Case Presentation: An 81-year-old woman was referred with a 1-month history of subacute progressive bilateral leg edema and a 1-week history of pain and inflammation in both lower legs. She had no history of fever or weight loss. Physical examination revealed pitting bilateral edema with tenderness. No heart murmurs or jugular venous distention were noted. Laboratory testing showed a white blood cell count of 7400 cells/µL, C-reactive protein level of 4.89 mg/dL, albumin level of 2.9 g/dL, creatinine level of 0.75 mg/dL, alanine transaminase level of 53 U/L, aspartate transaminase level of 11 U/L, alkaline phosphatase level of 87 U/L. No abnormal findings were observed to explain the edema, but the lactate dehydrogenase (LDH) level was significantly elevated to 1314 U/L. Chest radiography revealed a normal heart size. Contrast-enhanced computed tomography showed swelling of the soft tissues of both lower legs without thrombosis in the deep veins or inferior vena cava. Suspecting intravascular lymphoma, a skin biopsy was performed using the edematous lesions. The biopsy revealed clusters of large, atypical cells with conspicuous nucleoli within the vessels of subcutaneous adipose tissue, negative for CD3 and CD10, and positive for CD20 and CD79a, with a Ki67 labeling index over 90%. Bone marrow biopsy showed normal trilineage hematopoiesis without any monoclonal clusters of large, atypical lymphocytes. We diagnosed the patient with intravascular large B-cell lymphoma (IVLBCL). The edema improved within three weeks after initiating chemotherapy, with no recurrence during a further 8 months of follow-up.
Discussion: IVLBCL is a rare and aggressive form of non-Hodgkin lymphoma characterized by the proliferation of lymphoma cells predominantly within the lumens of blood vessels, obstructing normal blood flow and leading to a range of nonspecific symptoms, including fever (74% of cases), fatigue (26%), and neurological symptoms (25%), with approximately 10% presenting with edema. Edema is usually confined to the lower legs and feet, but can be generalized. IVLBCL causes vascular obstruction because of tumor cells within the blood vessels or thrombosis because of activation of the coagulation system, potentially leading to abnormal venous return and edema, and can lead to painful inflammatory symptoms such as stasis dermatitis.Though LDH can be elevated in various malignancies and diseases, levels > 800 U/L is one of the primary factors associated with IVLBCL. In cases of unexplained edema with a clear onset and without heart, renal, or liver failure, the presence of high levels of LDH, which is highly specific to malignant lymphomas, can be indicative of IVLBCL. In this case the diagnosis was confirmed through a random skin biopsy. In IVLBCL, random skin biopsies have a sensitivity of 77.8% and specificity of 98.7%. If the initial random skin biopsy is negative, repeating the biopsy increases the sensitivity.
Conclusions: IVLBCL should be suspected in cases of unexplained edema with a clear onset, accompanied by high LDH levels. A random skin biopsy is useful for diagnosis.