Intravascular large B-cell lymphoma (IVLBCL), also known as vasotrophic large cell lymphoma, usually spreads outside of lymph nodes and can involve almost any organ. It develops mainly in tissue and organs with a dense distribution of small vessels such as the skin, brain, liver, and adrenal glands, as was observed in this case. Current studies suggest that the absence of CD29 and CD54 adhesion molecules on tumor cells may be the cause of their intravascular growth patterns [4].
At present, IVLBCL can be divided into two clinical manifestations: Western and Asian. In Western European and American countries, the clinical manifestations mainly appear in the skin and nervous system, either simultaneously or successively. As for the nervous system, mainly the CNS is involved, with major manifestations being dementia, cerebrovascular disease, epilepsy, subacute encephalopathy, cranial neuropathy, and myelopathy [5]. Most patients (76%) are prone to CNS problems as the disease progresses, often presenting with pathologies of the spinal cord and nerve roots (38%). A subset of patients (25%) may show peripheral nervous system (PNS) involvement [6].
In the Asian population, patients mainly present with multiple organ failure or hematological abnormalities such as pancytopenia, autoimmune hemolytic anemia, diffuse intravascular coagulation, hemophagocytic syndrome, and hepatosplenomegaly. However, as the first symptom in our patient was myelopathy, she was diagnosed with NMOSD. The imaging findings showed void-like changes of myelopathy, which is relatively rare in the Asian population. Although immunohistochemical biopsy samples are the best diagnostic strategy for patients suspected of IVLBCL [7, 8], CNS diseases can only be confirmed by autopsy due to the lack of detectable, easily-recognizable pathologic tumor masses through clinical examination and the low positive rate of cerebrospinal fluid cell examination [9, 10]. Therefore, when IVLBCL is suspected in clinical practice, bone marrow puncture biopsy, positron emission tomography-CT, and chest and abdominal CT examinations are helpful in identifying abnormal lesions.
Some studies have reported that biopsy can be performed on seemingly normal skin when other sampling is difficult. The small blood vessels involved in IVLBCL are mainly located in the deep subcutaneous tissue; therefore, biopsy sampling should include this region [11]. Due to the growth characteristics of IVLBCL, tumor cells are often found in the lumen of small blood vessels or intermediate blood vessels in many organs during biopsy, with large size, prominent nucleoli, common mitotic images, necrosis, fibrin thrombus, or bleeding; rarely does IVLBCL present with small cells [12].
IVLBCL is an aggressive form of lymphoma that tends to respond poorly to chemotherapy. At present, most chemotherapy regimens can be used for diffuse large B-cell lymphoma. Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or CHOP-like regimens can slow disease progression. An intensive chemotherapy regimen is required for IVLBCL involving the CNS. However, even when drugs with high CNS bioavailability, such as methotrexate and cytarabine, are selected, prognosis remains poor [13]. Neither the type of clinical presentation nor clinical markers can predict survival. In recent years, it has been reported that early identification of IVLBCL with lesions limited to the skin, kidney, and prostate, followed by rapid treatment with rituximab, can significantly improve the prognosis [2, 14].
Importantly, our patient had both pSS and IVLBCL. NMOSD is an autoimmune neurological disorder characterized by the presence of serum anti-aquaporin-4 antibodies (AQP4) that interfere primarily with the function of astrocytes in the CNS, eventually manifesting as demyelination; currently, cases of NMOSD combined with pSS have been reported, with syringomyelia detected in a few NMOSD cases [17]. Studies have shown that the comorbidity of pSS and AQP4-positive NMOSD is estimated to be 10 to 20%, with a lower incidence of syringomyelia. Although the exact mechanisms underlying syringomyelia development in patients with NMOSD and pSS remain unclear [18], increasing evidence shows that the combination of AQP4 antibodies and AQP4-positive astrocytes is relevant to pathogenesis [19, 20]. Patients with NMOSD and pSS usually have other associated autoimmune diseases, such as rheumatoid arthritis or malignant lymphoma. AQP4-positive NMOSD and pSS are both autoimmune diseases, and they may share a common pathogenesis [17]. This case report describes the coexistence of these two autoimmune diseases with a hematologic malignancy.
When IVLBCL involves the CNS, cranial MRI lesions can show negative diffuse-weighted imaging and long T1 and T2 cortical or subcortical lesions in the frontal and temporal lobes as hallmark features of this disease [21]. In the case of our patient, the symptoms progressively worsened such that the intracranial lesions could not be explained by ischemic stroke. Multiple parts of the spinal cord and adrenal gland were involved, and the patient was secondarily diagnosed with IVLBCL through adrenal aspiration. IVLBCL, therefore, can explain the patient’s symptoms and clinical manifestations.
In conclusion, at present, cases of IVLBCL combined with NMOSD and pSS are rare. The current case was even more unusual in that the myelopathy in our patient presented with a long segmental cavity lesion. Early diagnosis in such patients is difficult, and the misdiagnosis rate is high. Patients with IVLBCL combined with NMOSD and pSS may have a common pathogenesis, which needs to be confirmed using a large sample of clinical data and further explored through basic research.