Case report of high-grade B-cell lymphoma with MYC and BCL2 rearrangements presenting as compartment syndrome of the leg

Introduction

Background

High-grade B-cell lymphoma with MYC and BCL2 rearrangements is an aggressive mature B-cell lymphoma characterized by concurrent MYC and BCL2 gene rearrangements (1). It is known for its aggressive clinical course and poor outcomes, with 4- to 5-year overall survival rates of approximately 40–50% (2). Timely oncological management is crucial for patients’ care. Clinical symptoms can vary depending on the site of involvement, but commonly manifest as lymphadenopathy with “B symptoms”. Acute compartment syndrome is a medical emergency characterized by painful swelling around muscles and the accumulation of excess pressure within the fascia surrounding the muscle, often associated with injury or repetitive stress. This condition can be life-threatening as it leads to tissue necrosis and permanent damage (3). Diagnosis typically relies on clinical presentation, medical history, imaging studies, and measurement of intercompartment pressure (ICP). Surgical intervention is necessary to treat acute compartment syndrome (4).

Rationale and knowledge gap

Acute compartment syndrome can be associated with exceedingly rare but treatable conditions, such as aggressive B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 gene arrangements. However, early recognition and diagnosis of this uncommon etiology of compartment syndrome can be very challenging, yet crucial for the timely management of patients.

Objective

In this case report, we describe a case of high-grade B-cell lymphoma with MYC and BCL2 rearrangements infiltrating the muscle and initially presenting as compartment syndrome. We also performed a literature review of all reported cases of lymphoma present as compartment syndrome and discuss the diagnostic challenges for this unique presentation of lymphomas. This manuscript is written following the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-154/rc).

Case presentation

A 68-year-old woman was brought to the emergency room with complaints of increased swelling and pain in her right leg, accompanied by weight loss and loss of appetite over the past 2 to 3 weeks. The patient’s medical history includes human immunodeficiency virus (HIV) infection treated with bictegravir, emtricitabine & tenofovir alafenamide, untreated hepatitis C, and a history of right breast cancer treated with lumpectomy and radiation therapy. Notably, there was no history of hematological malignancy. Physical examination revealed tenderness to palpation in the right leg with swelling extending from below the right inguinal ligament to the toes, along with pitting edema and palpable pulses. Non-compressible right femoral and popliteal veins were noted and suggestive of right lower extremity deep vein thrombosis (DVT). Angiography did not provide solid evidence of DVT; however, vasculature details were obscured by the soft tissue mass and associated necrosis. Given the presence of pulmonary embolism and clinical suspicion of DVT, a heparin drip was initiated for anticoagulation management, and an inferior vena cava (IVC) filter was placed. The patient’s HIV infection was well-controlled, with an undetectable viral load and a CD4 count of 828 cells/cmm (normal range, 332–1,642 cells/cmm) and a CD4/CD8 ratio of 3.63 (normal range, 0.7–4.8).

The abdominal computed tomography (CT) scan revealed severe asymmetric enlargement of the right leg compared to the left, accompanied by the loss of fat planes, decreased attenuation of the musculature, and diffuse subcutaneous edema (Figure 1A). A subsequent magnetic resonance imaging (MRI) of the right lower extremity confirmed the presence of severe swelling and edema within the thigh musculature, suggestive of myonecrosis and/or intramuscular abscesses. Enlarged lymph nodes were also noted on the abdominal CT, with the right inguinal lymph node measuring up to 1.6 cm and the right external iliac lymph node measuring 3.4 cm × 2.5 cm × 2.2 cm (Figure 1B,1C). Furthermore, a pulmonary embolism was identified on the CT angiography (CTA) of the chest.

Figure 1 Abdominal CT images show severe soft tissue swelling in the right thigh and enlarged lymph nodes. (A) Images from abdominal CT found severe asymmetrical enlargement of the right leg compared to the left with diffuse subcutaneous edema. On abdominal CT, the presence of an enlarged right inguinal lymph node (B) and right external iliac lymph node (C) were noted, as indicated by arrows in the images. “R” indicates the right side. Dashed lines indicate the sizes of measurements. CT, computed tomography.

The clinical history, radiological studies, and laboratory findings were evaluated and revealed concerns for compartment syndrome and rhabdomyolysis. Subsequently, the patient was diagnosed with compartment syndrome in the right thigh based on elevated compartment pressure measurements. The suspected underlying causes included bacterial infections leading to myositis, myonecrosis, osteomyelitis, or abscesses. Multiple blood cultures returned negative results. Broad-spectrum antibiotics were initiated, followed by an urgent fasciotomy and two subsequent debridement surgeries.

The soft tissue specimen was obtained from right thigh debridement excision and revealed dense confluent lymphoid infiltrates extending into the skeletal muscles. The infiltrate primarily consisted of monotonous, moderate-sized lymphocytes with round nuclei, dispersed chromatin, and indistinct nucleoli (Figure 2). Both small and large lymphocytes were noted, accompanied by tingible body macrophages and apoptotic bodies. Brisk mitotic activity was observed. No abscesses or acute infection was detected.

Figure 2 H&E sections of the excisional biopsy of right thigh soft tissue at 100× and 400×, and immunohistochemical stainings of paraffin-embedded tissue sections with appropriate controls of the lymphoma cells at 200× show diffuse strong positivity of CD20, CD10, BCL2, and MYC, and a high labeling of Ki-67. H&E, hematoxylin and eosin.

Immunohistochemical analysis (Figure 2) demonstrated that the neoplastic lymphocytes were of B-cell lineage, as evidenced by positive staining for CD20, with a germinal center immunophenotype strongly positive for CD10. Additionally, BCL2 and MYC were strongly positive, while chromogenic in situ hybridization for Epstein-Barr virus-encoded RNA (EBER), cyclin D1 and SOX11 were negative. Ki-67 staining revealed a high proliferation rate ranging from 40% to 70%. Notably, no follicular dendritic cell (FDC) meshworks were identified. A minor infiltrate of mixed CD4 and CD8 positive T-cells was also observed.

Next-generation sequencing (NGS) studies demonstrated variants of BCL2, DDX3X, EZH2, GNA13, KMT2D, SOCS1, TNFRSF14, and AFHX4. Fluorescence in situ hybridization (FISH) analysis identified MYC and BCL2 gene rearrangements. Given the patient’s history of HIV infection, the final diagnosis of diffuse large B-cell lymphoma (DLBCL)/high-grade B-cell lymphoma with MYC and BCL2 rearrangements arising in the context of immunodeficiency/dysregulation (lymphoma associated with HIV infection) was established.

Even though the patient tolerated fasciotomy and two subsequent debridement surgeries, the patient’s condition continued to decline postoperatively. The patient was under supportive treatments due to do not resuscitate/do not intubate status. She experienced shock and unfortunately expired 14 days after the initial presentation due to multisystem organ failure, septic shock, and hemorrhagic shock.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Publication of this case report and accompanying images was waived from patient consent according to the Institutional Review Board at Albany Medical College (Albany, NY, USA).

Discussion

Key findings

Here, we report a case of double-hit lymphoma initially presenting as compartment syndrome, which resulted in a poor clinical outcome.

Strengths and limitations

Only a few cases have been reported of lymphoma initially presenting as compartment syndrome with skeletal muscle infiltration. To the best of our knowledge, this is the first case report of double-hit lymphoma with an initial presentation as compartment syndrome. Due to the aggressive nature of high-grade B-cell lymphoma with MYC and BCL2 rearrangements and the rapid clinical course in this case, we were unable to collect information about the outcome of chemotherapy in this scenario.

Comparison with similar research

We conducted a literature review to identify all articles about lymphoma presenting as compartment syndrome, and summarized the findings in Table 1.

Explanations of findings

Across the literature, a variety of lymphomas, including Burkitt lymphoma (BL), DLBCL, and anaplastic large cell lymphoma (ALCL) have been reported to present as compartment syndrome (5-16). The majority of these cases reported a poor prognosis, with patients succumbing shortly after hospital admission. However, both cases of Burkitt lymphoma showed positive treatment response and excellent prognosis (6,7). This highlights a crucial clinical consideration: aggressive lymphoma should always be considered when patients present with compartment syndrome, warranting timely hematological and oncological treatment.

Implications and actions needed

In our case, despite the patient undergoing multiple surgeries for debridement, the patient succumbed to her condition a few weeks after admission. The pathological diagnosis was made 14 days after the patient’s initial encounter, with the molecular report being generated 6 days after the patient’s demise. Such delay raises concern about rapid initial clinical diagnosis, prolonged turnover time and shortages of staff, especially in the post-pandemic era, which have been reported to impact medical system (17,18). Efficient communication and collaboration among clinicians, pathologists, and all medical staff are essential to ensure the delivery of high-quality medical care to all patients.

Conclusions

In summary, we presented a rare case of high-grade B-cell lymphoma with MYC and BCL2 rearrangements initially presenting as compartment syndrome. Hematological malignancies manifesting in uncommon sites with atypical syndromes pose significant challenges for diagnosis, particularly in clinical emergencies. It is important to be cautious when encountering unusual presentations of compartment syndrome, as they may be associated with underlying systemic diseases, including high-grade aggressive lymphomas. Early recognition and prompt diagnostic evaluation are essential for ensuring timely and appropriate management and optimizing patient outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-154/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-154/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-154/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Publication of this case report and accompanying images was waived from patient consent according to the Institutional Review Board at Albany Medical College (Albany, NY, USA).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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