A previously fit and well 29-year-old man presented to his ophthalmologist with a 6 month history of an enlarging right lower eyelid mass, resulting in a right-sided visual acuity deficit and diplopia. There were no B symptoms or other systemic features of malignancy. Clinical examination revealed marked restriction of right extraocular muscle movements and a 6 mm right hyperglobus. A CT scan revealed a large orbital floor mass abutting the globe and the optic nerve.
He underwent an urgent right anterior orbitotomy, orbital mass debulk and biopsy, which resulted in an improvement in symptoms and reduction of the hyperglobus to 1.5 mm. The excised mass was 5 cm × 4 cm, having eroded through the floor of the orbit, and was in direct communication with the maxillary sinus.
Histology revealed a proliferative germinal centre B cell (GCB) lymphoma. Fluorescence in situ hybridization (FISH) showed a similar pattern in all three MYC probes, suggestive of an isolated MYC rearrangement. IGK was suspicious for an unbalanced rearrangement. A PET scan performed 2 weeks after surgery showed progressive disease: the hypermetabolic right orbital mass had increased in size and there were new areas of bony destruction and invasion into the right maxillary antrum. No disease was detected within the cerebrospinal fluid. Given the histological findings suggestive of Burkitt's lymphoma, the patient was started on cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine and rituximab (R-CODOX-M) chemotherapy, complicated by prolonged hospital admissions due to toxicity.
Sanger sequencing and gene expression profiling results became available following the first chemotherapy cycle. These revealed features more consistent with a germinal centre, non-MYC, non-Burkitt diffuse large B cell lymphoma (DLBCL). Further treatment was therefore adjusted to reflect this change in diagnosis and risk. He was switched to a lower intensity regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone [R-CHOP]), which was better tolerated and delivered entirely on an outpatient basis. He received six cycles of chemotherapy with adjuvant involved field radiotherapy. At the time of writing, he remains in clinical and radiological remission.
Where do the difficulties lie in differentiating Burkitt's lymphoma from DLBCL?
What diagnostic work-up was performed on tissue samples from this patient?
What histological and genetic features helped to differentiate Burkitt's lymphoma from DLBCL in this case?
What is the evidence for treatment of Burkitt's lymphoma with R-CODOX-M/rituximab, ifosfamide, etoposide and cytarabine (R-IVAC)?
Is there evidence for treatment of DLBCL with R-CODOX-M/R-IVAC?
What is the likelihood of a good long-term outcome for this patient?
There is overlap between Burkitt's lymphoma and other aggressive B cell malignancies in terms of both clinical and histological features. Burkitt's lymphoma classically exhibits monomorphic, medium-sized lymphocytes with small nucleoli and a starry-sky appearance, but these appearances may also be seen in DLBCL and lymphoblastic lymphoma. Whilst lymphoblastic lymphoma may be distinguished by the presence of convoluted nucleoli, fine chromatin and expression of markers such as ...