Primary intravascular natural killer/T cell lymphoma of the central nervous system

Abstract

Intravascular lymphoma (IVL) is a rare neoplasm charac terized by proliferation of malignant cells within the small vessel lumina, particularly capillaries. Cases of IVL almost always occur in extranodal sites, including the skin, cen tral nervous system (CNS), bone marrow, lung and liver [1,2]. B-cell lineage lymphoma is the major variant in IVL, accounting for approximately 85-90% of cases of IVL [3]. Intravascular natural killer (NK)/T cell lymphoma (IVNKTL) is regarded as a rare variant, involving mostly the skin [2], To the best of our knowledge, to date no cases of IVNKTL primarily involving the central nervous system (CNS) have been reported. Here, we report a case of primary IVNKTL of the brain with neurological symptoms as the initial presentation.A 46-year-old man developed a left frontotemporal headache and progressive decline of language ability for more than 1 month. Magnetic resonance imaging (MRI) of the brain showed multiple intracranial lesions within the left frontotemporal and right occipital lobes, and punctate ischemic changes in both the frontal and subcortical lobes. Cerebrospinal fluid (CSF) analysis revealed a normal protein level. Afterthepatientwastreatedwithmannitol,theheadache symptoms were slightly alleviated. No other organ alteration was found by computed tomography (CT) scan of the chest and abdomen. A whole body positron emission computed tomography (PECT) scan revealed only a lesion in the brain, and no lesions were detected in the skin. He received a left frontotemporal craniotomy tumor resection on 12 November 2012. A brain biopsy was taken from the left frontotemporal and right occipital lobes. Gross examination showed a grayred tissue that was 5 cm X 4 cm X 4 cm in size. Histologically, medium-to large-sized pleomorphic lymphoid cells with an abundant eosinophilic cytoplasm and irregular nuclei were confined within the small vasculature and capillaries, but not in the brain tissue [ Figure 1(a)]. The majority of the lumen was completely obstructed by neoplastic cells, and some capillaries contained neoplastic cells. Fibrin thrombi mixed with neoplastic cells were occasionally found in large lumina. Several vessels were surrounded by a small number of reac tive lymphocytes. Intraparenchymal necrosis was observed in localized areas. Based on the morphology, we suspected the case to be intravascular large B-cell lymphoma. However, immunohistochemical analysis did not support the diagnosis of B-cell lymphoma. The neoplastic cells were CD3e+, granzyme B + , CD8+, C D 4-, C D 5-, CD30-, CD20-, CD56-, (3F1 -and T cell receptor (TCR)y/8-. Approximately 100% of cells expressed Ki-67. Epstein-Barr virus (EBV) infection was detected in the tumor cells by in situ hybridization for EBV-encoded small RNA (EBER) [ Figure 1(b)]. Based on the morphology, immunophenotype and EBV infection, the case was diagnosed as IVNKTL of the brain. In addition, we took bone marrow from the patient for chromosome analysis and found no abnormalities. The bone marrow lacked CD3e and EBER positive neoplastic ...

Intravascular NK/T‐cell lymphoma: a report of five cases with cutaneous manifestation from China

“…Recently, Deetz et al and Metcalf et al reported that the vessels associated with intravascular anaplastic large cell lymphoma were actually D2‐40 positive, whereas those associated with intravascular NK/T‐cell lymphoma cases were D2‐40 negative . More importantly, all of the reported intravascular anaplastic large cell lymphoma cases were EBV‐negative, whereas nearly all of the reported intravascular NK/T‐cell lymphoma cases were EBV‐positive . According to these results, intravascular anaplastic large cell lymphoma actually appears to be intralymphatic anaplastic large cell lymphoma, and its growth pattern is very similar to the intravascular pattern observed with cutaneous metastasis …”

“…Given that one of our cases presented with positive CD30 staining, intravascular NK/T‐cell lymphoma should be distinguished from intravascular anaplastic large cell lymphoma; the latter is characterized by anaplastic cells with prominent polymorphisms, whereas the former features medium‐sized and rather uniform hyperchromatic cells . The neoplastic cells found in intravascular anaplastic large cell lymphomas usually occlude the vessels and form closely packed nodules, whereas the neoplastic cells found in intravascular NK/T‐cell lymphomas are usually scattered within the vessels .…”

“…The relationship between intravascular NK/T‐cell lymphoma and aggressive NK‐cell leukemia will require clarification in the future. Bone marrow examination has seldom been performed in reported cases . A bone marrow examination was performed for two of our cases, but no bone marrow involvement was observed.…”

“…Died of disease after 22 days 3 4 Female/24 Subcutaneous nodules and ulceration on the legs and trunk; high fever Died of disease after 4 months 4 4 Male/33 Subcutaneous nodules on the face, neck and leg; high fever Alive after 1 year 5 17 Female/71 Patches and nodules on the trunk and extremities Alive after 5 months 6 21 Male/40 Papules on legs and trunks; splenomegaly Died of disease after 14 months 7 18 Female/68 Patches on the trunk and extremities; fever Died of disease after 2 months 8 18 Male/22 Patches on the trunk and legs; splenomegaly and fever Died of disease after 2 months 9 19 Female/42 Plaques on the legs; malaise, dizziness and chilly sensations Alive after 14 months 10 20 Female/84 Patches and nodules on the trunk and legs Alive after 4 months 11 22 Female/38 Plaque on chest and back; fever Died of disease after 13 months 12 23 Male marrow examination was performed for two of our cases, but no bone marrow involvement was observed. In our case 5, flow cytometry examination of the peripheral blood showed 71% of lymphocytes were positive for CD56, suggesting a leukemia distribution of the neoplastic cells.…”

“…Cerroni et al reported four cases with an NK or T‐cell immunophenotype and reviewed similar cases in the literature, concluding that intravascular NK/T‐cell lymphoma is a highly aggressive lymphoma that is usually associated with Epstein‐Barr virus (EBV) infection. Despite the rarity of intravascular NK/T‐cell lymphoma, it appears prone to development in Chinese patients . In this article, we describe our observations of 5 cases of intravascular NK/T‐cell lymphoma with cutaneous manifestation and review 12 previously reported similar cases involving Chinese patients.…”