Orbital T‐cell lymphoblastic lymphoma in children: A case report and review of literature

Abstract

To the Editor: Lymphoblastic lymphomas (LBL) are the second most common subtype of childhood non-Hodgkin lymphoma (NHL). In most cases, immature T cells proliferate, resulting in T-lymphoblastic lymphoma (T-LBL). The incidence in children under 15 years is four per 1,000,000, with a median age between 7 and 10.5 years at presentation.1-3 Orbital involvement in pediatric T-LBL is rare.4 We present a case of this uncommon presentation and review existing literature on the management. An eight-year-old male presented to a pediatric cancer unit in Malawi with a 3-month history of worsening right eye swelling, pain, proptosis, and vision loss. He had no B-symptoms, or other masses, headaches, vomiting, or behavioral changes. Clinical examination revealed a right orbital mass, with proptosis, ruptured eye globe, and significant exposure keratopathy, but no cranial nerve impairment or lymphadenopathy (Figure 1A) (informed consent obtained). The left eye and other examinations were normal. The complete blood count showed a total white blood cell count of 13.38 × 103/μL, hemoglobin of 13.4 g/dL, and platelets of 301 × 103/μL. A computed tomography scan revealed an enhancing soft tissue mass in the right orbit that extended intracranially into the temporal fossa, involved the right temporalis muscle, and a periosteal reaction around the right greater wing of the sphenoid and temporal bones. (Figure 1B). An initial fine-needle aspiration showed small round blue cells with occasional but inconsistent nuclear crowding. Some nuclei appeared oval, and there were no cytoplasmic vacuoles. Morphological appearance on hematoxylin and eosin staining demonstrated sheets of small to intermediate-sized cells with a “starry-sky background.” Immunohistochemistry was positive for cluster of differentiation-3 (CD3) and terminal deoxynucleotidyl transferase (TdT), while CD20, myogenin, synaptophysin, and CD99 were negative. Bone marrow aspirate morphology and flow cytometry were normal. His cerebrospinal fluid was negative for lymphoid blasts cells. An abdominal ultrasound scan and chest x-ray were normal. A diagnosis of T-LBL was confirmed, and the patient began a four-drug induction regimen that included vincristine, dexamethasone, L-asparaginase, and doxorubicin, along with intrathecal methotrexate, cytarabine, and hydrocortisone, based on the UKALL2011 protocol.5 At the end of induction, the patient showed an excellent tumor response. An ophthalmology review however showed corneal scarring and absent vision in the affected eye, although a B-scan ultrasound showed no residual masses. He then proceeded to receive post-induction chemotherapy that included augmented Berlin–Frankfurt–Munster consolidation, escalating Capizzi methotrexate, and thereafter maintenance chemotherapy. Radiation therapy was unavailable in Malawi and was not offered. The patient has remained in clinical remission for 26 months. Over 70% of LBLs have a T-cell immunophenotype. Most patients (∼75%) present with an anterior mediastinal mass, and lymph node involvement is usually above the diaphragm, with pleural and/or pericardial effusions being common.6, 7 Orbital involvement with T-LBL is very infrequent, with only seven reported cases till date (Table 1).4, 8-13 In children with rapidly growing orbital masses, more typical conditions include inflammatory diseases and common childhood cancers like rhabdomyosarcoma, neuroblastoma, and retinoblastoma.14 Diagnosing orbital LBL becomes even more challenging in settings like Malawi with limited access to pathology. Approximately 95% of cases of T-LBL express TdT and show cytoplasmic CD3 positivity, CD7 positivity, and variable expression of other T-cell antigens like CD2, CD4, CD5, and CD8. T-LBL exhibits many of the genomic alterations seen in T-cell acute lymphoblastic leukemia (T-ALL), including NOTCH1 and FBXW7 mutations; however, with the rareness of this presentation, there are no indications that biology informs a distinct clinical presentation for orbital T-LBL.3, 15-21 Age (years) Despite its aggressive nature, T-LBL has seen disease-free survival rates of greater than 80%, with modern high-risk T-ALL treatment regimens. The Capizzi methotrexate and pegasparaginase-based regimens showed high efficacy in the Children's Oncology Group AALL0434 study, with radiation therapy now reserved only for emergent management of life-threatening conditions.22-26 As treatment for T-LBL has improved, survival rates have increased, but relapse still occurs in 8%–16% of cases, and typically within 12 months, with up to 80%–90% of patients relapsing within 2 years.27, 28 In our unit in Malawi, all patients who have relapsed were within 16 months of initial remission (Supporting Information). Most reported cases of orbital T-LBL have been in adults, and involved multiple disease sites and varied management strategies (Table1). The only pediatric case of isolated orbital T-LBL was an 8-year-old female treated with intrathecal cytarabine and methotrexate, along with a regimen of cyclophosphamide, vincristine, methotrexate, daunomycin, and prednisone, plus 16.2 Gy of whole brain irradiation. She remained in remission at 33 months of follow-up.4 Due to the rarity of this presentation, there are limited data on its prognostic impact, particularly with respect to central nervous system (CNS) relapse. While T-LBL is radiosensitive, locoregional radiotherapy is debated for children with orbital T-LBL because of potential neurocognitive impairments and vision loss. Studies already show that excluding cranial irradiation in first-line treatment of T-ALL with CNS3 disease has not significantly increased the occurrence of CNS relapse.29 In conclusion, data on orbital T-LBL are limited to case reports. While the role of cranial irradiation is still debated in orbital T-LBL, its exclusion in patients receiving contemporary CNS-directed intensive chemotherapy does not appear to adversely impact outcomes. The authors declare no conflicts of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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