Navigating Rare Presentations: Recurrent Burkitt Lymphoma Presenting as a Jejunal Mass

ABSTRACT

Burkitt lymphoma (BL) is an aggressive B‐cell malignancy characterized by rapid progression and MYC gene translocations. Jejunal involvement in BL is rare compared to more common sites like the lymph nodes and central nervous system. Diagnosing BL in the jejunum is particularly challenging as it can mimic other gastrointestinal conditions, necessitating a high index of suspicion and histopathological confirmation. We present the case of a 37‐year‐old male with a history of stage III non‐seminomatous testicular carcinoma, BL, deep venous thrombosis, pulmonary embolism, and hypogammaglobulinemia, who presented with abdominal pain and nausea. Imaging revealed peritoneal carcinomatosis and a left hemiabdomen mass concerning malignancy. Given his medical history of previously diagnosed BL in the gastrohepatic ligament lymph node and imaging findings, BL relapse was suspected. Push enteroscopy with biopsy confirmed the recurrence of BL in the jejunum, with positive markers for CD45, CD20, BCL6, and c‐Myc. Despite aggressive supportive care, the patient succumbed to his disease. This case highlights the importance of early recognition of BL, particularly in rare extra‐nodal sites like the jejunum. Further research is needed to improve early detection and treatment outcomes for patients with relapsed or refractory BL.

Abbreviations

BCL‐2

B‐cell lymphoma 2

BCL6

B‐cell lymphoma 6

BL

Burkitt lymphoma

CD20

Cluster of Differentiation 20

CD45

Cluster of Differentiation 45

CK AE 1/3

Cytokeratin AE1/AE3

c‐Myc

(Refers to the protein product of the MYC gene)

DVT

Deep vein thrombosis

ED

Emergency Department

H&E

Hematoxylin & eosin

hyper‐CVAD

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone

ICU

Intensive Care Unit

IR

Interventional Radiology

IVIG

Intravenous immunoglobulin

NCCN

National Comprehensive Cancer Network

PE

Pulmonary embolism

PET/CT

Positron Emission Tomography/Computed Tomography

WHO

World Health Organization

Summary.

• Burkitt Lymphoma can recur years after initial treatment and present with vague symptoms in anatomically distinct, extra‐nodal sites such as the jejunum.

• Our case highlights the need for regular and long‐term surveillance for prior aggressive lymphomas, as failure to promptly recognize atypical presentations often results in disease progression and unfavorable outcomes.

1. Introduction

Burkitt lymphoma (BL) is an aggressive B‐cell lymphoma characterized by its rapid growth and distinct cytogenetic abnormalities, particularly the MYC gene translocation [1]. There are three variants: endemic, sporadic, and immunodeficiency‐associated [2]. Jejunal involvement in BL is uncommon compared to other sites, such as lymph nodes or the central nervous system [3]. Diagnosing jejunal BL can be particularly challenging, as it may mimic other gastrointestinal conditions, and confirmation often requires histopathological analysis [4].

We report a rare instance of relapse of BL, with tumor recurrence in a different and rare location in the jejunum as compared to the initial presentation. It was diagnosed through a combination of push enteroscopy and biopsy, which was positive for markers suggestive of BL.

2. Case Description

2.1. Case History

We present the case of a 37‐year‐old male with a history significant for stage III non‐seminomatous testicular carcinoma in 2010, BL in 2015, deep venous thrombosis, pulmonary embolism, and hypogammaglobulinemia who presented to the emergency department in May 2024 with 5 days of abdominal pain during a recent trip to the Philippines.

The patient was diagnosed with stage III non‐seminomatous testicular carcinoma in 2010 and underwent right radical orchiectomy with subsequent chemotherapy with etoposide and cisplatin. The patient was thereafter diagnosed with BL in 2015 after a PET/CT revealed an enlarged gastrohepatic ligament lymph node, confirmed by surgical pathology. He underwent 6 cycles of hyper‐CVAD chemotherapy for BL from January to May 2016, with a partial response noted on follow‐up PET scan in March 2019. He also had a history of hypogammaglobulinemia, for which he received intravenous immunoglobulin (IVIG) infusions, though he had not received treatment in the past year.

When our team first saw the patient, he presented to the ED in May 2024, the same day after returning from the Philippines, complaining of abdominal pain and nausea for 5–6 days. The pain was 6/10 in intensity, localized to the lower abdomen, crampy in nature, and associated with nausea. He reported that his symptoms started while he was in the Philippines. The patient returned to the United States following a recommendation from a local physician to seek hospital admission.

2.2. Physical Examination and Investigations

Patient had mild tachypnea, though the patient was saturating well on room air. Initial laboratory results were concerning for metabolic acidosis with a high anion gap (lactate 15.4 mmol/L, bicarbonate 13 mEq/L) and acute kidney injury. Imaging studies, including abdominal CT, revealed diffuse omental caking and peritoneal carcinomatosis, incidental finding of segmental and subsegmental pulmonary emboli, bilateral cardiophrenic lymphadenopathy, and left hemiabdomen mass concerning for malignancy (Figure 1a,b). As the patient had pulmonary embolism (PE) and deep vein thrombosis (DVT) in the past, he was started on a heparin drip. The patient was not on anticoagulation for 6 months prior to this presentation due to insurance issues.

FIGURE 1.

(a) Non‐contrast CT abdomen revealed Multiple nodules suggestive of peritoneal carcinomatosis, (b) 6.7 cm jejunal mass in left hemiabdomen.

2.3. Differential Diagnosis

Given the patient's history and findings on imaging, there was concern for abdominal malignancy. Other differential diagnoses included peritoneal carcinomatosis from non‐seminomatous testicular carcinoma, infectious etiologies like abdominal tuberculosis due to a history of travel to an endemic area, opportunistic infections, or lymphoproliferative disorder given his immunocompromised state post chemotherapy.

2.4. Treatment and Interventions

IR‐guided biopsy of the peritoneal carcinomatosis was considered, but an endoscopic biopsy of the jejunal mass was preferred for more definitive visualization and histopathological diagnosis. The patient underwent push enteroscopy to obtain a biopsy of the jejunal mass (Figure 2a,b). Hematoxylin & eosin (H&E) staining of histopathology showed classic “starry sky” appearance due to scattered macrophages engulfing apoptotic tumor cells against a background of dense, basophilic lymphocytes (Figure 3a,b). Overall, immunohistochemistry returned positive for CD20, CD45, BCL6, and c‐Myc and negative for CK AE 1/3, BCL‐2, SCL L4, and OCD 4 (Figure 4a,b,c,d). CD 20 (B‐cell marker) and BCL6 were positive and negative for BCL2, distinguishing it from diffuse large B‐cell lymphoma. These findings are indicative of a late recurrence of BL, relapsing in 2024 after initial diagnosis in 2015.

FIGURE 2.

Push enteroscopy showed (a) Ulcerated mass with no bleed in the jejunum. (b) Biopsies were taken with cold forceps for histopathology.

FIGURE 3.

Histopathology revealed classic ‘starry sky’ appearance on H&E stain (a) 20X, (b) 40X magnification.

FIGURE 4.

Immunohistochemistry staining was positive for (a) c‐myc, (b) CD20, (c) BCL‐6, and negative for (d) BCL‐2.

2.5. Outcome

The patient was found to have elevated lactate and acidosis and was treated with rasburicase for suspected tumor lysis syndrome. Despite aggressive supportive care, the patient's condition worsened. His oxygen requirement was increasing, and he was transferred to the ICU for further management. The patient was intubated for acute hypoxemic respiratory failure and required multiple vasopressors due to profound shock. Despite resuscitation, the patient had cardiorespiratory arrest and expired.

3. Discussion

Our case presents a case of relapse of BL in the rare location of the jejunum. Lymphomas are classified into two types, Hodgkin's and non‐Hodgkin's lymphomas. Non‐Hodgkin's lymphomas most commonly involve the lymph nodes, wherein the second most common site of involvement is the gastrointestinal tract, constituting 5%–10% cases [4]. Non‐Hodgkin's lymphomas are either of T‐cell or B‐cell lymphoid origin. B‐cell non‐Hodgkin's lymphomas are divided into five histological subgroups, according to the WHO classification: diffuse large B‐cell lymphoma, Burkitt's lymphoma, mantle cell lymphoma, follicular lymphoma, and extra‐nodal marginal lymphoma [5] [Table 1].

TABLE 1.

Morphological features and IHC markers differentiating Non‐Hodgkin Lymphomas (NHL).

Lymphoma subtype	Morphological features	IHC profile
Diffuse Large B‐Cell Lymphoma (DLBCL)	Diffuse sheets of large atypical B‐cells Prominent nucleoli, variable cytoplasm High mitotic activity	CD19+, CD20+, CD10±, BCL6±, BCL2±, Ki‐67: 40%–90%
Burkitt Lymphoma (BL)	Monomorphic medium‐sized cells Starry sky” pattern (macrophages among tumor cells) Scant cytoplasm	CD19+, CD20+, CD10+, BCL6+, BCL2−, Ki‐67: ~100%
Mantle Cell Lymphoma (MCL)	Small to medium cells Irregular nuclear contours Mantle zone/nodular or diffuse pattern	CD19+, CD20+, CD5+, Cyclin D1+, CD23−, SOX11+
Follicular Lymphoma (FL)	Nodular/follicular architecture Mixture of centrocytes and centroblasts Graded by proportion of blasts	CD19+, CD20+, CD10+, BCL6+, BCL2+, Ki‐67: variable
Extra‐nodal Marginal Zone Lymphoma (MALT)	Small B‐cells with monocytoid or centrocyte‐like features Reactive follicles common	CD19+, CD20+, CD5−, CD10−, BCL2+, CD23−

Out of all the non‐Hodgkin's lymphomas, 1%–2% are classified as BL [6]. They are highly aggressive tumors with rapid progression and early onset of clinical symptoms. They frequently affect males (3.2 times more than females) and have a tri/bimodal age distribution with peaks around 10 years, 40 years, and 75 years [7]. Up to 65% of Non‐Hodgkin's lymphoma arises in the stomach, followed by the small intestines (20%–30%) and then thirdly, the colorectal region, which constitutes 10%–20% of all cases [4, 6]. Nakamura et al. in their retrospective study found that 9% of all BL originates in the small intestines [8]. BL mostly affects the ileocecal region. BL presenting in the jejunum is relatively rare, with few reported cases [9, 10, 11]. Classified into endemic, sporadic, and immunodeficiency‐associated subtypes, BL exhibits varying incidence rates. In the United States, the immunodeficiency‐associated form has an incidence of approximately 220 per 1 million individuals, whereas the sporadic form occurs at a rate of approximately 2.5 per 1 million adults [12].

BL of the intestine often has variable presenting features, which can be misinterpreted. It can present with vague abdominal pain, nausea, vomiting, constipation, or weight loss. In severe cases, it can present with gastrointestinal bleeding, bowel obstruction, intussusception, or peritonitis due to bowel obstruction. There have been few case reports of jejunal BL presenting as obstruction, perforation, or intussusception [10]. Imaging is rarely able to discern the cause of the patient's symptoms. BL can present as a bulky mass, bowel wall thickening, enlarged intra‐abdominal lymph nodes, or peritoneal carcinomatosis in cases of disseminated disease with metastasis or perforation [13, 14, 15]. Biopsy is required to confirm the diagnosis. Capsule endoscopy, push and pull enteroscopy, or colonoscopy are also used to allow for visualization and evaluation while allowing sample collection for biopsy at the same time [14].

Malignant lymphomas of the intestine, which present with ulcers, can be confused with Crohn's disease. Crohn's disease initially presents as small punched‐out superficial erosions mostly in the terminal and ileocecal valve region, but the erosions can coalesce and form large serpiginous ulcers mimicking the ulcers of malignant lymphomas [16, 17]. Moreover, lymphomas and Crohn's disease can present as bowel wall thickening on radiologic imaging; hence, biopsy is pertinent to confirm the diagnosis. Histopathology from the biopsy specimen is characteristic of a starry sky appearance with basophilic lymphoma cells in the background and pale macrophages dispersed throughout it [18]. Immunohistochemical staining is positive for CD10, CD20, BCL6, and negative for BCL2 with proliferative fraction > 95% as per WHO guidelines [19]. In most cases of BL, c‐Myc translocation is present, but it can be negative in 10%–15% of cases. Chromosomal translocations like t (8,14), t (2,8) or t (8,22) are also frequently seen in BL [20].

Due to the high proliferation rate of BL, spontaneous tumor lysis syndrome may occur, leading to severe metabolic disturbances and potential multiorgan failure [21]. Early intervention is imperative as the increased incidence of thromboembolism further contributes to hemodynamic instability. Management of intestinal BL requires a multidisciplinary approach, including surgeons and oncologists. Chemotherapy is the initial treatment option for uncomplicated BL, with different chemotherapy combinations recommended by NCCN (National Comprehensive Cancer Network), with no specific combination showing superior clinical efficacy [22]. Recurrence after chemotherapy is common, especially in cases of abdominal BL. Those with recurrence have been found to have a poor prognosis [23]. Recent studies have shown that early intervention with complete surgical resection prevents the risk of peritoneal carcinomatosis due to perforation and has been shown to improve survival outcomes [24, 25]. In cases of complications such as perforation, obstruction, or intussusception, surgery is required for palliation.

In our case, the patient was previously treated with appropriate chemotherapy for abdominal BL but relapsed with the initial presentation of abdominal pain. The presence of pulmonary emboli and peritoneal carcinomatosis indicated the advanced stage of BL. The presence of multiorgan failure with severe lactic acidosis suggested possible ongoing spontaneous tumor lysis. The immunohistochemistry satisfied the diagnosis of recurrent BL. Before any surgical intervention could have been taken, the patient died due to cardiorespiratory failure despite the best supportive measures in the ICU. This indicates the poor prognosis and highly aggressive nature of recurrent BL.

Most relapses after BL are observed within a year of remission. Early relapse occurs within 3 months of initial treatment and late relapses occur after more than 3 months of initial treatment [26]. Recurrence after more than 3 years is considered to be a ‘very late relapse’ as seen in our case. In our case, the relapse occurred after 9 years, hence the need for continued surveillance and documenting complete remission following a diagnosis of BL, both of which were not possible in our case.

4. Conclusion

This case highlights the aggressive and complex nature of BL, particularly when it presents in rare locations such as the jejunum. Early recognition and prompt intervention with multidisciplinary teams, including oncologists and surgeons, are critical in managing such aggressive tumors. This clinical scenario also emphasizes the crucial role of patient compliance and long‐term surveillance in patients with high‐grade lymphomas. Additionally, clinicians must remain vigilant regarding the possibility of relapse at atypical sites, even years after initial remission.

Author Contributions

Tejas Nikumbh: conceptualization, visualization, writing – original draft, writing – review and editing. Archit Garg: writing – original draft. Himani Mongia: visualization. Tushar Abhinav: writing – original draft. Nivesh Yadav: resources. Udit Asija: resources, validation. Jialing Huang: visualization. Danial Nadeem: writing – review and editing. Kishore Kumar: supervision. Amit Sohagia: supervision, writing – review and editing.

Consent

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy. IRB approval was granted by the Wright Center for GME.

Conflicts of Interest

The authors declare no conflicts of interest.

Nikumbh T., Garg A., Mongia H., et al., “Navigating Rare Presentations: Recurrent Burkitt Lymphoma Presenting as a Jejunal Mass,” Clinical Case Reports 13, no. 9 (2025): e70763, 10.1002/ccr3.70763.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.