Introduction
Intravascular large B-cell lymphoma (IVLBCL) is a rare form of extranodal non-Hodgkin’s lymphoma (NHL). The real incidence is unknown and the average age at diagnosis is between 60 and 70 years with no sex predilections. This type of lymphoma is characterised by the uncontrolled proliferation of lymphoid cells in the lumen of small vessels, in particular capillaries and post-capillary venules in the absence of tumour masses. Immunophenotypic analysis showed that lymphocyte clone is generally represented by B cells but have also been reported cases of T or NK differentiation.
The tumour itself can potentially affect any organs, but the most frequent locations are the skin and the central nervous system (CNS). The heterogeneity in clinical presentation is due to the fact that the symptoms are caused by the occlusion of small vessels and, therefore, vary according to the affected organs. Systemic symptoms or B-cell symptoms (fever, night sweats, and weight loss) are present in 55–85% of the cases. Typical laboratory findings are anaemia and elevation of lactate dehydrogenase (LDH), beta-2-microglobulin, and erythrocyte sedimentation rate, but they are not specific [1].
The diagnosis can only be confirmed by the presence of lymphoid cells of great size within the lumen of small vessels.
Given the low incidence of this condition, data regarding its treatment are provided with relative stability and only come from case reports and retrospective analyses. Due to the presence of lymphoma cells inside the vessels, all cases of IVLBCL are to be considered scattered and, therefore, require systemic chemotherapy treatment.
Case
The patient, an 84-year-old independent and cognitively intact female, attended our Geriatrics Acute Section with progressively deteriorating dyspnoea and fever, resistant to antibiotic cycle.
Patient’s history: strong smoking status and pneumonia treated at home in the previous year.
Upon presentation at Emergency Department, the patient appeared feverish and dyspnoeic, with partial respiratory failure responsive to oxygen. ECG: sinus rhythm without signs of myocardial ischemia; echocardiographic showed hypertensive heart disease with mild valvular degeneration changes; and a slight increase of the estimated pressure of the small circle. A clinical examination showed bronchospasm, globular abdomen fat, treatable and painless, regular bowel function, and mild pitting edema of lower limbs. There was also no sign of superficial palpable enlarged lymph nodes, skin lesions, night sweats, or weight loss.
The initial laboratory tests showed: hemoglobin 14.5 g/dl, leukocit count 9210/ml (of which 7.880 neutrophils/ml, 680 lymphocytes/ml, 590 monocytes/ml), platelet 168.000/ml, LDH 1620 U/L, C-reactive protein 2.4 mg/dl, and D-dimer 1.12 mg/L. Liver and kidney function was normal. Chest X-ray and pulmonary CT angiography excluded pleural-parenchymal injury and intraluminal filling defects related to thromboembolic formations.
In the suspect of bronchitis and initial heart failure, we started treatment with furosemide, cortisone, and broad-spectrum antibiotic (Piperacillin/Tazobactam and Clarithromycin) with partial benefits. Blood cultures, serology for Chlamydia and Mycoplasma, and research of urinary antigen of Legionella pneumophila and Pneumococcus were negative. The tests confirmed once again LDH elevation, beta-2-microglobulin values of 5.6 mg/L, and normal blood count with lymphocytic formula preserved and without evidence of blast cells.
During the hospitalisation, despite the gradual normalisation of inflammatory markers, the patient experienced progressive deterioration of lung function. We performed a thoracic-abdominal CT with iodinated contrast. This highlighted basal reticulonodular thickening of the interlobular septa and nuanced areolas of ground-glass apparently related to inflammatory phenomena. The test also showed concomitant hazy centrilobular nodules as the initial inflammation of the small airways. The abdomen was free from major injuries. There was also no sign of superficial and deep lymphadenopathy in the explored areas.
After 20 days in hospital, the situation related to hypoxemic acute respiratory failure dramatically deteriorated resulting in Acute Respiratory Distress Syndrome (ARDS). The patient was administered with additional diuretic therapy and steroids, new empirical antibiotic therapy, and non-invasive ventilation with only partial and provisional answer. The patient died after 3 weeks since the onset of symptoms.
The autopsy revealed the spread intravascular proliferation at lymphoid elements into the lung and cardiac tissue, consisting of large breed elements with scant cytoplasm, nucleus prominent, and frequent mitotic figures (Fig. 1). Immunophenotyping showed large cell intravascular lymphoma derived from B lymphocytes (CD20+, CD5-, rare CD10+, BLC2 rare, and a hamlet of non-assessable growth/MB1).
Discussion
What prompted us to analyse this case is the fact that despite the efforts, it was not possible to achieve a diagnosis of IVLBCL before the patient died.
IVLBCL is a rare and aggressive form of non-Hodgkin’s lymphoma often fatal characterised by the proliferation of a lymphoblastic clone within the small vessels, particularly the capillaries and post-capillary venules, with no or minimal parenchymal involvement. Its clinical presentation shows different peculiarities depending on different geographical areas. In particular, in the Western regions, the disease presents tropism for skin and CNS, while in Asian regions frequently occurs with haemophagocytic syndrome associated with bone marrow and spleen involvement, and thrombocytopenia [1, 2].
In our patient, the only aspects that suggested the existence of haematological disease were higher levels of LDH and Beta-2-microglobulin. There were no signs of anaemia or circulating blast cells identifiable, as well as no signs of lymphadenopathy, splenomegaly, or B symptoms except low-grade fever. There were also no signs of cutaneous (39%) or neurological (39%) involvement, described in the literature as the most frequently affected organs. The intravascular lymphoma may occur in the skin with lesions ranging from bluish erythematous plaques in subcutaneous nodules, detected or infiltrated, soft or hard, of variable shape and size, most frequently located on the trunk or lower limbs. In addition, signs of CNS involvement can include mental confusion, focal neurological deficits, or progressive cognitive decline.
Lymphoma is a systemic disease that can potentially affect any organ, including the lung tissue such as in our case. The literature describes few cases of primary lung involvement characterised by progressive hypoxic respiratory failure rapidly fatal. In most cases, t post-mortem diagnosis was made. In one case, lung biopsy allowed the diagnosis of the disease followed by specific therapy, but the patient did not survive [3, 4].
The diagnostic work up in all these cases has initially provided laboratory investigations. Most of the patients presented a pathological blood count because of the presence of anaemia (approximately 65% of cases), with elevation of LDH and Beta 2 microglobulin in almost 90%. Despite the intravascular growth pattern, lymphoma is rarely associated with peripheral involvement. Blast cells can be identified by a common hemocromocytometric analysis in only 5–9% of cases.
The common imaging methods used for the staging of NHL, being the disease free from extravascular localizations, are associated with high false negative rates. Despite the worsening dyspnoea and hypoxemia in our patient, the thoracic-abdominal CT scan showed no significant alterations and no signs of lymphoid disease. The few cases where the disease affected the lungs have reported non-specific findings as pulmonary infiltrates, signs of pulmonary hypertension and pleural effusions, but no signs of lymphadenopathy or splenomegaly. The bone marrow biopsy which was not performed to our patient, showed a normal haematopoiesis in the absence of abnormal infiltrates in most circumstances (the bone marrow involvement is reported in 33% of cases).
This prevalence data derived from the broader analysis of lymphoma cases in Western countries as indicated in the literature. 38 cases were analysed and the research was conducted by Ferreri et al. [1], who have contributed to the drafting of guidelines for clinical practice sponsored by the International Extranodal Lymphoma Study Group [5]. In accordance with the recommendations indicated in the literature, if you suspect an IVLBCL, the diagnosis must be confirmed by biopsy of skin lesion if present, or “random” of unharmed skin. If IVLBCL is still not diagnosed, biopsies of the organs affected by disease should be considered (e.g., liver, lung, and cerebrospinal fluid) [5].
Up until now, there are no randomised controlled studies that have looked at IVLBCL treatments. Despite this, most authors recommend the use of the CHOP regimen (combination of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) alongside Rituximab. The introduction of anti-CD 20 monoclonal antibody has been shown to have a positive impact on the patients, resulting in a 60% response rate with 3-year survival of over 30%. An agreement was reached related to the use of local therapies including radiation therapy, in elderly patients who have cutaneous single lesion variant.
Conclusion
IVLBCL is a rare form of lymphoid disease and it can be devious and aggressive. There are no clinical, laboratory, or pathognomonic radiological signs, and because of the heterogeneity of its clinical manifestations, its diagnosis represents a real diagnostic challenge for the physician and is often only identified during post-mortem tests. The diagnosis can only be made by histological analysis by looking at the lumen of small vessels; however, clinical suspicion is the key element to achieve an early diagnosis in life.
Abbreviations
- IVLBCL:
-
Intravascular large B-cell Lymphoma
- NHL:
-
Non-Hodgkin’s lymphoma
- ARDS:
-
Adult respiratory distress syndrome
- LDH:
-
Lactate dehydrogenase
- CHOP:
-
Cyclophosphamide, hydroxydaunorubicin, oncovin (vincristine), prednisone, or prednisolone
References
Ferreri AJ, Campo E, Seymour JF et al (2004) Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the “cutaneous variant”. Br J Haematol 127:173–178
Murase T, Yamaguchi M, Suzuki R et al (2007) Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5. Blood 109:478–485
Walls JG, Hong YG, Cox JE et al (1999) Pulmonary intravascular lymphomatosis: presentation with dyspnea and air trapping. Chest 115:1207–1210
Martusewicz-Boros M, Wiatr E, Radzikowska E et al (2007) Pulmonary intravascular large B-cell lymphoma as a cause of severe hypoxemia. J Clin Oncol 25:2137–2139
Ponzoni M, Ferreri AJ, Campo E et al (2007) Definition, diagnosis and management of intravascular large B-cell lymphoma: proposal and perspectives from an international consensus meeting. J Clin Oncol 25:3168–3173
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Statement of human and animal rights
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
For this type of study informed consent is not required.
Rights and permissions
About this article
Cite this article
Lazzari, I., Galetti, C., Corvalli, G. et al. Intravascular large B-cell lymphoma as a cause of terminal acute respiratory distress syndrome: atypical presentation of a rare disease. Aging Clin Exp Res 30, 97–99 (2018). https://doi.org/10.1007/s40520-017-0754-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40520-017-0754-3