In 332 of 728 (45.6%) vaccinated patients, hypermetabolic ASLN were identified ipsilateral to the vaccine injection site. This finding was found in 36.4% of the patients after the first vaccine and in 53.9% of patients after the booster one. In 17 of the vaccinated patients with HLN (5.1%), the “hot” nodes reflected malignant nodal disease (MHL). In 266 (80.1%) the “hot” nodes were benign nodes associated with the vaccine (VAHL), and in 49 patients (14.8%), the nature of the nodes was equivocal (EqHL) (Table 2).
Vaccine-associated hypermetabolic lymphadenopathy
The incidences of VAHL were 36.5%, 26.3%, and 45.8% in All-Vac, Vac-1, and Vac-2 groups, respectively. Table 3 summarizes the grade, location, intensity of uptake, and size of VAHL after the first and after the booster vaccine doses as well as detection of increased uptake in the vaccination site. After the booster vaccine, the incidence of high-intensity VAHL was statistically significantly higher than after the first vaccine, and so was the size of nodes, detection of “hot” nodes beyond level 1 of the axilla, and detection of the vaccination site.
Figure 2 illustrates the proportion of vaccinated patients with VAHL and the grade of VAHL at various time points after the first vaccine administration. Using CHAID algorithm, it appears that in the first 5 days and beyond 13 days after the first vaccination, the incidence of VAHL is statistically lower compare to the higher incidence observed 6–12 days after vaccination (Table 4). Figure 3 and Table 5 illustrate that after the booster vaccine, the incidence and grade of VAHL are highest on the first 6 days, decrease gradually over time, and are significantly lower beyond 20 days after vaccination. However, 3 weeks after booster vaccine administration, 29% of vaccinated patients still presented VAHL in our cohort, but only 7% had grade 3 or 4 VAHL.
Patients younger than 62 years of age show a higher incidence of VAHL after the first vaccine as well as VAHL of a higher grade (see Fig. 4 and Table 6). Similar results were found after the booster vaccine with 64 years being the age that statistically separates the incidence and grade of VAHL in the different age groups (see Fig. 5 and Table 7). Of note, we found another increase in the incidence of VAHL after the age of 85 in Vac-2 group (Fig. 5).
PET–CT interpretation in vaccinated patients presenting with hypermetabolic lymphadenopathy in the axilla and supraclavicular region
As demonstrated in Table 2, VAHL was identified and reported in 80.1% of the vaccinated patients presenting with hypermetabolic ASLN. There was no statistically significant difference in the incidence of VAHL when comparing patients with no evidence of disease on PET-CT and those with active malignant disease. The proportions of VAHL reports were not different in patients receiving chemotherapy, radiotherapy, biologic treatment, or immunotherapy.
Malignant hypermetabolic ASLN (MHL) ipsilateral to the vaccination site was interpreted in 5.1% of the vaccinated patients presenting with “hot” nodes in these nodal stations. These patients were either patients with proven nodal disease in these stations or patients with extensive lymphadenopathy mainly above the diaphragm, including the contralateral axilla.
However, in 49 patients, differentiation between MHL and VAHL could not be made, and the nature of the “hot” LN was considered nonconclusive (EqHL). This group of patients consists of 6.8% of the 719 oncologic patients referred for PET-CT post vaccination and 14.8% of the 332 vaccinated patients presenting with hypermetabolic ASLN ipsilateral to the vaccine injection site. Of the 49 EqHL cases, 20 patients were women with breast cancer ipsilateral to the vaccination arm (eight patients at staging), and 16 were lymphoma patients with nodal disease above the diaphragm. In the remaining 13 patients, the ASLN were relevant lymphatic drainage basins, including patients with upper limb sarcoma, melanoma, and head and neck malignancy with extensive cervical and nodal involvement. Figure 6 illustrates two cases which were interpreted as EqHL.