Early orbital involvement in a rare diagnosis of Burkitt-like lymphoma with 11q aberration

Abstract

Burkitt-like lymphoma with 11q aberration is a rare condition that poses a diagnostic challenge due to similarities with Burkitt’s lymphoma. Due to the rarity of cases, no specific guidelines exist for therapy, and it is treated the same way as Burkitt’s lymphoma. We present such a case with initial orbital involvement, an unusual manifestation. Our patient achieved remission with induction chemotherapy, although he will need regular follow-up given the paucity of information on long-term monitoring in these patients.

Lymphomas are a malignant proliferation of lymphocytes, subclassified as Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, the former presenting as nodal disease and the latter with some predilection for extranodal sites.¹ Burkitt’s lymphoma (BL) is an aggressive B-cell non-Hodgkin’s lymphoma associated with chromosomal translocations that cause overexpression of the oncogene c-myc. The World Health Organization (WHO) classifies BL into three variants: endemic, sporadic, and immunodeficiency related. Endemic is associated with Epstein-Barr virus and malaria, while immunodeficiency related is typically associated with HIV.² Burkitt-like lymphoma with 11q aberration (BLL-11q) is an entity defined by WHO in 2016. It resembles BL phenotypically, morphologically, and by gene expression profiling but lacks the MYC rearrangements. It is defined by proximal gains and telomeric losses of chromosome 11q.³ Compared to BL, BLL-11q has more complex karyotypes and a degree of cytological pleomorphism. The clinical course is similar to BL, and the number of reported cases is limited.⁴

CASE DESCRIPTION

A man in his 20s with no significant past medical history presented with complaints of persistent left eye pain with lateral gaze for 2 weeks. He noted increased tearing of the eye and blurry peripheral vision. He denied headache, nausea, vomiting, fever, chills, night sweats, pruritus, bleeding, weight loss, recent illness, sick contacts, trauma to the eye, or discharge from the eye. Family history was significant for Hodgkin’s lymphoma in his mother. He was normotensive and afebrile on admission. Physical exam was notable for periorbital swelling of the left eye and a palpable swollen left supraclavicular node. The left pupil was smaller than the right but maintained direct and consensual constriction to light. Visual acuity was near uncorrected 20/20 in the right eye and 20/20 in the left eye. Intraocular pressure was 15 in both eyes by tonopen. The white blood cell count was 9.5 × 10⁹/L; hemoglobin, 14.7 g/dL; platelet count, 274 × 10⁹/L; creatinine, 1.1 mg/dL; and thyroid-stimulating hormone, 1.48 mIU/L. Liver enzymes were normal, and heterophile antibody screen, HIV, hepatitis B, and hepatitis C panel were negative. Computed tomography of the orbit revealed a 28 mm left intraorbital soft tissue mass displacing the adjacent extraocular muscles. Magnetic resonance imaging (MRI) of the orbit revealed a left-sided mass measuring 2.5 × 2.2 × 2.7 cm (Figure 1a). Optic nerve involvement was seen, with mass effect affecting both medial and lateral rectus muscles.

Figure 1.

(a) Initial MRI of the orbit showing a left-sided mass involving the optic nerve (arrow) and (b) repeat MRI showing a significantly smaller left-sided orbital mass (arrow).

Left supraclavicular lymph node biopsy revealed high-grade B-cell lymphoma, suggestive of BL. Immunohistochemical studies showed positive CD20, PAX 5, CD10, BCL-6, MYC with weak staining pattern, and MIB1 (100%) and negative CD3, CD5, BCL-2, CD30, TDT, CD34, CD21, CD23, pan-CK, and CAM5.2. EBER-ISH was negative and no MYC/IGH translocations were detected. Fluorescence in situ hybridization analysis was revealing for 11q aberration. The initial positron emission tomography (PET) scan revealed stage IV disease above and below the diaphragm, skeletal involvement, and mass encasing the left optic nerve.

Given the rapid growth and impending vision compromise, the patient was started on rituximab and a combination of cyclophosphamide, vincristine, adriamycin, and dexamethasone (R-hyperCVAD). After two cycles, he achieved complete remission, as seen on a repeat PET scan, and near-normal vision of the left eye. Repeat MRI showed a significantly smaller left-sided orbital mass (Figure 1b). Bone marrow biopsy was deferred until the completion of therapy.

DISCUSSION

BLL-11q is typically present in young adults <40 years with a male predominance, both seen in our case. A higher incidence of nodal presentation, especially in the head and neck region, is seen.⁵ Central nervous system (CNS) and bone marrow are typically not involved, unlike in BL, which has been shown to affect these areas 30% to 38% and 13% to 17% of the time, respectively.^6,7 HIV and Epstein-Barr virus are typically negative, as seen in our case.⁸ Immunohistochemistry findings mirror BL, with positive CD10, BCL-6, CD20, and PAX5 and negative MUM1 expression. CD16/56 expression has been associated with BLL-11q, although it was not analyzed.⁹ Other similarities include BCL-2 negativity and high MIB-1 positivity.¹⁰ MYC expression is seen in both, although it is weaker in BLL-11q, as seen in our case. While not analyzed, BLL-11q shows specific driver mutations involving BTG2, ETS1, EP300, GNA13, and DDX3X, suggesting it differs from BL at a molecular level.¹¹

The hallmark feature, 11q aberration, is present in most published cases. However, according to some studies, 11q aberration may also be present in BL and high-grade B-cell lymphoma with myc rearrangement. It is hypothesized that the 11q aberration, which seems to replace the classic t(8q24) myc-negative lymphomas, might enhance the translocation and co-drive pathogenesis of myc-positive lymphomas. Due to their overlapping features, distinguishing BLL-11q from BL is a challenge and requires further molecular and detailed cytogenetics. Differentials to consider are high-grade B cell lymphoma and diffuse large B-cell lymphoma, the former associated with myc/BCL2/BCL6 rearrangements and the latter with BCL2 positivity.¹²

Using the St. Jude/Murphy staging system, our patient was diagnosed with stage IV disease, having nodal involvement on both sides of the diaphragm and initial CNS involvement manifesting as blurry vision from the optic nerve mass.¹³ Orbital involvement is a rare presentation of extranodal non-Hodgkin’s lymphoma, occurring in <1% of cases.¹⁴ It is often misdiagnosed as an infection or inflammation and treated with antibiotics or steroids with no improvement.¹⁵ Poor prognostic factors include CNS or bone marrow involvement and older age at diagnosis.¹⁶ BLL-11q is treated in the same manner as BL, as no standard of therapy exists.¹⁷ Our patient will need further diagnostic studies, with regular follow-up and monitoring.

Disclosure statement/Funding

The authors report no funding or conflicts of interest. The patient provided written informed consent for publication of his case.