Intravascular Large B-Cell Lymphoma: A Diagnostic Dilemma

Abstract

Intravascular large B-cell lymphoma is a rare malignancy characterized by the presence of lymphoma cells within the lumen of blood vessels. The annual incidence of cases is fewer than 0.5 cases per 1,000,000. It usually affects the elderly with an average age of diagnosis around 70 years. Due to the absence of lymphoma cells in the peripheral smear and lymphadenopathy, it is difficult to diagnose these cases. Although the central nervous system and skin are the commonly involved organs, they can involve any organ system. Prompt diagnosis and initiation of treatment are very crucial as it carries a high mortality. We describe two patients who presented with constitutional symptoms and fever of unknown origin, later diagnosed as intravascular large B- cell lymphoma. The diagnosis was difficult in both cases as the presenting symptoms were atypical. One of the patients was diagnosed at autopsy. The delay in diagnosis often leads to fatal outcomes as the disease is very aggressive. A high degree of clinical suspicion is the key to prompt diagnosis and improved outcomes.

Keywords: b-symptoms; bone marrow biopsy; diffuse large b cell lymphoma; fever of unknown origin; intravascular large b-cell lymphoma; intravascular lymphoma; rituximab.

Figure 1. Bone marrow biopsy revealing intravascular large B-cell lymphoma

Histologic sections of the bone marrow demonstrated focal aggregates of large, centroblast-like mononuclear cells with irregular nuclei and prominent nucleoli. They were distributed predominantly in a sinusoidal pattern (A – H&E stain, 60x). A CD34 stain highlighted tumor cells which were localized to the small vessels (B – 100x). The atypical lymphoid cells expressed CD20 (C – 20x) and CD79a (D – 60x). Overall, these features were most consistent with an intravascular large B-cell lymphoma.

Figure 2. Autopsy findings showing the involvement of IVLCL cells

Pituitary gland: The atypical hematolymphoid cells in the blood vessels show large nuclei, open chromatin pattern, prominent nucleoli, and mitotic activity (A, arrow indicate lymphoma cells within blood vessels). These cells are highlighted with the B-cell marker CD20 (B). Lungs: There are numerous large atypical cells present in the vasculature (arrows) that range from capillaries to small and medium-sized vessels. Atypical cell involvement is present also in subpleural vessels and almost all capillaries in the alveolar septae (C, D). IVLCL - Intravascular large B-cell lymphoma