| The patient was an 82-year-old man without notable medical history. He had felt a loss of appetite in late January 2001, which was associated with progressively worsening strange behavior. On February 2, he could no longer write letters, and he was then admitted to our hospital on February 3. On admission the patient's blood pressure was 190/100 mmHg, and body temperature was 36.6ºC. Neurological examination revealed disorientation, memory function disturbance and delirium with visual hallucination like fireworks. There was spasticity of right extremities without weakness. On hematological examination, white cell count was 3,800/μl, with monocytes comprising 23% and no abnormal cells. Hemoglobin was 12.2 g/dl; platelet count 14.9×104/μl. There was no evidence of hemophagocytic syndrome. On biochemical examination, the LDH level had become elevated to 881 IU/l (LDH3 and LDH4 were prominent). The levels of glucose, ammonium and electrolyte were normal. Serum soluble IL2 receptor antibody was elevated to 6,270 U/ml. Cerebrospinal fluid (CSF) examination revealed a normal cell count but the protein level was elevated at 179 mg/dl and the IgG level was also elevated at 31.9 mg/dl. CT scanning of the brain performed on the day of admission (Fig. 1A) revealed a small low-density lesion at the left corona radiata. CT scanning of the whole body (Fig. 2) revealed bilateral adrenal swelling. There was no evidence of lymphadenopathy or pulmonary lesion. The patient's level of consciousness was worsening, so a follow-up brain CT was performed. This showed a new subcortical lesion at the left occipital lobe (Fig. 1B). In view of the subacute progressing clinical course and data, intravascular lymphomatosis was suspected. In order to establish a histological diagnosis, further examination was performed. Bone marrow aspiration from the ilium revealed almost normal cellular marrow with 1.2% abnormal cells. The abnormal cells were large and had small amounts of basophilic cytoplasm, hyperchromatic nucleoli with irregular nuclear contours, and prominent nucleoli. Bone marrow biopsy showed no specific findings indicative of lymphomatosis. Brain biopsy and adrenal biopsy were abandoned, considering the patient's poor general condition. Therefore, although there was no specific skin eruption, we performed skin biopsy from two ordinary senile angiomas (the diameters of which were 3 mm and 2 mm) on the anterior chest wall on Day 15. Chemotherapy with CHOP regimen was started soon after skin biopsy on Day 16. For a time, consciousness and appetite appeared to be improving, but massive hemorrhagic infarction (Fig. 1C) occurred on Day 21, and the patient died on Day 26. His family did not permit an autopsy. Skin biopsy In one of the two skin biopsy specimens a capillary hemangioma was present in the mid-reticular dermis and filled with abnormal lymphoid cells (Fig. 3). Immunohistochemically, the lymphoid cells were positive for B cell markers L26 and CD79a, and negative for CD34 and CD3. A diagnosis of intravascular B cell lymphoma was thus established. |
| IVL is a rare subtype of extranodal diffuse large B cell lymphoma characterized by the presence of lymphoma cells only in the lumina of small vessels first described in 1959 by Pfleger and Tappeiner (1, 2). The median age at onset is 60 years (range, 12 to 87 years). It develops as subacute encephalopathy, and is usually fatal in a few weeks to several months. However, it is recently thought that if the diagnosis is established early, aggressive chemotherapy increases survival and is potentially curative (3). There may be hesitation with these therapies, however, without a definite diagnosis. Due to a lack of specific laboratory or clinical features of the disease, and a lack of specific imaging and its rare incidence, it is difficult to diagnose IVL. It is said that almost half the cases are diagnosed at autopsy. And if there are no appropriate lesions to perform a biopsy, the diagnosis and therapy are inevitably delayed. Autopsy records of patients have revealed involvement of intravascular lymphoma to the kidney, adrenals, lungs and liver in more than 80% of all cases (4). There is nonspecific imaging for diagnosis of IVL, but CT findings of swelling of adrenals (4) and multiple white matter lesions or hemorrhages, both found in the present case, are said to be common in patients with IVL. These findings might be of importance for diagnosis of IVL. Diagnosis is typically by biopsy of the skin or brain or bone marrow (5, 6) or other lesion in certain variant cases (7, 8) including the adrenal grands (9), although occasional worsening has been described after brain or spinal cord biopsy (10). Skin lesions of IVL include teleangiectasias, hemorrhagic nodules and leg lymphedema (3). There was no specific skin eruption in the present case. Considering the severe general function of our patient, we gave up performing a brain or adrenal biopsy. Instead, we performed bone marrow biopsy to diagnose IVL but the result was negative. We finally performed a skin biopsy of ordinary senile hemangiomas. There is a case report by Munakata et al (11) of IVL diagnosed by skin biopsy of senile angiomas. In that case, the authors presented histological findings that the lymphoma cells were filling the vessel lumen of the senile angiomas and suggested the importance of skin biopsy for more than one skin rash for the diagnosis of IVL. Our case similarly showed that malignant B lymphocytes filled the vessel lumen of the senile angioma. A diagnosis of IVL was thus made. Senile angioma is a skin eruption also known as cherry angioma or Campbell de Morgan spots that are seen commonly on the trunk of middle aged or elderly people. Histologically, these are angiokeratomata. They feature reduplicated membranes and fenestration of the endothelium on ultrastructural examination (12). On the other hand, IVL is characterized by a proliferation of large atypical lymphoid cells within the vascular lumina. The lymphoma cells might be trapped by the histological rich-in-vessel structure of the senile angioma, or the senile angioma shown in this case might have had consequently vessel occlusion of tumor cells. We speculated that is why lymphoma cells were seen in the senile angioma vessels. Treatment has included corticosteroids, cyclophosphamide, a combination of chemotherapy, radiation, plasmapheresis and intrathecal chemotherapy. Although complete responses have been observed, median survival is only 6 months (3). Such poor prognosis reflects in part delays in diagnosis. Among these therapies, patients treated by a combination of chemotherapy were reported to have long-term survival and to be alive in complete remission (4, 6–10, 13). It is the most favorable therapy at present. Unfortunately, CHOP therapy failed to improve disease in our case, but early diagnosis is very important to treat IVL. Senile angioma is a skin eruption considered to be prevalent for the most part in elderly people. If a patient is suspected to have IVL, and there is no appropriate site of biopsy, it might be beneficial to try skin biopsy aiming at senile angiomas for early diagnosis. |