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ACG Case Rep J
ACG Case Rep J
ACGCRJ
AC9
ACG Case Reports Journal
2326-3253
Wolters Kluwer Maryland, MD

ACGCR-24-0537
10.14309/crj.0000000000001489
00014
3
Case Report
Liver
Epstein-Barr Virus-Negative Plasmablastic Lymphoma Post-liver Transplantation
https://orcid.org/0000-0001-9702-0726
Lin Jonathan K. MD 1jonathan.lin@utsouthwestern.edu

https://orcid.org/0000-0002-0837-5689
Grant Lafaine MD 1
1 Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX
Correspondence: Lafaine Grant, MD (lafaine.grant@utsouthwestern.edu).
9 2024
11 9 2024
11 9 e0148910 6 2024
29 7 2024
© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

ABSTRACT

Existing on the spectrum of post-transplant lymphoproliferative disorders (PTLD), plasmablastic lymphoma (PBL) is a highly aggressive form of B-cell non-Hodgkin lymphoma. Since its discovery in 1997, fewer than 5 cases of postliver transplantation–associated PBL have been recorded. Despite increased awareness of PTLD and improvement in imaging, PBL often presents with disseminated disease at the time of diagnosis. Treatment usually involves immunosuppression reduction and the use of chemo/immunotherapy, but the prognosis remains poor, with median survival being less than 12 months. We present to you a case of Epstein–Barr virus–negative PBL occurring more than 6 years postliver transplantation.

KEYWORDS:

post-transplant lymphoproliferative disorder
liver transplantation
plasmablastic lymphoma
Epstein–Barr virus
immunosuppression
OPEN-ACCESSTRUE
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pmcINTRODUCTION

First described in the 1990s in the oral cavity of HIV-infected individuals and then in the early 2000s within the context of post-transplant lymphoproliferative disorder (PTLD), plasmablastic lymphoma (PBL) is an extremely rare and aggressive subtype of B-cell non-Hodgkin lymphoma.1–3 Performing a search on PubMed and Google using the search terms “PBL” and “liver,” only 4 other case reports of PBL postliver transplantation are noted. Of these 4 cases, only 2 involve adults.3–6

Most cases of PTLD occur within 12 months post-transplant.7 However, as post-transplant survival rates increase in the setting of surgical and medical innovations, a second peak of PTLD has been noted to occur 5–15 years post-transplant with some cases occurring more than 20 years later.8

We present to you a case of an Epstein–Barr Virus (EBV)-negative PBL occurring more than 6 years after liver transplantation.

CASE REPORT

A 73-year-old White man with a history of ulcerative colitis (UC) and primary sclerosing cholangitis and liver transplantation in 2017 transferred to our hospital in September 2023 after computed tomography (CT) imaging revealed a possible sigmoid colon perforation.

The patient had a history of poorly controlled UC having failed multiple biologics including infliximab, adalimumab, and vedolizumab. At the time of presentation, the patient had been off all biologics for approximately 1 year and was only taking prednisone 20 mg daily.

The patient initially started experiencing abdominal pain in November 2022. A CT scan of the abdomen and pelvis at that time showed a new heterogenous, ill-defined mass measuring up to 9.0 cm along the gastric outlet and proximal duodenum (Figure 1). Subsequent magnetic resonance imaging done in December 2022 showed inflammatory stranding about the proximal duodenum, the presence of at least 1 polypoid lesion in the proximal duodenum and thickening of the right colon.

Figure 1. Computed tomography abdomen and pelvis without intravenous contracts shows a heterogenous ill-defined mass measuring up to 9 cm present along the gastric outlet and first and second portion of the duodenum. This abuts the liver, gallbladder, fossa, portions of the transverse colon, and the duodenum.

Based on these imaging findings, providers thought that the patient's UC remained suboptimally controlled and that he would benefit from close follow-up with his outpatient gastroenterologist for treatment, with considerations for a colonoscopy and repeat imaging in 3–6 months.

Repeat magnetic resonance imaging in May 2023 showed enhancing soft tissue nodules in the proximal duodenum abutting the gastric antrum. At this point, radiology raises concern for PTLD (Figure 2).

Figure 2. Magnetic resonance imaging abdomen with and without intravenous contrast show enhancing soft tissue nodules in the proximal duodenum abutting the gastric antrum, and along hepatic segment 4B.

An esophagogastroduodenoscopy and colonoscopy were performed in September 2023 for evaluation of the patient's imaging findings, and this revealed an ulcerated gastric mass at the antrum and a second mass in the duodenum (Figure 3). Biopsies of the masses confirm the presence of EBV-negative PBL. Colonoscopy was mainly notable for granularity throughout the colon with biopsies showing moderately active chronic colitis.

Figure 3. (A and B) Malignant tumor (plasmablastic lymphoma) noted in the gastric antrum on upper endoscopy.

Four days after endoscopy, the patient developed severe abdominal pain with associated vomiting and abdominal distension. Outside hospital CT imaging raised concern for sigmoid perforation, triggering the patient's transfer to our hospital.

The patient's bowel perforation was managed conservatively with broad-spectrum antibiotics and bowel rest. Per hepatology recommendation, the home dosing of tacrolimus was continued with a goal trough of 3–5 ng/mL. Both mycophenolic acid (360 mg twice a day) and prednisone were discontinued.

The patient was subsequently readmitted to our hospital in October 2023 to initiate cycle 1 of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. The patient's tacrolimus therapy was now discontinued. Unfortunately, his hospital course was complicated by pneumonia, atrial fibrillation, and multiple aspiration events leading to intubation, initiation of pressors, and the patient ultimately died.

DISCUSSION

PBL exists on the spectrum of lymphomas that can occur postsolid-organ transplantation. Lymphoma accounts for more than 20% of all cancers in individuals with solid organ transplants, and the incidence of PTLD is rising. This is most likely multifactorial in the setting of the increasing number of transplants offered, increased awareness of PTLD, and improved tools for detecting early malignancies.8 Despite advances in oncologic care, PBL continues to be associated with a grim prognosis.

The pathogenesis behind the development of PBL is poorly understood. PBL shows a predilection for men with up to 75% of cases being reported in males.1 On histology, PBL is characterized by the proliferation of sheets of immunoblasts or plasmablasts that are intermediate to large in size with eccentric nuclei, prominent central nucleoli, and abundant blue cytoplasm.3,9 Similar to most cases of PTLD where EBV is assumed to be the culprit virus for triggering uncontrolled proliferation of lymphocytes, PBL is noted to have EBV positivity in up to 75% of cases.1,10,11 Both our patient and the liver donor had a history of EBV and cytomegalovirus (CMV) IgG positivity, but immunohistochemical staining of his gastrointestinal masses was EBV and CMV negative. In addition, the patient's serum EBV and CMV polymerase chain reaction were negative at the time of his cancer diagnosis.

This raises the possibility of a hit-and-run hypothesis in which a latent EBV/CMV infection triggered lymphocyte proliferation before ultimately disappearing. Alternate hypotheses include the possibility of an unknown virus triggering the lymphoma. This could have also been an incidental lymphoma that arose from the patient's background of significant immunosuppression in the context of his UC and transplant history.8

As seen in this patient, PBL is characterized by a high incidence of extranodal involvement. The most commonly affected sites include the oral cavity, gastrointestinal tract, and skin. Lymph node involvement is rare but can be seen in post-transplant cases.9 Symptoms are often nonspecific and include weight loss, fever, and night sweats.1,2

Given its aggressive nature, most patients with PBL present with disseminated disease at the time of diagnosis, with 50% of post-transplant patients presenting with Ann Arbor Stage III-IV disease at the time of diagnosis. Given the rarity of the disease, optimal treatment for PBL remains unknown, with the cornerstone of therapy involving a reduction in immunosuppression and varying chemo/immunotherapy agents involving EPOCH.1,2

With the current landscape of available treatments, prognosis remains poor in these patients, with average survival ranging from 3 to 12 months.2,12 Given the aggressive nature of PBL and its overall unfavorable prognosis, providers should collaborate with palliative care early on to guide patients and families through goals of care and transitions of care discussions.

DISCLOSURES

Author contributions: JK Lin: wrote and edited the manuscript; L. Grant: hepatology mentor, reviewer, and is the article guarantor.

Financial disclosure: None to report.

Informed consent to publish the information and imaging related to the patient's case was obtained verbally by telephone from the patient's wife on April 23, 2024.
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