Fatty intra-abdominal lymph nodes in chronic lymphocytic leukemia
Authors: C.L. Cooley, M.S. Davids, A. Giardino
Journal: American Journal of Hematology (2013)

A 52-year-old female with refractory chronic lymphocytic leukemia (CLL) presented to our tertiary care institution for management of progressive lymphadenopathy. She was diagnosed 3 years earlier during a routine physical examination, which revealed mild cervical lymphadenopathy. A staging CT scan confirmed extensive lymphadenopathy in the chest, abdomen, and pelvis. Further workup revealed a white blood cell count of 18,000/ µL with a normal hematocrit and platelet count. An excisional biopsy of a left axillary lymph node demonstrated a population of small lymphocytes positive for CD19 and CD5, with dim CD20 and kappa light chain restriction, confirming a diagnosis of chronic lymphocytic leukemia. Because she was asymptomatic, she underwent observation. A restaging examination 1 year after diagnosis demonstrated marked progression of bulky mesenteric lymphadenopathy leading to bilateral hydronephrosis. Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) was started, initially with some response; however, shortly after completing therapy, restaging scans revealed steady progression of retroperitoneal and mesenteric lymphadenopathy over the course of nearly 2 years. The patient was referred to our institution for management of FCR-refractory CLL, with a goal of achieving remission prior to reduced intensity conditioning allogeneic hematopoietic cell transplant (alloHCT). Prior to starting therapy, restaging CT scans demonstrated an uncommon finding, with several of the intra-abdominal mesenteric lymph nodes demonstrating abundant macroscopic fat within the lymph node hilar regions (Image 1). The patient was enrolled in a Phase 1 clinical trial of the BH3-mimetic oral small molecule ABT-199 (GDC-0199), a new drug that targets the anti-apoptotic protein BCL-2, on which CLL cells depend for their survival 1. At 8 weeks, CT scans showed an excellent partial response, with significant interval decrease in lymphadenopathy; however, there was no significant change in the amount of fat within the lymph nodes (Image 1). Although current guidelines do not support routine staging CT scans in CLL patients, our patient was enrolled in a clinical trial necessitating restaging CT scans to assess clinical response to this new agent 1. CLL is an indolent B cell lymphoid malignancy with a heterogeneous clinical presentation that typically affects older adults, with an average age at diagnosis of 72 1. Patients typically present with lymphocytosis, and can develop progressive lymphadenopathy (often bulky) and cytopenias due to bone marrow infiltration. Asymptomatic patients with indolent disease may not require therapy for many years, if ever. Other patients have progressive disease within months of diagnosis. Powerful prognostic factors such as fluorescence in situ hybridization (FISH) for cytogenetic abnormalities, and immunoglobulin heavy chain variable region (IGHV) mutation status are useful both to predict the disease course and to guide treatment decisions 1. Chemoimmunotherapy can put the disease into remission for several years, but is generally not considered curative. AlloHCT is potentially curative in about 40% of patients, but is typically reserved for relapsed and refractory patients due to a significant level of treatment related morbidity and mortality 1. Survival is highly variable ranging from 18 months to greater than 10 years 1. Intra-abdominal lymphoproliferative disorders have variable imaging presentations. Findings may include unifocal or multifocal lymphadenopathy or diffuse soft tissue infiltration throughout the mesentery, retroperitoneum, and solid organs 2. The adenopathy or soft tissue masses are typically homogeneous and may undergo necrosis with increasing size 2. Calcification is rare without treatment. Lymphomatous involvement of the mesentery may appear as numerous enlarged lymph nodes or confluent soft tissue surrounding mesenteric arteries and veins without causing ischemia. Mesenteric lymphoma often displaces bowel loops without obstruction. Normal lymph nodes often contain a small amount of macroscopic fat within the lymph node hilum, a well-known imaging feature. However, the presence of abundant macroscopic fat expanding the lymph node hila in lymphoproliferative disorders is a distinctly unusual finding. To our knowledge, only 1 other case of bulky lymphadenopathy with abundant macroscopic fat has been reported in CLL patients. Karaosmanoglu et al. described the first reported case of abundant macroscopic fat expanding lymph node hilar regions in a CLL patient in 2012. This patient demonstrated progressive enlargement of macroscopic fat within lymph node hila after the completion of chemotherapy 3. Given concern for an atypical presentation of relapse or a second malignancy such as liposarcoma, a biopsy was performed which confirmed benign fibroadipose tissue within involved CLL lymph nodes. Macroscopic fat within lymph nodes has also been rarely reported in other lymphoproliferative disorders. For example, in their 1986 case report, Smith et al. described rapidly enlarging macroscopic fat within lymph nodes in a patient with diffuse large B cell lymphoma immediately after the completion of chemotherapy 4. Excisional biopsy demonstrated complete fatty replacement of the lymph node without evidence for recurrent lymphoma. Both of these case reports describe growth of the macroscopic fatty hilar region in lymphoproliferative disorders after chemotherapy treatment. After achieving near complete remission, our patient underwent alloHCT, and remains in remission several months since transplant. The large amount of macroscopic fat within the lymph node hila of multiple intra-abdominal lymph nodes has remained stable. Although a pathologic diagnosis was not obtained in our patient, stability of the abundant macroscopic fat is reassuring and biopsy/excision was not warranted. The etiology of this phenomenon of accumulation of macroscopic fat in CLL lymph nodes is unclear. Other authors have speculated that adipocytes within the affected lymph nodes may expand as lymphatic tissue atrophies during the course of therapy 3. We believe that biopsy or excision of these lymph nodes with abundant macroscopic fat in CLL patients is generally not necessary. Though rare, macroscopic fat represents an atypical feature of nodal involvement in CLL, of which hematologists and radiologists alike should be aware.