HL is considered a highly curable disease among other malignancies; it has a worldwide clinical and epidemiological variation [16]. Our study discussed the epidemiological, clinical characteristics, and current management strategies with special attention to long-term outcome and late toxicity of pediatric HL in one of the biggest referral center in Saudi Arabia.
Our cohort revealed male: female ratio 1.3:1; this male predominance and other clinical feature like older age at presentation were reported in many other studies [17, 18]. Nodal presentation, in our cohort, is more prominent than extra-nodal presentation, 63.8% and 36.2% respectively, which are the same clinical features reported by Sherief et al. [17].
In our cohort, advanced or extensive disease (stages III-IV) showed a higher percentage than early or localized one (stages I-II); they were 62.5% and 37.5% respectively. Other countries with low socioeconomic level showed a similar percentage [19], Sherief et al. showed a higher percentage of advanced stage 56% in comparison to the early stage 44% [17]. In contrast, the European countries with higher socioeconomic level showed a lower percentage of advanced disease, may be due to early diagnosis, Aquino et al. showed early and advanced stages, 70% and 30%, respectively [16].
According to WHO, HL classified into classic HL (cHL) represented 95% of all HL which incorporate 4 subtypes; nodular sclerosis (NS), mixed cellularity (MC), lymphocyte rich (LR) and lymphocyte depleted (LD), and nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL) represented 5% of all HL [20]. In our cohort, the percentage of cHL and NLPHL were 88.7% and 11.3%; respectively. NS subtype was more prominent than MC, 55% and 22.5% respectively, which is similar to several European and US studies [16, 21]. On the other hand, some developing countries showed that MC subtype was more prominent than NS. In Egypt, MC and NS were 50.8% and 28.9% respectively [17]; in Nicaragua MC and NS, subtypes were 52.1% and 31% respectively [19], and in India MC subtype was 71% [22]. No cases detected with LD among our cohort.
The pathogenesis of HL in childhood has been largely attributed to viral oncogenic pathway stimulation. Epstein-Barr virus (EBV) has been identified, serologically by detecting IgG and IgM, as the most common associated virus. Genetic predisposition has also been associated in some cases [23]. The majority of patients in the cohort (50%) were positive for Epstein-Barr virus (EBV).
HL characterized by a higher curative rate and lower late toxicity among other malignancies especially in childhood. Our study showed high 5-year OS and EFS, 95% and 75%, respectively, which is similar to Turkish study reported by Uysal et al., the OS and EFS were 96% and 72%, respectively [24]. An Egyptian study reported by Sherief et al. showed OS and EFS, 96.6% and 84.7%, respectively [17], and Greek study reported by Pourtsidis et al. showed OS and EFS, 98% and 86.2%, respectively [21].
Survival rate was significantly affected by few clinical and pathological factors, B symptoms, stage, and risk group. In our study, 5-year survival rate was significantly lower in advanced stage (III and IV) in comparison with early stage (I and II) p = 0.022. Sherief et al., Dinand et al., and Smith et al. reported similar results, p = 0.006, p = 0.0001, p < 0.001, respectively [17, 25, 26]. Presence of B symptoms was borderline significantly associated with lower 5-year survival rate (p = 0.05) while it was significant in other studies, p = 0.005 [25], p < 0.001 [27], respectively. We did not find any significant association between histopathological subtypes and 5-year survival rate (p = 0.395). But Sherief et al. and Smith et al. found significant correlation between NS subtype and lower survival rate (p = 0.001) [17] and (p = 0.02) [26], respectively.
A previous study performed on a HL cohort in Saudi Arabia found that the xeroderma pigmentosum complementation group G (XPG) repair gene had statistically significant association with cHL patient survival [27]. The limitation of our study was that we did not correlate our results with genetic studies.
The association of DADA2 (deficiency of adenosine deaminase 2) with lymphoproliferation is well known [28]. In our study, we report familial HL in two children with a novel deleterious mutation in ADA2 and associated with DADA2. The details of both cases were reported before [29].
In our cohort, one patient developed secondary leukemia (AML). This 14-year-old patient was diagnosed with intermediate risk HL (stage IIIA, non-bulky), and was in remission for 54 months. He presented with fever, fatigue, lymphadenopathy, and hepatosplenomegaly. The BM and immunophenotype was compatible with AML (FAB: M0). A lymph node biopsy showed a myeloid sarcoma. The details were reported before [30].