Sporadic Burkitt’s lymphoma/acute B-cell leukaemia presenting with progressive proptosis and orbital mass in a child

Abstract

Burkitt’s lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma that is found predominantly in children, with the highest incidence occurring in Africa. The sporadic form occurs in non-endemic areas and typically involves the ileo-caecum and the bowel, whereas orbital and paranasal sinus involvement is rare. Here, we present an unusual case of sporadic BL in a Caucasian male child with rapidly progressive painful proptosis of the right eye. Magnetic resonance imaging showed an oval-shaped, extraconal mass in the supero-lateral part of the right orbit that deformed and dislocated the eyeball antero-inferiorly. The patient underwent anterior orbitotomy, and a biopsy of the excised tissue revealed a starry-sky appearance characteristic of BL. Postoperative aggressive chemotherapy was initiated with a good response after one week.

Introduction

Burkitt’s lymphoma (BL) is one of the most aggressive malignancies of lymphoid origin, usually found in the paediatric population. The sporadic form is rare in non-endemic areas and very infrequently involves the head and neck. BL often presents with a relatively acute onset of symptoms (proptosis, lid swelling, palpable mass) that progress rapidly with growth.^1,2 Radiologically, BL may mimic orbital inflammatory mass and other orbital malignancies. Computed tomography (CT) and magnetic resonance imaging (MRI) are the imaging techniques of choice for complete evaluation; diffusion-weighted sequences could help to distinguish benign from malignant neoplasms. Use of contrast enhancement and fat suppression are mandatory for tissue differentiation and characterisation. The non-specific radiological presentation makes obtaining a diagnosis difficult, particularly in non-endemic areas and for atypical localisation.^3,4 A prompt diagnosis plays a key role, especially in children. Despite the aggressive nature of the tumour, favourable outcomes are seen, even with extensive disease.

We present an unusual case of sporadic BL in a Caucasian male child with painful swelling of the right eye.

Clinical presentation

A three-year-old male child was referred to our hospital with a one-week history of rapidly progressive painful proptosis of the right eye. He was healthy and had no relevant past medical history. Clinical examination demonstrated severe non-axial proptosis with infero-nasal displacement of the eyeball, chemosis and restricted ocular motility. A solid mass was palpable in the supero-lateral part of the globe (Figure 1). Pupillary reactions, intraocular pressure and ocular fundus were normal. The left eye was normal. At presentation, no alteration of visual acuity was found in either eye. His complete blood cell count was within the normal range.

Figure 1.

Clinical examination revealed swelling and proptosis of the right eye with infero-nasal displacement of the globe. (Image origin: Department of Diagnostic Imaging, Ospedali Riuniti, Foggia, Italy.)

Two months before acute proptosis, the child underwent a brain CT scan (due to a trauma) that showed no significant alterations in the brain or the eyes (Figure 2). After clinical examination, an MRI exam (1.5 T Achieva®; Philips Medical System, Eindhoven, The Netherlands) of the brain and the orbit was performed with contrast injection and narcosis. Axial and sagittal T1 weighted, axial and coronal T2 weighted/FLAIR without and with fat suppression, DWI (b = 0;1000) and post-contrast T1 sequences with fat suppression on axial, sagittal and coronal plane were performed. Axial T1, T2 and coronal T2 Turbo Spin Echo sequences showed a homogeneous hypointense solid, well-defined, extraconal mass occupying the superior and lateral part of the right orbit. The mass (38 mm × 28 mm × 18 mm) enclosed and displaced the lateral and the superior rectus muscles of the right eye, and deformed and displaced the eyeball antero-inferiorly with encasement of the lacrimal gland. The lesion appeared to have eroded the lateral wall of the orbit without a clear scalloping of the bone due to its rapid growth (Figure 3(a)–(d)). On diffusion weighted imaging, the mass appeared hyperintense and showed restricted diffusion of the water due to hypercellularity and high nucleus-to-cytoplasm ratio; ADC maps showed a marked hypointensity of the lesion (Figure 4(a) and (b)). A homogeneous peripheral enhancement was seen on post-contrast T1 sequences with fat suppression (Figure 5(a) and (b)). Right-sided anterior orbitotomy was conducted under general anaesthesia, and a polylobulated soft tumour was excised (Figure 6).

Figure 2.

Two months before acute proptosis, a computed tomography (CT) scan showed no significant alteration of the orbital region. (Image origin: Department of Diagnostic Imaging, Ospedali Riuniti, Foggia, Italy.)

Figure 3.

(a)–(d) Axial T1 TSE, FLAIR, T2 TSE and coronal T2 TSE sequences showed an homogeneous hypointense, solid, well-defined, extraconal mass occupying the superior and lateral part of the right orbit. The mass (38 mm × 28 mm × 18 mm) enclosed and displaced the lateral and the superior rectus muscle of the right eye, and deformed the eyeball, causing an antero-inferior dislocation. (Image origin: Department of Diagnostic Imaging, Ospedali Riuniti, Foggia, Italy.)

Figure 4.

(a) On diffusion weighted imaging, the mass appeared hyperintense at b = 1000 and showed restricted diffusion of the water due to hypercellularity and high nucleus-to-cytoplasm ratio. (b) ADC maps showed a marked hypointensity of the lesion. (Image origin: Department of Diagnostic Imaging, Ospedali Riuniti, Foggia, Italy.)

Figure 5.

(a) and (b) Post-contrast T13D with fat suppression axial and coronal sequences showed an homogeneous and peripheral enhancement of the mass. (Image origin: Department of Diagnostic Imaging, Ospedali Riuniti, Foggia, Italy.)

Figure 6.

After anterior orbitotomy, the surgical specimen demonstrated a polylobulated soft tumour. (Image origin: Department of Diagnostic Imaging, Ospedali Riuniti, Foggia, Italy.)

After surgical treatment, the histomorphological analysis of the excised tissue revealed a starry-sky appearance that is characteristic of BL. The child was transferred to the paediatric oncohaematology department at another hospital for appropriate stadiation and treatment. Immunohistochemical evaluation of the tissue confirmed CD20+ and Ki-67 proliferation marker of the cells. Osteomedullary biopsy showed high aggressive L3 blastic infiltration (35%). Polymerase chain reaction of medullary blood demonstrated the presence of the translocation t(8;14) q(24;32). The diagnosis of BL/B cell CD20+ leukaemia was confirmed. A staging CT scan, 25 days after clinical onset of the symptoms, showed the rapid growth of the right retrobulbar mass with erosion of orbital floor, homolateral mandibular osteolysis, mascellar sinus involvement, hepatosplenomegaly, right apical lung consolidation and bilateral nephromegaly with diffuse infiltration of both kidneys (stage IV St. Jude/Murphy classification). An aggressive multidrug chemotherapeutic protocol with prednisone, vincristine, cyclophosphamide and rituximab was initiated postoperatively, with a good response after one week. The child is currently doing well, with complete reduction of the orbital and renal masses at one-month follow-up.

Discussion

BL is a highly aggressive B-cell non-Hodgkin lymphoma (NHL) often presenting at extranodal sites or as acute leukaemia, composed of monomorphic medium-sized B cells with basophilic cytoplasm and mitotic figures. It typically occurs in children (40% of childhood NHL), with three forms: endemic (African), non-endemic/sporadic (American) and acquired immunodeficiency syndrome (AIDS). Although the highest incidence is reported in African children between 5 and 10 years of age, the sporadic form is rare, occurring in non-endemic areas with an incidence of just two to three cases per million. It usually involves the abdomen, distal ileum, caecum or mesentery during the first two decades of life (average age 12.2 years). Orbital, paranasal sinuses and facial bones involvement is rare (the African variant often presents as a jaw mass), with lack of recognition or misdiagnosis of this aggressive form.¹ BL often presents with an acute onset of symptoms and growing and painless mass of the head, the abdomen and the bone that progress rapidly.

Chromosomal translocations are associated with BL disease. In 60–70% of cases, the primary chromosome anomaly is the translocation t(8;14) (q24;q32) with c-myc (proto-oncogene) rearrangement and overexpression. An association with Epstein–Barr virus infection, stronger for the endemic form and in about 20% of the sporadic form, has been reported. Microscopic examination of the tumour shows the typical starry-sky appearance (perception of small points of light in a dark blue background) characterised by monomorphic medium-sized lymphoid cell with basophilic cytoplasm spaced out by benign tingible body macrophages. The tumour cells are CD19+, CD20+, CD22+, CD10+ and CD21+ (B-cell antigens). MIB-1 (Ki-67) a cell proliferating marker positivity in >95% of the tumour cells is characteristic of BL.

Involvement of head and neck, commonly in the form of cervical lymphadenopathy, was described in 25% of sporadic BL and rarely found in endemic BL.² Very infrequently, patients present with nasal obstruction, facial swelling or unilateral tonsillar enlargement, with possible delayed diagnosis in case of acute proptosis in a child. Orbital involvement is extremely rare in sporadic BL: two large reviews of paediatric orbital tumours demonstrated no positive bioptic case in non-endemic areas.^5,6

There are some previous reports in literature of sporadic BL presenting as complicated bacterial sinusitis^7,8 or as conjunctival mass⁹ or painless proptosis^10–12 or a mass in the nasopharynx¹³ and in the cavernous sinus.¹⁴ Our case report is noteworthy because of the unusual presentation with orbital involvement and the young age of the child.

Imaging plays a central role in the accurate diagnosis of orbital masses and can be used to localise a lesion, to establish a diagnosis or generate a differential diagnosis and to follow progression of a known lesion. CT and MRI are complementary imaging techniques in the evaluation of orbital tumours before and after treatment and for assessing residual or recurrent disease.

CT is excellent for confirming the presence of a mass, depicting ocular calcifications and evaluating potential bony involvement. MRI provides superior soft-tissue contrast and demonstrates a better ability to image the orbit using appropriate protocols with high-resolution sequences and correct surface coils. Use of gadolinium and fat suppression is essential for tissue differentiation and characterisation. Diffusion weighted imaging (DWI) is crucial for tissue characterisation; ADC mapping may help in the differentiation of benign and malignant lesions, and occasionally may allow for assessment of treatment response.

Lymphoma is usually extraconal and can be nodular, typically involving the supero-lateral quadrant of the eye and lacrimal gland, or it may be infiltrative with intraconal extension and encasement of the posterior part of the orbit. Lymphoid cell tumours typically appear as homogeneous, lobulated masses on CT and MRI that mould around normal structures without deforming them and with erosion of the adjacent bone. Commonly, a CT scan shows a hyperdense contrast-enhancing mass; MRI reveals a homogenous, hypointense T1 and T2 signal mass with lobulated margins, homogeneous post-contrast enhancement, brighter DWI signal and lower ADC than surrounding normal orbital tissues.³

Other malignancies (orbital rhabdomyosarcoma, uveal melanoma, lacrimal gland tumours, orbital metastases), idiopathic orbital inflammatory pseudo-tumour and thyroid associated orbitopathy are the most common differential diagnosis. DWI has recently proven effective in distinguishing lymphoma (typically high signal with restriction in DWI and low signal in ADC map due to hypercellularity) and inflammatory lesions (intermediate DWI signals and ADC similar to lacrimal gland).⁴

BL requires intensive multi-agent therapy. In relation to the extremely high mitotic index of BL (cell doubling time of 24–26 hours), it is imperative that the time course from diagnosis and staging to initial treatment be as short as possible. Due to the high sensitivity of the tumour, in particular the endemic form, the mainstay of management involves chemotherapy. However, sporadic and immunodeficiency-associated BL can be less sensitive than the endemic variant to chemotherapy.¹⁵ Surgical debulking and use of locoregional radiotherapy to reduce tumour volume has been reported. The prognosis is directly related to tumour burden: younger age and localised disease that can be completely resected respond well to chemotherapy. An aggressive therapy can result in a favourable outcome in patients with disseminating sporadic BL at the time of diagnosis.

In conclusion, patients presenting with acute painful proptosis and orbital mass need a quick diagnosis because of rapidly progressive nature of BL (if suspected) and a good response to treatment. A tissue biopsy and CT or MRI scans are mandatory for proper diagnosis, staging and tissue characterisation.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflict of interest

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.