Hodgkin lymphoma involving the extra-axial CNS: an AHOD1331, PHL-C1, and PHL-C2 report from the COG and EuroNet-PHL

Abstract

Hodgkin lymphoma (HL) involving the central nervous system (CNS) is exceedingly rare. Information regarding the presentation, management, treatment, and outcome of patients with CNS HL is limited to case reports or small series. We describe 45 pediatric patients with 55 extra-axial CNS lesions at diagnosis with HL from a cohort of 4995 patients enrolled on Children's Oncology Group AHOD1331 and the European Network for Pediatric Hodgkin lymphoma C1 and C2 trials, with an overall incidence of 0.9%. Up to 82.2% of patients had a single CNS lesion in the thoracic, lumbar, or sacral spine. In the evaluated cohort, HL did not occur within the CNS parenchyma. Lesions extended into the extra-axial CNS space from adjacent soft tissue or bone and never directly infiltrated through the dura into the brain or spinal cord. Patients with CNS involvement had a twofold greater incidence of extranodal lesions than previously reported cohorts without CNS involvement. After 2 cycles of chemotherapy, 89.1% of CNS lesions demonstrated a complete metabolic response and >75% decrease in volume. Thirteen CNS lesions (23.6%) received irradiation; none were sites of disease relapse. Relapse occurred at the site of 2 lesions involving the CNS, both of which had an adequate interim response to chemotherapy. In summary, we present, to our knowledge, the largest reported cohort of systemic HL involving the CNS at diagnosis, demonstrating that these lesions originate from surrounding tissues, extend into the extra-axial CNS space, and respond similarly to other nodal and extranodal disease. The trials were registered at www.clinicaltrials.gov as #NCT02166463, #NCT00433459, and #NCT02684708.

Graphical abstract

Figure 1.

Defining CNS involvement. (A) Normal anatomy of the spine and surrounding anatomic structures. (B) Tumor originating within the spinal cord. (C) Tumor infiltrating through the neuroforamen, compressing the spinal cord.

Figure 2.

Locations of HL CNS involvement. (A) Tumor in the dorsal part of the thoracic spinal canal and (B) ventral part of the lumbar spine (T2-weighted MRI sequences of the same patient, red arrow indicating tumor location), (C) tumor originating from the skull (bone window with subtle osteolysis, and (D) PET-fusion demonstrating the same lesion as in panel C extending into orbit and middle cranial fossa.

Figure 3.

Different origins of CNS HL lesions. (A) Tumor originating from bone (vertebral body of T12, L1, and L2). (B) Unclear tumor origin but very likely bone, with circumferential involvement and an associated soft tissue component. (C) Paravertebral tumor mass of the upper thoracic spine infiltrating through the right neuroforamen, demonstrated by the red arrow, likely originating from soft tissue.

Figure 4.

Spreading pattern of CNS HL. (A) Tumor spreading through the neural foramina into the thoracic spine. (B) Direct spread from lumbar spinal vertebrae, (C) Lytic cortical bony lesions (same patient as shown in panel B).

Figure 5.

Local impact on CNS structures. (A) Displacement and mild compression of spinal cord to the right without contrast enhancement in the transverse T1 fat saturated image. (B) The same patient with edema clearly visible in the spinal cord in a sagittal T2-weighted MRI image.

Figure 6.

Staging and response assessment. Imaging at staging shows a large paraspinal mass (A, MRI) with intense glucose metabolism (B, 18F-FDG-PET/CT; red arrows = lymphoma; white arrows = normal kidneys). The mass originates from the bone and extends into the neuroforamen and the spinal canal (A-B). After 2 courses of OEPA chemotherapy, 18F-FDG-PET shows a good metabolic response (C, maximum intensity projection; red circle surrounds the slight residual uptake of the former CNS lesion; [D-E] 18F-FDG-PET/CT; same height as panel B; minimal glucose metabolism within the residual mass [red arrows]).

Figure 7.

Summary of baseline and IRA results.