Case (2). The patient had a PET–CT scan ordered for a 10 × 7–cm mesenteric lymph node mass within the right side of the mid abdomen with an SUV max of 18.2 and several enlarged hypermetabolic mesenteric and para–aortic lymph nodes surrounding it. Additionally, the patient had bilateral pelvic, inguinal, axillary, and cervical lymph nodes present (Fig. 3.2a, b). Considering the patient had known extensive relapsed disease, a PET–CT scan was not necessary, and a CT of the chest/abdomen/pelvis would suffice in this scenario.

Staging of FL follows that of other NHLs using the Ann Arbor system. Work-up should include a patient medical history and physical examination (focused on the lymphatic region) for evaluation of B symptoms, extent of disease, and performance status. Blood work should include a complete blood count, a lactate dehydrogenase test (LDH), a beta-2 (B2) microglobulin test, a comprehensive metabolic panel test, hepatitis B testing, and a pregnancy test for women of child-bearing age. Bone marrow biopsy should be performed in all cases. Imaging should include a diagnostic CT scan of the chest/abdomen/pelvis with consideration of a CT of the neck and/or a PET-CT scan. PET-CT scans are important if considering definitive treatment with radiation for early-stage FL. Wirth et al. demonstrated that a PET-CT scan upstaged patients who were thought to have early-stage (I/II) FL by conventional assessment to stage III/IV in 31 % of the cases [6]. Additionally, PET-CT scan showed more extensive stage I/II disease than previously thought, which would increase the radiation field in 14 % of the cases.

In a large pooled analysis that led to the development of the FLIPI, several important clinical features were observed, including an even distribution of disease between the sexes (male, 51 %, female, 49 %), 63 % of patients under 60 years old, 22 % with stage I/II disease, 19 % with B symptoms, 35 % with five or more nodal sites, 38 % with extranodal involvement (other than bone marrow), 48 % with bone marrow involvement, 22 % with splenic involvement, 41 % with elevated serum B2 microglobulin, 21 % with elevated LDH, 18 % with hemoglobin below 120 g/L, and 10 % with albumin <35 g/L [2]. The factors that were found to be most prognostic for outcomes were age ≥60 years, stage III/IV disease, hemoglobin <120 g/L, elevated LDH, and >4 involved nodal sites. Based on these factors, the following risk groups were created: low risk, 0–1 factor; intermediate risk, 2 factors; and high risk, 3 or more factors. The 5-year and 10-year overall survival rates are 91 %, and 71 % for low-risk disease were 78 and 51 % for intermediate-risk disease and 53 and 36 % for high-risk disease.

In a follow-up project that involved a more modern patient cohort treated in the era of rituximab, a FLIPI2 was developed [7]. The factors found to have the strongest prognosis were B2 microglobulin levels (above normal), longest diameter of the largest involved node (>6 cm), bone marrow involvement, hemoglobulin <12 g/dL, and age >60 years. Based on these factors, the 3-year overall survival and progression-free survival (PFS) rates were 99 and 91 % for low-risk disease (0 factor), 96 and 69 % for intermediate-risk disease (1–2 factors), and 84 and 51 % for high-risk disease (3–5 factors).