Intravascular large B-cell lymphoma
A 53-year-old woman visited the dermatology clinic reporting a worsening vascular skin lesions with a history of 3 months and fever that had been present for about a month. During the physical examination, diffuse telangiectasias, hyperpigmented plaques, and several ulcerated nodules were noted on her chest, abdomen (Panel A), and legs. No palpable lymphadenopathy or hepatosplenomegaly was detected. Laboratory tests revealed an elevated lactate dehydrogenase level of 356 U per liter (normal range: 120 to 250). A deep skin biopsy from the abdomen revealed an intravascular aggregation of round, atypical lymphocytes (Panel B, hematoxylin and eosin staining). In this particular case, the patient’s skin involvement alone was indicative of the cutaneous subtype of intravascular large B-cell lymphoma (IVLCL). The treatment began with systemic chemotherapy, leading to remission as confirmed during the 6-month follow-up visit.
The subsequent immunohistochemical staining showed positivity for CD20, PAX-5, and MUM-1 in the neoplastic cells. A positron-emission tomographic–computed tomographic scan yielded negative results. Consequently, a diagnosis of intravascular large B-cell lymphoma was established. This type of lymphoma is rare and often aggressive, primarily affecting tissues outside of the lymph nodes and characterized by malignant cells within small vessel lumens. Diagnosing this disease is challenging due to its nonspecific symptoms and signs (such as fever, fatigue, and lack of lymph node enlargement) and its diverse clinical presentations.
Intravascular large B-cell lymphoma is an uncommon cancer marked by the presence of lymphoma cells within blood vessel lumens
Its annual incidence is less than 0.5 cases per 1,000,000 individuals, primarily affecting older adults with an average diagnosis age of about 70 years. Diagnosing these cases poses challenges due to the lack of lymphoma cells in peripheral blood smears and absence of lymph node enlargement. Although it commonly involves the central nervous system and skin, it can affect any organ.
Prompt diagnosis and treatment initiation are critical due to its high mortality rate. We describe two patients who initially presented with vague symptoms and fever of unknown origin, later determined to have intravascular large B-cell lymphoma. Diagnosis proved difficult in both cases due to their atypical symptoms, with one patient only diagnosed at autopsy. Delayed diagnosis often leads to dire consequences given the disease’s aggressive nature. Maintaining a high index of suspicion clinically is vital for prompt diagnosis and better patient outcomes.
Intravascular large B-cell lymphoma (IVLCL) is an extremely rare cancer characterised by the proliferation of lymphoma cells within the lumens of small blood vessels, without an obvious tumour mass outside the vessels or circulating lymphoma cells. Although intravascular lymphoma with T-cell and natural killer (NK) cell phenotypes has been reported, intravascular large cell lymphoma is now classified as a subtype of diffuse large B-cell lymphoma according to the recent WHO classification. The estimated annual incidence of IVLCL is less than 0.5 cases per 1,000,000, making most of our understanding of this condition derived from case reports and series due to its rarity.
IVLCL is an aggressive and often fatal cancer with poor outcomes, primarily affecting the elderly, typically diagnosed around the age of 70 with no specific gender preference
While central nervous system (CNS) and skin involvement are frequently seen, IVLCL can affect any organ in the body, including the lungs, spleen, and bone marrow. Its diverse presentation, lack of lymphoma cells in peripheral blood smears, and absence of enlarged lymph nodes make timely diagnosis challenging, often leading to cases being identified only at autopsy.
IVLCL has the potential to affect any part of the body’s organ systems. According to a meta-analysis conducted by Fonkem et al., the central nervous system (CNS) is the most commonly affected organ (60%), followed by the bone marrow and spleen (11%), skin (8%), and lungs (7%). There are also reports of IVLCL affecting the kidneys, adrenal glands, reproductive organs, thyroid glands, and gall bladder. The clinical presentation can vary depending on which organ system is involved. Many cases initially present with constitutional symptoms, fever of unknown origin, B-symptoms, and low blood counts. Additionally, a wide range of neurological symptoms, from confusion to stroke, can occur, mirroring the experiences of our two patients.
Diagnosing IVLCL often requires a biopsy of the affected organ. While intravascular involvement is a hallmark of IVLCL, peripheral blood involvement is exceptionally rare. Bone marrow biopsies can provide a diagnosis if there is marrow involvement, although findings can sometimes be nonspecific, as seen in the second case. Laboratory tests typically reveal anaemia, thrombocytopenia, and elevated serum LDH levels. Given the spleen’s frequent involvement and the reported occurrence of adrenal involvement in 60% of autopsied cases, abdominal imaging is recommended. Lung involvement may manifest as ground glass opacities on chest imaging.
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