18F-FDG PET has been increasingly incorporated into the diagnostic and therapeutic work-flow of many pediatric malignancies. This imaging modality allows an earlier identification of primary tumors as well as their metastatic spread, thus significantly improving treatment planning and overall survival. In particular, 18F-FDG PET is a well-established modality for the initial assessment of adult and pediatric HD. As a noninvasive imaging technique, it allows for a whole-body detection of all lymphatic and extralymphatic sites of disease. At initial staging 18F-FDG PET/CT shows a sensitivity, specificity, and accuracy of 96.5 %, 100 %, and 96.7 %, respectively, markedly superior to conventional imaging, including computed tomography (CT) [11–13]. This performance is maintained throughout the entire range of histological subtypes of HD that are in general characterized by a high avidity for the tracer [14]. The use of morphological imaging such as CT or even MRI should be anyhow considered in the initial evaluation of HD patients in case of unusual extralymphatic involvement or when bulky masses are detected, in order to better define structural infiltration and plan consolidation radiotherapy.

In HD staging, a crucial site of disease localization is represented by bone/bone marrow. Although the rate of bone marrow involvement is not as high as in adult population, still there is an incidence of 4–6.5 % in more advanced HD stages in pediatric population [15, 16]. Traditionally, bone marrow biopsy (BMB) at the level of the iliac crests was considered as gold standard and should still be performed in case no advanced imaging with PET is available prior to treatment start. Nowadays, the results obtained by 18F-FDG PET/CT in defining bone marrow involvement guarantee a better detection of HD extent and overcome completely the necessity to perform a BMB in case of positive findings [5, 17]. The patterns of bone marrow involvement are variegate and comprise either a multifocal pattern, with three to more lesions located in the axial skeleton or proximal limbs, single foci of 18F-FDG uptake, or diffused heterogeneous uptake with sites of more intense focal involvement [15, 17]. This later pattern should not be confused with the homogenously increased bone marrow activation present in advanced HD cases and consistent with systemic/paraneoplastic symptoms [15]. Recent recommendations in adult lymphoma imaging also support the superior performance of 18F-FDG PET/CT in bone marrow assessment either at an early stage, when the risk of bone marrow infiltration is very low, or in advanced HD, given the high positive predictive value of the modality [18].

As a consequence of the better assessment of HD, 18F-FDG PET/CT determines a significant impact in patient treatment, either by upstaging or downstaging the disease. The percentage of change varies from 9 to 50 % of the cases, but by summarizing the results from different papers [19–25], the cumulative change can be estimated around 20 %.

Posttreatment evaluation with 18F-FDG PET/CT is known to be significantly correlated with patient outcome [26]. Its proper application during the course of treatment or after completion of chemotherapy can help identify patients who could benefit from additional therapy and avoid unnecessary treatment in patients with a low risk of relapse and a complete metabolic response [27]. In clinical practice the imaging response, including qualitative criteria such as the metabolic response to treatment, is used as a surrogate for patient outcome [28]. In limited-stage HD, the PET evaluation at the end of treatment has been reported to be highly predictive of PFS and overall survival [29]. Also in advanced-stage HD, consolidation radiotherapy can be safely omitted in PET-negative patients after completion of chemotherapy. In response assessment, a negative 18F-FDG PET after chemotherapy anticipates an excellent prognosis in contrast to a positive scan where the risk of disease recurrence increases significantly [21, 30]. No significantly increased risk of early relapse or progression has been reported in these patients even in those with residual masses on CT, but metabolically silent on 18F-FDG PET [31]. The abovementioned results have led to the new recommendations for the assessment of lymphoma, also known as the Lugano classification [18]. For response assessment in FDG-avid lymphoma, the criteria suggested are based on the 5-point scale (Deauville score) [32], both for clinical practice and research trials including interim and end-treatment evaluation.

In pediatric population response assessment can be obtained either after two cycles of chemotherapy, thus defining the early response, or at the end of treatment (Figs. 12.1, 12.2 and 12.3). In the first case the information is regarded as crucial for the planning, and in different multicenter protocols, the achievement of a complete metabolic response early in time could safely lead to reduction in chemotherapy exposure and/or the omission of radiotherapy [33, 34]. In other cases, response-adapted therapy from the Children’s Cancer Group (CCG) followed a gender-tailored consolidation protocol in advanced HD based on early response on PET [35].

As for response criteria in pediatric HD, no universally accepted criteria have been reported. However, many attempts have been done, either by applying the International Harmonization criteria for assessment of FDG PET response or by investigating the 5-point scale [5, 36, 37]. An alternative method to define metabolic response on PET has been proposed by the study group of the EuroNet-PHL-C1 trial (EudraCT 2006-000995-33), after dedicated evaluation of 898 patients [38]. The method gives a quantitative analysis (qPET) computed as an extension of the Deauville scale, resulting more consistent with the continuum in metabolic response observed in reality. This quantification however requires dedicated software, and upon the availability of the nuclear medicine center, qPET can be used as a reliable method for early response assessment in pediatric HD. Otherwise, as for adult lymphoma, the 5-point scale suggested by the Lugano classification is recommended [18].

At the end of chemotherapy, 18F-FDG PET is carried out to determine the need for consolidative radiation therapy and is reported a have a very high and independent prognostic role [3, 26]. Especially in case of positive findings after two cycles of chemotherapy, the use of end-treatment PET is almost mandatory. What is considered to be very high at this point in time is the negative predictive value of the method, whereas the positive predictive value is reported rather variable and can lead to false-positive findings [39]. Therefore, the proper timing for the scanning is defined by the day of the last cycles of chemotherapy and should be comprised between 3 and 4 weeks after the completion of therapy [36].

No consolidated use of 18F-FDG PET/CT exists in the follow-up of pediatric HD, unless end-treatment evaluation shows equivocal findings or noncomplete metabolic response. On counterpart, the integration of PET/CT into radiation treatment planning is advised because of the substantial impact it can have on treatment volumes within the target definition by reducing the risk of acute radiation-induced toxicity and potentially lowering the rate of long-term sequelae, including secondary malignancies [40].

Non-Hodgkin lymphoma (NHL) accounts for 60 % of childhood lymphomas and represents about 7.5 % of pediatric cancer; it is rare in infants and has its peak incidence at the age of 7 years [1]. NHL includes a large and very heterogeneous group of systemic malignancies but in childhood and adolescence is an aggressive systemic disease characterized by mature B cell immunophenotype. In particular most pediatric NHL cases belong to one of four categories: Burkitt lymphoma and B cell acute lymphoblastic leukemia (40–50 % of cases), followed by lymphoblastic lymphoma (20–25 %), anaplastic large-cell lymphoma (10–15 %), and diffuse large B cell lymphoma (10 %) [41, 42]. In addition, unlike in Hodgkin lymphoma with only few tumor cells, NHL consists of about 85–99 % of highly proliferative neoplastic cells (Fig. 12.4).

Burkitt lymphoma is an aggressive and rapidly proliferating tumor and doubles within 12–48 h [43, 44], and it often leads to gastrointestinal and urogenital obstructions.

The most common localization of lymphoblastic lymphomas is the mediastinum (large mediastinal mass) followed by the spleen, bone marrow, central nervous system, and peripheral lymph nodes [45].

Anaplastic large-cell lymphomas are characterized by peripheral adenopathy but often show extranodal involvement such as the skin, soft tissues, lungs, and cortical bone [45, 46]. Most children affected by anaplastic large-cell lymphomas carry the ALK-gene translocation. The prognosis of ALK+ patients is better than that of ALK− [47].

Diffuse large B cell lymphoma (DLBCL) is rare in pediatric patients. However, it is the most common lymphoma subtype in patients with congenital, iatrogenic, or acquired immunodeficiency. DLBCL is often characterized by nodal and extranodal localizations, but a solely gastrointestinal presentation is not uncommon.