Primary Orbital Lymphomatoid Granulomatosis in a 1-Year-Old Child.

Lymphomatoid granulomatosis (LyG) is a rare, angiocentric, angiodestructive, B-cell lymphoproliferative disease, presenting with pulmonary involvement in more than 80% of cases. We describe a case of primary orbital LyG in a 1-year-old child.

INTRODUCTION

Lymphomatoid granulomatosis (LyG) is a rare, angiocentric, angiodestructive, B-cell lymphoproliferative disease, presenting with pulmonary involvement in more than 80% of cases. We describe a case of primary orbital LyG in a 1-year-old child.

CASE REPORT

The child's mother became concerned about a progressive swelling of the right eye over a period of weeks. There was no relevant previous medical or birth history and the mother tested negative for human immunodeficiency virus (HIV). Examination revealed gross, nonaxial proptosis associated with periorbital edema, erythema, and nasal conjunctival chemosis [Figure 1]. Ocular motility was restricted horizontally and in elevation. On fundoscopy, there was pale disc swelling on the right, with tortuous retinal vessels.

Figure 1

Right nonaxial proptosis with periorbital edema, erythema, and nasal conjunctival chemosis

A full blood count showed no leukocytosis and there was no evidence of renal dysfunction. Hepatitis B surface antibody was positive, but hepatitis B surface antigen and core antibody immunoglobulin M were negative. The erythrocyte sedimentation rate was 32 mm (range 0–15). The child was HIV negative, and a lumbar puncture showed no abnormalities. However, further immunological testing identified a nonspecific T-cell immunodeficiency, with low T-cell subsets (absolute and percentages). Due to resource limitations, the specific features of the immunodeficiency could not be further elucidated.

Magnetic resonance imaging revealed a large mass (4.5 cm × 4.6 cm), originating in the right orbit. This extended through the medial orbital wall into the ethmoid air cells, with frontal leptomeningeal enhancement [Figure 2]. There was restricted diffusion centrally and enhancement of the lesional rim. Her chest X-ray was normal.

Figure 2

T1-weighted magnetic resonance imaging showing large medial orbital mass with ethmoidal extension, restricted central diffusion, and rim enhancement

A transnasal biopsy led to the provisional diagnosis of a diffuse, large B-cell lymphoma. Induction therapy consisting of cyclophosphamide, vincristine, and prednisone was commenced, according to the French Society of Pediatric Ophthalmology LMB89 protocol for large B-cell lymphoma.1 Later immunohistochemistry showed more than 50 Epstein-Barr virus (EBV) positive cells per high power field (hpf), CD 20 positive B-cells in a background of CD 3 positive T-cells, and tumor cells in and around blood vessels [Figure 3]. These findings are consistent with the diagnosis of LyG Grade III. Ganciclovir was therefore added to her treatment, in addition to methotrexate, cytarabine, and etoposide.2 Within a week, there was a marked reduction in tumor size on this regime.

Figure 3

Angiocentric and angiodestructive tumor cells occluding a blood vessel

She then received two induction doses of rituximab, 1-week apart, followed by 6 maintenance doses at 3 weekly intervals. This led to complete tumor resolution on imaging.

Comment

LyG was first described by Liebow et al. in 1972, who reported the largest case series of 152 patients.3 It is a multisystem disorder, primarily affecting the lungs, but also affects the skin, central nervous system, and kidneys. A mortality rate of 63% has been reported, due to either respiratory failure or progression to malignant lymphoma. The disease is known to be driven by EBV and is often associated with an underlying immunodeficiency.34 The lesion is graded according to the number of EBV-positive cells/hpf. Grade I lesions exhibit <5 EBV positive cells/hpf; Grade II between 5 and 50 EBV positive cells/hpf; and Grade III >50 EBV positive cells/hpf.2 Histological features required for diagnosis include: A mixed mononuclear infiltrate of small and large lymphoid cells; CD20 positive large B-cells in a background of CD3 positive small T lymphocytes; central necrosis and positive immunohistochemistry for EBV.5

To date, there have been 22 reported cases of LyG with ophthalmic manifestations.6 These include conjunctival, pupillary, choroidal, retinal, optic nerve, and orbital (including lacrimal gland) involvement.678 All but one of these cases were described in association with pulmonary or other systemic involvement. The only other report of primary orbital involvement occurred in an otherwise healthy 54-year-old man.8 The disease is most common after the fifth decade and is very rare is children. There are three previously reported cases of pediatric ophthalmic LyG, in children of ages 7, 8, and 13. Two had neuro-ophthalmologic manifestations and one had choroidal infiltrates.369 All three were secondary manifestations of primary pulmonary LyG. Due to the rarity of the condition, there is no consensus regarding optimal management. Options include corticosteroids, chemotherapeutic agents (singly or in combination), antiviral agents, radiotherapy, as well as newer agents like rituximab.10 To our knowledge, this is the youngest reported case of LyG and only the second with primary orbital involvement.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.