Hematologic imaging

Histology and clinical background

The current 2016 WHO classification of lymphoid tumors recognizes a wide variety of lymphoma subtypes ( ), detailed knowledge of which may not be required for the radiologist or nuclear medicine physician in his clinical practice. However, knowledge of the most common lymphoma subtypes is relevant and helpful for correct imaging interpretation and also, for determining the most appropriate imaging test.

Hodgkin lymphoma, which accounts for 9%–10% of all lymphomas, typically occurs in young adults, although there is a second peak in adulthood. Classical Hodgkin lymphoma is found in >90% of patients and has as its histological tell-tale sign the so-called Reed-Sternberg cells (which originates from B lymphocytes), with a marked surrounding immune infiltrate that leads to the actual lymphadenopathy ( )—Reed-Sternberg cells themselves constitute less than 1% of the tumor mass. With 5%–10%, nodular lymphocyte-predominant Hodgkin lymphoma is the second variant of Hodgkin lymphoma and usually has a different, more slowly progressing clinical course ( ).

Neck and chest lymph nodes are the most common sites of Hodgkin lymphoma, with the spread from one lymph node station to the neighboring one as the expected route of progression. Nevertheless, extranodal spread, particularly to the lungs, spleen, liver, kidneys, and bone marrow is however also frequently observed. In larger nodal lymphoma bulks, the criterion for which is a 10 cm maximum diameter according to the Ann Arbor classification ( ), cystic components are frequently seen in the mediastinum (probably of thymic origin) ( )—and often mistaken for necrosis. Hodgkin lymphoma generally has an excellent prognosis, at least when compared to many other non-Hodgkin lymphomas, with cure rates of 85%–90% using standard chemotherapy ( ), or less frequently immunochemotherapy regimens.

Non-Hodgkin lymphomas on the other hand are a far more heterogeneous and, in terms of biological characteristics, diverse group of lymphoid neoplasms. Over 60 entities are recognized in the WHO classification ( ), the most common ones being: diffuse large B cell lymphoma with 30%–35% of cases; follicular lymphoma with 25% of cases; marginal zone lymphoma (MZL) with 10%–12% of cases; CLL/small-cell lymphocytic lymphoma (CLL/SLL), 7%–8% of cases; and mantle cell lymphoma (MCL), with up to 7% of cases. Based on the REAL classification ( ), DLBCL represents the most common aggressive, fast-growing NHL subtype, whereas follicular lymphoma is the most common indolent subtype and can, similarly to MZL and CLL/SLL, transform into an aggressive histology over time. Prognosis varies heavily within the NHL group, with MCL, which can have an aggressive or indolent course, generally having the poorest prognosis, with a 5-year survival rate of just about 50% ( ). Treatment approaches also vary considerably, ranging from antibiotic treatment or local radiation therapy in the case of extranodal mucosa-associated lymphoid tissue MZL (MALT lymphoma) to immunotherapy and/or chemotherapy ( ). More cutting-edge treatments, for instance with targeted therapies such as Bruton's tyrosine kinase inhibitor ibrutinib, or anti-PD-1 or -PD-L1 checkpoint inhibitors, are also increasingly used both in indolent and aggressive lymphoma subtypes ( ; ; ).

Current imaging state of the art

According to the current Lugano classification of the International Conference on Malignant Lymphomas (ICML), the two preferred imaging techniques for assessment of disease extent, disease staging and treatment response assessments are FDG-PET/CT and contrast-enhanced CT (CE-CT) ( ; ). Since the vast majority of lymphoma subtypes show an elevated glucose metabolism, FDG-PET/CT is generally the preferred test in lymphomas ( ; ). FDG uptake is considerably higher in aggressive NHL as well as Hodgkin lymphoma, with typical maximum standardized uptake values (SUV _max ) between 10 and 30. Other, more indolent subtypes, including follicular lymphoma, show moderate, but still elevated FDG uptake relative to the background. However, some very slowly growing lymphomas such as the MZL group (which consists of nodular, splenic, and MALT variants), CLL/SLL, lymphoplasmacytic lymphoma (macroglobulinemia of Waldenström), and also cutaneous T cell lymphomas show a variable, frequently very low FDG uptake ( Fig. 9.1 ) ( ; ). It is for the latter group that PET/CT is not recommended by the ICML, and thus, CT remains the standard test.

Notably, MRI is currently only officially recommended for the assessment of CNS lymphoma ( ), because the CNS shows a high physiologic FDG uptake that leads to a markedly reduced tumor to background contrast. This is surprising given that MRI also offers superior soft-tissue evaluation in many anatomic sites such as the head and neck ( Fig. 9.2 ) and that there is an increasing body of evidence that supports the use of whole-body MRI as a possible alternative to PET/CT. Whole-body MRI appears to be only slightly to moderately inferior to FDG-PET/CT ( ; ; ; ), especially when DWI sequences are included in the MRI protocol. This is because DWI can indirectly capture cell density—which is generally high in lymphomas—and, by using apparent diffusion coefficients based on DWI, quantification of treatment response in terms of reduction in cellularity is possible ( ). Nevertheless, a limitation of whole-body MRI, and DWI in particular, is its sensitivity to motion artifacts, especially in the mediastinum (due to breathing and cardiac motion) and the lower neck, which are two common sites of lymphoma involvement. Given its lack of ionizing radiation, however, MRI may be considered an alternative technique in children and young adults, who might require lifelong imaging follow-up. Also, patients undergoing so-called watchful waiting (active surveillance), which is a frequently employed management strategy in indolent lymphomas, represents another possible application of whole-body MRI ( ).