Question
[Fig. 1] is a composite of microscopic images of a resected tonsil of a child who presented
with tonsillar hypertrophy. The child had a past medical history significant for a
heart transplant 1 year prior to this presentation. What is your diagnosis?
Fig. 1 (A,B) Representative microscopic images from tonsil (hematoxylin and eosin [H&E] stained)
showing preserved follicular architecture of tonsil. (C) Immunohistochemical staining for CD20 highlighting the lymphoid follicles. (D) In situ hybridization staining for Epstein–Barr virus (EBV) encoded RNA (EBER) is
shown.
The Diagnosis
The diagnosis is nondestructive posttransplant lymphoproliferative disorder (PTLD).
Discussion
In this tonsil, the basic architecture of the tonsil appears intact but an expansion
of the interfollicular T zone is noted. This change―especially in a transplant recipient―should
trigger a workup to rule out viral infection. Epstein–Barr virus (EBV) infection,
whether reactivation of a dormant infection or newly acquired, is a major driver behind
lymphoproliferative disorders that have the potential of evolving to full-blown lymphoma
if not managed properly, especially in an immunosuppressed host.
PTLD is a rare but serious complication that occurs after transplant of a solid organ,
such as kidney, heart, or liver, or after a hematopoietic stem cell transplant.[1]
[2] It is more common in children and in those who receive a more intense immunosuppressive
regimen.[3]
PTLD occurs due to uncontrolled replication of the EBV in B cells.[1] The immune defenses that halt EBV replication under physiologic conditions are iatrogenically
suppressed in posttransplant patients with the aim of preventing donor organ rejection.
The majority of PTLD cases (>85%) are observed in the first year after transplantation.[1] PTLD can occur in several organs, including the lymph nodes, liver, spleen, and
gastrointestinal tract. The mucosa-associated lymphatic tissue in the nasopharynx
and oropharynx is the primary site where the EBV enters and infects B cells.[4] Roughly 30% of all PTLD patients experience posttransplant tumor masses in the sinonasal,
nasopharyngeal, or oropharyngeal regions, with the tonsils being the most affected
area.[4]
Symptoms of PTLD can vary depending on the location and extent of the disease. In
its initial stages, PTLD can present as EBV-related lymphoid hyperplasia or as fulminant
monomorphic PTLD, which can be observed in the tonsils and adenoids.[5] In pediatric patients, PTLD affecting the tonsils and/or adenoids can pose an acute
life-threatening risk due to upper airway obstruction or progress to systemic involvement,
resulting in irreversible monomorphic PTLD or high-grade lymphoma.[6]
Treatment for PTLD typically involves reducing immunosuppressive therapy to enable
the immune system to combat cancer. In certain situations, chemotherapy or radiation
therapy may also be required. In refractory cases, removing the transplanted organ
may be necessary.[1]
[7]
Early detection of PTLD involves monitoring transplant recipients for signs of the
disease, testing for EBV infection, and adjusting immunosuppressive therapy as necessary.
Additionally, antiviral medications may be used to prevent EBV infection.[1]
[7]
PTLD is a prototypic disorder that illustrates the intricate relationships between
infections and cancers, and the importance of the immune status in determining the
clinical pathologic course and outcome ([Fig. 2] is a visual reminder of these complex relationships).
Fig. 2 Representation of the intricate relationships between infection, immunity, and cancer
that an Epstein–Barr virus (EBV) infection may uncover.
Add [Figure 2] here
In summary, PTLD is a serious but rare complication of organ transplantation. Close
monitoring, early detection, and appropriate treatment can improve outcomes for transplant
recipients with PTLD.
