Intravascular Large B-Cell Lymphoma: A Report of Two Cases and Literature Review. What s Next?

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Ann Hematol Onco. 2024; 11(1): 1446.

Intravascular Large B-Cell Lymphoma: A Report of Two Cases and Literature Review. What’s Next?

Meléndez MR¹; Cadavid N¹; Véliz AS¹; Merino B²; López-Rodríguez M²; Hidalgo F²; Perna C¹; Pian H¹; Moreno E¹; García-Cosío M¹*

1Department of Pathology, Ramón y Cajal University Hospital, Spain

2Department of Internal Medicine, Ramón y Cajal University Hospital, Spain

*Corresponding author: García-Cosío M Department of Pathology, Ramón y Cajal University Hospital, Carretera de Colmenar KM 9, 100, 28034, Madrid, Spain; CIBERONC, IRYCIS; University of Alcala, Madrid, Spain. Tel: +34-913368140 Email: monica.garciacosio@salud.madrid.org

Received: January 19, 2024 Accepted: February 29, 2024 Published: March 07, 2024

Abstract

Intravascular Large B-Cell Lymphoma (IVLBCL) is an aggressive and rare extranodal B-cell lymphoma characterized by the proliferation of large neoplastic B cells virtually exclusively within the lumen of blood vessels. Three clinical variants have been described: the classic variant, the hemophagocytic syndrome-associated variant and the cutaneous variant. This entity usually is not suspected clinically and the diagnosis is based on histopathological confirmation and in many cases is made at autopsy. We report two autopsy cases of IVLBCL at our institution and a literature review of cases from the last ten years. We also discuss the latest advances about pathogenesis and molecular features of IVLBCL.

Despite advances in understanding the molecular landscape of this disease, earlier diagnosis and treatment remains a challenge.

Keywords: Intravascular large B-cell lymphoma; Review; Diagnosis; Autopsy; Molecular pathology

Background

Intravascular Large B-Cell Lymphoma (IVLBCL), historically known as angiotropic lymphoma, was first described in 1959 as an endothelial neoplasm with vascular spread [1]. Nowadays it is considered a rare subtype of non-Hodgkin lymphoma which has been updated and revised in 2022 World Health Organization (WHO) classification of lymphoid neoplasms. It is defined as an aggressive extranodal B-cell lymphoma characterized by the proliferation of large neoplastic B-cells almost exclusively within the lumen of blood vessels [2]. There are two main histologic variants of IVLBCL, historically classified by geographic presentation: the classic or ‘‘Western’’ type and hemophagocytic syndrome–associated or ‘‘Asian’’ type [3]. However, a third “cutaneous variant” has been described in virtue of their clinical features rather than by their geographical distribution [4]. The classical variant is consistently associated with involvement of systemic organs, whereas the cutaneous variant is restricted to the skin. The hemophagocytic syndrome-associated variant presents as hemophagocytic syndrome, hepatosplenomegaly and thrombocytopenia (>75%) [2]. The latter follows a very aggressive course associated with multiorgan failure, while the cutaneous variant has a better prognosis, possibly related to earlier diagnosis and more favorable clinical features [4,5]. Diagnosis of IVLBCL remains challenging because of the wide variability in clinical presentation. Consequently, it is not uncommon for patients with IVLBCL to have a first diagnosis at post-mortem. Because of the rarity of IVLBCL and the difficulty of its diagnosis, we present two recent autopsy cases and a review of the literature on cases that have been reported in the last ten years.

Case Reports

Case 1

An 87-year-old woman with a previous history of recurrent lower urinary tract infections was admitted to our hospital because of fever and signs of neurological impairment in the last 24 hours. She presented with elevated phase reactants and lower urinary tract infection. She started empirical antibiotic treatment, but she relapsed with fever and clinical worsening. An abdominal CT scan was performed showing a soft tissue mass involving the left middle ureter with extension to the kidney, suggestive of a primary tumor. Other findings were ill-defined liver lesions and pseudonodular thickening of the right adrenal gland. In the following days, the patient presented deterioration with progressive loss of consciousness and marked thrombopenia. A new CT scan showed a reduction in the size of the mass described suggesting an inflammatory lesion. The patient developed unfavorably and died. A clinical autopsy was performed.

Autopsy Findings

Gross findings included mild hepatomegaly (1870 grams; reference range 1500-1800 grams [6]), a congested appearance of the liver and multiple intrahepatic nodules in segment IV. Microscopic examination of several organs showed infiltration by a poorly differentiated, high-grade and discohesive neoplastic cell proliferation. These cells were of medium to large size with sparse cytoplasm and irregular nuclei with vesicular chromatin and prominent nucleolus. Numerous mitotic figures were seen. This proliferation was mainly found in the lumen of small and medium-sized blood vessels (Figure 1). However, we also observed extravascular infiltration in some organs such as the liver and adrenal glands (Figure 2). Additionally prominent histiocytic cell hyperplasia was observed in the spleen and bone marrow, with frequent images of hemophagocytosis (Figure 3). The bone marrow was not infiltrated by lymphoma cells. Immunohistochemistry (Figure 4) showed that the neoplastic cells were positive for CD45, CD20, CD79a, Bcl6 (weak) and CD5 (weak), with negativity for TdT, Bcl2, CD3, CD10, CD21, CD23, CD30, Cyclin-D1, MUM-1 and c-Myc. Epstein-Barr virus was not detected by in situ hybridization (EBER). The tumor was negative for other markers such as CKAE1/AE3, CK7, CK20, CK5/6, S100 and Melan-A. There was no overexpression of p53. No restriction of immunoglobulin light chains (kappa, lambda) was observed. The proliferation index (Ki67) was close to 80%.