By the new World Health Organization (WHO) classification, IVLBCL is a rare type of extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of vessels, particularly capillaries, with exception of larger arteries and veins . It is a rare and aggressive variant of intravascular proliferation of clonal lymphocytes with little to no parenchymal involvement.
The clinical manifestations of IVLBCL are highly variable and depend on the preferentially involved organs. There are no pathognomonic, clinical, laboratory, or radiological signs of IVLBCL. Nearly half of cases present fever of unknown origin, night sweats, malaise, fatigue, unexplained weight loss. Anemia, high lactic acid,dehydrogenase levels, and high sedimentation rates are typical. In Western countries, CNS and cutaneous symptoms account for close to 80 % of presentations, while in Asian countries, hemaphagocytic syndrome are much more commonly seen. And some authors found that 68 % of IVLBCL patients had symptoms present in at least one of these organs. Although autopsy findings indicated that lung involvement in IVLBCL is relatively frequent (approximately 60 %) , predominat or primary presentation in lung has been rare. Diagnosis for our patient was so difficult because she did not demonstrate any cutaneous or neurological symptoms. Only chest CT revealed diffuse interstitial changes. Then she was treated with antibiotics and after transient improvement of symptoms, the treatment was not effective and the chest CT-scan remained shadows. For the purpose of diagnosis, surgical lung biopsy was performed. All biopsied specimens demonstrated obstruction of the small vessels by large neoplastic lymphoid cells, which expressed B-cell associated antigen CD20. These histological findings confirmed the diagnosis of IVLBCL. Radiological examinations in pulmonary IVLBCL present various findings. The majority of cases with lung involvement showed diffuse interstitial infiltrates, pleural effusion, signs of pulmonary hypertension, or consolidation in the lung. In this case, our patient did not demonstrate any cutaneous or neurological symptoms. The laboratory findings were normal. And except her chest CT appeared interstitial pneumonitis alike, there was no involvement of any other organ considered typical of IVLBCL. All of these made the diagnosis challenging and difficult. Recently, FDG-PET has emerged as a powerful functional imaging tool in the assessment of patients with non-Hodgkin’s lymphoma (NHL). Several authors have reported that FDG-PET is useful for the diagnosis of IVLBCL when this type of lymphoma is clinically suspected. FDG-PET is a powerful tool for the early diagnosis of IVLBCL with pulmonary involvement, if the possibility of this disease presents in the patient with respiratory symptoms without abnormal findings by CT [3, 4].
IVLBCL is characterized by a massive intravascular proliferation of atypical mononuclear cells which lodged in the lumina of small or intermediate vessels in many organs. The neoplastic lymphoid cells are large with prominent nucleoli and frequent mitotic figures. Fibrin thrombi, haemorhage and necrosis may be seen. IVLBCL needs to be differentiated from venous thromboembolism, bland thrombus mixed with lymphoma cells, metastatic carcinoma or melanoma. The other differential diagnosis of intravascular malignancy in the lung includes lymphomatoid granulomatosis, angiocentric lymphoma, sarcoma, and pulmonary involvement by acute and chronic lymphocytic leukemias. Immunohistochemistry will provide great help for the correct diagnosis. In this case, the neoplastic cells showed ground or oval shape with large, vesicular nuclei, and little to moderate amounts of pale cytoplasm. No adhesion was seen between tumor cell. Neuroendocrine tumor and other mesenchymal differentiated tumors (smooth muscle tissue, neuro tissue et al.) can not be excluded. So we perform antibodies like Syn, Chr-A, desmin, S-100 to help differentiation diagnosis.
The mechanism of selective intravascular location of IVLBCL are largely unknown. Several studies showed that the defective interactions between lymphoma cells and vessels may play a role in the pathogenesis of this disorder [5–7]. Lymphocyes circulating in the blood vessels bind to high endothelial venules (HEV) with lymphocyte homing receptor, traverse vessels walls and enter lymphoid organs. They also found that IVLBCL cells had normal levels of lymphocyte homing receptor, while the presence of HEV is selectively low or absent in organs where IVLBCL commonly occurs, such as brain and skin. These observations suggest that a deficiency of HEV in particular sites of blood vessels may block lymphoma cells transvascular passage and result in the unusual intravascular location of lymphoma cells. CD29 and CD54 are key molecules for transvascular trafficking and migration. Recently, it was found that IVLBCL cells express low levels of CD29 and CD54, which may be responsible for the selective growth of IVLBCL. In addition, IVLBCL cells have lower levels of another adhesion molecule CD18, which may also contribute to their inability to extravasate . CXCL9-CXCR3 also provide a possible new clue to the pathogenesis of IVLBCL by virtue of the characteristic expression of them. CXCR3 was expressed in IVLBCL and its ligand, CXCL9, was expressed in blood vessels, which might explain the aggregation of atypical lymphocytes in the vascular lumen .
Patients with IVLBCL are thought to have a systemic disease with an aggressive clinical course . The site of disease influences the prognosis. Patients with CNS involvement at initial diagnosis developed early CNS progression. Conversely, the duration between initial diagnosis and CNS recurrence was long in patients without CNS involvement . These findings might reflect differences in clinical manifestations between patients with CNS IVLBCL and patients with cutaneous IVLBCL. The latter have a significantly longer survival. Combination chemotheraphy is the mainstay of treatment. CHOP or CHOP-like therapy has been more commonly offered. The addition of rituximab to CHOP therapy substantially improved the prognosis of IVLBCL. But the difficulties and delays in diagnosis oftern result in the poor prognosis which make it urgent need to better understand this lymphoma and to optimize its therapeutic management.