Geel et al.⁵ recently demonstrated improved survival of children and adolescents with cHL in South Africa, an upper middle-income country, who were treated on a harmonised protocol that encouraged risk-stratified, response-adapted treatment. The authors acknowledged that BM biopsies are no longer required for paediatric cHL when PET-CT is available for staging and response assessment.^2,4,5 However, since most African countries do not have access to PET-CT, they continue to recommend BM biopsies and surveillance CT in resource-restricted settings.⁵ No specific recommendation was made regarding bilateral BM biopsies.

The Lugano classification, which omits routine BM biopsy staging in cHL, recommends a unilateral 25 mm BM biopsy where this is required in the absence of PET-CT.⁴ International Council for Standardization in Hematology guidelines for the standardisation of BM specimens and reports recommend a minimum biopsy length of 20 mm, and suggest that bilateral BM biopsies may be performed to increase the yield of detecting focal lesions.¹⁰ In this patient, the right-sided biopsy, which had an adequate length of 25 mm, showed only reactive features. The left-sided biopsy (15 mm) did not meet the recommended biopsy length requirements. Nevertheless, focal BM involvement by cHL was demonstrated on this side. These findings suggest that not only biopsy length, but also laterality may increase the yield of detecting focal BM lesions, and provides anecdotal support for the International Council for Standardization in Hematology suggestion to perform bilateral BM biopsies.

In addition to the anecdotal nature of a single case report, the lack of comparator data in the form of a PET-CT at initial staging limits the definitive value and generalisability of our observations. However, the value of bilateral BM biopsies in the staging of cancers has been demonstrated in several studies, including a local study by Van Marle et al.^7,8,11,12 Of the 118 paediatric cancer patients included in this study, 28 patients had BM metastases, of which five (17.8%) had discrepant left and right BM involvement.¹¹ Two of the five discrepant cases (40%) were children with cHL.¹¹ Larger studies have documented discrepant BM involvement by lymphoma in 39% – 43% of cHL, and 9% – 22% of NHL.^7,8 Wang et al.⁸ included 362 patients with cHL in their study. Of the 36 BM specimens (9.9%) that demonstrated involvement by cHL, 22/36 specimens (61%) showed bilateral involvement, while 14/36 specimens (39%) showed only unilateral involvement. Of the 97 patients with cHL included in the study by Brunning et al.,⁷ seven patients had BM involvement and in three patients (43%) tumour was detected on only one side. In contrast with these studies, unilateral BM involvement was less frequent in a single-centre retrospective South African study by Phillips and Opie⁶: 10.7% of cHL with BM involvement (3.8% of all cHL; n = 6) and 7.2% of NHL with BM involvement (3.2% of all NHL; n = 19). Another interesting observation from this study was the rate of BM involvement (35.7%) in newly diagnosed cHL (n = 157), which far exceeded the developed world rate of 5%.⁶ Late presentation at diagnosis and initial misdiagnosis as tuberculosis were proposed as possible explanations.⁶

Ultimately, larger prospective studies are needed to validate current recommendations about BM biopsy length and laterality in the setting of paediatric cHL where PET-CT is unavailable.

The late and advanced stage of presentation of our patient is not unique in the South African context. Geel et al.⁵ reported that 87/132 (66%) of the children with cHL in South Africa presented with high-risk disease and advanced clinical stage. These observations may, in part, be explained by the delayed diagnosis of paediatric cancers in resource-restricted settings.¹³

Prospective data on cHL survival from other African countries are minimal.⁵ Disparities in survival rates in childhood cancer are wide, ranging from 30% in low- and middle-income countries to 80% in high-income countries.¹³ In this context, the World Health Organization’s Global Initiative for Childhood Cancer focuses on six index cancers, including cHL.¹⁴ Factors that contribute to the global differences in cancer outcomes in children include access to diagnostics or therapeutics, human resources, financial barriers, lack of supportive care, and more advanced stages at diagnosis in low- and middle-income countries.¹⁵ Cotache-Condor et al.¹³ found the barriers to timely childhood cancer care to be multifactorial across the continuum of care, with key determinants including geographic, social, financial, health system, and health policy factors. All of these factors were barriers that contributed to the 2-year delay between symptom onset and referral of our patient from rural Lesotho to a paediatric oncology unit in South Africa. However, correct staging and risk stratification at diagnosis and follow-up ensured optimal treatment selection and a favourable outcome.

Delayed diagnosis of paediatric cancers remains a problem in Africa and may contribute to advanced disease stage, including BM involvement, at diagnosis. Although PET-CT detects BM involvement accurately in cHL and is recommended over BM biopsies in the staging of paediatric cHL, this imaging modality is not available widely in most African countries, and BM biopsies continue to be performed. This case suggests that bilateral BM biopsies may increase the yield of detecting focal lesions in cHL and should be considered in children, especially where advanced-stage cHL is suspected. However, the anecdotal nature of our case report and lack of comparator data in the form of a PET-CT at initial staging limits the definitive value and generalisability of our results. Further studies are needed to guide optimal strategies for the diagnosis, staging, and restaging of cHL in resource-restricted settings, with particular focus on the value of bilateral versus unilateral BM biopsies.