Teaching Case

Progressive lumbar pain for the past three months, unresponsive to painkiller medications, in a long-standing Human Immunodeficiency Virus (HIV)-infected male patient on antiretroviral treatment. Orthotopic liver transplantation because of Hepatitis B+D-virus-related cirrhosis 5 years earlier, followed by tacrolimus immunosuppressive therapy. Associated symptoms including 5 kg weight loss, malaise, occasional febrile episodes.

Pretransplant imaging with multidetector CT (MDCT) 5 years earlier (not shown) showed characteristic findings of liver cirrhosis with portal hypertension, splenomegaly, and recanalized periumbilical vein.
Currently, an initial lumbar MRI scan acquired at another facility (Fig. 1) showed some scattered centimetric foci of low T1-signal intensity in the lumbar vertebral bodies, with corresponding hyperintensity on short-tau inversion recovery (STIR) images. Strict follow-up was suggested.
Three months later, repeated MRI (Figs. 2-3) showed extensive signal intensity changes involving most of the bone marrow in the lumbar spine, sacrum, and bony pelvis, indicating progression of bone marrow infiltrative disease, without vertebral body collapses. Additionally, body MDCT (Fig. 4) revealed several 1-4 cm non-confluent, non-necrotic adenopathies in the porta hepatis, mesentery, and retroperitoneum.
Histology and immunohistochemistry on bone marrow biopsy and on a surgically removed mesenteric lymph node diagnosed nodular sclerosis-type Hodgkin lymphoma, that was treated with ABVD chemotherapy, transfusions and haemopoietic growth factors.

Orthotopic liver transplantation (OLT) is an established therapy that allows patients a greatly improved life expectancy, with 10-year survival approaching 70%, and a good quality of life although with considerable long-term complications related to lifelong immunosuppressive therapy necessary to prevent graft rejection. Furthermore, OLT is a feasible option in selected HIV-positive disease with end-stage liver disease [1, 2].
As other solid organ transplant recipients, patients with OLT develop an elevated cancer risk reaching a cumulative incidence of 16-42% at 20 years, and de novo malignancies represent a leading cause of mortality. Because of immunosuppression and oncogenic viral infections, several neoplasms occur more frequently in OLT recipients than in the general populations, particularly nonmelanoma skin cancers and lymphoma with a 10-fold greater risk, plus head and neck, oesophageal, colorectal carcinomas, and Kaposi’s sarcoma [1, 3, 4].
Mostly reported in paediatric patients, post-transplantation lymphoproliferative disorders (PTLD) represent a spectrum of life-threatening complications of organ transplantation, that encompasses polyclonal lymphocyte proliferations to high-grade monoclonal lymphomas. Epstein-Barr (EBV) and Hepatitis B virus (HBV) reactivation probably have a role in the pathogenesis of PTLD, which occur after a 5-year median time after OLT. Compared to early-onset PTLD, Hodgkin-type disease is very uncommon and tends to occur late after transplantation [5-7].
As this case exemplifies, the development of lymphoma should be strongly suspected in patients with history of organ transplant and immunosuppression, when imaging detects systemic bone marrow changes, lymph node enlargement, and/or visceral lesions [1, 3].
Post-transplantation lymphomas commonly display extranodal involvement, which may involve every organ system or tissue in the body. Skeletal changes may be detected radiographically only when destructive osteolysis or sclerosis occurs. Conversely, MRI provides a noninvasive picture of the bone marrow cellular and structural composition, particularly in the spine and pelvis. Marrow infiltration by malignancy is exquisitely depicted as focal or confluent deposits, or extensive replacement, characteristically with hypointense T1 signal compared to the normal (adult) fatty marrow, a lower intensity compared to muscles on unenhanced T1-weighted scans and corresponding hyperintensity on fat-suppressed T2-weighted and short-tau inversion recovery (STIR) acquisitions. In lymphomas, bone marrow involvement automatically represents stage 4 (systemic) disease, and MRI may serve to choose biopsy sites to the most abnormal areas [8, 9].
Treatment of PTLD includes reduction of immunosuppressive regimens and systemic chemotherapy with ABVD as the gold standard regimen, and allows a fair prognosis with a 60% survival rate [7, 10].