A rare case of precursor B-cell lymphoblastic lymphoma of the orbit in a child

Abstract

A 5-year-old boy presented with gradually progressive painful proptosis of the left eye for 5 months. He had an incidental testicular swelling for which he underwent high inguinal orchidectomy and histopathology showed atypical lymphoid cells. His vision was 6/6, N6 in the right eye, and no perception of light in the left eye. Left eye examination revealed an inferior dystopia and total ophthalmoplegia with corneal exposure changes. A computerized tomography scan showed an isodense mass molding around the globe. An incision biopsy from the subconjunctival mass showed atypical large lymphocytes on histopathology which on immunohistochemistry confirmed a diagnosis of precursor B-cell lymphoblastic lymphoma (B-LBL). Bone marrow aspiration and biopsy were normal. The patient was started on oral steroids and high-risk acute LBL chemotherapy protocol to which he showed excellent response. Precursor B-LBL is a rare neoplasm of the pediatric and adolescent age group. A total of 22 cases involving the orbit have been reported to date of which 17 belonged to the pediatric age group. Early detection and prompt initiation of multiagent chemotherapy have shown good survival rates in these patients.

Introduction

Precursor lymphoblastic lymphoma (LBL) is a subtype of LBL which is a type of non-Hodgkin lymphoma (NHL). Precursor LBL is a highly aggressive malignancy affecting mainly children and young adults.[1] It is a high-grade neoplasm arising from either B-cell or T-cell lineage. Precursor B-cell LBL (B-LBL) is an uncommon type of LBL accounting for <10% of the cases.[2] Orbital involvement has been reported in 22 cases to date.[1,3,4,5] We herein report a child with orbital precursor B-LBL with associated testicular NHL.

Case Report

A 5-year-old boy presented with a gradually progressive painful prominence of his left eye for the past 5 months. He was diagnosed elsewhere to have a left testicular swelling for which he underwent a high inguinal orchidectomy 3 months ago. Histopathology examination of the specimen revealed atypical lymphoid proliferation with a high mitotic index suggestive of NHL. No further treatment was done for the same. On presentation, the visual acuity in the right eye was 6/6, N6; and there was no perception of light in the left eye. Right eye anterior and posterior segment examinations were normal. The left eye showed an eccentric proptosis, raised retrobulbar resistance, total ophthalmoplegia, lagophthalmos with inferior corneal exposure changes, and a mid-dilated pupil [Figure 1a]. The posterior segment had a hazy view and globe indentation. Ultrasound B scan showed a diffuse choroidal thickening and hypoechoic spaces in the orbit suggestive of an orbital mass [Figure 2a]. A computed tomography (CT) scan done elsewhere showed a diffuse periocular isodense mass molding around the globe and extending into the retrobulbar space. The optic nerve was encased by the mass. There were no signs of bone erosion [Figure 1b and c]. An incisional biopsy of the subconjunctival mass was performed through superior perilimbal subconjunctival approach under general anesthesia. Intraoperatively, a medial and lateral tarsorrhaphy was done to ensure complete eye closure. Postoperatively, he was given copious lubricants for corneal protection. Histopathology showed atypical large lymphocytes (precursor cells) with occasional mitosis [Figure 2b]. Immunohistochemistry (IHC) was positive for BCL-2, CD10, CD19, PAX-5, and Terminal deoxynucleotidyl transferase (Tdt) with Ki67 proliferation index of 95% and thus a diagnosis of precursor B-LBL was made. Positron emission tomography-computed tomography (PET-CT) scan showed increased metabolic activity in the left orbit with no systemic metastasis. Bone marrow aspiration and biopsy were normal. The child was started on oral prednisolone at 60 mg/m²/day under the supervision of a pediatric oncologist. He was started on the Berlin–Frankfurt–Münster (BFM)-95, high-risk acute lymphoblastic leukemia (ALL) protocol. He underwent induction therapy for 2.5 months, consolidation therapy for 2 months, a reinduction therapy for 2 months, and is currently on a 24-month maintenance therapy. On presentation 1 year later, he showed significant clinical improvement with no evidence of proptosis or chemosis [Figure 3a]. His visual acuity was no perception of light with a left eye mature cataract. Visually evoked potential showed no response in the left eye. A PET-CT and ultrasound B-scan at 1 year follow-up showed no evidence of orbital residual lesion [Figure 3b and c] or metabolic activity anywhere in the body. He has been advised left eye cataract surgery postcompletion of maintenance therapy.

Figure 1.

(a) 5-year-old boy with left eye proptosis, lagophthalmos, and inferior corneal exposure at initial presentation; (b) Coronal and (c) Axial sections of computed tomography (CT) scan showing diffuse periocular isodense mass molding around the globe extending into the retrobulbar space

Figure 2.

(a) Ultrasound B-scan showing diffuse choroidal thickening (blue arrow) and hypoechoic spaces in the orbit; (b) Histopathology (Hematoxylin and Eosin stain) of orbital mass showing atypical large precursor lymphocytes (yellow arrow) with occasional mitosis (×20)

Figure 3.

(a) Clinical photography at 1-year follow-up showing significant clinical improvement; (b) Positron emission tomography imaging at 1-year follow-up showed no metabolic activity in the orbit; (c) Ultrasound B-scan showing decreased choroidal thickening (blue arrow) and no hypoechoic spaces in orbit

Discussion

Orbital precursor B-LBL is a rare aggressive neoplasm which accounts for <10% of LBL.[2] It has a male predilection and is mainly a disease of children and young adults.[1] They present as nodal masses or extranodal lesions involving the skin, bone, stomach, colon, mediastinum (commonly seen in T-LBL), breast, and eye.[1,2,6] A review of literature shows 22 cases of precursor B-LBL with orbital involvement out of which 17 were seen in children and 5 in adults.[1,3,4,5]

Although the exact molecular pathogenesis is unknown, a deregulation in the genes affecting the growth and differentiation of the B-cell lineage has been implied as the probable cause. Philadelphia chromosome translocation is seen in some cases.[3] Deletion of CDKN2A/B is highly characteristic and is associated with poor outcomes in B-LBL patients. BCR/ABL gene translocation is also found in few cases.[1]

LBL and ALL are spectrums of the same disease and the collective term ALL/LBL is currently used in the latest WHO classification of lymphoid neoplasms.[5]

They arise from precursor lymphocytes of B-cell or T-cell lineage. Most cases of ALL arise from immature B-cell lineage, whereas 90% of LBL are of immature T-cell origin. Precursor B-LBL without evidence of ALL is rare. The cells of B-LBL and B-ALL are morphologically indistinguishable.[2] LBL is distinguished from ALL by focal or absent bone marrow involvement and absence of peripheral blood involvement.[7]

The neoplastic cells of B-LBL are typically of small-to-medium size, with fine chromatin, inconspicuous nucleoli, and a high mitotic rate. The cells express B-cell antigens such as CD10, CD19, CD22, CD79a, and TdT.[2] IHC plays an important role in diagnosis. Systemic blood and bone marrow investigations are necessary to rule out leukemic involvement.

Several cytogenetic abnormalities are seen in B-LBL. Molecular studies such as multiplex ligation-dependent probe amplification, comparative genomic hybridization, and fluorescent in situ hybridization help in the DNA analysis and prognostication of the disease in the pediatric age group. These are also used for the precise characterization of tumors in case of diagnostic uncertainty.[1]

The differential diagnosis of precursor B-LBL includes the T-cell variant (more common in presentation), blastoid variant of mantle cell lymphoma (which is histologically similar to B-LBL but occurs in the elderly age group), or Ewing’s family of tumors.[7] Burkitt’s lymphoma is commonly seen in the pediatric population, which has an aggressive and rapid growth. Extranodal marginal zone lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma can rarely present in children.

Children with localized lesions respond well to multiagent chemotherapy which is the cornerstone of treatment. There is no fixed protocol for B-LBL and the treatment is according to the regimens followed for ALL. Various treatment protocols have been used such as the high-risk Nordic Society of Paediatric Hematology and Oncology (NOPHO) ALL protocol, LSA2-L2 regimen, BFM therapy, modified BFM-90 protocol with event-free survival of 64%–82%.[1,6,8,9,10] In our case, the patient was started on oral steroids and high-risk ALL-based multidrug chemotherapy which includes vincristine, doxorubicin, L-asparaginase, cytarabine, cyclophosphamide, and intrathecal methotrexate to which he showed good response.

With timely diagnosis and prompt multidrug chemotherapy, the disease-free survival rate for B-LBL in children and adolescents is 75%–85%.[6] The possibility of survival advantage in these patients can be due to the disease biology, localized disease, and low propensity for peripheral blood involvement.[2] Poor prognosis is seen in patients with higher age at presentation and in cases of relapse.[1]

Precursor B-LBL is a rare neoplasm of the pediatric and adolescent age group. This case shows the disease as a secondary presentation in a child with previous testicular NHL. IHC aids in confirming the diagnosis, whereas a bone marrow examination helps to differentiate it from its leukemia counterpart. Early detection and prompt initiation of multiagent chemotherapy have shown good survival rates in these patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.