononucleosis-like symptoms (eg, fever, night sweats, lymphadenopathy, hepatosplenomegaly, leukopenia) with biopsy showing large, atypical B cells completely effacing the lymph node architecture. This constellation of findings likely indicates posttransplantation lymphoproliferative disorder (PTLD). PTLD is a plasmocytic or lymphoid proliferation that occurs in the weeks or months following solid-organ or hematopoietic stem cell transplantation. It is generally caused by proliferation of Epstein-Barr virus (EBV) in donor or host cells due to reduced cytotoxic T-cell immunosurveillance from high dose immunosuppressive therapy. EBV replication promotes B-cell proliferation due to the expression of viral membrane proteins (latent membrane protein 1/2A) that mimic B-cell antigen stimulation signals; it also promotes B-cell survival due to the expression of viral nuclear transcription factors (EBNA-2/LP) that activate host survival genes. These virus-mediated changes generate immortalized plasmocytic or lymphoid cells that proliferate widely in the reticuloendothelial system, leading to lymphadenopathy, hepatosplenomegaly, and B-symptoms (eg, fever, night sweats). (Choice A) Invasive aspergillosis is common in those with profound neutropenia following transplantation. However, it primarily affects the lung (not lymph nodes) and is marked by fungi with septate hyaline hyphae and acute angle branching. Tissue necrosis, hemorrhage, and invasion of tissue planes are prominent. (Choice B) Bartonella henselae infection causes cat-scratch disease, which is associated with regional lymphadenopathy. Histopathology demonstrates necrotizing granulomatous adenitis with multinucleated giant cells, stellate granulomas, and microabscesses. Specialized stains can reveal the bacterium. (Choice C) Patients with severe immunocompromisation from AIDS or immunosuppressive medications can develop Cryptococcus neoformans infection, which usually presents with meningoencephalitis (eg, headache, vomiting, confusion) or pneumonitis. Disseminated infection is less common and primarily affects the skin and skeletal system. In addition, histopathology will show budding, encapsulated yeasts. (Choice E) Chronic or reactivated parvovirus infection can occur in severely immunosuppressed individuals. Although this frequently causes fever, fatigue, and (sometimes) leukopenia, most cases are marked by severe anemia due to red cell aplasia. In addition, generalized lymphadenopathy would be atypical. Educational objective: Posttransplantation lymphoproliferative disorder occurs in patients who have undergone solid-organ or stem cell transplantation and are taking high-dose immunosuppressive medications. Most cases are caused by the reactivation of Epstein-Barr virus, which generates viral proteins that stimulate B-cell proliferation and survival. Patients usually have mononucleosis-like symptoms.

A 13-Year-Old Boy Is Admitted to the Hospital Due to Fever