Discussion
This study represents a population-based description of primary OAL in the paediatric population in the USA, using data available from the SEER registry. The histological spectrum was broad with EMZL accounting for nearly half of paediatric OAL cases.4–7 32–35 While still rare, the percentages of BL and T-cell lymphomas were higher compared with adult OAL cohorts, whereas FL was less commonly observed.5–7 36 None of the T-cell lymphomas originated on the eyelids, which is the highest-risk area for T-cell OAL development.6
While lymphoblastic lymphoma generally develops from immature T-cells, lymphoblastic OAL in children was of B-cell origin in all specified cases. Our findings are in line with the large cohorts in the literature showing that B-LBL of the ocular adnexa is primarily a disease of children and young adults. In a study by Jenkins et al, all four lymphoblastic lymphomas in a cohort of 192 patients with ocular adnexal lymphoma were diagnosed in children, three of which demonstrated a B-cell phenotype.34 Similarly, in a multicentre study by Olsen et al, three out of four B-LBLs in a cohort of 797 patients with orbital lymphoma were diagnosed in children aged 12 years or less.7 In a study by Sjö et al, two out of three B-LBLs in a cohort of 228 ophthalmic lymphomas were seen in children,4 while in a cohort of 353 OALs, the one lymphoblastic lymphoma diagnosed in a child was a precursor B lymphoblastic lymphoma.32
The conjunctiva was by far the most common location of paediatric EMZL, as opposed to adults, where the orbit is the most frequently involved anatomical structure.4 32 33 35 37 It is possible that orbital tumours may have been underdiagnosed in the paediatric age group, due to the less frequent use of neuro-imaging techniques in children, which require anaesthesia. However, aggressive histological subtypes, such as DLBCL, BL, T-cell lymphomas and B-LBLs, demonstrated a predilection for the orbit. While the conjunctiva was most frequently affected, it is important to note that most conjunctival lesions in children are benign. In a large series reporting on conjunctival tumours observed in 262 children, only 3% were malignant and only 1.5% represented a lymphoid proliferation.38
In contrast to adult OAL, which is characterised by equal gender distribution or a slight female predominance,32 39 40 males in the paediatric population demonstrated higher risk for OAL development. Moreover, while in the USA the risk of OAL is higher in the white population,41 black children in our study exhibited a higher tendency towards OAL development.
Radiotherapy, the most commonly used therapy for localised adult OAL, was less frequently used in the paediatric population, possibly owing to its side effects, which can be detrimental in children—namely cataract formation, dry eye, keratitis, retinopathy, facial bony deformities and the life-long risk of secondary malignancies. Similar to adult OAL,39 42 chemotherapy was the preferred treatment for advanced stages and more aggressive histological subtypes in our cohort (table 3 and figure 2). Excision of the tumour alone was performed mainly in the case of localised, low-grade, unilateral tumours, particularly of the conjunctiva (table 3 and figure 2), in accordance with case reports and other reports on paediatric ocular adnexal lymphoma and lymphoma in general.13 17 18 43–46 During the follow-up period that lasted for up to 35 years from diagnosis, no second primary malignancies were observed in our cohort. More focused multicentre studies are needed to establish these patients’ risk for second malignancy development and association with radiation therapy and chemotherapy.
Figure 2Treatment of paediatric ocular adnexal lymphoma according to (A) tumour stage, (B) tumour location and (C) tumour grade.
Overall and subtype-specific survival rates were comparable to survival in adults. The histological subtype was the primary predictor of outcome, with DLBCL and ALCL demonstrating higher mortality.36 47 Orbital involvement and advanced stage seem to also contribute to prognosis; however, this may be explained by the fact that these high-grade lymphomas were frequently located in the orbit and were commonly advanced at diagnosis. Similar to the 90%–96% disease-specific survival of ocular adnexal marginal zone lymphoma,37 no deaths were witnessed among patients with EMZL in our cohort. Similarly, no deaths were also documented among the patients with FL.48
The rarity of OAL in children and adolescents hampers the feasibility of large-scale investigations. Our data were derived from a large, population-based cancer registry that spans over four decades. To our knowledge, this is the first study investigating this rare entity. Our findings can be a reference point for clinicians who encounter these cases.
Limitations of our study include its retrospective design and missing data on chemotherapy and use of rituximab, radiation dose, immunodeficiency, patient symptomatology, tumour recurrences, immunohistochemistry and the presence of multifocal disease. Moreover, due to the rarity of paediatric OAL, the sample size may not be adequate for subgroup analyses and for achieving statistical significance in IR differences. Finally, in this study, staging categorisation was largely based on the SEER summary stage, rather than the TNM-based staging which is frequently used in clinical practice.48–51
In summary, our study provides insight on the clinicopathological features and survival of paediatric OAL per histological subtype. EMZL comprised the majority of tumours. Radiotherapy may be less frequently used in children. Future studies should supplement our data with the radiation doses and chemotherapeutic regimens used in this patient group.
